Author Report for: Wang JNo contact information in database for Wang J
Chen Y, Chen L, Xu H, Cao R, Morisseau C, Zhang M, Shi Y, Hammock BD, Wang J and Chen G <2 more author(s)> Chen Y, Chen L, Xu H, Cao R, Morisseau C, Zhang M, Shi Y, Hammock BD, Wang J, Zhuang J, Liu Z, Chen G (- 2) Ref: Journal of Medicinal Chemistry, :, 2023 : PubMed ESTHER: Chen_2023_J.Med.Chem__ PubMedSearch: Chen 2023 J.Med.Chem PubMedID: 36689364 Abstract Soluble epoxide hydrolase (sEH) has been identified as an attractive target for anti-inflammatory drug design in recent years. Picomolar level compound G1 against sEH was obtained by introducing the hydrophilic group homopiperazine and hydrophobic fragment propionyl onto the structure of lead compound A. G1 showed good microsomal stability, a moderate plasma protein binding rate, and good oral bioavailability and was well tolerated in rats. G1 has significant analgesic effects on CFA-induced AIA mice, ameliorated the pancreatic injury in acute pancreatitis induced by l-arginine, reversed pancreatic injury, edema, and neutrophil infiltration, and increased the survival time of C57BL/6 mice in a lipopolysaccharide (LPS)-induced sepsis model. Moreover the expression levels of sEH, COX-2, NOS-2, vascular cell adhesion molecule (VCAM), IL-6, MCP-5, and tumor necrosis factor alpha (TNF-alpha) were measured by Western blot or enzyme-linked immunosorbent assay (ELISA), with varying degrees of decrease. These results suggested that G1 is a drug candidate worthy of further evaluation for the treatment of inflammation-induced diseases such as arthritis, acute pancreatitis, and sepsis. Title: Effects of Methyl Jasmonate Fumigation on the Growth and Detoxification Ability of Spodoptera litura to Xanthotoxin Chen L, Song J, Wang J, Ye M, Deng Q, Wu X, Ren B Ref: Insects, 14:, 2023 : PubMed ESTHER: Chen_2023_Insects_14_ PubMedSearch: Chen 2023 Insects 14 PubMedID: 36835714 Abstract Methyl jasmonate (MeJA) is a volatile substance derived from jasmonic acid (JA), and it responds to interbiotic and abiotic stresses by participating in interplant communication. Despite its function in interplant communication, the specific role of MeJA in insect defense responses is poorly understood. In this study, we found that carboxylesterase (CarE) activities, glutathione-S-transferase (GSTs) activities, and cytochrome mono-oxygenases (P450s) content increased more after the feeding of diets containing xanthotoxin, while larvae exposed to MeJA fumigation also showed higher enzyme activity in a dose-dependent manner: lower and medium concentrations of MeJA induced higher detoxification enzyme activities than higher concentrations of MeJA. Moreover, MeJA improved the growth of larvae fed on the control diet without toxins and diets with lower concentrations of xanthotoxin (0.05%); however, MeJA could not protect the larvae against higher concentrations of xanthotoxin (0.1%, 0.2%). In summary, we demonstrated that MeJA is effective at inducing S. litura defense response, but the enhanced detoxifying ability could not overcome the strong toxins. Title: Molecular insights into the catalytic mechanism of plasticizer degradation by a monoalkyl phthalate hydrolase Chen Y, Wang Y, Xu Y, Sun J, Yang L, Feng C, Wang J, Zhou Y, Zhang ZM Ref: Commun Chem, 6:45, 2023 : PubMed ESTHER: Chen_2023_Commun.Chem_6_45 PubMedSearch: Chen 2023 Commun.Chem 6 45 PubMedID: 36859434 Gene_locus related to this paper: 9acto-q2mhh5 Abstract Phthalate acid esters (PAEs), a group of xenobiotic compounds used extensively as plasticizers, have attracted increasing concern for adverse effects to human health and the environment. Microbial degradation relying on PAE hydrolases is a promising treatment. However, only a limited number of PAE hydrolases were characterized to date. Here we report the structures of MehpH, a monoalkyl phthalate (MBP) hydrolase that catalyzes the reaction of MBP to phthalic acid and the corresponding alcohol, in apo and ligand-bound form. The structures reveal a positively-charged catalytic center, complementary to the negatively-charged carboxyl group on MBP, and a penetrating tunnel that serves as exit of alcohol. The study provides a first glimpse into the enzyme-substrate binding model for PAE hydrolases, leading strong support to the development of better enzymes in the future. Title: Oligomerization of a plant helper NLR requires cell-surface and intracellular immune receptor activation Feehan JM, Wang J, Sun X, Choi J, Ahn HK, Ngou BPM, Parker JE, Jones JDG Ref: Proc Natl Acad Sci U S A, 120:e2210406120, 2023 : PubMed ESTHER: Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120 PubMedSearch: Feehan 2023 Proc.Natl.Acad.Sci.U.S.A 120 e2210406120 PubMedID: 36877846 Abstract Plant disease resistance involves both detection of microbial molecular patterns by cell-surface pattern recognition receptors and detection of pathogen effectors by intracellular NLR immune receptors. NLRs are classified as sensor NLRs, involved in effector detection, or helper NLRs required for sensor NLR signaling. TIR-domain-containing sensor NLRs (TNLs) require helper NLRs NRG1 and ADR1 for resistance, and helper NLR activation of defense requires the lipase-domain proteins EDS1, SAG101, and PAD4. Previously, we found that NRG1 associates with EDS1 and SAG101 in a TNL activation-dependent manner [X. Sun et al., Nat. Commun. 12, 3335 (2021)]. We report here how the helper NLR NRG1 associates with itself and with EDS1 and SAG101 during TNL-initiated immunity. Full immunity requires coactivation and mutual potentiation of cell-surface and intracellular immune receptor-initiated signaling [B. P. M. Ngou, H.-K. Ahn, P. Ding, J. D. G. Jones, Nature 592, 110-115 (2021), M. Yuan et al., Nature 592, 105-109 (2021)]. We find that while activation of TNLs is sufficient to promote NRG1-EDS1-SAG101 interaction, the formation of an oligomeric NRG1-EDS1-SAG101 resistosome requires the additional coactivation of cell-surface receptor-initiated defense. These data suggest that NRG1-EDS1-SAG101 resistosome formation in vivo is part of the mechanism that links intracellular and cell-surface receptor signaling pathways. Title: Carboxylesterase 1 family knockout alters drug disposition and lipid metabolism Gan C, Wang J, Martinez-Chavez A, Hillebrand M, de Vries N, Beukers J, Wagenaar E, Wang Y, Lebre MC and Schinkel AH <6 more author(s)> Gan C, Wang J, Martinez-Chavez A, Hillebrand M, de Vries N, Beukers J, Wagenaar E, Wang Y, Lebre MC, Rosing H, Klarenbeek S, Ali RB, Pritchard C, Huijbers I, Beijnen JH, Schinkel AH (- 6) Ref: Acta Pharm Sin B, 13:618, 2023 : PubMed ESTHER: Gan_2023_Acta.Pharm.Sin.B_13_618 PubMedSearch: Gan 2023 Acta.Pharm.Sin.B 13 618 PubMedID: 36873183 Gene_locus related to this paper: mouse-Ces1a, mouse-Ces1b, mouse-Ces1c, mouse-Ces1d, mouse-Ces1e, mouse-Ces1f, mouse-Ces1g, mouse-Ces1h Abstract The mammalian carboxylesterase 1 (Ces1/CES1) family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids. To investigate the pharmacological and physiological roles of Ces1/CES1, we generated Ces1 cluster knockout (Ces1 (-/-) ) mice, and a hepatic human CES1 transgenic model in the Ces1 (-/-) background (TgCES1). Ces1 (-/-) mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues. TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney. Ces1 and hCES1 activity increased irinotecan toxicity, likely by enhancing the formation of pharmacodynamically active SN-38. Ces1 (-/-) mice also showed markedly increased capecitabine plasma exposure, which was moderately decreased in TgCES1 mice. Ces1 (-/-) mice were overweight with increased adipose tissue, white adipose tissue inflammation (in males), a higher lipid load in brown adipose tissue, and impaired blood glucose tolerance (in males). These phenotypes were mostly reversed in TgCES1 mice. TgCES1 mice displayed increased triglyceride secretion from liver to plasma, together with higher triglyceride levels in the male liver. These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification. Ces1 (-/-) and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes. Title: Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities Gan D, Li C, Shu Y, Wang J, Wang C, Zhu L, Yang Y, Liu J, He B and Ding Z <1 more author(s)> Gan D, Li C, Shu Y, Wang J, Wang C, Zhu L, Yang Y, Liu J, He B, Cai L, Ding Z (- 1) Ref: Chin J Nat Med, 21:154, 2023 : PubMed ESTHER: Gan_2023_Chin.J.Nat.Med_21_154 PubMedSearch: Gan 2023 Chin.J.Nat.Med 21 154 PubMedID: 36871983 Abstract The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C(28)-steroid with an unusual beta- and gamma-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC(50) value of 2.61 +/- 0.05 micromol.L(-1). The beta-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 microg.mL(-1). Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 microg.mL(-1), respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC(50) values of 9.2 +/- 0.03 and 13.3 +/- 0.01 micromol.L(-1), respectively. Title: Ecological risk assessment of environmentally relevant concentrations of propofol on zebrafish (Danio rerio) at early life stage: Insight into physiological, biochemical, and molecular aspects Jiang N, Li X, Wang Q, Baihetiyaer B, Fan X, Li M, Sun H, Yin X, Wang J Ref: Chemosphere, :137846, 2023 : PubMed ESTHER: Jiang_2023_Chemosphere__137846 PubMedSearch: Jiang 2023 Chemosphere 137846 PubMedID: 36646180 Abstract Propofol is an intravenous anesthetic injection extensively used in clinic, which has been proved to be neurotoxic in humans. Improper use and disposal of propofol may lead to its release into the aquatic environment, but the potential ecological risk of propofol to aquatic organisms remains poorly understood. For this study, we comprehensively explored the ecotoxicological effects and potential mechanisms of propofol (0.04, 0.2 and 2 mg L(-1)) on 120 hpf zebrafish (Danio rerio) embryos from physiological, biochemical, and molecular perspectives. The results showed that propofol has moderate toxicity on zebrafish embryos (96 h LC(50) = 4.260 mg L(-1)), which could significantly reduce the hatchability and delay the development. Propofol can trigger reactive oxygen species (ROS) generation, lipid peroxidation (Malondialdehyde, MDA) and DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG). The glutathione peroxidase (GPX) activity of zebrafish embryos in 0.04 and 0.2 mg L(-1) propofol treatment group was activated in response to oxidative damage, while activities of superoxide dismutase (SOD), catalase (CAT) and GPX in zebrafish treated with 2 mg L(-1) was significant inhibited compared with the control group (p0.05). Moreover, the expression of antioxidant genes and related pathways was inhibited. Apoptosis was investigated at genes level and histochemistry. Molecular docking confirmed that propofol could change in the secondary structure of acetylcholinesterase (AChE) and competitively inhibited acetylcholine (ACh) binding to AChE, which may disturb the nervous system. These results described toxic response and molecular mechanism in zebrafish embryos, providing multiple aspects about ecological risk assessment of propofol in water environment. Title: Do 'Newly Born' orphan proteins resemble 'Never Born' proteins? A study using three deep learning algorithms Liu J, Yuan R, Shao W, Wang J, Silman I, Sussman JL Ref: Proteins, :, 2023 : PubMed ESTHER: Liu_2023_Proteins__ PubMedSearch: Liu 2023 Proteins PubMedID: 37092778 Abstract "Newly Born" proteins, devoid of detectable homology to any other proteins, known as orphan proteins, occur in a single species or within a taxonomically restricted gene family. They are generated by the expression of novel open reading frames, and appear throughout evolution. We were curious if three recently developed programs for predicting protein structures, namely, AlphaFold2, RoseTTAFold, and ESMFold, might be of value for comparison of such "Newly Born" proteins to random polypeptides with amino acid content similar to that of native proteins, which have been called "Never Born" proteins. The programs were used to compare the structures of two sets of "Never Born" proteins that had been expressed-Group 1, which had been shown experimentally to possess substantial secondary structure, and Group 3, which had been shown to be intrinsically disordered. Overall, although the models generated were scored as being of low quality, they nevertheless revealed some general principles. Specifically, all four members of Group 1 were predicted to be compact by all three algorithms, in agreement with the experimental data, whereas the members of Group 3 were predicted to be very extended, as would be expected for intrinsically disordered proteins, again consistent with the experimental data. These predicted differences were shown to be statistically significant by comparing their accessible surface areas. The three programs were then used to predict the structures of three orphan proteins whose crystal structures had been solved, two of which display novel folds. Surprisingly, only for the protein which did not have a novel fold, and was taxonomically restricted, rather than being a true orphan, did all three algorithms predict very similar, high-quality structures, closely resembling the crystal structure. Finally, they were used to predict the structures of seven orphan proteins with well-identified biological functions, whose 3D structures are not known. Two proteins, which were predicted to be disordered based on their sequences, are predicted by all three structure algorithms to be extended structures. The other five were predicted to be compact structures with only two exceptions in the case of AlphaFold2. All three prediction algorithms make remarkably similar and high-quality predictions for one large protein, HCO_11565, from a nematode. It is conjectured that this is due to many homologs in the taxonomically restricted family of which it is a member, and to the fact that the Dali server revealed several nonrelated proteins with similar folds. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Proteins:3. Title: Strategy of In Situ Electrochemical Regulation for Highly Enhanced Nonenzymatic Sensing of Carbaryl Lv Y, Zhang Y, Yang Y, Li J, Wang J, Xiao X, Zhang M Ref: Analytical Chemistry, :, 2023 : PubMed ESTHER: Lv_2023_Anal.Chem__ PubMedSearch: Lv 2023 Anal.Chem PubMedID: 36802553 Abstract Specific and sensitive sensing of most pesticide residues relies on enzymes such as acetylcholinesterase and advanced materials, which need to be loaded on the surface of working electrodes, leading to instability, uneven surface, tedious process, and high cost. Meanwhile, employing certain potential or current in electrolyte solution could also modify the surface in situ and overcome these drawbacks. However, this method is only regarded as electrochemical activation widely applied in the pretreatment of electrodes. In this paper, by means of regulating the electrochemical technique and its parameters, we prepared a proper sensing interface and derivatized the carbaryl (a carbamate pesticide) hydrolyzed form (1-naphthol) to enhance sensing by 100 times within several minutes. After regulation I by chronopotentiometry with 0.2 mA for 20 s or chronoamperometry with 2 V for 10 s, abundant oxygen-containing groups form and the ordered carbon structure is destroyed. Sweeping from -0.5 to 0.9 V through cyclic voltammetry for only one segment, following regulation II, the composition of oxygen-containing groups changes and the disordered structure is alleviated. Finally, on the constructed sensing interface, test by regulation III through differential pulse voltammetry from 0.8 to -0.4 V, resulting in derivatization of 1-naphthol during 0.8-0 V, followed by electroreduction of the derivative at around -0.17 V. Compared with the electro-oxidation peak at 0.5 V in previous reports, it is essential to improve specificity, even toward several other carbamate pesticides with similar structures. Hence, the in situ electrochemical regulation strategy has demonstrated great potential for effective sensing of electroactive molecules. Title: Genome-wide identification and analysis of the SUPPRESSOR of MAX2 1-LIKE gene family and its interaction with DWARF14 in poplar Sun M, Wang D, Liu C, Liu Y, Niu M, Wang J, Li J Ref: BMC Plant Biol, 23:105, 2023 : PubMed ESTHER: Sun_2023_BMC.Plant.Biol_23_105 PubMedSearch: Sun 2023 BMC.Plant.Biol 23 105 PubMedID: 36814183 Abstract BACKGROUND: Strigolactones (SLs) are important phytohormones that can regulate branch development in plants. Although SUPPRESSOR of MAX2 1-LIKE proteins (SMXLs) play a crucial role in SL signaling transduction, the SMXL gene family has not been well characterized in poplar. RESULTS: In this study, 12 members of the poplar SMXL gene family were identified and phylogenetically classified into four clades. Motif and 3D structural analyses revealed that PtSMXL proteins are structurally very conserved; however, the P-loop NTPase domain at the C-terminal was found to vary substantially among clades. A genomic collinearity analysis indicated that PtSMXL gene family members have expanded during recent genome doubling events in poplar, with all gene pairs subsequently undergoing purifying selection. According to a Cis-element analysis, PtSMXL promoters contain many light-responsive elements. In an expression pattern analysis, all 12 PtSMXL genes displayed tissue-specific expression, especially PtSMXL8a. PtSMXL7b expression was significantly downregulated after axillary bud growth begins. In addition, the expressions of PtSMXL7b and PtSMXL8a were highly induced by 2 microM GR24, a synthetic SL analog, thus suggesting that these genes are involved in SL-regulated axillary bud growth. In a yeast two-hybrid assay, only PtSMXL7b in clade II was able to interact with the SL receptor PtD14a in an SL dependent manner, which indicates that PtSMXL7b may be the functional homolog of D53/SMXL6/7/8 in poplar. Finally, we established its ability to affect axillary bud growth by constructing poplar overexpressing the PtSMXL7b gene. CONCLUSIONS: Our findings may inform future research on the functions of SMXLs in poplar, especially with respect to branch development. Title: Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys Wang J, Zheng W, Zheng S, Yuan Y, Wen W, Cui W, Xue L, Sun X, Shang H and Zhang X <3 more author(s)> Wang J, Zheng W, Zheng S, Yuan Y, Wen W, Cui W, Xue L, Sun X, Shang H, Zhang H, Xiao RP, Gao S, Zhang X (- 3) Ref: Mol Ther Nucleic Acids, 31:68, 2023 : PubMed ESTHER: Wang_2023_Mol.Ther.Nucleic.Acids_31_68 PubMedSearch: Wang 2023 Mol.Ther.Nucleic.Acids 31 68 PubMedID: 36618267 Abstract Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by insvivo and insvitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15sweeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development. Title: Molecular, morphological and behavioral alterations of zebrafish (Danio rerio) embryos/larvae after clorprenaline hydrochloride exposure Wang B, Wang A, Xu C, Tong Z, Wang Y, Zhuo X, Fu L, Yao W, Wang J, Wu Y Ref: Food & Chemical Toxicology, 176:113776, 2023 : PubMed ESTHER: Wang_2023_Food.Chem.Toxicol_176_113776 PubMedSearch: Wang 2023 Food.Chem.Toxicol 176 113776 PubMedID: 37059383 Abstract Chlorprenaline hydrochloride (CLOR) is a typical representative of beta-adrenergic agonists that may be used illegally as a livestock feed additive and may have adverse impacts on the environment. In the present study, zebrafish embryos were exposed to CLOR to investigate its developmental toxicity and neurotoxicity. The results demonstrated that CLOR exposure led to adverse effects on developing zebrafish, such as morphological changes, a high heart rate, and increased body length, resulting in developmental toxicity. Moreover, the up-regulation of activities of superoxide dismutase (SOD) and catalase (CAT) and the enhancement of malondialdehyde (MDA) content illustrated that CLOR exposure activated oxidative stress in exposed zebrafish embryos. Meanwhile, CLOR exposure also caused alterations in locomotive behavior in zebrafish embryos, including an increase in acetylcholinesterase (AChE) activity. Quantitative polymerase chain reaction (QPCR) results showed that the transcription of genes related to the central nervous system (CNS) development, namely, mbp, syn2a, alpha1-tubulin, gap43, shha, and elavl3, indicated that CLOR exposure could lead to neurotoxicity in zebrafish embryos. These results showed that CLOR exposure could cause developmental neurotoxicity in the early stages of zebrafish development and that CLOR might induce neurotoxicity by altering the expression of neuro-developmental genes, elevating AChE activity, and activating oxidative stress. Title: Adipose triglyceride lipase: the first transacylase for FAHFAs Wang J, Liang G, Zhao TJ Ref: Life Metab, 2:, 2023 : PubMed ESTHER: Wang_2023_Life.Metab_2_ PubMedSearch: Wang 2023 Life.Metab 2 PubMedID: 37168434 Abstract In a recent article published in Nature, Patel et al. identified adipose triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2) as the first biosynthetic enzyme of fatty acid esters of hydroxy fatty acids (FAHFAs), further expanding the knowledge on bioactive lipid research and being a potential paradigm shift for ATGL studies. Title: A portable acetylcholinesterase-based electrochemical sensor for field detection of organophosphorus Wen L, Wang J, Liu Z, Tao CA, Rao J, Hang J, Li Y Ref: RSC Adv, 13:6389, 2023 : PubMed ESTHER: Wen_2023_RSC.Adv_13_6389 PubMedSearch: Wen 2023 RSC.Adv 13 6389 PubMedID: 36874943 Abstract A portable acetylcholinesterase (AChE)-based electrochemical sensor based on a screen-printed carbon electrode (SPCE) and a miniature potentiostat was constructed for the rapid field detection of organophosphorus pesticides (OPs). Graphene (GR) and gold nanoparticles (AuNPs) were successively introduced onto SPCE for surface modification. Due to the synergistic effect of the two nanomaterials, the signal of the sensor has a significant enhancement. Take isocarbophos (ICP) as a model for chemical warfare agents (CAWs) and Ops; the SPCE/GR/AuNPs/AChE/Nafion sensor shows a wider linear range (0.1-2000 microg L(-1)), and a lower limit of detection (0.012 microg L(-1)) than SPCE/AChE/Nafion and SPCE/GR/AChE/Nafion sensors. Tests in actual fruit and tap water samples also yielded satisfactory results. Therefore, the proposed method can be used as a simple and cost-effective strategy for construction of portable electrochemical sensors for OP field detection. Title: Toxic effects of isofenphos-methyl on zebrafish embryonic development Wu Y, Wang J, Xia Y, Tang K, Xu J, Wang A, Hu S, Wen L, Wang B, Yao W Ref: Ecotoxicology & Environmental Safety, 254:114723, 2023 : PubMed ESTHER: Wu_2023_Ecotoxicol.Environ.Saf_254_114723 PubMedSearch: Wu 2023 Ecotoxicol.Environ.Saf 254 114723 PubMedID: 36871354 Inhibitor(s) related to this paper: Isofenphos-methyl Abstract Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks to the environment and humans, but little information is available on its sublethal toxicity to aquatic organisms. To address this knowledge gap, the current study exposed zebrafish embryos to 2, 4, and 8 mg/L IFP within 6-96 h past fertilization (hpf) and measured mortality, hatching, developmental abnormalities, oxidative stress, gene expressions, and locomotor activity. The results showed that IFP exposure reduced the rates of heart and survival rate, hatchability, and body length of embryos and induced uninflated swim bladder and developmental malformations. Reduction in locomotive behavior and inhibition of AChE activity indicated that IFP exposure may induce behavioral defects and neurotoxicity in zebrafish larvae. IFP exposure also led to pericardial edema, longer venous sinus-arterial bulb (SV-BA) distance, and apoptosis of the heart cells. Moreover, IFP exposure increased the accumulation of reactive oxygen species (ROS) and the content of malonaldehyde (MDA), also elevated the levels of antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), but decreased glutathione (GSH) levels in zebrafish embryos. The relative expressions of heart development-related genes (nkx2.5, nppa, gata4, and tbx2b), apoptosis-related genes (bcl2, p53, bax, and puma), and swim bladder development-related genes (foxA3, anxa5b, mnx1, and has2) were significantly altered by IFP exposure. Collectively, our results indicated that IFP induced developmental toxicity and neurotoxicity to zebrafish embryos and the mechanisms may be relevant to the activation of oxidative stress and reduction of acetylcholinesterase (AChE) content. Title: Rosmarinic acid potentiates and detoxifies tacrine in combination for Alzheimer's disease Yang M, Zhang X, Qiao O, Ji H, Zhang Y, Han X, Wang W, Li X, Wang J and Gao W <2 more author(s)> Yang M, Zhang X, Qiao O, Ji H, Zhang Y, Han X, Wang W, Li X, Wang J, Guo L, Huang L, Gao W (- 2) Ref: Phytomedicine, 109:154600, 2023 : PubMed ESTHER: Yang_2023_Phytomedicine_109_154600 PubMedSearch: Yang 2023 Phytomedicine 109 154600 PubMedID: 36610144 Abstract BACKGROUND: There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection. PURPOSE AND STUDY DESIGN: In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice. METHODS: In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on. RESULTS: RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A beta oligomer, inhibit the deposition of A beta, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK. CONCLUSION: The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease. Title: Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease Yang F, Zhao J, Chen G, Han H, Hu S, Wang N, Wang J, Chen Y, Zhou Z and Liu Y <2 more author(s)> Yang F, Zhao J, Chen G, Han H, Hu S, Wang N, Wang J, Chen Y, Zhou Z, Dai B, Hou Y, Liu Y (- 2) Ref: Bioorg Chem, 133:106432, 2023 : PubMed ESTHER: Yang_2023_Bioorg.Chem_133_106432 PubMedSearch: Yang 2023 Bioorg.Chem 133 106432 PubMedID: 36841050 Abstract Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca(2+) homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca(2+) release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC(50) = 0.162 microM) and AChE (inhibition (%) = 93.5, IC(50) = 0.372 microM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD. Title: Green biosynthesis of rare DHA-phospholipids by lipase-catalyzed transesterification with edible algal oil in solvent-free system and catalytic mechanism study Zhang T, Li B, Wang Z, Hu D, Zhang X, Zhao B, Wang J Ref: Front Bioeng Biotechnol, 11:1158348, 2023 : PubMed ESTHER: Zhang_2023_Front.Bioeng.Biotechnol_11_1158348 PubMedSearch: Zhang 2023 Front.Bioeng.Biotechnol 11 1158348 PubMedID: 37064237 Abstract Docosahexaenoic acid (DHA)-enriched phosphatidylcholine (PC) has received significant scientific attention due to the health benefits in food and pharmaceutical products. In this work, the edible algal oil rich in DHA-triacylglycerol (DHA-TAG) without pretreatment was first used as the DHA donor for the transesterification of phospholipids (PLs) to prepare three kinds of rare PLs, including DHA-PC, DHA-phosphatidylethanolamine (DHA-PE), and DHA-phosphatidylserine (DHA-PS). Here, 153 protein structures of triacylglycerol lipase (EC 3.1.1.3) were virtually screened and evaluated by transesterification. PLA1 was the best candidate due to a higher DHA incorporation. Results showed that the transesterification of PC with DHA-TAG at 45 degreesC and 0.7% water content (without additional water addition) could produce DHA-PC with 39.1% DHA incorporation at 30 min. The different DHA donors, including forms of fatty acid, methyl ester, and triglycerides, were compared. Molecular dynamics (MD) was used to illustrate the catalytic mechanism at the molecular level containing the diffusions of substrates, the structure-activity relationship of PLA1, and the effect of water content. Title: Reduced Fitness and Elevated Oxidative Stress in the Marine Copepod Tigriopus japonicus Exposed to the Toxic Dinoflagellate Karenia mikimotoi Chen SC, Yang CS, Chen JJ, Chen H, Wang J, Zhuang Y, Yu W, Liu G Ref: Antioxidants (Basel), 11:, 2022 : PubMed ESTHER: Chen_2022_Antioxidants.(Basel)_11_ PubMedSearch: Chen 2022 Antioxidants.(Basel) 11 PubMedID: 35883874 36421485 Abstract Blooms of the toxic dinoflagellate Karenia mikimotoi cause devastation to marine life, including declines of fitness and population recruitment. However, little is known about the effects of them on benthic copepods. Here, we assessed the acute and chronic effects of K. mikimotoi on the marine benthic copepod Tigriopus japonicus. Results showed that adult females maintained high survival (>85%) throughout 14-d incubation, but time-dependent reduction of survival was detected in the highest K. mikimotoi concentration, and nauplii and copepodites were more vulnerable compared to adults. Ingestion of K. mikimotoi depressed the grazing of copepods but significantly induced the generation of reactive oxygen species (ROS), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and acetylcholinesterase. Under sublethal concentrations for two generations, K. mikimotoi reduced the fitness of copepods by prolonging development time and decreasing successful development rate, egg production, and the number of clutches. Our findings suggest that the bloom of K. mikimotoi may threaten copepod population recruitment, and its adverse effects are associated with oxidative stress. Title: Plin5, a New Target in Diabetic Cardiomyopathy Cui X, Wang J, Zhang Y, Wei J, Wang Y Ref: Oxid Med Cell Longev, 2022:2122856, 2022 : PubMed ESTHER: Cui_2022_Oxid.Med.Cell.Longev_2022_2122856 PubMedSearch: Cui 2022 Oxid.Med.Cell.Longev 2022 2122856 PubMedID: 35509833 Abstract Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches. Title: Immobilization of Rhizomucor miehei lipase on magnetic multiwalled carbon nanotubes towards the synthesis of structured lipids rich in sn-2 palmitic acid and sn-1,3 oleic acid (OPO) for infant formula use Ghide MK, Li K, Wang J, Abdulmalek SA, Yan Y Ref: Food Chem, 390:133171, 2022 : PubMed ESTHER: Ghide_2022_Food.Chem_390_133171 PubMedSearch: Ghide 2022 Food.Chem 390 133171 PubMedID: 35551020 Abstract Nowadays, breast milk is considered as the ideal food for infants owing to the most common oleic acid-palmitic acid-oleic acid (OA-PA-OA) fatty acid distribution of the human milk fat (HMF). This study reports the synthesis of 1,3-dioleoyl-2-palmotoylglycerol (OPO)-rich human milk fat substitutes in a two-step enzymatic acidolysis reaction with Rhizomucor miehei lipase (RML) immobilized on magnetic multi-walled carbon nanotubes(mMWCNTs). The immobilized RML (RML-mMWCNTs) showed better thermal and pH stability, convenient recovery and reusability than the free soluble form. Under optimized reaction conditions (1:8 tripalmitin (PPP)/OA, 10%wt. enzyme, 50 degreesC, 5 h), PA content at the sn-2 position and OA incorporation at the sn-1,3 positions reached 93.46% and 59.54%, respectively. Comparison tests have also showed that RML-mMWCNTs has better catalytic activity and reusability than the commercial lipase Lipozyme RM IM. The results suggest that RML-mMWCNTs is a promising biocatalyst for the synthesis of OPO-rich TAGs with potential use in infant formulas. Title: Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry Hu C, Zhuang X, Zhang J, Wang T, Du S, Wang J, Peng X, Cao Q, Zhang M, Jiang Y Ref: Lab Med, :, 2022 : PubMed ESTHER: Hu_2022_Lab.Med__ PubMedSearch: Hu 2022 Lab.Med PubMedID: 35075477 Abstract OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. METHODS: Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. RESULTS: A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. CONCLUSION: The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM. Title: Design of 2,5-furandicarboxylic based polyesters degraded in different environmental conditions: Comprehensive experimental and theoretical study Hu H, Li J, Luo S, Tian Y, Wang J, Zhao YL, Zhang R, Zhu J Ref: J Hazard Mater, 425:127752, 2022 : PubMed ESTHER: Hu_2022_J.Hazard.Mater_425_127752 PubMedSearch: Hu 2022 J.Hazard.Mater 425 127752 PubMedID: 34906869 Gene_locus related to this paper: canar-LipB Abstract Nowadays, the promotion and application of aliphatic-aromatic copolyesters, such as poly (butylene adipate-co-terephthalate) (PBAT), are growing into a general trend. Although the structures of diacids exerted substantial impacts on degradation behavior, the underlying mechanisms have rarely been studied. In this work, 2,5-Furandicarboxylic acid was combined with succinic acid (PBSF), adipic acid (PBAF) and diglycolic acid (PBDF) to prepare three kinds of copolyesters. They showed unique degradation behaviors in buffer, enzyme environment and artificial seawater. These characteristics are closely related to the structural compositions of diacids. PBAFs displayed impressive biodegradability when catalyzed by Candida antarctica lipase B (CALB), while the more hydrophilic PBDFs exhibited faster hydrolysis in both buffer and artificial seawater. PBSFs, with hydrophobic and short segments, obtained a relatively slower rate of hydrolysis and enzymatic degradation. The reactivity sites and hydrolytic pathway were revealed by the combination of DFT calculation and Fukui function analysis. MD simulations, QM/MM optimizations and theozyme calculations showed that PBAF-CALB was prone to form a pre-reaction state, leading to the reduced energy barrier in the acylation process. This work revealed the effects of different structural features of diacids on polymer degradation and paved a way to design target biodegradable polymers in different degradation conditions. Title: Pharmacological treatments for psychotic symptoms in dementia: A systematic review with pairwise and network meta-analysis Huang YY, Teng T, Shen XN, Chen SD, Wang RZ, Zhang RQ, Dou KX, Zhong XL, Wang J and Yu JT <5 more author(s)> Huang YY, Teng T, Shen XN, Chen SD, Wang RZ, Zhang RQ, Dou KX, Zhong XL, Wang J, Chen KL, Zhao QH, Tan L, Dong Q, Zhou XY, Yu JT (- 5) Ref: Ageing Res Rev, 75:101568, 2022 : PubMed ESTHER: Huang_2022_Ageing.Res.Rev_75_101568 PubMedSearch: Huang 2022 Ageing.Res.Rev 75 101568 PubMedID: 35051646 Abstract Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] -0.30, 95% credible interval [CrI] -0.50 to -0.12; SUCRA, 0.85), memantine (SMD -0.20, 95%CrI -0.34 to -0.07; SUCRA, 0.68) and aripiprazole (SMD -0.17, 95% CrI -0.32 to -0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD -0.16, 95% CrI -0.28 to -0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06-2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from -0.36 to -0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from -0.47 to -0.36). Most of the results were rated as "low" to "very low". Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted. Title: High-Resolution Bioassay Profiling with Complemented Sensitivity and Resolution for Pancreatic Lipase Inhibitor Screening Jian J, Yuan J, Fan Y, Wang J, Zhang T, Kool J, Jiang Z Ref: Molecules, 27:, 2022 : PubMed ESTHER: Jian_2022_Molecules_27_ PubMedSearch: Jian 2022 Molecules 27 PubMedID: 36296516 Abstract How to rapidly and accurately screen bioactive components from complex natural products remains a major challenge. In this study, a screening platform for pancreatic lipase (PL) inhibitors was established by combining magnetic beads-based ligand fishing and high-resolution bioassay profiling. This platform was well validated using a mixture of standard compounds, i.e., (-)- epigallocatechin gallate (EGCG), luteolin and schisandrin. The dose-effect relationship of high-resolution bioassay profiling was demonstrated by the standard mixture with different concentrations for each compound. The screening of PL inhibitors from green tea extract at the concentrations of 0.2, 0.5 and 1.0 mg/mL by independent high-resolution bioassay profiling was performed. After sample pre-treatment by ligand fishing, green tea extract at the concentration of 0.2 mg/mL was specifically enriched and simplified, and consequently screened through the high-resolution bioassay profiling. As a result, three PL inhibitors, i.e., EGCG, (-)-Gallocatechin gallate (GCG) and (-)-Epicatechin gallate (ECG), were rapidly identified from the complex matrix. The established platform proved to be capable of enriching affinity binders and eliminating nonbinders in sample pre-treatment by ligand fishing, which overcame the technical challenges of high-resolution bioassay profiling in the aspects of sensitivity and resolution. Meanwhile, the high-resolution bioassay profiling possesses the ability of direct bioactive assessment, parallel structural analysis and identification after separation. The established platform allowed more accurate and rapid screening of PL inhibitors, which greatly facilitated natural product-based drug screening. Title: Bioaccumulation and toxicity of terbuthylazine in earthworms (Eisenia fetida) Li S, Yuan Y, Wang X, Cai L, Wang J, Zhao Y, Jiang L, Yang X Ref: Environ Toxicol Pharmacol, 97:104016, 2022 : PubMed ESTHER: Li_2022_Environ.Toxicol.Pharmacol_97_104016 PubMedSearch: Li 2022 Environ.Toxicol.Pharmacol 97 104016 PubMedID: 36435387 Abstract Terbuthylazine is an effective and widely used s-triazine herbicide. However, limited data exists on its toxicity and bioaccumulation in earthworms (Eisenia fetida). In this study, we investigated the bioaccumulation, antioxidant enzyme activity, detoxification enzyme activity, and DNA damage in earthworms when exposed to terbuthylazine. The results indicated that terbuthylazine in soil had low bioaccumulation in earthworms and the biota-soil accumulation factors of terbuthylazine declined with an increasing soil terbuthylazine concentration. In the enzyme activity assays, the superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities showed upward trends when compared with the control. The carboxylesterase (CarE) activity increased on day 21. The 8-hydroxy-2-deoxyguanosine (8-OHdG) content, a DNA damage bioindicator, was higher than that of the control on day 21. Combined with the integrated biological response index version 2 analysis, these results can provide a comprehensive evaluation of the toxicological effects that terbuthylazine has on earthworms and soil ecosystems. Title: Evaluation of the toxicity effects of microplastics and cadmium on earthworms Liang X, Zhou D, Wang J, Li Y, Liu Y, Ning Y Ref: Sci Total Environ, :155747, 2022 : PubMed ESTHER: Liang_2022_Sci.Total.Environ__155747 PubMedSearch: Liang 2022 Sci.Total.Environ 155747 PubMedID: 35533859 Abstract Microplastics (MPs) and heavy metal pollution have become research hotspots in recent years. This study focused on the comprehensive evaluation of the toxicity effect on Eisenia fetida under combined exposure to MPs and the heavy metal cadmium (Cd). With Cd concentration, MPs concentration and MPs partical size as stress factors, the TOPSIS model was constructed to explore the toxicity levels of the stress factors. A short-term co-exposure test and a long-term co-exposure test were designed by orthogonal combination tests with equivalent toxicity levels. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione peroxidase (GPX), glutathione S transferase (GST), and acetylcholinesterase (AChE) and the contents of protein (TP), glutathione (GSH), and malondialdehyde (MDA) in earthworms were determined. Integrated biological responses version 2 (IBRv2) was used to evaluate the toxicity of MPs and Cd combined exposure on earthworms. The results showed that the toxicity ratio of Cd concentration, MPs concentration and MPs partical size was 46 to 29 to 25. Combined exposure to MPs and Cd enhanced the activities of SOD, POD, CAT, GPX and GST, MDA and GSH contents also increased, while the AChE activities were inhibited. SOD, GPX and GST play important roles in the resistance of earthworms to pollutant stress. During short-term co-exposure, Cd concentration had antagonistic effects with on MPs concentration and MPs partical size, while they showed synergistic effects during long-term co-exposure. Title: Metal-Organic Frameworks-Based Immobilized Enzyme Microreactors Integrated with Capillary Electrochromatography for High-Efficiency Enzyme Assay Liu M, Yang J, Wang J, Liu Z, Hu C, Liu Y, Wei X, Chen J, Yu YL and Fu Q <8 more author(s)> Liu M, Yang J, Wang J, Liu Z, Hu C, Liu Y, Wei X, Chen J, Yu YL, Wang JH, Qiu H, Liu R, Yi G, Ji B, Liu X, Gui Y, Xia Z, Fu Q (- 8) Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Liu_2022_Anal.Chem__ PubMedSearch: Liu 2022 Anal.Chem PubMedID: 34978797 35385268 35465669 Abstract Enzyme assays are important for studying enzyme-mediated biochemical reactions and for clinical diagnosis and drug development. The technique of an immobilized enzyme microreactor (IMER) integrated with capillary electrophoresis (CE) has been frequently utilized in online enzyme assays. However, the traditional approaches for IMER-CE enzyme analysis have some defects such as low loading capacity and poor stability. Herein, metal-organic frameworks (MOFs), which have enormous potential in the fields of enzyme immobilization and capillary electrochromatographic (CEC) separation, were first explored as novel support materials with good enzyme immobilization performance and stationary phases with excellent separation abilities to construct an integrated MOFs-IMER-CEC microanalysis system for a high-efficiency online enzyme assay. As a proof-of-concept demonstration, acetylcholinesterase (AChE) was immobilized on a densely packed UiO-66-NH(2) nanocrystal coating on a capillary inner surface with abundant intercrystalline mesoporosity and was employed as a highly effective and robust IMER for CEC-integrated online enzyme analysis. The excellent separation performance of the UiO-66-NH(2)-modified capillary was verified by high-efficiency separation of three types of neutral, acidic, and basic compounds. The Michaelis-Menten constant and enzyme inhibition kinetics of UiO-66-NH(2)-IMER were systematically assessed, exhibiting distinct advantages such as remarkably increased enzyme loadability, superior affinity for substrates, and greatly improved stability and repeatability compared to CE-integrated IMERs prepared by the traditional covalent bonding method. Furthermore, the developed method was successfully utilized for detecting organophosphorus pesticides in leguminous vegetable samples, demonstrating its strong practicality. The study not only proposed a novel support material and construction strategy for a high-performance microchannel-based IMER but also can be widely used in bioanalysis and biosensing research. Title: Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA Liu T, Zhang X, Zhang H, Cheng Z, Liu J, Zhou C, Luo S, Luo W, Li S and Wan J <12 more author(s)> Liu T, Zhang X, Zhang H, Cheng Z, Liu J, Zhou C, Luo S, Luo W, Li S, Xing X, Chang Y, Shi C, Ren Y, Zhu S, Lei C, Guo X, Wang J, Zhao Z, Wang H, Zhai H, Lin Q, Wan J (- 12) Ref: Plant Cell, 34:3301, 2022 : PubMed ESTHER: Liu_2022_Plant.Cell_34_3301 PubMedSearch: Liu 2022 Plant.Cell 34 3301 PubMedID: 35670739 Abstract Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development. Title: Asperbenzophenone A and Versicolamide C, New Fungal Metabolites from the Soft Coral Derived Aspergillus sp. SCSIO 41036 Long J, Pang X, Lin X, Liao S, Zhou X, Wang J, Yang B, Liu Y Ref: Chem Biodivers, :e202100925, 2022 : PubMed ESTHER: Long_2022_Chem.Biodivers__e202100925 PubMedSearch: Long 2022 Chem.Biodivers e202100925 PubMedID: 35194907 Abstract Two new compounds, asperbenzophenone A (1) and versicolamide C (5), together with fifteen known compounds were isolated from a soft coral derived fungus Aspergillus sp. SCSIO 41036. Their structures were elucidated by spectroscopic methods, ECD analysis, and by a comparison with data from the literature. In bioassay, compound 8 showed significant inhibitory activity against lipopolysaccharide-inducted nitric oxide (NO) in RAW264.7 cells at the concentration of 10microM. Additionally, the anti-acetylcholinesterase activity assay showed that 14 exhibited weak inhibition with an IC(50) value of 157.8microM. Title: Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020 Ma C, Wei D, Liu P, Fan K, Nie L, Song Y, Wang M, Wang L, Xu Q and Zeng X <10 more author(s)> Ma C, Wei D, Liu P, Fan K, Nie L, Song Y, Wang M, Wang L, Xu Q, Wang J, Shi J, Geng J, Zhao M, Jia Z, Huan C, Huo W, Wang C, Mao Z, Huang S, Zeng X (- 10) Ref: Front Public Health, 10:901485, 2022 : PubMed ESTHER: Ma_2022_Front.Public.Health_10_901485 PubMedSearch: Ma 2022 Front.Public.Health 10 901485 PubMedID: 35757605 Abstract BACKGROUND: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province. METHODS: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions. RESULTS: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) (P < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all P < 0.05). CONCLUSION: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management. Title: Characterization of a new chlorimuron-ethyl-degrading strain Cedecea sp. LAM2020 and biodegradation pathway revealed by multiomics analysis Ma Q, Han X, Song J, Wang J, Li Q, Parales RE, Li L, Ruan Z Ref: J Hazard Mater, 443:130197, 2022 : PubMed ESTHER: Ma_2022_J.Hazard.Mater_443_130197 PubMedSearch: Ma 2022 J.Hazard.Mater 443 130197 PubMedID: 36272371 Gene_locus related to this paper: 9entr-CarHBioH Abstract The widespread use of the herbicide chlorimuron-methyl is hazard to rotational crops and causes soil degradation problems. Biodegradation is considered a promising way for removing herbicide residues from the environment. Here, a new isolated strain, Cedecea sp. LAM2020, enabled complete degradation of 100 mg/L chlorimuron-methyl within five days. Transcriptome analysis revealed that ABC transporters, atrazine degradation and purine metabolism were enriched in the KEGG pathway. Integrating GO and KEGG classification with related reports, we predict that carboxylesterases are involved in the biodegradation of chlorimuron-methyl by LAM2020. Heterologous expression of the carboxylesterase gene carH showed 26.67% degradation of 50 mg/L chlorimuron-methyl within 6 h. The intracellular potential biological response and extracellular degradation process of chlorimuron-ethyl were analyzed by the nontarget metabolomic and mass spectrometry respectively, and the biodegradation characteristics and complete mineralization pathway was revealed. The cleavage of the sulfonylurea bridge and the ester bond achieved the first step in the degradation of chlorimuron-methyl. Together, these results reveal the presence of acidolysis and enzymatic degradation of chlorimuron-methyl by strain LAM2020. Hydroponic corn experiment showed that the addition of strain LAM2020 alleviated the toxic effects of chlorimuron-ethyl on the plants. Collectively, strain LAM2020 may be a promising microbial agent for plants chlorimuron-ethyl detoxification and soil biofertilizer. Title: Moringa Oleifera Alleviates Abeta Burden and Improves Synaptic Plasticity and Cognitive Impairments in APP/PS1 Mice Mahaman YAR, Feng J, Huang F, Salissou MTM, Wang J, Liu R, Zhang B, Li H, Zhu F, Wang X Ref: Nutrients, 14:, 2022 : PubMed ESTHER: Mahaman_2022_Nutrients_14_ PubMedSearch: Mahaman 2022 Nutrients 14 PubMedID: 36296969 Abstract Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Abeta and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Abeta burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases. Title: Engineered small extracellular vesicles as a versatile platform to efficiently load ferulic acid via an esterase-responsive active loading strategy Man F, Xing H, Wang H, Wang J, Lu R Ref: Front Bioeng Biotechnol, 10:1043130, 2022 : PubMed ESTHER: Man_2022_Front.Bioeng.Biotechnol_10_1043130 PubMedSearch: Man 2022 Front.Bioeng.Biotechnol 10 1043130 PubMedID: 36440451 Abstract As nano-drug carriers, small extracellular vesicles (sEVs) have shown unique advantages, but their drug loading and encapsulation efficiency are far from being satisfied, especially for the loading of hydrophilic small-molecule drugs. Inspired by the strategies of active loading of liposomal nanomedicines, pre-drug design and immobilization enzyme, here we developed a new platform, named "Esterase-responsive Active Loading" (EAL), for the efficient and stable drug encapsulation of sEVs. Widely used ferulic acid ester derivatives were chosen as prodrugs based on the EAL of engineered sEVs to establish a continuous transmembrane ion gradient for achieving efficient loading of active molecule ferulic acid into sEVs. The EAL showed that the drug loading and encapsulation efficiency were around 6-fold and 5-fold higher than passive loading, respectively. Moreover, characterization by nano-flow cytometry and Malvern particle size analyzer showed that differential ultracentrifugation combined with multiple types of membrane filtration methods can achieve large-scale and high-quality production of sEVs. Finally, extracellular and intracellular assessments further confirmed the superior performance of the EAL-prepared sEVs-loaded ferulic acid preparation in terms of slow release and low toxicity. Taken together, these findings will provide an instructive insight into the development of sEV-based delivery systems. Title: Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel Nan J, Wang Q, Yan Q, Wang J, Zhang Y, Zhao X Ref: Curr Issues Mol Biol, 44:3779, 2022 : PubMed ESTHER: Nan_2022_Curr.Issues.Mol.Biol_44_3779 PubMedSearch: Nan 2022 Curr.Issues.Mol.Biol 44 3779 PubMedID: 36005155 Abstract Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelusdromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction. Title: Catalytically active inclusion bodies (CatIBs) induced by terminally attached self-assembling coiled-coil domains: To enhance the stability of (R)-hydroxynitrile lyase Pei X, Wang J, Zheng H, Xiao Q, Wang A, Su W Ref: Enzyme Microb Technol, 153:109915, 2022 : PubMed ESTHER: Pei_2022_Enzyme.Microb.Technol_153_109915 PubMedSearch: Pei 2022 Enzyme.Microb.Technol 153 109915 PubMedID: 34670185 Abstract The catalytically-active inclusion bodies (CatIBs) represent a promising strategy for immobilizing enzyme without additional carriers and chemicals, which has aroused great attention in academic and industrial communities. In this work, we discovered two natural parallel right-handed coiled-coil tetramer peptides from PDB database by a structural mining strategy. The two self-assembling peptides, NSPdoT from rotavirus and HVdoT from human Vasodilator-stimulated phosphoprotein, efficiently induced the CatIBs formation of a (R)-Hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) in Escherichia coli cells. This is convenient to simultaneously purify and immobilize the target proteins as biocatalysts. As expected, HVdoT-AtHNL and NSPdoT-AtHNL possessed drastically increased tolerance toward lower pH values, which will be very critical to synthesize cyanohydrins under acidic condition for suppressing the non-enzymatic side reaction. In addition. AtHNL-CatIBs are produced at high yield in host cells as bioactive microparticles, which exhibited high thermal and pH stabilities. Therefore, the CatIBs method represent a promising application for the immobilization of enzymes in the biocatalysis field. Title: The longitudinal triglyceride phenotype in heterozygotes with LPL pathogenic variants Perera SD, Wang J, McIntyre AD, Dron JS, Hegele RA Ref: J Clin Lipidol, :, 2022 : PubMed ESTHER: Perera_2022_J.Clin.Lipidol__ PubMedSearch: Perera 2022 J.Clin.Lipidol PubMedID: 36476373 Abstract BACKGROUND: Biallelic pathogenic variants in lipoprotein lipase (LPL) cause familial chylomicronemia syndrome with severe hypertriglyceridemia (HTG), defined as plasma triglycerides (TG) > 10 mmol/L (> 885 mg/dL). TG levels in individuals with one copy of a pathogenic LPL gene variant is less familiar; some assume that the phenotype is intermediate between homozygotes and controls. OBJECTIVE: We undertook an evaluation of the longitudinal TG phenotype of individuals heterozygous for pathogenic LPL variants. METHODS: Medically stable outpatients were evaluated based on having: (1) a single copy of a rare pathogenic LPL variant; and (2) serial fasting TG measurements obtained over > 1.5 years of follow-up. RESULTS: Fifteen patients with a single pathogenic LPL variant were followed for a mean of 10.3 years (range 1.5 to 30.3 years). TG levels varied widely both within and between patients. One patient had normal TG levels < 2.0 mmol/L (< 175 mg/dL) continuously, while four patients had at least one normal TG level. Most patients fluctuated between mild-to-moderate and severe HTG: five patients had only mild-to-moderate HTG, with TG levels ranging from 2.0 to 9.9 mmol/L (175 to 885 mg/dL), while 6 patients had at least one instance of severe HTG. Of the 203 total TG measurements from these patients, 14.8%, 67.0% and 18.2% were in the normal, mild-to-moderate and severe HTG ranges, respectively. CONCLUSION: The heterozygous LPL deficient phenotype is highly variable both within and between patients. Heterozygosity confers susceptibility to a wide range of TG phenotypes, with severity likely depending on secondary factors. Title: Point-of-care SARS-CoV-2 sensing using lens-free imaging and a deep learning-assisted quantitative agglutination assay Potter CJ, Hu Y, Xiong Z, Wang J, McLeod E Ref: Lab Chip, :, 2022 : PubMed ESTHER: Potter_2022_Lab.Chip__ PubMedSearch: Potter 2022 Lab.Chip PubMedID: 36047372 Abstract The persistence of the global COVID-19 pandemic caused by the SARS-CoV-2 virus has continued to emphasize the need for point-of-care (POC) diagnostic tests for viral diagnosis. The most widely used tests, lateral flow assays used in rapid antigen tests, and reverse-transcriptase real-time polymerase chain reaction (RT-PCR), have been instrumental in mitigating the impact of new waves of the pandemic, but fail to provide both sensitive and rapid readout to patients. Here, we present a portable lens-free imaging system coupled with a particle agglutination assay as a novel biosensor for SARS-CoV-2. This sensor images and quantifies individual microbeads undergoing agglutination through a combination of computational imaging and deep learning as a way to detect levels of SARS-CoV-2 in a complex sample. SARS-CoV-2 pseudovirus in solution is incubated with acetyl cholinesterase 2 (ACE2)-functionalized microbeads then loaded into an inexpensive imaging chip. The sample is imaged in a portable in-line lens-free holographic microscope and an image is reconstructed from a pixel superresolved hologram. Images are analyzed by a deep-learning algorithm that distinguishes microbead agglutination from cell debris and viral particle aggregates, and agglutination is quantified based on the network output. We propose an assay procedure using two images which results in the accurate determination of viral concentrations greater than the limit of detection (LOD) of 1.27 x 10(3) copies per mL, with a tested dynamic range of 3 orders of magnitude, without yet reaching the upper limit. This biosensor can be used for fast SARS-CoV-2 diagnosis in low-resource POC settings and has the potential to mitigate the spread of future waves of the pandemic. Title: Characterization of the anti-AChE potential and alkaloids in Rhizoma Coptidis from different Coptis species combined with spectrum-effect relationship and molecular docking Qi L, Zhong F, Liu N, Wang J, Nie K, Tan Y, Ma Y, Xia L Ref: Front Plant Sci, 13:1020309, 2022 : PubMed ESTHER: Qi_2022_Front.Plant.Sci_13_1020309 PubMedSearch: Qi 2022 Front.Plant.Sci 13 1020309 PubMedID: 36388527 Abstract Coptis species are the main source of Rhizoma Coptidis (RC) drugs, which have always been used to treat Alzheimer's disease in the clinical experience of ancient China. However, many species of this genus have been largely underutilized until now. With this fact, this research has been designed to investigate for the first time the anti-acetylcholinesterase (AChE) property of different extracts for RC drugs from four Coptis species (C. chinensis, C. deltoidea, C. teeta and C. omeiensis) and to quantify the main alkaloids. Petroleum ether, ethyl acetate and n-butanol fractions of RC drugs were sequentially collected using an accelerated solvent extraction technique. Spectrum-effect relationship and molecular docking were applied to analyse the relationships between alkaloids and AChE inhibitory activity. The N-butanol extract was proven to be the main active fraction, and C. teeta may be the best source of RC drugs for Alzheimer's disease treatment, with significantly lower IC 20, IC 50 and IC 80 values for AChE inhibition. The UPLC/QqQ-MS quantitative analysis showed that the accumulations of 10 alkaloids in RC drugs from different sources greatly varied. Three data processing methods (Random forest, Boruta and Pearson correlation) comprehensively analysed the spectrum-effect relationship and revealed that columbamine, berberine and palmatine were the most important AChE inhibitors that could be used as quality markers to select RC drugs for Alzheimer's disease treatment. In addition, the dominant compounds were successfully docked against AChE to verify the binding affinity and interactions with the active site. The present study can contribute to the reasonable development and utilization of RC drugs from different sources, especially to provide certain evidence for their application in the treatment of Alzheimer's disease. Title: Genome-wide expression analysis of carboxylesterase (CXE) gene family implies GBCXE49 functional responding to alkaline stress in cotton Rui C, Peng F, Fan Y, Zhang Y, Zhang Z, Xu N, Zhang H, Wang J, Li S and Ye W <7 more author(s)> Rui C, Peng F, Fan Y, Zhang Y, Zhang Z, Xu N, Zhang H, Wang J, Li S, Yang T, Malik WA, Lu X, Chen X, Wang D, Chen C, Gao W, Ye W (- 7) Ref: BMC Plant Biol, 22:194, 2022 : PubMed ESTHER: Rui_2022_BMC.Plant.Biol_22_194 PubMedSearch: Rui 2022 BMC.Plant.Biol 22 194 PubMedID: 35413814 Abstract BACKGROUND: Carboxylesterase (CXE) is a type of hydrolase with alpha/beta sheet hydrolase activity widely found in animals, plants and microorganisms, which plays an important role in plant growth, development and resistance to stress. RESULTS: A total of 72, 74, 39, 38 CXE genes were identified in Gossypium barbadense, Gossypium hirsutum, Gossypium raimondii and Gossypium arboreum, respectively. The gene structure and expression pattern were analyzed. The GBCXE genes were divided into 6 subgroups, and the chromosome distribution of members of the family were mapped. Analysis of promoter cis-acting elements showed that most GBCXE genes contain cis-elements related to plant hormones (GA, IAA) or abiotic stress. These 6 genes we screened out were expressed in the root, stem and leaf tissues. Combined with the heat map, GBCXE49 gene was selected for subcellular locate and confirmed that the protein was expressed in the cytoplasm. CONCLUSIONS: The collinearity analysis of the CXE genes of the four cotton species in this family indicated that tandem replication played an indispensable role in the evolution of the CXE gene family. The expression patterns of GBCXE gene under different stress treatments indicated that GBCXE gene may significantly participate in the response to salt and alkaline stress through different mechanisms. Through the virus-induced gene silencing technology (VIGS), it was speculated that GBCXE49 gene was involved in the response to alkaline stress in G. barbadense. Title: Development of indole-2-carbonyl piperazine urea derivatives as selective FAAH inhibitors for efficient treatment of depression and pain Shang Y, Wang M, Hao Q, Meng T, Li L, Shi J, Yang G, Zhang Z, Yang K, Wang J Ref: Bioorg Chem, 128:106031, 2022 : PubMed ESTHER: Shang_2022_Bioorg.Chem_128_106031 PubMedSearch: Shang 2022 Bioorg.Chem 128 106031 PubMedID: 36037600 Abstract Fatty acid amide hydrolase (FAAH), aserinehydrolase with significant role in thehydrolysis of endocannabinoids, is a promising therapeutic target for peripheral and central nervous system related disorders, including pain, neuroinflammation and depression. Employing a structure-based approach, a novel series of indole-2-carbonyl piperazine urea derivatives were designed and synthesized as FAAH inhibitors for the treatment of pain-depression comorbidity. Among them, compound 4i emerged as the most potent inhibitor (IC(50) = 0.12 microM) with fine selectivity versus CES2, ABHD6, MAGL and the cannabinoid receptor, which also displayed superior metabolic stability in human liver microsome and an adequate pharmacokinetic profile in rodents. Treatment of depressed rats with 4i demonstrated favorable antidepressant-like effects not only by increasing the level of BDNF in the hippocampus but also by restraining the apoptosis of hippocampal neurons. Also, 4i effectively suppressed the LPS-induced neuroinflammation in vitro. Moreover, 4i exhibited potent analgesic activity, which indicated its promising therapeutical application for pain and depression. These meaningful results shed light on FAAH inhibitors as promising pain-depression comorbidity therapeutics. Title: Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus Sun T, Xu W, Wang J, Wang T, Wang S, Liu K, Liu J Ref: Andrology, :, 2022 : PubMed ESTHER: Sun_2022_Andrology__ PubMedSearch: Sun 2022 Andrology PubMedID: 36113503 Abstract BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. OBJECTIVES: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. METHODS: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into 3 groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. RESULTS: We found erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. CONCLUSION: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4is may be beneficial to the management of DMED. This article is protected by copyright. All rights reserved. Title: Functional enzyme-polymer complexes Waltmann C, Mills CE, Wang J, Qiao B, Torkelson JM, Tullman-Ercek D, Olvera de la Cruz M Ref: Proc Natl Acad Sci U S A, 119:e2119509119, 2022 : PubMed ESTHER: Waltmann_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2119509119 PubMedSearch: Waltmann 2022 Proc.Natl.Acad.Sci.U.S.A 119 e2119509119 PubMedID: 35312375 Abstract SignificanceThe use of biological enzyme catalysts could have huge ramifications for chemical industries. However, these enzymes are often inactive in nonbiological conditions, such as high temperatures, present in industrial settings. Here, we show that the enzyme PETase (polyethylene terephthalate [PET]), with potential application in plastic recycling, is stabilized at elevated temperature through complexation with random copolymers. We demonstrate this through simulations and experiments on different types of substrates. Our simulations also provide strategies for designing more enzymatically active complexes by altering polymer composition and enzyme charge distribution. Title: Effect of propeptide mutations on the directed evolution of Rhizomucor miehei lipase Wang J, Bai R, Wu N, Zhang Y, Hu L Ref: Protein Pept Lett, :, 2022 : PubMed ESTHER: Wang_2022_Protein.Pept.Lett__ PubMedSearch: Wang 2022 Protein.Pept.Lett PubMedID: 35289250 Gene_locus related to this paper: rhimi-lipas Abstract BACKGROUND: A series of mutants of Rhizomucor miehei lipase (RML) screened through four rounds of directed evolution was studied as the research object. The hydrolysis activity of mutants to triglycerides was determined, and their genes were sequenced. Results showed that mutations in the propeptide can improve the activity of RML during the evolution. Two parts of propeptide (wild-type and mutant) and mature region were connected by molecular simulation technology. METHODS: The spatial structure of the most positive mutants containing the mutations in the propeptide was mainly characterized by the increase in the opening angle of the lid structure in the mature region of RML, the enhancement of the hydrophobicity of the active center, and the triad of the active center shifted outward. RESULTS: The three indexes above explain the mechanism of propeptide mutations on the activity change of the target protein. In addition, statistical analysis of all the mutants screened in directed evolution showed that: (1) most of the mutants with increased activity contained mutations of the propeptide; (2) In the later stage of directed evolution, the number of active mutants decreased gradually, and the mutations of inactivated protein mainly occurred in the mature region; and (3) In the last round of directed evolution, the mutations distributed in the propeptide improved the mutant activity further. The results show the propeptide down the evolutionary pressure of RML and delayed emergence of the evolutionary platform. CONCLUSION: These findings reveal the role of propeptide in the evolution of RML and provide strategies for the molecular transformation of other lipases. Title: Enrichment of polystyrene microplastics induces histological damage, oxidative stress, Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus) Wang X, Jian S, Zhang S, Wu D, Wang J, Gao M, Sheng J, Hong Y Ref: Ecotoxicology & Environmental Safety, 237:113540, 2022 : PubMed ESTHER: Wang_2022_Ecotoxicol.Environ.Saf_237_113540 PubMedSearch: Wang 2022 Ecotoxicol.Environ.Saf 237 113540 PubMedID: 35453027 Abstract Polystyrene microplastics (PS-MPs, particle size<5 mm) cause great harm to aquatic organisms. However, their precise effects are not completely understood. In China, placing plastic film at the pond bottom has become an important loach aquaculture mode. In this mode, MPs will affect loach health. This study investigated the enrichment of PS-MPs and its effects on the growth, liver histomorphology, antioxidant enzymes, and Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus). The loach juveniles were raised at the concentration of 1000 microg/L fluorescent polystyrene microplastics (PS-MPs) with particle size of 0.5 microm or 5 microm for seven days, the results showed that fluorescent PS-MPs were found to be enriched in liver, intestine, and gill, and the enrichment amount was higher in liver than in gill and intestine (P < 0.05). Furthermore, the enrichment amount of different-sized PS-MPs was different in liver, gill, and intestine. The loach juveniles were cultured for 21 days in the water of the concentration of 100 or 1000 microg/L PS-MPs with particle size of 0.5 microm or 5 microm, the results showed that the survival rate, weight gain rate, and specific growth rate of loach juveniles were significantly reduced. The histological analysis revealed that PS-MPs caused liver damage. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and acetylcholinesterase (AChE) were decreased with the extended exposure to PS-MPs. Generally, the expressions of Nrf2 and Keap1 showed the similar change trend. From 7-14 day, the expression trend of oxidative stressed-related genes was not completely consistent with that of Nrf2 gene, but on day 21, the gene expression trend of oxidative stress-related SOD, CAT, and GSH-PX in the downstream of Keap1-Nrf2 signaling pathway was roughly consistent with that of Nrf2 gene. Basically, the change trends of these three gene expression were similar to those of their corresponding enzyme activities. This study provides theoretical basis for the toxicological effects of PS-MPs on freshwater fish. Title: Retrospective detection for V-type OPNAs exposure via phosphonylation and disulfide adducts in albumin Wang J, Sun F, Lu X, Gao R, Pei C, Wang H Ref: Sci Rep, 12:10979, 2022 : PubMed ESTHER: Wang_2022_Sci.Rep_12_10979 PubMedSearch: Wang 2022 Sci.Rep 12 10979 PubMedID: 35768567 Abstract Organophosphorus nerve agents (OPNAs) that damage the central nervous system by inhibiting acetylcholinesterase activity, pose severe threats to human health and life security. Reliable biomarkers that quickly and accurately detect OPNAs exposure are urgently needed to help diagnose quickly and treat in time. Albumins that covalently bind to OPNAs could serve as important targets for retrospective verification of OPNAs exposure. The goal of this study is to explore the potential biomarkers in albumins with high reactivity and good stability and expand the group of potential biomarkers in different species for detecting the exposure of V-type OPNAs including O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). Taking human serum albumin (HSA), bovine serum albumin (BSA) and rabbit serum albumin (RSA) as the research objectives, multiple active sites including phosphonylation and disulfide adduct sites were observed in albumins from different species. Numerous phosphonylation sites labeled by all agents in one type of albumin were found. Among the different species, four shared phosphonylation sites with high reactivity include K499, K549, K249, and Y108. In addition, Y108 on ETY*GEMADCCAK, Y287 on Y*ICENQDSISSK, Y377 on TY*ETTLEK and Y164 on YLY*EIAR in HSA were stably phosphonylated by all agents in gradient concentration, making them stable and suitable potential biomarkers for V-type OPNAs exposure. Notably, Y108 on ETY*GEMADCCAK in HSA, on DTY*GDVADCCEK in RSA, and on ETY*GDMADCCEK in BSA were highly reactive to all V-type agents, regardless of species. It was also successfully labeled in HSA exposed to class V agents in gradient concentration. Y108 is expected to be used to screen and identify the exposure of V-type agents in the retrospective research. Disulfide adducts sites, consisted of four sites in HSA and two sites in BSA were also successfully labeled by V-type agents, and characteristic ion fragments from these disulfide adducts were also identified by secondary mass spectrometry. Molecular simulation of the stably modified sites were conducted to discover the promoting factors of covalent adduct formation, which help further clarify formation mechanism of albumin adducts at active sites. Title: Role of Natural Compounds and Target Enzymes in the Treatment of Alzheimer's Disease Wang S, Kong X, Chen Z, Wang G, Zhang J, Wang J Ref: Molecules, 27:, 2022 : PubMed ESTHER: Wang_2022_Molecules_27_ PubMedSearch: Wang 2022 Molecules 27 PubMedID: 35807418 Abstract Alzheimer's disease (AD) is a progressive neurological condition. The rising prevalence of AD necessitates the rapid development of efficient therapy options. Despite substantial study, only a few medications are capable of delaying the disease. Several substances with pharmacological activity, derived from plants, have been shown to have positive benefits for the treatment of AD by targeting various enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), beta-secretase, gamma-secretase, and monoamine oxidases (MAOs), which are discussed as potential targets. Medicinal plants have already contributed a number of lead molecules to medicine development, with many of them currently undergoing clinical trials. A variety of medicinal plants have been shown to diminish the degenerative symptoms associated with AD, either in their raw form or as isolated compounds. The aim of this review was to provide a brief summary of AD and its current therapies, followed by a discussion of the natural compounds examined as therapeutic agents and the processes underlying the positive effects, particularly the management of AD. Title: Substrate-free fluorescence ratiometric detection of serum acetylcholinesterase activity with a self-assembled CsPbBr(3) perovskite nanocrystals/tetraphenylporphyrin tetrasulfonic acid nanocomposite Wang H, Wang J, Li Q, Du J Ref: Talanta, 250:123746, 2022 : PubMed ESTHER: Wang_2022_Talanta_250_123746 PubMedSearch: Wang 2022 Talanta 250 123746 PubMedID: 35872485 Abstract A dual-emission fluorescent nanoprobe was successfully constructed through self-assembling CsPbBr(3) perovskite nanocrystals (CsPbBr(3) PNCs) and tetraphenylporphyrin tetrasulfonic acid (TPPS). Acetylcholinesterase (AChE) is observed to directly quench the green fluorescence of CsPbBr(3) PNCs at 520 nm in the absence of an enzyme substrate, but has no significant influence on the red emission of TPPS at 650 nm. The decreased value of the fluorescence intensities ratio at 520 to 650 nm (deltaF(520)/F(650)) is proportional to the logarithmic value of AChE activity ranging from 0.05 to 1.0 U/L. The limit of detection is as low as 0.0042 U/L. The relative standard deviation is 3.6% in eleven consecutive measurements of 0.2 U/L AChE. The method exhibits a good anti-interference capacity since it does not respond to most concomitant species. Satisfactory results are acquired for the determination of AChE activity in human serum samples. Title: Novel Ce-based coordination polymer nanoparticles with excellent oxidase mimic activity applied for colorimetric assay to organophosphorus pesticides Wang J, Wang X, Wang M, Bian Q, Zhong J Ref: Food Chem, 397:133810, 2022 : PubMed ESTHER: Wang_2022_Food.Chem_397_133810 PubMedSearch: Wang 2022 Food.Chem 397 133810 PubMedID: 35917788 Abstract Cerium, as a lanthanide, has attracted considerable interest because of its excellent catalytic activity. Here, we propose a novel cerium-based coordination polymer nanoparticles named DPA-Ce-GMP, which have excellent oxidase-mimicking properties. Furthermore, a colorimetric probe that can act as an inhibitor to suppress the activity of acetylcholinesterase (AChE) was developed for detecting organophosphorus pesticides (OPs). DPA-Ce-GMP catalyzes colorless 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue color, and AChE catalyzes acetylthiocholine to produce thiocholine (TCh), which can weaken DPA-Ce-GMP-catalyzed TMB. After the addition of OPs, the enzymatic activity of AChE was inhibited to produce less amount of TCh, resulting in more DPA-Ce-GMP-catalyst oxidized TMB to show an increasing blue color. Dichlorvos, as the samples, with the limit of 0.024 microg/L. Overall, we believe that the colorimetric probe can be used for the rapid, low-cost, and large-scale field detection of OPs in food samples. Title: MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR Wang J, Hao Z, Hu L, Qiao L, Luo Y, Hu J, Liu X, Li S, Zhao F and Zhao Z <2 more author(s)> Wang J, Hao Z, Hu L, Qiao L, Luo Y, Hu J, Liu X, Li S, Zhao F, Shen J, Li M, Zhao Z (- 2) Ref: Front Vet Sci, 9:948873, 2022 : PubMed ESTHER: Wang_2022_Front.Vet.Sci_9_948873 PubMedSearch: Wang 2022 Front.Vet.Sci 9 948873 PubMedID: 35990270 Abstract In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep. Title: Analysis of the performance of the efficient di-(2-ethylhexyl) phthalate-degrading bacterium Rhodococcus pyridinovorans DNHP-S2 and associated catabolic pathways Wang L, Gan D, Gong L, Zhang Y, Wang J, Guan R, Zeng L, Qu J, Dong M Ref: Chemosphere, 306:135610, 2022 : PubMed ESTHER: Wang_2022_Chemosphere_306_135610 PubMedSearch: Wang 2022 Chemosphere 306 135610 PubMedID: 35810862 Abstract The widespread use of plastic has led to the global occurrence of phthalate esters (PAEs) pollution. PAEs can be effectively removed from polluted environments by microbe-mediated degradation. Di-(2-ethylhexyl) phthalate (DEHP) has the highest residual concentration in agricultural soil-contaminated areas compared to other PAEs in most of China. The Rhodococcus pyridinovorans DNHP-S2 microbial isolate identified was found to efficiently degrade DEHP. Within a 72 h period, the bacteria were able to degrade 52.47% and 99.75% of 500 mg L(-1) DEHP at 10 degreesC and 35 degreesC, respectively. Dimethyl phthalate (DMP) was first identified as an intermediate metabolite of DEHP, which is different from the previously reported DEHP catabolic pathway. Genomic sequencing of DNHP-S2 identified benzoate 1,2-dioxygenase and catechol 2,3/1,2-dioxygenase as potential mediators of DEHP degradation, consistent with the existence of two downstream metabolic pathways governing DEHP degradation. Three targets DEHP metabolism-related enzymes were found to be DEHP-inducible at the mRNA level, and DNHP-S2 was able to mediate the complete degradation of DEHP at lower temperatures, as confirmed via RT-qPCR. DNHP-S2 was also found to readily break down other PAEs including DMP, di-n-butyl phthalate (DBP), di-n-octyl phthalate (DnOP), and n-butyl benzyl phthalate (BBP). Together, these results thus highlight DNHP-S2 as a bacterial strain with great promise as a tool for the remediation of PAE pollution. In addition to providing new germplasm and genetic resources for use in the context of PAE degradation, these results also offer new insight into the potential mechanisms whereby PAEs undergo catabolic degradation, making them well-suited for use in PAE-contaminated environments. Title: Probing strigolactone perception mechanisms with rationally designed small-molecule agonists stimulating germination of root parasitic weeds Wang D, Pang Z, Yu H, Thiombiano B, Walmsley A, Yu S, Zhang Y, Wei T, Liang L and Xi Z <4 more author(s)> Wang D, Pang Z, Yu H, Thiombiano B, Walmsley A, Yu S, Zhang Y, Wei T, Liang L, Wang J, Wen X, Bouwmeester HJ, Yao R, Xi Z (- 4) Ref: Nat Commun, 13:3987, 2022 : PubMed ESTHER: Wang_2022_Nat.Commun_13_3987 PubMedSearch: Wang 2022 Nat.Commun 13 3987 PubMedID: 35810153 Abstract The development of potent strigolactone (SL) agonists as suicidal germination inducers could be a useful strategy for controlling root parasitic weeds, but uncertainty about the SL perception mechanism impedes real progress. Here we describe small-molecule agonists that efficiently stimulate Phelipanchce aegyptiaca, and Striga hermonthica, germination in concentrations as low as 10(-8) to 10(-17) M. We show that full efficiency of synthetic SL agonists in triggering signaling through the Striga SL receptor, ShHTL7, depends on the receptor-catalyzed hydrolytic reaction of the agonists. Additionally, we reveal that the stereochemistry of synthetic SL analogs affects the hydrolytic ability of ShHTL7 by influencing the probability of the privileged conformations of ShHTL7. Importantly, an alternative ShHTL7-mediated hydrolysis mechanism, proceeding via nucleophilic attack of the NE2 atom of H246 to the 2'C of the D-ring, is reported. Together, our findings provide insight into SL hydrolysis and structure-perception mechanisms, and potent suicide germination stimulants, which would contribute to the elimination of the noxious parasitic weeds. Title: The binding pocket properties were fundamental to functional diversification of the GDSL-type esterases/lipases gene family in cotton Wang J, Zhao H, Qu Y, Yang P, Huang J Ref: Front Plant Sci, 13:1099673, 2022 : PubMed ESTHER: Wang_2022_Front.Plant.Sci_13_1099673 PubMedSearch: Wang 2022 Front.Plant.Sci 13 1099673 PubMedID: 36743561 Abstract Cotton is one of the most important crops in the world. GDSL-type esterases/lipases (GELPs) are widely present in all kingdoms and play an essential role in regulating plant growth, development, and responses to abiotic and biotic stresses. However, the molecular mechanisms underlying this functional diversity remain unclear. Here, based on the identification of the GELP gene family, we applied genetic evolution and molecular simulation techniques to explore molecular mechanisms in cotton species. A total of 1502 GELP genes were identified in 10 cotton species. Segmental duplication and differences in evolutionary rates are the leading causes of the increase in the number and diversity of GELP genes during evolution for ecological adaptation. Structural analysis revealed that the GELP family has high structural diversity. Moreover, molecular simulation studies have demonstrated significant differences in the properties of the binding pockets among cotton GELPs. In the process of adapting to the environment, GELPs not only have segmental duplication but also have different evolutionary rates, resulting in gene diversity. This diversity leads to significant differences in the 3D structure and binding pocket properties and, finally, to functional diversity. These findings provide a reference for further functional analyses of plant GELPs. Title: Resistance selection of triflumezopyrim in Laodelphax striatellus (falln): Resistance risk, cross-resistance and metabolic mechanism Wen S, Liu C, Wang X, Wang Y, Wang J, Xia X Ref: Front Physiol, 13:1048208, 2022 : PubMed ESTHER: Wen_2022_Front.Physiol_13_1048208 PubMedSearch: Wen 2022 Front.Physiol 13 1048208 PubMedID: 36523557 Abstract The risk assessment and resistance mechanisms of insecticide resistance are critical for resistance management strategy before a new insecticide is widely used. Triflumezopyrim (TFM) is the first commercialized mesoionic insecticide, which can inhibit nicotinic acetylcholine receptor with high-performance against the small brown planthopper (SBPH), Laodelphax striatellus (Fallen). In our study, the resistance of SBPH to TFM increased 26.29-fold, and the actual heritability of resistance was 0.09 after 21 generations of continuous selection by TFM. After five generations of constant feeding under insecticide-free conditions from F(16) generation, the resistance level decreased 2.05-fold, and the average resistance decline rate per generation was 0.01, but there were no statistical decline. The TFM resistant strains had no cross-resistance to imidacloprid, nitenpyram, thiamethoxam, dinotefuran, flonicamid, pymetrozine, and chlorfenapyr. The third and fifth nymphal stage duration, pre-adult stage, adult preoviposition period, longevity, emergence rate, and hatchability of the resistant strain were significantly lower than those of the susceptible strain, while the female-male ratio was considerably increased. The fitness cost was 0.89. Further, cytochrome P450 monooxygenase (P450) and carboxylesterase (CarE) activities were markedly increased, but only the enzyme inhibitor piperonyl butoxide (PBO) had a significant synergistic effect on the resistant strain. The expression of CYP303A1, CYP4CE2, and CYP419A1v2 of P450 genes was significantly increased. SBPH has a certain risk of resistance to TFM with continuous application. The TFM resistance may be due to the increased activity of P450 enzyme regulated by the overexpression of P450 genes. Title: Non-classical digestive lipase BmTGL selected by gene amplification reduces the effects of mulberry inhibitor during silkworm domestication Wen F, Wang J, Shang D, Yan H, Yuan X, Wang Y, Xia Q, Wang G Ref: Int J Biol Macromol, :, 2022 : PubMed ESTHER: Wen_2022_Int.J.Biol.Macromol__ PubMedSearch: Wen 2022 Int.J.Biol.Macromol PubMedID: 36587639 Abstract Efficient utilization of dietary lipids is crucial for Bombyx mori, also known as domesticated silkworms. However, the effects of domestication on the genes encoding lipases remain unknown. In this study, we investigated the expression difference of one triacylglycerol lipase (BmTGL) between B.mori and wild (ancestor) silkworm strains (Bombyx mandarina). An immunofluorescence localization analysis showed that BmTGL was present in all parts of the gut and was released into the intestinal lumen. BmTGL expression was significantly enhanced in different domesticated silkworm strains compared to that in the B. mandarina strains. The genomes of the domesticated silkworm strains harbored 2-to-3-fold higher BmTGL copy numbers than those in the B. mandarina strains and accounted for the enhanced expression of BmTGL in the domesticated silkworm strains. The Ser144Asn substitution in the Ser-Asp-His catalytic triads of BmTGL resulted in relatively lower lipase activity and reduced sensitivity to the lipase inhibitor morachalcone A. Moreover, BmTGL overexpression significantly increased the weights of the B. mori silkworms compared to those of the non-transgenic controls. Thus, the selection of BmTGL by gene amplification may be a trade-off between maintaining high enzymatic activity and reducing the effects of mulberry inhibitors during silkworm domestication. Title: A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase Xia M, Li C, Liu L, He Y, Li Y, Jiang G, Wang J Ref: Biosensors (Basel), 12:, 2022 : PubMed ESTHER: Xia_2022_Biosensors.(Basel)_12_ PubMedSearch: Xia 2022 Biosensors.(Basel) 12 PubMedID: 35884287 Abstract Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 microU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals. Title: A new quinolone and acetylcholinesterase inhibitors from a sponge-associated fungus Penicillium sp. SCSIO41033 Xu F, Chen W, Ye Y, Qi X, Zhao K, Long J, Pang X, Liu Y, Wang J Ref: Nat Prod Res, :1, 2022 : PubMed ESTHER: Xu_2022_Nat.Prod.Res__1 PubMedSearch: Xu 2022 Nat.Prod.Res 1 PubMedID: 36318871 Abstract The chemical investigation of the EtOAc extract from the solid rice medium cultured with a sponge-associated fungus Penicillium sp. SCSIO41033 led to the isolation of two quinolones including a new one, penicinolone (1), three xanthone derivatives (3-5), and four anthraquinones (6-9). Their structures were determined by comprehensive analysis of (1)H and (13)C NMR, COSY, HSQC, and HMBC spectroscopic, and HRESIMS mass spectrometric data. The bioactive assays revealed that compounds 1 and 2 showed no antimicrobial activities against five bacteria and eight fungi, and compounds 5, 8 and 9 exhibited inhibition against AChE with IC(50) values of 45.9, 42.5 and 40.5 microg/mL. Molecular docking analysis was performed to explore the interactions between active molecules and AChE protein, which indicated that xanthone and anthraquinone derivatives had the potential for developing AChE inhibitors. Title: Possible Charged Residue Switch for Acylglycerol Selectivity of Lipase MAS1 Yang Y, Wang J, Yang B, Lan D, Wang Y Ref: Appl Biochem Biotechnol, :, 2022 : PubMed ESTHER: Yang_2022_Appl.Biochem.Biotechnol__ PubMedSearch: Yang 2022 Appl.Biochem.Biotechnol PubMedID: 35695952 Gene_locus related to this paper: 9actn-h0b8d4 Abstract The amino acid residues lining the substrate binding pocket play quite an important role during the lipase catalytic process. The conversion of those residues might cause a dramatic change in the lipase properties, such as the substrate selectivity of lipase. In our study, T237 residue sitting on the entrance of the catalytic pocket in lipase MAS1 was important for the catalytic performance. When replacing polar Thr with the positively charged Arg, the synthesis ratio of partial glycerides/triglycerides increases to 6.32 rather than 1.21 of MAS1 wild type (WT), as the substrate ratio of glycerol and fatty acids is 1:3. And the fatty acid preference shifted to long-chain substrates for mutant T237R rather than middle-chain substrates for MAS1 WT. Molecular docking analysis revealed that hydrophobic and side chain properties of Arg might contribute to the change of the MAS1 lipase catalytic performance. This work would pave a way for the accurate rational transformation of the lipases to produce value lipid for industrial application. Title: Probing the interaction of superparamagnetic iron oxide nanoparticles with lipase and their interacting consequences at the molecular level Yang B, Jia R, Fang M, Wang S, Lv Z, Wang J Ref: Toxicol Res (Camb), 11:654, 2022 : PubMed ESTHER: Yang_2022_Toxicol.Res.(Camb)_11_654 PubMedSearch: Yang 2022 Toxicol.Res.(Camb) 11 654 PubMedID: 36051670 Abstract BACKGROUND: Although superparamagnetic iron oxide nanoparticles (SPIONs) are used as carriers for candida rugosa lipase (CRL) in biomedical fields, their interactions and the influences on CRL are still unknown. Consequently, SPIONs were synthesized, characterized, and incubated with CRL to explore their molecular interactions and interacting consequences in this study. METHODS: The toxic effects of SPIONs on CRL and their molecular interactions were explored through transmission electron microscope, isothermal titration calorimetry, zeta potential measurements, multi-spectroscopic techniques, and biological enzyme activity tests. RESULTS: Results revealed the adsorption of SPIONs to CRL and the reduction of CRL aggregation. The unfolding and loosening of CRL structure as well as the change of secondary structure with the decrease of alpha-helix were found under SPIONs exposure. Moreover, higher SPIONs concentrations contributed to larger conformational changes and less aggregation of CRL. Meanwhile, it showed that hydrophobic forces were the dominant driving forces in the binding process, with the participation of electrostatic forces. CRL binds to SPIONs with the stoichiometry of 20.7 and the binding constant of 9.9 x 10(6) M(-1). No obvious changes were found in CRL activity due to no interference to Ser-209, Glu-341, and His-449 residues. CONCLUSION: This study examined the biological compatibility of SPIONs at the molecular level and provided important information about the structure and function of CRL upon binding to SPIONs. Our work might contribute to comprehend the molecular toxicity of SPIONs and the risks of engineered nanoparticles to human health. Title: Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe Yang Y, Zhang L, Wang J, Cao Y, Li S, Qin W, Liu Y Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Yang_2022_Anal.Chem__ PubMedSearch: Yang 2022 Anal.Chem PubMedID: 36121878 Abstract Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases. Title: Comparative genomic analysis of carboxylesterase genes in Tenebrio molitor and other four tenebrionids Yang YL, Li X, Wang J, Song QS, Stanley D, Wei SJ, Zhu JY Ref: Archives of Insect Biochemistry & Physiology, :e21967, 2022 : PubMed ESTHER: Yang_2022_Arch.Insect.Biochem.Physiol__e21967 PubMedSearch: Yang 2022 Arch.Insect.Biochem.Physiol e21967 PubMedID: 36111353 Abstract Carboxylesterases (COEs) have various functions in wide taxons of organisms. In insects, COEs are important enzymes involved in the hydrolysis of a variety of ester-containing xenobiotics, neural signal transmission, pheromone degradation, and reproductive development. Understanding the diversity of COEs is basic to illustrate their functions. In this study, we identified 53, 105, 37, and 39 COEs from the genomes of Tenebrio molitor, Asbolus verucosus, Hycleus cichorii, and H. phaleratus in the superfamily of Tenebrionidea, respectively. Phylogenetic analysis showed that 234 COEs from these four species and those reported in Tribolium castaneum (63) could be divided into 12 clades and three major classes. The alpha-esterases significantly expanded in T. molitor, A. verucosus, and T. castaneum compared to dipteran and hymenopteran insects. In T. molitor, most COEs showed tissue and stage-specific but not a sex-biased expression. Our results provide insights into the diversity and evolutionary characteristics of COEs in tenebrionids, and lay a foundation for the functional characterization of COEs in the yellow mealworm. Title: Development of an esterase fluorescent probe based on naphthalimide-benzothiazole conjugation and its applications for qualitative detection of esterase in orlistat-treated biosamples Yin Y, Kong X, Li M, Wang J, Dai X, Zhang Y, Lin W Ref: Anal Chim Acta, 1190:339248, 2022 : PubMed ESTHER: Yin_2022_Anal.Chim.Acta_1190_339248 PubMedSearch: Yin 2022 Anal.Chim.Acta 1190 339248 PubMedID: 34857133 Abstract Esterase is a large hydrolysis family, and widely distributed in many kinds of cells. It is responsible for multiple physiological and pathological functions including metabolism, gene expression. While abnormality of esterase is associated with many pathological activities in obesity, Wolman's disease, and cancer. Thereby, it is essential to design an effective tool for esterase in situ detection in biological systems. Herein, a novel fluorescent probe Y-1 for monitoring esterase in living cells was rationally designed. Probe Y-1 was synthesized by the conjugation between an acetylation of 4-hydroxy naphthalimide and benzothiazole group. Benzothiazole moiety is a typical Excited-state intramolecular proton transfer (ESIPT) controller. Acetate group was selected as the responsive site and ESIPT initiator. As the acetate group could block the ESIPT effect, the probe emits no fluorescence under the excitation of 455 nm. When binding with esterase, Y-1 shows distinct fluorescence with the peak at 560 nm with short time when ESIPT is on. Y-1 displays high sensitivity (LOD is 0.216 x 10(-3) U/mL), fast response (within 5 min), high selectivity and photostability towards esterase. Furthermore, the %RSD (relative standard deviation) of within-day and day-to-day precision was no more than 13.0% and the accuracy ranged from -6.5 to -12.3%. Kinetics performance of Y-1 indicates that esterase has high affinity and hydrolysis to Y-1. For biological applications, our probe is a time-dependent visualizing esterase in living HepG2 and CoLo205 cells within 15 min. After the treatment of orlistat (1 and 5 microM) for inhibiting the activity of esterase, the bright fluorescence has also been detected using our probe. Furthermore, it has been successful in monitoring the esterase in zebrafish, the data were consistent with cellular phenomena. Therefore, all these findings indicate that the robust probe Y-1 is a useful qualitative tool for detecting esterase in biological systems. Title: Design, Synthesis and Bioactivity Evaluation of Coumarin-BMT Hybrids as New Acetylcholinesterase Inhibitors Zeng F, Lu T, Wang J, Nie X, Xiong W, Yin Z, Peng D Ref: Molecules, 27:, 2022 : PubMed ESTHER: Zeng_2022_Molecules_27_ PubMedSearch: Zeng 2022 Molecules 27 PubMedID: 35408542 Abstract Coumarin possesses the aromatic group and showed plentiful activities, such as antioxidant, preventing asthma and antisepsis. In addition, coumarin derivatives usually possess good solubility, low cytotoxicity and excellent cell permeability. In our study, we synthesized the compound bridge methylene tacrine (BMT), which has the classical pharmacophore structure of Tacrine (THA). Based on the principle of active substructure splicing, BMT was used as a lead compound and synthesized coumarin-BMT hybrids by introducing coumarin to BMT. In this work, 21 novel hybrids of BMT and coumarin were synthesized and evaluated for their inhibitory activity on AChE. All obtained compounds present preferable inhibition. Compound 8b was the most active compound, with the value of K(i) as 49.2 nM, which was higher than Galantamine (GAL) and lower than THA. The result of molecular docking showed that the highest binding free energy was -40.43 kcal/mol for compound 8b, which was an identical trend with the calculated K(i). Title: Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women Zhang B, Yu L, Cheng M, Zhang Q, Wu J, Yang J, Liu Q, Lu S, Zhao X and Zhao P <3 more author(s)> Zhang B, Yu L, Cheng M, Zhang Q, Wu J, Yang J, Liu Q, Lu S, Zhao X, Deng K, Liu Y, Wang J, Zhao P (- 3) Ref: Food Sci Nutr, 10:3, 2022 : PubMed ESTHER: Zhang_2022_Food.Sci.Nutr_10_3 PubMedSearch: Zhang 2022 Food.Sci.Nutr 10 3 PubMedID: 35035905 Abstract To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues. Title: GR24-mediated enhancement of salt tolerance and roles of H(2)O(2) and Ca(2+) in regulating this enhancement in cucumber Zhang XH, Ma C, Zhang L, Su M, Wang J, Zheng S, Zhang TG Ref: J Plant Physiol, 270:153640, 2022 : PubMed ESTHER: Zhang_2022_J.Plant.Physiol_270_153640 PubMedSearch: Zhang 2022 J.Plant.Physiol 270 153640 PubMedID: 35168135 Abstract This study investigated the regulation of the exogenous strigolactone (SL) analog GR24 in enhancing the salt tolerance and the effects of calcium ion (Ca(2+)) and hydrogen peroxide (H(2)O(2)) on GR24's regulation effects in cucumber. The seedlings were sprayed with (1) distilled water (CK), (2) NaCl, (3) GR24, then NaCl, (4) GR24, then H(2)O(2) scavenger, then NaCl, and (5) GR24, then Ca(2+) blocker, then NaCl. The second true leaf was selected for biochemical assays. Under the salt stress, the exogenous GR24 maintained the ion balance, increased the activity of antioxidant enzymes, reduced the membrane lipid peroxidation, and increased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), accompanied by a decrease in relative conductivity, an increase in the proline content, and elevated gene expression levels of antioxidant enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, calcium-dependent protein kinases (CDPKs), salt overly sensitive SOS1, CBL-interacting protein kinase 2 (CIPK2), and calcineurin B-like protein 3 (CBL3). Such protective effects triggered by GR24 were attenuated or almost abolished by ethylene glycol tetraacetic acid (EGTA), lanthanum chloride (LaCl3, Ca(2+) channel blocker), diphenyleneiodonium (DPI, NADPH oxidase inhibitor), and dimethylthiourea (DMTU, hydroxyl radical scavenger). Our data suggest that exogenous GR24 is highly effective in alleviating salt-induced damages via modulating antioxidant capabilities and improving ionic homeostasis and osmotic balance and that H(2)O(2) and Ca(2+) are required for GR24-mediated enhancement of salt tolerance. Title: Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation Zhang T, Kim MJ, Wu X, Yang HJ, Yuan H, Huang S, Yoon SM, Kim KN, Park S and Wang J <46 more author(s)> Zhang T, Kim MJ, Wu X, Yang HJ, Yuan H, Huang S, Yoon SM, Kim KN, Park S, Zhang Y, Yao J, Yin K, Liu Z, Deng C, Liu J, Hou S, Zhang H, Yu D, Zhao N, Zhao R, Chen S, Zhang ZP, Bai X, Cui WB, Chen XH, Liu X, Zhi DJ, Zhang ZX, Fei DQ, Wang DS, Zhang X, Wang Y, Zhu H, Zhong Z, Zhang CY, Tan XH, Yang HH, Jin L, Hong JR, Zhou Y, Huang XT, Zhang M, Xiang R, Glorieux C, Huang P, Young C, Morishita Y, Kim K, Kabil OO, Clarke OB, Di Jeso B, Arvan P, Wang D, Sun J, Wu S, Wang J (- 46) Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_23_ PubMedSearch: Zhang 2022 Int.J.Mol.Sci 23 PubMedID: 35328781 35563299 35743309 35887300 35897843 36233022 36362390 36555825 Abstract Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1beta, IL-18, CD16, and TNF-alpha). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation. Title: Structural Basis for the Regiospecificity of a Lipase from Streptomyces sp. W007 Zhao Z, Chen S, Xu L, Cai J, Wang J, Wang Y Ref: Int J Mol Sci, 23:5822, 2022 : PubMed ESTHER: Zhao_2022_Int.J.Mol.Sci_23_5822 PubMedSearch: Zhao 2022 Int.J.Mol.Sci 23 5822 PubMedID: 35628632 Gene_locus related to this paper: 9actn-h0b8d4 Abstract The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a alpha-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases. Title: Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform Zhao J, Tang Z, Selvaraju M, Johnson KA, Douglas JT, Gao PF, Petrassi HM, Wang MZ, Wang J Ref: ACS Cent Sci, 8:1424, 2022 : PubMed ESTHER: Zhao_2022_ACS.Cent.Sci_8_1424 PubMedSearch: Zhao 2022 ACS.Cent.Sci 8 1424 PubMedID: 36313155 Abstract Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators of signaling pathways by leveraging the power of a clustered regularly interspaced short palindromic repeats (CRISPR) knockout library. This platform links the expression of a suicide gene to the small-molecule-activated signaling pathway to create a selection system. With this system, loss-of-function screening using a CRISPR single-guide (sg) RNA library positively enriches cells in which the target has been knocked out. The identities of the drug targets and other essential genes required for the activity of small molecules of interest are then uncovered by sequencing. We tested this platform on BDW568, a newly discovered type-I interferon signaling activator, and identified stimulator of interferon genes (STING) as its target and carboxylesterase 1 (CES1) to be a key metabolizing enzyme required to activate BDW568 for target engagement. The platform we present here can be a general method applicable for target identification for a wide range of small molecules that activate different signaling pathways. Title: Sequence and structure-based method to predict diacylglycerol lipases in protein sequence Ali S, Liu X, Sen L, Lan D, Wang J, Hassan MI, Wang Y Ref: Int J Biol Macromol, :, 2021 : PubMed ESTHER: Ali_2021_Int.J.Biol.Macromol__ PubMedSearch: Ali 2021 Int.J.Biol.Macromol PubMedID: 33836195 Abstract Lipase enzymes play a central role in biotechnology and the food industry. Diacylglyceride lipases (DAG) have received considerable attention due to their physiological significance and potential industrial usage. However, compared to the wide application of triacylglycerol (TAG) lipases, DAG lipases have a limited application due to their low thermostability and specific activity. The molecular basis of substrate specificity of DAG lipases remains elusive, making structure-guided engineering of TAG to DAG lipase difficult. Besides, the number of available DAG lipases is limited compared to TAG lipases. In the current study, we identified structural consensus motifs of DAG lipases that contribute to their DAG specificity on a structural comparison of DAG and TAG lipases. To find potential DAG lipases, sequence motifs and predicted secondary structures were used to screen millions of protein sequences and predict new DAG lipases. In total, 83 new putative DAG lipases were identified. The predicted DAG lipases were validated by expression of randomly chosen putative DAG lipases followed by functional assay for their DAG and TAG specific activity. The reported method is efficient and cost-effective for discovering new DAG lipases used in the food industry after the required characterization to meet potential application needs. Title: Accurate prediction of protein structures and interactions using a three-track neural network Baek M, DiMaio F, Anishchenko I, Dauparas J, Ovchinnikov S, Lee GR, Wang J, Cong Q, Kinch LN and Baker D <22 more author(s)> Baek M, DiMaio F, Anishchenko I, Dauparas J, Ovchinnikov S, Lee GR, Wang J, Cong Q, Kinch LN, Schaeffer RD, Millan C, Park H, Adams C, Glassman CR, DeGiovanni A, Pereira JH, Rodrigues AV, van Dijk AA, Ebrecht AC, Opperman DJ, Sagmeister T, Buhlheller C, Pavkov-Keller T, Rathinaswamy MK, Dalwadi U, Yip CK, Burke JE, Garcia KC, Grishin NV, Adams PD, Read RJ, Baker D (- 22) Ref: Science, 373:871, 2021 : PubMed ESTHER: Baek_2021_Science_373_871 PubMedSearch: Baek 2021 Science 373 871 PubMedID: 34282049 Abstract DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research. Title: Fluorescent and colorimetric dual-response sensor based on copper (II)-decorated graphitic carbon nitride nanosheets for detection of toxic organophosphorus Chen Y, Zhu Y, Zhao Y, Wang J Ref: Food Chem, 345:128560, 2021 : PubMed ESTHER: Chen_2021_Food.Chem_345_128560 PubMedSearch: Chen 2021 Food.Chem 345 128560 PubMedID: 33601648 Abstract An efficient and convenient detection method for organophosphorus pesticide (OP) residues is needed because of their high neurotoxicity and severe threat to food safety. OPs effectively reduce the production of thiocholine in the acetylcholinesterase/acetylthiocholine reaction by inhibiting the activity of acetylcholinesterase. Therefore, we developed a feasible and convenient fluorescent and colorimetric dual-response sensor based on the competitive complexation of Cu(2+) between graphitic carbon nitride nanosheets and thiocholine for the rapid detection of OPs with high sensitivity. Malathion was used as a model OP, and a linear range of 70-800 nM with a detection limit of 6.798 nM for a fluorescent signaling platform and 2.5-25 nM with a detection limit of 1.204 nM for a colorimetric probe were attained. The constructed probe was successfully applied to determine OP in actual samples of cabbages leaves and tap water. The results indicated that the dual-response probe was reliable and sensitive to actual samples. Title: Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase Chen X, Deng X, Zhang Y, Wu Y, Yang K, Li Q, Wang J, Yao W, Tong J and Yao J <2 more author(s)> Chen X, Deng X, Zhang Y, Wu Y, Yang K, Li Q, Wang J, Yao W, Tong J, Xie T, Hou S, Yao J (- 2) Ref: Angew Chem Int Ed Engl, :, 2021 : PubMed ESTHER: Chen_2021_Angew.Chem.Int.Ed.Engl__ PubMedSearch: Chen 2021 Angew.Chem.Int.Ed.Engl PubMedID: 34351032 Inhibitor(s) related to this paper: Benzoic-acid Abstract Benzoylecgonine (BZE) is the major toxic metabolite of cocaine, and is responsible for the long-term cocaine-induced toxicity due to its long residence time in humans. BZE is also the main contaminant following cocaine consumption, representing a risk to our environment and non-target organisms. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo , a single dose of BZEase2 (1 mg/kg, IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme have the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was determined, providing additional insights in support of our simulation results. Title: Synthesis, biological evaluation and molecular modeling of benzofuran piperidine derivatives as Abeta antiaggregant Chowdhury SR, Gu J, Hu Y, Wang J, Lei S, Tavallaie MS, Lam C, Lu D, Jiang F, Fu L Ref: Eur Journal of Medicinal Chemistry, 222:113541, 2021 : PubMed ESTHER: Chowdhury_2021_Eur.J.Med.Chem_222_113541 PubMedSearch: Chowdhury 2021 Eur.J.Med.Chem 222 113541 PubMedID: 34116326 Abstract A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Abeta antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Abeta antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Abeta peptides binding to the cell membrane. The different modifications introduced in the structure of our lead compound 3 (hAChE IC(50) = 61 microM and self induced Abeta (25-35) aggregation 45.45%), to increase its activity toward AD related targets. The most interesting multifunctional Abeta antiaggregants were compounds 3a, 3h and 3i, highlighting 3h as potent Abeta antiaggregant and good antiacetylholinesterase inhibitor (self induced Abeta (25-35) aggregation 57.71% and hAChE IC(50) = 21 microM), with good neuroprotective and antioxidant activity. In addition, these three most promising compounds prevent intracellular reactive oxygen species (ROS) formation and cell apoptosis induced by Abeta(25-35) peptides in SH-SY5Y cells. Molecular docking studies were also accomplished to understand the binding interaction of these compounds on Abeta monomer, Abeta fibril and AChE. Based on all data, compounds 3a, 3h and 3i were concluded as potent multifunctional Abeta antiaggregant, useful candidate for the treatment of AD. Title: Role of epoxide hydrolases and cytochrome P450s on metabolism of KZR-616, a first-in-class selective inhibitor of the immunoproteasome Fang Y, Johnson H, Anderl JL, Muchamuel T, McMinn D, Morisseau C, Hammock BD, Kirk C, Wang J Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, :, 2021 : PubMed ESTHER: Fang_2021_Drug.Metab.Dispos__ PubMedSearch: Fang 2021 Drug.Metab.Dispos PubMedID: 34234005 Gene_locus related to this paper: human-EPHX1 Abstract KZR-616 is an irreversible tripeptide epoxyketone-based selective inhibitor of the human immunoproteasome. Inhibition of the immunoproteasome results in anti-inflammatory activity in vitro and, based on promising therapeutic activity in animal models of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), KZR-616 is being developed for potential treatment of multiple autoimmune and inflammatory diseases. The presence of a ketoepoxide pharmacophore presents unique challenges in the study of drug metabolism during lead optimization and clinical candidate profiling. This study presents a thorough and systematic in vitro and cell-based enzymatic metabolism and kinetic investigation to identify the major enzymes involved in the metabolism and elimination of KZR-616. Upon exposure to liver microsomes in the absence of NADPH, KZR-616 and its analogs were converted to their inactive diol derivatives with varying degrees of stability. Diol formation was also shown to be the major metabolite in pharmacokinetic studies in monkeys and correlated with in vitro stability results for individual compounds. Further study in intact hepatocytes and a hepatocellular carcinoma cell line revealed that KZR-616 metabolism was sensitive to an inhibitor of microsomal epoxide hydrolase (mEH) but not inhibitors of cytochrome P450 (CYP) or soluble epoxide hydrolase (sEH). Primary human hepatocytes were determined to be the most robust source of mEH activity for study in vitro These findings also suggest that the exposure of KZR-616 in vivo is unlikely to be affected by co-administration of inhibitors or inducers of CYP and sEH. Significance Statement This work presents a thorough and systematic investigation of metabolism and kinetic of KZR-616 and other peptide epoxyketones in in vitro and cell-based enzymatic systems. Gained information could be useful in assessing novel covalent proteasome inhibitors during lead compound optimization. The study also demonstrates a robust source of in vitro metabolism identification that correlated very well with in vivo PK metabolism for peptide epoxyketones. Title: Biochemical and Structural Characterization of a Novel Bacterial Tannase From Lachnospiraceae bacterium in Ruminant Gastrointestinal Tract Guan L, Wang K, Gao Y, Li J, Yan S, Ji N, Ren C, Wang J, Zhou Y and Lu S <1 more author(s)> Guan L, Wang K, Gao Y, Li J, Yan S, Ji N, Ren C, Wang J, Zhou Y, Li B, Lu S (- 1) Ref: Front Bioeng Biotechnol, 9:806788, 2021 : PubMed ESTHER: Guan_2021_Front.Bioeng.Biotechnol_9_806788 PubMedSearch: Guan 2021 Front.Bioeng.Biotechnol 9 806788 PubMedID: 34976993 Gene_locus related to this paper: 9firm-TanALb Abstract Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds present in hydrolyzable tannins to release gallic acid. Here, a novel tannase from Lachnospiraceae bacterium (TanA(Lb)) was characterized. The recombinant TanA(Lb) exhibited maximal activity at pH 7.0 and 50 degreesC, and it maintained more than 70% relative activity from 30 degreesC to 55 degreesC. The activity of TanA(Lb) was enhanced by Mg(2+) and Ca(2+), and was dramatically reduced by Cu(2+) and Mn(2+). TanA(Lb) is capable of degrading esters of phenolic acids with long-chain alcohols, such as lauryl gallate as well as tannic acid. The Km value and catalytic efficiency (k (cat) /Km) of TanA(Lb) toward five substrates showed that tannic acid (TA) was the favorite substrate. Homology modeling and structural analysis indicated that TanA(Lb) contains an insertion loop (residues 341-450). Based on the moleculer docking and molecular dynamics (MD) simulation, this loop was observed as a flap-like lid to interact with bulk substrates such as tannic acid. TanA(Lb) is a novel bacterial tannase, and the characteristics of this enzyme make it potentially interesting for industrial use. Title: Lipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafish Han SL, Qian YC, Limbu SM, Wang J, Chen LQ, Zhang ML, Du ZY Ref: Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids, 1866:158988, 2021 : PubMed ESTHER: Han_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1866_158988 PubMedSearch: Han 2021 Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids 1866 158988 PubMedID: 34111526 Abstract Neutral lipases-mediated lipolysis and acid lipases-moderated lipophagy are two main processes for degradation of lipid droplets (LDs). However, the individual and interactive roles of these metabolic pathways are not well known across vertebrates. This study explored the roles of lipolysis and lipophagy from the aspect of neutral and acid lipases in zebrafish. We established zebrafish strains deficient in either adipose triglyceride lipase (atgl(-/-); AKO fish) or lysosomal acid lipase (lal(-/-); LKO fish) respectively, and then inhibited lipolysis in the LKO fish and lipophagy in the AKO fish by feeding diets supplemented with the corresponding inhibitors Atglistatin and 3-Methyladenine, respectively. Both the AKO and LKO fish showed reduced growth, swimming activity, and oxygen consumption. The AKO fish did not show phenotypes in adipose tissue, but mainly accumulated triacylglycerol (TAG) in liver, also, they had large LDs in the hepatocytes, and did not stimulate lipophagy as a compensation response but maintained basal lipophagy. The LKO fish reduced total lipid accumulation in the body but had high cholesterol content in liver; also, they accumulated small LDs in the hepatocytes, and showed increased lipolysis, especially Atgl expression, as a compensatory mechanism. Simultaneous inhibition of lipolysis and lipophagy in zebrafish resulted in severe liver damage, with the potential to trigger mitophagy. Overall, our study illustrates that lipolysis and lipophagy perform individual and interactive roles in maintaining homeostasis of TAG and cholesterol metabolism. Furthermore, the interactive roles of lipolysis and lipophagy may be essential in regulating the functions and form of mitochondria. Title: Expression of an alkaline feruloyl esterases from thermophilic Chaetomium thermophilum and its boosting effect on delignification of pulp Hou Y, Yang Z, Yin Y, Meng Z, Wang J, Zhao T, Yang Q Ref: Enzyme Microb Technol, 150:109859, 2021 : PubMed ESTHER: Hou_2021_Enzyme.Microb.Technol_150_109859 PubMedSearch: Hou 2021 Enzyme.Microb.Technol 150 109859 PubMedID: 34489049 Abstract Exploration of feruloyl esterase (FAE) with the resistance to heat and alkali conditions in biobleaching process to improve the separation efficiency of lignocellulose is the key to achieving green papermaking. Herein, we expressed FAEB of C. thermophilum and obtained a thermostable alkaline FAE that can effectively promote the removal of lignin from pulp. The faeB gene was successfully obtained through genomic Blast strategy and high-efficiency expressed under the control of strong alcohol oxidase promoter in Pichia pastoris. The recombinant CtFAEB has an optimal temperature of 65 degreesC and pH of 7.0. After treated at 65 degreesC for 1 h, CtFAEB can still retain 63.21 % of its maximum activity, showing a good thermal stability. In addition, the recombinant CtFAEB has broad pH stability and can retain about 56 % of the maximum activity even at pH 11.0. Compared with the effect of mesophilic FAE, pretreatment with thermostable CtFAEB can promote the delignification by laccase and alkaline hydrogen peroxide from the pulp at 70 degreesC and pH 9.0. Alignment of the protein sequences of CtFAEB and mesophilic FAE suggested that the percentage of amino acids that easily form alpha helix in CtFAEB increases, which enhances its structural rigidity and thereby improves its thermal stability and alkali tolerance. Our study provides an effective method to obtain thermostable and alkaline FAEs, which will promote its application in biobleaching and other biorefining industries. Title: Explainable machine learning model for predicting spontaneous bacterial peritonitis in cirrhotic patients with ascites Hu Y, Chen R, Gao H, Lin H, Wang J, Wang X, Liu J, Zeng Y Ref: Sci Rep, 11:21639, 2021 : PubMed ESTHER: Hu_2021_Sci.Rep_11_21639 PubMedSearch: Hu 2021 Sci.Rep 11 21639 PubMedID: 34737270 Abstract Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis. We aimed to develop an explainable machine learning model to achieve the early prediction and outcome interpretation of SBP. We used CatBoost algorithm to construct MODEL-1 with 46 variables. After dimensionality reduction, we constructed MODEL-2. We calculated and compared the sensitivity and negative predictive value (NPV) of MODEL-1 and MODEL-2. Finally, we used the SHAP (SHapley Additive exPlanations) method to provide insights into the model's outcome or prediction. MODEL-2 (AUROC: 0.822; 95% confidence interval [CI] 0.783-0.856), liked MODEL-1 (AUROC: 0.822; 95% CI 0.784-0.856), could well predict the risk of SBP in cirrhotic ascites patients. The 6 most influential predictive variables were total protein, C-reactive protein, prothrombin activity, cholinesterase, lymphocyte ratio and apolipoprotein A1. For binary classifier, the sensitivity and NPV of MODEL-1 were 0.894 and 0.885, respectively, while for MODEL-2 they were 0.927 and 0.904, respectively. We applied CatBoost algorithm to establish a practical and explainable prediction model for risk of SBP in cirrhotic patients with ascites. We also identified 6 important variables closely related to the occurrence of SBP. Title: Structural and biochemical mechanisms of NLRP1 inhibition by DPP9 Huang M, Zhang X, Toh GA, Gong Q, Wang J, Han Z, Wu B, Zhong F, Chai J Ref: Nature, :, 2021 : PubMed ESTHER: Huang_2021_Nature__ PubMedSearch: Huang 2021 Nature PubMedID: 33731929 Gene_locus related to this paper: rat-dpp9 Abstract Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND)(1-7). In resting cells, the dipeptidyl peptidases DPP8 and DPP9 interact with the FIIND of NLRP1 and suppress spontaneous NLRP1 activation(8,9); however, the mechanisms through which this occurs remain unknown. Here we present structural and biochemical evidence that full-length rat NLRP1 (rNLRP1) and rat DPP9 (rDPP9) form a 2:1 complex that contains an autoinhibited rNLRP1 molecule and an active UPA-CARD fragment of rNLRP1. The ZU5 domain is required not only for autoinhibition of rNLRP1 but also for assembly of the 2:1 complex. Formation of the complex prevents UPA-mediated higher-order oligomerization of UPA-CARD fragments and strengthens ZU5-mediated NLRP1 autoinhibition. Structure-guided biochemical and functional assays show that both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on the activation of the NLRP1 inflammasome. Title: Directionally Modified Fluorophores for Super-Resolution Imaging of Target Enzymes: A Case Study with Carboxylesterases Jia Y, Wang J, Li P, Ma X, Han K Ref: Journal of Medicinal Chemistry, :, 2021 : PubMed ESTHER: Jia_2021_J.Med.Chem__ PubMedSearch: Jia 2021 J.Med.Chem PubMedID: 34694804 Abstract In the need for improving the labeling quality of super-resolution imaging, multifarious fluorescent labeling strategies have sprang up. Among them, a small molecule inhibitor-probe (SMI-probe) shows its advancement in fine mapping due to its smaller size and its specific binding to a specific site. Herein, we report a novel protocol of mechanism-guided directional modification of fluorophores into fluorescent inhibitors for enzyme targeting, which could half the size of the SMI-probe. To confirm the feasibility of the strategy, carboxylesterase (hCE) inhibitors are designed and developed. Among the constructed molecule candidates, NIC-4 inhibited both isoforms of hCE1 and hCE2, with IC(50) values of 4.56 and 4.11 microM. The CE-targeting specificity of NIC-4 was confirmed by colocalizing with an immunofluorescent probe in fixed-cell confocal imaging. Moreover, NIC-4 was used in live-cell super-resolution microscopy, which indicates dotlike structures instead of the larger staining with the immunofluorescent probe. Moreover, it enables the real-time tracking of dynamic flow of carboxylesterases in live cells. Title: A role of peptidoglycan recognition protein in mediating insecticide detoxification in Glyphodes pyloalis Jiang DL, Ding JH, Liu ZX, Shao ZM, Liang XH, Wang J, Wu FA, Sheng S Ref: Archives of Insect Biochemistry & Physiology, :e21842, 2021 : PubMed ESTHER: Jiang_2021_Arch.Insect.Biochem.Physiol__e21842 PubMedSearch: Jiang 2021 Arch.Insect.Biochem.Physiol e21842 PubMedID: 34499777 Abstract Glyphodes pyloalis Walker has become one of the most significant mulberry pests, and it has caused serious economic losses in major mulberry growing regions in China. Peptidoglycan recognition proteins (PGRPs) are responsible for initiating and regulating immune signalling pathways in insects. However, their roles responding to chemical pesticides is still less known. This study aimed to investigate the possible detoxication function of GpPGRP-S2 and GpPGRP-S3 in G. pyloalis in response to chlorfenapyr and phoxim. The chlorfenapyr and phoxim treatment significantly induced the expression level of GpPGRP-S3 at 48 h. In addition, the expression levels of GpPGRP-S2 and GpPGRP-S3 in the chlorfenapyr/phoxim treatment group were significantly higher in midgut than those in the control group at 48 h. The results of the survival experiment showed that silencing either GpPGRP-S2 or GpPGRP-S3 would not influence the survival rate of G. pyloalis which treated with phoxim, however, silencing GpPGRP-S2 or GpPGRP-S3 would cause G. pyloalis to be more easily killed by chlorfenapyr. The expression of carboxylesterase GpCXE1 was significantly induced by chlorfenapyr/phoxim treatment, while it was suppressed once silenced GpPGRP-S2 followed with chlorfenapyr treatment or silenced GpPGRP-S3 followed with phoxim treatment. These results might suggest that under the chlorfenapyr/phoxim treatment condition, the connection between GpPGRPs and detoxification genes in insect was induced to maintain physiological homeostasis; and these results may further enrich the mechanisms of insects challenged by insecticides. Title: Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure Kang L, Chen J, Wang J, Zhao T, Wei Y, Wu Y, Han L, Zheng X, Shen L and Wu S <2 more author(s)> Kang L, Chen J, Wang J, Zhao T, Wei Y, Wu Y, Han L, Zheng X, Shen L, Long C, Wei G, Wu S (- 2) Ref: Environ Sci Pollut Res Int, :, 2021 : PubMed ESTHER: Kang_2021_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Kang 2021 Environ.Sci.Pollut.Res.Int PubMedID: 34595713 Abstract The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP. Title: Structure-Guided Rational Design of a Mono- and Diacylglycerol Lipase from Aspergillus oryzae: A Single Residue Mutant Increases the Hydrolysis Ability Lan D, Zhao G, Holzmann N, Yuan S, Wang J, Wang Y Ref: Journal of Agricultural and Food Chemistry, :, 2021 : PubMed ESTHER: Lan_2021_J.Agric.Food.Chem__ PubMedSearch: Lan 2021 J.Agric.Food.Chem PubMedID: 33929832 Abstract Engineering of enzymes on the basis of protein structures are rational and efficient approaches to acquire biocatalysts of desired performances. In this study, we focused on a special mono- and diacylglycerol lipase (MDGL) isolated from the lipolytic enzyme-enriched fungus Aspergillus oryzae and discovered improved variants based on its crystal structure. We first solved the crystal structure of Aspergillus oryzae lipase (AOL) at 1.7 A resolution. Structure analysis and sequence alignment of AOL and other MDGLs revealed that the residue V269 is of vital importance for catalysis. Replacement of the V269 in AOL with the corresponding residues in other MDGLs has led to noticeable changes in hydrolysis without sacrificing the thermostability and substrate specificity. Among the investigated variants, V269D exhibited about a six-fold higher hydrolysis activity compared to the wild type. Molecular dynamics simulations and protein-ligand interaction frequency analyses revealed that the Asp substitution enhanced the substrate affinity of AOL. Our work sheds light on understanding the catalytic process of AOL and helps tailoring MDGLs with desired catalytic performance to fulfill the demand for biotechnological applications. Title: Inducing new bioactive metabolites production from coculture of Pestalotiopsis sp. and Penicillium bialowiezense Li F, Yan S, Huang Z, Gao W, Zhang S, Mo S, Lin S, Wang J, Hu Z, Zhang Y Ref: Bioorg Chem, 110:104826, 2021 : PubMed ESTHER: Li_2021_Bioorg.Chem_110_104826 PubMedSearch: Li 2021 Bioorg.Chem 110 104826 PubMedID: 33780746 Abstract Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD calculation. The delta(10,11) double bond of pestaloficin D (5) was revised to E-configurated based on the extensive spectroscopic analyses. Compounds 1a/1b and 2a/2b were the first examples of enantiomeric isoprenylated chromane derivatives, which were successfully separated by chiral HPLC. Additionally, all the isolated compounds were evaluated for the in vitro beta-glucuronidase (GUS) and butyrylcholinesterase (BChE) inhibitory activities. Compounds 1a and 1b showed significant beta-glucuronidase inhibitory potency with IC(50) values of 7.6 and 10.3 microM, respectively. Compound 14 exhibited moderate BChE inhibitory activity with an IC(50) value of 21.3 microM. In addition, the structure-enzyme inhibitory activity relationship of compounds 1-14 is discussed. Title: Morphine increases myocardial triacylglycerol through regulating adipose triglyceride lipase S406 phosphorylation Li L, Wang J, Li D, Zhang H Ref: Life Sciences, 283:119866, 2021 : PubMed ESTHER: Li_2021_Life.Sci_283_119866 PubMedSearch: Li 2021 Life.Sci 283 119866 PubMedID: 34352257 Abstract AIMS: Morphine, a commonly used drug for anesthesia, affects lipid metabolism in different tissues, but the mechanism is currently unclear. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme responsible for the first step of triglyceride (TG) hydrolysis. Here we aim to investigate whether ATGL phosphorylation is involved in morphine-induced TG accumulation. MAIN METHODS: Oil red O staining and TG content analysis were used to detect the effect of morphine on lipid storage. A series of ATGL phosphoamino acid site mutant plasmids were constructed by gene synthesis and transfected to HL-1 cells to evaluate the phosphorylation levels of ATGL phosphoamino acid in morphine-treated HL-1 cells with immunoprecipitation and immunoblotting assay. KEY FINDINGS: Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. Of note, the phosphorylation positive mutation of ATGL Ser406 to aspartic acid effectively reversed morphine-induced excessive accumulation of TG in HL-1 cells. SIGNIFICANCE: This discovery will help to fully understand the lipid regulation function of morphine in a new scope. In addition, it will expand the phosphorylation research of ATGL more comprehensively and provide powerful clues for lipid metabolism regulation. Title: Cyclic Peptides from the Soft Coral-Derived Fungus Aspergillus sclerotiorum SCSIO 41031 Long J, Chen Y, Chen W, Wang J, Zhou X, Yang B, Liu Y Ref: Mar Drugs, 19:, 2021 : PubMed ESTHER: Long_2021_Mar.Drugs_19_ PubMedSearch: Long 2021 Mar.Drugs 19 PubMedID: 34940700 Abstract Three novel cyclic hexapeptides, sclerotides C-E (1-3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus sclerotiorum SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey's method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (4) exhibited acetylcholinesterase inhibitory activity with an IC(50) value of 15.6 microM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC(50) value of 10.1 microM. Title: Iridium Single-Atomic Site Catalysts with Superior Oxygen Reduction Reaction Activity for Sensitive Monitoring of Organophosphorus Pesticides Luo X, Luo Z, Wei X, Jiao L, Fang Q, Wang H, Wang J, Gu W, Hu L, Zhu C Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Luo_2021_Anal.Chem__ PubMedSearch: Luo 2021 Anal.Chem PubMedID: 34969242 Abstract Tremendous efforts have been made in developing single-atomic site catalysts (SASCs) for oxygen reduction reaction (ORR), which is regarded as a pivotal cornerstone in electrochemical energy conversion. However, SASCs for ORR have not been explored for electrochemical sensing. Herein, a template-sacrificed strategy is reported for the synthesis of atomically dispersed Ir SASCs, serving as a sensing platform to detect organophosphorus pesticides (OPs) with high sensitivity and selectivity. Owing to abundant Ir single-atom active sites, Ir SASCs show excellent ORR activity and stability in a neutral medium. It is found that the ORR activity of Ir SASCs can be inhibited by thiocholine, which is the hydrolysate of acetylthiocholine. After being integrated with acetylcholinesterase (AChE), the AChE-Ir SASC-based electrochemical sensor is established and shows a superior sensitivity, which shows a wide detection range of 0.5-500 ng mL(-1) with a low detection limit of 0.17 ng mL(-1) for OPs. This work exhibits a broad application prospect of ORR for sensitive detection of biomolecules. Title: Molecular response uncovers neurotoxicity of Pardosa pseudoannulata exposed to cadmium pressure Lv B, Wang J, He Y, Zeng Z, Tang YE, Li N, Chen LJ, Wang Z, Song QS Ref: Environ Pollut, 280:117000, 2021 : PubMed ESTHER: Lv_2021_Environ.Pollut_280_117000 PubMedSearch: Lv 2021 Environ.Pollut 280 117000 PubMedID: 33784568 Abstract Cadmium (Cd) is a widely distributed heavy metal in south of China. Growing evidence indicates that systemic exposure to Cd, particularly the long-term exposure, may cause neurotoxic effects. Nevertheless, mechanisms underlying Cd neurotoxicity remain not completely understood. In this report, we investigated the neural alterations in the spider Pardosa pseudoannulata (Bosenberg and Strand, 1906) exposed to long-term Cd (LCd) and short-term Cd (SCd) pressure. Cd stress lowered foraging ability and prey consuming time in the spiders. In addition, enzymatic analysis results indicated that Cd exposure reduced the level of acetylcholinesterase at subcellular level. We then identified differentially expressed genes (DEGs) in the Cd exposed spiders using pairwise comparisons and found that a large number of DEGs were related to neurotransmitter receptors and ion transport and binding proteins. Notably, LCd exposure harbored more altered genes in ion transporter activity comparing with SCd exposure. From six K-means clusters, 53 putative transcriptional factors (TFs) belonging to 21 families were characterized, and ZBTB subfamily displayed the most distinctive alterations in the characterized genes, which is assumed to play a key role in the regulation of ion transmembrane process under Cd stress. A protein-to-protein interaction network constructed by the yielded DEGs also showed that ion and receptor binding activities were affected under long-term Cd exposure. Four key modules from the network indicated that Cd may further down-regulate energy metabolism pathway in spiders. Collectively, this comprehensive analysis provides multi-dimensional insights to understand the molecular response of spiders to Cd exposure. Title: Adsorption mechanism of two pesticides on polyethylene and polypropylene microplastics: DFT calculations and particle size effects Mo Q, Yang X, Wang J, Xu H, Li W, Fan Q, Gao S, Yang W, Gao C and Zhang Y <2 more author(s)> Mo Q, Yang X, Wang J, Xu H, Li W, Fan Q, Gao S, Yang W, Gao C, Liao D, Li Y, Zhang Y (- 2) Ref: Environ Pollut, 291:118120, 2021 : PubMed ESTHER: Mo_2021_Environ.Pollut_291_118120 PubMedSearch: Mo 2021 Environ.Pollut 291 118120 PubMedID: 34520951 Abstract Polyethylene (PE) and polypropylene (PP) microplastics (MPs), as carriers, can bind with pesticides, which propose harmful impacts to aqueous ecosystems. Meanwhile, carbofuran and carbendazim (CBD), two widely used carbamate pesticides, are toxic to humans because of the inhibition of acetylcholinesterase activity. The interaction between two MPs and two pesticides could start in farmland and be maintained during transportation to the ocean. Herein, the adsorption behavior and mechanism of carbofuran and carbendazim (CBD) by PE and PP MPs were investigated via characterization and density functional theory (DFT) simulation. The adsorption kinetic and thermodynamic data were best described by pseudo-second-order kinetics and the Freundlich models. The adsorption behaviors of individual carbofuran/CBD on both MPs were very similar. The CBD adsorption rate and capacity of PE and PP MPs were higher than those of carbofuran. This phenomenon explained the lower negative effects of DOM (oxalic acid, glycine (Gly)) on CBD adsorption relative to those of carbofuran. The presence of oxalic acid and Gly decreased the PE adsorption by 20.40-48.02% and the PP adsorption by 19.27-42.11%, respectively. It indicated the significance of DOM in carbofuran cycling. The adsorption capacities were negatively correlated with MPs size, indicating the importance of specific surficial area. Fourier transformation infrared spectroscopy before and after adsorption suggested that the adsorption process did not produce any new covalent bond. Instead, intermolecular van der Waals forces were one of the primary adsorption mechanisms of carbofuran and CBD by MPs, as evidenced by DFT calculations. Based on the zeta potential, the electrostatic interaction explained the higher adsorption CBD by MPs than carbofuran. Title: A loss-of-function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA/VSD) and tetralogy of Fallot (TOF) Peng J, Wang Q, Meng Z, Wang J, Zhou Y, Zhou S, Song W, Chen S, Chen AF, Sun K Ref: FEBS Open Bio, 11:375, 2021 : PubMed ESTHER: Peng_2021_FEBS.Open.Bio_11_375 PubMedSearch: Peng 2021 FEBS.Open.Bio 11 375 PubMedID: 33211401 Gene_locus related to this paper: human-NDRG4 Abstract Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N-myc downstream-regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase-9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell-cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF. Title: Evaluation of Sensitivity to Phoxim and Cypermethrin in an Endoparasitoid, Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae), and Its Parasitization Efficiency Under Insecticide Stress Sheng S, Wang J, Zhang XR, Liu ZX, Yan MW, Shao Y, Zhou JC, Wu FA Ref: J Insect Sci, 21:, 2021 : PubMed ESTHER: Sheng_2021_J.Insect.Sci_21_ PubMedSearch: Sheng 2021 J.Insect.Sci 21 PubMedID: 33580255 Abstract Insecticides can have consequences for beneficial arthropods. Insect parasitoids can contact insecticides through direct exposure spray droplets or residues on crop foliage. Here, we focus on better understand the response of Meteorus pulchricornis (Wesmael), a parasitoid wasp of lepidopteran pests, and its detoxification mechanisms on stress caused by phoxim and cypermethrin. Hence, we determined the dose-mortality curves and estimating the sublethal concentrations (LC30 and LC50). Then, we applied the sublethal concentrations against adult parasitoids to assess its survival, parasitism efficacy, and also developmental and morphometric parameters of their offspring. Simultaneously, we check the activities of glutathione S-transferase (GST), acetylcholinesterase (AChE), and peroxidase (POD) after sublethal exposure of both insecticides, which has measured until 48 h after treatment. Overall, phoxim and cypermethrin exhibited acute lethal activity toward the parasitoid with LC50 values 4.608 and 8.570 mg/liter, respectively. Also, we detect that LC30 was able to trigger the enzymatic activity of GST, AChE, and POD, suggesting a potential detoxification mechanism. However, even when subjected to sublethal exposure, our results indicate strong negatives effects, in particular for phoxim, which has affected the parasitism efficacy and also the developmental and morphometric parameters of M. pulchricornis offspring. Therefore, it can be concluded that both phoxim and cypermethrin have negative impacts on M. pulchricornis and we suggest cautioning their use and the need for semifield and field assessments to confirm such an impact. Title: Osthole-Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer's Disease via Intranasal Administration Song Y, Wang X, Wang J, Hao Q, Hao J, Hou X Ref: Oxid Med Cell Longev, 2021:8844455, 2021 : PubMed ESTHER: Song_2021_Oxid.Med.Cell.Longev_2021_8844455 PubMedSearch: Song 2021 Oxid.Med.Cell.Longev 2021 8844455 PubMedID: 33564364 Abstract Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer's disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer's disease. Title: Genome-Wide Identification of Tannase Genes and Their Function of Wound Response and Astringent Substances Accumulation in Juglandaceae Wang J, Wang K, Lyu S, Huang J, Huang C, Xing Y, Wang Y, Xu Y, Li P and Li Y <4 more author(s)> Wang J, Wang K, Lyu S, Huang J, Huang C, Xing Y, Wang Y, Xu Y, Li P, Hong J, Xi J, Si X, Ye H, Li Y (- 4) Ref: Front Plant Sci, 12:664470, 2021 : PubMed ESTHER: Wang_2021_Front.Plant.Sci_12_664470 PubMedSearch: Wang 2021 Front.Plant.Sci 12 664470 PubMedID: 34079571 Gene_locus related to this paper: camsi-CsTA Abstract Tannins are important polyphenol compounds with different component proportions in different plant species. The plants in the Juglandaceae are rich in tannins, including condensed tannins and hydrolyzable tannins. In this study, we identified seven tannase genes (TAs) responsible for the tannin metabolism from walnut, pecan, and Chinese hickory, and three nut tree species in the Juglandaceae, which were divided into two groups. The phylogenetic and sequence analysis showed that TA genes and neighboring clade genes (TA-like genes) had similar sequences compared with other carboxylesterase genes, which may be the origin of TA genes produced by tandem repeat. TA genes also indicated higher expressions in leaf than other tissues and were quickly up-regulated at 3 h after leaf injury. During the development of the seed coat, the expression of the synthesis-related gene GGTs and the hydrolase gene TAs was continuously decreased, resulting in the decrease of tannin content in the dry sample of the seed coat of Chinese hickory. However, due to the reduction in water content during the ripening process, the tannin content in fresh sample increased, so the astringent taste was obvious at the mature stage. In addition, the CcGGTs' expression was higher than CiGGTs in the initiation of development, but CcTAs continued to be down-regulated while CiTA2a and CiTA2b were up-regulated, which may bring about the significant differences in tannin content and astringent taste between Chinese hickory and pecan. These results suggested the crucial role of TAs in wound stress of leaves and astringent ingredient accumulation in seed coats of two nut tree species in the Juglandaceae. Title: The protonation state of Glu202 in acetylcholinesterase Wang J, Lai S, Kong Y, Yao W, Chen X, Liu J Ref: Proteins, :, 2021 : PubMed ESTHER: Wang_2021_Proteins__ PubMedSearch: Wang 2021 Proteins PubMedID: 34546589 Abstract Acetylcholinesterase (AChE) is the crucial enzyme in the central nervous system. It is the target of various organophosphorus nerve agents and pesticides, and the inhibition of AChE is a therapeutic strategy for the treatment of various neurological-related diseases. The Glu202 is a key residue adjacent to the catalytic His447 and plays important role in catalysis. Although the Glu202 has long been considered as negatively charged in many studies, more and more evidences support a protonated Glu202. However, Glu202 is freely accessible by solvent, and thus it seems more reasonable for Glu202 to majorly take the deprotonated state. In the present work, we carried out a series of molecular dynamics simulations with the Glu202 adopting different protonation states. Our results show that the protonated Glu202 is important in maintaining the key hydrogen bond network that supports the catalytic triad, whereas the deprotonated Glu202 results in the collapse of the key hydrogen bond network which consequently destabilizes the catalytic His447. We also notice that different protonation states of Glu202 merely alters the binding mode of ACh. However, since the catalytic His447 is disrupted if Glu202 is deprotonated, His447 can not facilitate the nucleophilic attack performed by Ser203. Therefore, the catalytic efficiency of ACh hydrolysis should be remarkably decreased if Glu202 is deprotonated. Our findings suggest that, when designing and developing highly active AChE inhibitors or proposing mechanistic hypotheses for AChE-catalyzed reactions, the protonated state of Glu202 should be considered. This article is protected by copyright. All rights reserved. Title: Enhancing the thermostability of a mono- and diacylglycerol lipase from Malassizia globose by stabilizing a flexible loop in the catalytic pocket Xing YN, Tan J, Wang Y, Wang J Ref: Enzyme Microb Technol, 149:109849, 2021 : PubMed ESTHER: Xing_2021_Enzyme.Microb.Technol_149_109849 PubMedSearch: Xing 2021 Enzyme.Microb.Technol 149 109849 PubMedID: 34311886 Gene_locus related to this paper: malgo-a8puy1 Abstract A lipase from Malassizia globose, named SMG1, is highly desirable for industrial application due to its substrate specificity towards mono- and diacylglycerol. To improve its thermostability, we constructed a mutant library using an error-prone polymerase chain reaction, which was screened for both initial and residual enzymatic activity. Selected mutants were further studied using purified proteins for their kinetic thermostability at 45 degC, T(50) (the temperature at which the enzyme loses half of its activity), and the optimal reaction temperature. Results showed that the majority of mutations with improved thermostability were on the protein surface. D245N and L270P showed the most significant thermostability enhancement with an approximately 3 degC increase in T(50) compared to wild-type (WT). In addition, combining these two mutations resulted in an increase of T(50) by 5 degreesC. Also, the optimal reaction temperatures of L270P and this double mutant are 10 degC higher than WT. The double mutant showed an approximately 100-fold increase in half-life at 45 degC and higher enzymatic activities at 30 degC and above compared to WT. High-temperature unfolding molecular dynamics simulation suggested that the double mutant stabilized a flexible loop in the catalytic pocket. Title: Vitamins A and D fail to protect against tuberculosis-drug-induced liver injury: A post hoc analysis of a previous randomized controlled trial Xiong K, Wang J, Zhang B, Xu L, Hu Y, Ma A Ref: Nutrition, 86:111155, 2021 : PubMed ESTHER: Xiong_2021_Nutrition_86_111155 PubMedSearch: Xiong 2021 Nutrition 86 111155 PubMedID: 33601121 Abstract OBJECTIVES: Vitamins A and D provided protection from xenobiotic-induced liver injury in previous animal studies. We conducted a post hoc analysis of our previous randomized controlled trial to investigate the effects of vitamin A and D supplementation on tuberculosis-drug-induced liver injury. METHODS: The trial was conducted in a hospital in Qingdao, China, from October 2012 to March, 2015. The control group received only tuberculosis treatment. The vitamin A, vitamin D, and vitamins A & D groups received, respectively, additional supplementation of 2000 IU/d vitamin A, 400 IU/d vitamin D, and a combination of 2000 IU/d vitamin A and 400 IU/d vitamin D. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase were monitored throughout the treatment. Liver injury was defined as ALT or AST three times higher than the upper limit of normal, which was defined for AST, ALT, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase, respectively, as 40 U/L, 40 U/L, 150 U/L, 40 U/L, and 10 500 U/L. RESULTS: Among the 753 participants, 11% exhibited liver injury. No significant effect of vitamin A or D supplementation was observed on the incidence of liver injury or on elevated liver indices including ALT, AST, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase. The interaction between vitamin A and D supplementation was not significant. CONCLUSIONS: Vitamin A and D supplementation did not protect against tuberculosis-drug-induced liver injury. Future work should evaluate the effects of higher dosages of vitamins A and D and the effects of different genotypes for vitamin A and D metabolic enzymes or receptors. Title: An efficient and robust continuous-flow bioreactor for the enzymatic preparation of phytosterol esters based on hollow lipase microarray Xu L, Wang J, Huang F, Zheng M Ref: Food Chem, 372:131256, 2021 : PubMed ESTHER: Xu_2021_Food.Chem_372_131256 PubMedSearch: Xu 2021 Food.Chem 372 131256 PubMedID: 34627092 Abstract In this study, a continuous-flow bioreactor packed with well-organized lipase microarrays was developed for the sustainable synthesis of functional lipid-phytosterol esters (PEs). Hollow mesoporous silicon spheres with a suitable pore size were prepared for lipase immobilization, and the hydrophobic modification endowed the lipase with excellent catalytic activity and stability. The results showed that the condensely packed lipase microarrays offered large specific surface areas and guaranteed the thorough interaction between the lipase and substrates in the continuous-flow bioreactor. Meanwhile, the substrate could pass through the reactor at 1 mL/min with a high conversion of 93.6% due to the hollow structure of the packing spheres. Moreover, the reactors were able to produce 1564 g PEs/g catalyst in a continuous 30-day processing period, which set the highest records for PEs synthesis. This sustainable and highly-converting flow system provided a feasible path for scale-up production of PEs in the food processing area. Title: Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis Yi J, Wang S, Wang Z, Wang X, Li G, Zhang X, Pan Y, Zhao S, Zhang J and Xi J <2 more author(s)> Yi J, Wang S, Wang Z, Wang X, Li G, Zhang X, Pan Y, Zhao S, Zhang J, Zhou JJ, Wang J, Xi J (- 2) Ref: Front Physiol, 12:674023, 2021 : PubMed ESTHER: Yi_2021_Front.Physiol_12_674023 PubMedSearch: Yi 2021 Front.Physiol 12 674023 PubMedID: 34566671 Abstract Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela. Title: Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells Zhang Y, Li K, Li Y, Zhao W, Wang L, Chen Z, Ma X, Yao T, Wang J and Fu R <3 more author(s)> Zhang Y, Li K, Li Y, Zhao W, Wang L, Chen Z, Ma X, Yao T, Wang J, Dong W, Li X, Tian X, Fu R (- 3) Ref: Pharmacol Res, 169:105630, 2021 : PubMed ESTHER: Zhang_2021_Pharmacol.Res_169_105630 PubMedSearch: Zhang 2021 Pharmacol.Res 169 105630 PubMedID: 33932609 Gene_locus related to this paper: human-DPP8, human-DPP9 Abstract BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-beta1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-beta1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF. Title: Metabolic degradation of lentinan in liver mediated by CYP450 enzymes and epoxide hydrolase Zheng Z, Zhang Y, Liu Y, Wang J, Cui Z, Pan X, Tang W, Wang K Ref: Carbohydr Polym, 253:117255, 2021 : PubMed ESTHER: Zheng_2021_Carbohydr.Polym_253_117255 PubMedSearch: Zheng 2021 Carbohydr.Polym 253 117255 PubMedID: 33279005 Abstract Lentinan (LNT), a typical triple helix beta-glucan, has been widely used as drug and biomaterial. However, its pharmacokinetics in vivo is rarely reported, which severely limits its further development and application. The aim of this study is to establish a sensitive method for detecting LNT in biosamples and to evaluate the plasma level, tissue distribution and metabolic degradation of LNT in rats. 5-([4,6-Dichlorotriazin-2-yl] amino) fluorescein (DTAF) was labelled to LNT. After purification and identification, FLNT was intravenously administered to rats at dose of 32 mg/kg. LNT was predominantly incorporated into the liver and liver microsomes were used to study the degradation mechanism of LNT in the liver. The results showed that two cytochrome P450 (CYP450) enzymes subtypes (CYP2D6 and CYP2C9), as well as epoxide hydrolase, were involved in the metabolic degradation of LNT. These findings provide a pharmacokinetic reference for further study and application of LNT and other beta-glucans. Title: Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure Zhou W, Li X, Wang Y, Wang J, Zhang J, Wei H, Peng C, Wang Z, Li G, Li D Ref: J Hazard Mater, 416:126142, 2021 : PubMed ESTHER: Zhou_2021_J.Hazard.Mater_416_126142 PubMedSearch: Zhou 2021 J.Hazard.Mater 416 126142 PubMedID: 34492931 Abstract 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure. Title: Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy Zou S, Dong R, Wang J, Liang B, Zhu T, Zhao S, Zhang Y, Wang T, Zou P and Luo L <5 more author(s)> Zou S, Dong R, Wang J, Liang B, Zhu T, Zhao S, Zhang Y, Wang T, Zou P, Li N, Wang Y, Chen M, Zhou C, Zhang T, Luo L (- 5) Ref: J Proteomics, :104124, 2021 : PubMed ESTHER: Zou_2021_J.Proteomics__104124 PubMedSearch: Zou 2021 J.Proteomics 104124 PubMedID: 33545297 Abstract We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP. Title: An Overview on the Mechanisms and Applications of Enzyme Inhibition-Based Methods for Determination of Organophosphate and Carbamate Pesticides Cao J, Wang M, Yu H, She Y, Cao Z, Ye J, Abd El-Aty AM, Hacimuftuoglu A, Wang J, Lao S Ref: Journal of Agricultural and Food Chemistry, 68:7298, 2020 : PubMed ESTHER: Cao_2020_J.Agric.Food.Chem_68_7298 PubMedSearch: Cao 2020 J.Agric.Food.Chem 68 7298 PubMedID: 32551623 Abstract Acetylcholinesterase inactivating compounds, such as organophosphate (OP) and carbamate (CM) pesticides, are widely used in agriculture to ensure sustainable production of food and feed. As a consequence of their applications, they would result in neurotoxicity, even death. In this essence, the development of enzyme inhibition methods still shows great significance as rapid detection techniques for on-site large-scale screening of OPs and CMs. Initially, mechanisms and applications of various enzyme-inhibition-based methods and devices, including optical colorimetric assay, fluorometric assays, electrochemical biosensors, rapid test card, and microfluidic device, are highlighted in the present overview. Further, to enhance the enzyme sensitivity for detection; alternative enzyme sources or high yield enrichment methods (such as abzyme, artificial enzyme, and recombinant enzyme), as well as enzyme reactivation and identification, are also addressed in this comprehensive overview. Title: ABHD5 suppresses cancer cell anabolism through lipolysis-dependent activation of the AMPK/mTORC1 pathway Chen G, Zhou G, Lotvola A, Granneman JG, Wang J Ref: Journal of Biological Chemistry, 296:100104, 2020 : PubMed ESTHER: Chen_2020_J.Biol.Chem_296_100104 PubMedSearch: Chen 2020 J.Biol.Chem 296 100104 PubMedID: 33219129 Gene_locus related to this paper: human-ABHD5 Inhibitor(s) related to this paper: SR-3420 Abstract ABHD5 is an essential coactivator of ATGL, the rate-limiting triglyceride (TG) lipase in many cell types. Importantly, ABHD5 also functions as a tumor suppressor, and ABHD5 mRNA expression levels correlate with patient survival for several cancers. Nevertheless, the mechanisms involved in ABHD5-dependent tumor suppression are not known. We found that overexpression of ABHD5 induces cell-cycle arrest at the G1 phase and causes growth retardation in a panel of prostate cancer cells. Transcriptomic profiling and biochemical analysis revealed that genetic or pharmacological activation of lipolysis by ABHD5 potently inhibits mTORC1 signaling, leading to a significant downregulation of protein synthesis. Mechanistically, we found that ABHD5 elevates intracellular AMP content, which activates AMPK, leading to inhibition of mTORC1. Interestingly, ABHD5-dependent suppression of mTORC1 was abrogated by pharmacological inhibition of DGAT1 or DGAT2, isoenzymes that re-esterify fatty acids in a process that consumes ATP. Collectively, this study maps out a novel molecular pathway crucial for limiting cancer cell proliferation, in which ABHD5-mediated lipolysis creates an energy-consuming futile cycle between TG hydrolysis and resynthesis, leading to inhibition of mTORC1 and cancer cell growth arrest. Title: FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling Chen Y, Liu P, Shen D, Liu H, Xu L, Wang J, Sun H, Wu H Ref: Biol Open, 9:, 2020 : PubMed ESTHER: Chen_2020_Biol.Open_9_bio048462 PubMedSearch: Chen 2020 Biol.Open 9 bio048462 PubMedID: 31988090 Gene_locus related to this paper: human-f172a Abstract FAM172A, as a newly discovered gene, is little known in cancer development, especially in pancreatic cancer (PC). We investigated the potential role and molecular mechanism of FAM172A in epithelial to mesenchymal transition (EMT) in both human clinical samples and PC cells. FAM172A was downregulated in human PC tissues compared with that in non-cancerous pancreas cells by immunohistochemistry and qRT-PCR. FAM172A expression was negatively associated with tumor size (P=0.015), T stage (P=0.006), lymph node metastasis (P=0.028) and the worst prognosis of PC patients (P=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, P=0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (P=0.014). FAM172A silencing induced EMT in both AsPC-1 and BxPC-3 cells, including inducing the increase of Vimentin, MMP9 and pERK and the decrease of E-cad and beta-catenin expression, stimulating EMT-like cell morphology and enhancing cell invasion and migration in PC cells. However, MEK1 inhibitor PD98059 reversed FAM172A silencing-enhanced EMT in PC cells. We conclude that FAM172A inhibits EMT of PC cells via ERK-MAPK signaling. Title: Lipopeptide Epimers and a Phthalide Glycerol Ether with AChE Inhibitory Activities from the Marine-Derived Fungus Cochliobolus Lunatus SCSIO41401 Dai Y, Li K, She J, Zeng Y, Wang H, Liao S, Lin X, Yang B, Wang J and Liu Y <3 more author(s)> Dai Y, Li K, She J, Zeng Y, Wang H, Liao S, Lin X, Yang B, Wang J, Tao H, Dai H, Zhou X, Liu Y (- 3) Ref: Mar Drugs, 18:, 2020 : PubMed ESTHER: Dai_2020_Mar.Drugs_18_ PubMedSearch: Dai 2020 Mar.Drugs 18 PubMedID: 33143384 Abstract A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo(2) (OAc)(4)-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC(50) values of 1.3-2.5 M, and an in silico molecular docking study was also performed. Title: Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets Gong Y, Lv S, Tian C, Gao Y, Chen B, Wen L, Gao H, Aimaiti W, Ma R and Wang J <1 more author(s)> Gong Y, Lv S, Tian C, Gao Y, Chen B, Wen L, Gao H, Aimaiti W, Ma R, Zhao J, Wang J (- 1) Ref: J Biomed Nanotechnol, 16:827, 2020 : PubMed ESTHER: Gong_2020_J.Biomed.Nanotechnol_16_827 PubMedSearch: Gong 2020 J.Biomed.Nanotechnol 16 827 PubMedID: 33187579 Inhibitor(s) related to this paper: Harmine Abstract Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 mol . L (-1). Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs. Title: Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007 Han W, Cai J, Zhong W, Xu G, Wang F, Tian X, Zhou X, Liu Q, Liu Y, Wang J Ref: Bioorg Chem, 96:103646, 2020 : PubMed ESTHER: Han_2020_Bioorg.Chem_96_103646 PubMedSearch: Han 2020 Bioorg.Chem 96 103646 PubMedID: 32036160 Abstract Three new compounds, including two new 3,4,6-trisubstituted alpha-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), alpha-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 mug/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme. Title: Molecular characterization and functional analysis of a novel candidate of cuticle carboxylesterase in Spodoptera exigua degradating sex pheromones and plant volatile esters He P, Mang DZ, Wang H, Wang MM, Ma YF, Wang J, Chen GL, Zhang F, He M Ref: Pestic Biochem Physiol, 163:227, 2020 : PubMed ESTHER: He_2020_Pestic.Biochem.Physiol_163_227 PubMedSearch: He 2020 Pestic.Biochem.Physiol 163 227 PubMedID: 31973861 Abstract Odorant-degrading enzymes (ODEs) are considered to play key roles in odorant inactivation to maintain the odorant receptor sensitivity of insects. Some members of carboxylesterase (CXE) is a major sub-family of ODEs. However, only a few CXEs have been functionally characterized so far. In the present study, we cloned the antennal esterase SexiCXE11 cDNA full-length sequences from the male antennae of a notorious crop pest, Spodoptera exigua, and its encoded 538 amino acids. It was similar to other insect esterases and had the characteristics of a carboxylesterase. We expressed recombinant enzyme in High-Five insect cells and obtained the high level purified recombinant protein by affinity column. Furthermore we test enzyme activity toward its two acetate sex pheromone components (Z9,E12-Tetradecadienyl acetate, Z9E12-14:Ac and Z9-Tetradecenyl acetate, Z9-14:Ac) and other 18 ester plant volatiles. Our results demonstrated that SexiCXE11 degraded acetate sex pheromone components with similar degradation activities (about 15.75% with Z9E12-14:Ac and 19.28% with Z9-14:Ac) and plant volatiles with a relatively high activity such as pentyl acetate and (Z)-3-hexenyl caproate. SexiCXE11 had high hydrolytic activity with these two ester odorants (>50% degradation), which is characterized that although a ubiquitous expression esterase SexiCXE11 may be partly involved with olfaction. This study may facilitate a better understanding of moth ODE differentiation and suggest strategies for the development of new pest behavior inhibitors. Title: Dipeptidyl Peptidase-4 Is a Target Protein of Epigallocatechin-3-Gallate Hou H, Wang Y, Li C, Wang J, Cao Y Ref: Biomed Res Int, 2020:5370759, 2020 : PubMed ESTHER: Hou_2020_Biomed.Res.Int_2020_5370759 PubMedSearch: Hou 2020 Biomed.Res.Int 2020 5370759 PubMedID: 32104696 Inhibitor(s) related to this paper: Epigallocatechin-gallate Abstract Epigallocatechin-3-gallate (EGCG), a major active ingredient in green tea, has various health benefits. It affects glucose metabolism, but the mechanism is not well understood. This study aimed to identify targets of EGCG related to glucose metabolism. The core fragment of EGCG is a flavonoid. The flavonoid scaffold was used as a substructure to find proteins cocrystallized with flavonoids in the Protein Data Bank. The proteins identified were screened in PubMed for known relationships with diabetes. Dipeptidyl peptidase-4 (DPP4; PDB 5J3J) was identified following this approach. By molecular docking, the interactions of EGCG and DPP4 were assessed. To test the stability of the interactions between EGCG and DPP4, molecular dynamics simulation for 100 ns was performed using Desmond software. In vitro, the concentration of EGCG required to inhibit DPP4 activity by 50% (the IC50 value) was 28.42 muM. These data provide a theoretical basis for intervention in glucose metabolism with EGCG. Title: Silencing of soluble epoxide hydrolase 2 gene reduces H2O2-induced oxidative damage in rat intestinal epithelial IEC-6 cells via activating PI3K/Akt/GSK3beta signaling pathway Li J, Luo J, Zhang Y, Tang C, Wang J, Chen C Ref: Cytotechnology, :, 2020 : PubMed ESTHER: Li_2020_Cytotech__ PubMedSearch: Li 2020 Cytotech PubMedID: 31907700 Abstract Oxidative stress plays a vital role in the occurrence and development of intestinal injury. Soluble epoxide hydrolase 2 gene (EPHX2) is a class of hydrolytic enzymes. We aim to explore the effects and molecular mechanism of siEPHX2 on H2O2-induced oxidative damage in rat intestinal epithelial IEC-6 cells. IEC-6 cells were transfected with EPHX2-siRNA and control si RNA plasmids by lipofectamine 2000 transfection reagent. The transfected samples were treated with H2O2 (50, 100, 200, 300, 400, and 500 micromol/L) for 12, 24, and 48 h, respectively. Cell viability was determined by cell counting kit-8 (CCK-8). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) were assessed by respective detection kits. Mitochondrial membrane potential (MMP), cell apoptosis and reactive oxygen species (ROS) and the levels of factors were determined by flow cytometer, quantitative real-time PCR (qRT-PCR) and western blot assays, respectively. We found that the IC50 of H2O2 was 200 micromol/L at 24 h, and the transfection of siEHPX2 in H2O2-induced IEC-6 cells significantly promoted the cell viability, SOD activity and MMP rate, and reduced the rates of ROS and apoptosis as well as LDH and MDA contents. siEHPX2 up-regulated the B-cell lymphoma-2 (Bcl-2) level and down-regulated the levels of fibroblast-associated (Fas), Fas ligand (Fasl), Bcl-2 associated X protein (Bax), and Caspase-3. Moreover, the phosphorylation levels of phosphoinositide 3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase3beta (GSK3beta) were up-regulated. We proved that siEPHX2 had a protective effect on H2O2-induced oxidative damage in IEC-6 cells through activating PI3K/Akt/GSK3beta signaling pathway. Title: Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease Li X, Lu J, Xu Y, Wang J, Qiu X, Fan L, Li B, Liu W, Mao F and Li J <2 more author(s)> Li X, Lu J, Xu Y, Wang J, Qiu X, Fan L, Li B, Liu W, Mao F, Zhu J, Shen X, Li J (- 2) Ref: Acta Pharm Sin B, 10:646, 2020 : PubMed ESTHER: Li_2020_Acta.Pharm.Sin.B_10_646 PubMedSearch: Li 2020 Acta.Pharm.Sin.B 10 646 PubMedID: 32322468 Abstract Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting beta-amyloid (Abeta) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD. Title: MnO(2) switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides Li W, Rong Y, Wang J, Li T, Wang Z Ref: Biosensors & Bioelectronics, 169:112605, 2020 : PubMed ESTHER: Li_2020_Biosens.Bioelectron_169_112605 PubMedSearch: Li 2020 Biosens.Bioelectron 169 112605 PubMedID: 32947079 Abstract Cholinesterases (ChEs) are important indicators of neurological disease, hepatocellular carcinoma, and organophosphate poisoning. In this work, a MnO(2) switch-bridged DNA walker was developed for ultrasensitive sensing of ChEs activity. The fuel strands loaded MnO(2) switch was designed to bridge the hydrolysis activity of ChEs and the running of the DNA walker. Under the action of ChE, the substrate butyrylcholine is first catalytically hydrolyzed to thiocholine, which then mediates MnO(2) nanosheet reduction to Mn(2+), releasing the fuel strands into solution. The fuel strands as substitute targets then trigger the continuous operation of DNA walker with the aid of Mn(2+), generating detectable fluorescence responses. The detection of ChE activity is converted to DNA detection in this method. Benefited from the robust operation and amplification effect of DNA walker, a wide linear range between the BChE activity and fluorescence intensity of nearly six orders of magnitude (1000-0.005 U/mL) and a limit of detection as low as 0.0008 U/mL are achieved. This allows the direct determination of BChE activity in clinical serum samples without any pretreatments. Moreover, the proposed method has remarkable capabilities for inhibitor (organophosphorus pesticide) screening and quantification, and organophosphorus pesticide detection in real samples is also achieved. Therefore, the MnO(2) switch-bridged DNA walker represents a powerful tool for ultrasensitive sensing of ChEs and organophosphorus pesticides, and has great application potential in clinical diagnosis, therapeutics, and drug screening. Title: Immobilized angiotensin II type I receptor: A powerful method of high throughput screening for antihypertensive compound identification through binding interaction analysis Liang Q, Fu X, Zhang J, Hao J, Feng G, Wang J, Li Q, Ahmad F, Zhao X Ref: Journal of Chromatography A, :461003, 2020 : PubMed ESTHER: Liang_2020_J.Chromatogr.A__461003 PubMedSearch: Liang 2020 J.Chromatogr.A 461003 PubMedID: 32156458 Abstract The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT1R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT1R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0mum microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT1R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT1R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (kd) of azilsartan, candesartan, valsartan and olmesartan to AT1R were 0.01138 +/- 0.003, 0.05142 +/- 0.003, 0.07547 +/- 0.004 and 0.01310 +/- 0.005 min(-1) by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (KA: 0.12x10(4) and 1.5x10(4)/M) and slower kinetics (kd: 0.6864 +/- 0.03 and 0.3005 +/- 0.01 min(-1)) to the receptor. These results, taking together, indicated that the immobilized AT1R has the capacity to probe antihypertensive compounds. Title: Protective effect of Soluble Epoxide Hydrolase Inhibition in Retinal Vasculopathy associated with Polycystic Kidney Disease Lin J, Hu J, Schlotterer A, Wang J, Kolibabka M, Awwad K, Dietrich N, Breitschopf K, Wohlfart P and Hammes HP <6 more author(s)> Lin J, Hu J, Schlotterer A, Wang J, Kolibabka M, Awwad K, Dietrich N, Breitschopf K, Wohlfart P, Kannt A, Lorenz K, Feng Y, Popp R, Hoffmann S, Fleming I, Hammes HP (- 6) Ref: Theranostics, 10:7857, 2020 : PubMed ESTHER: Lin_2020_Theranostics_10_7857 PubMedSearch: Lin 2020 Theranostics 10 7857 PubMedID: 32685025 Abstract Rationale: Vasoregression secondary to glial activation develops in various retinal diseases, including retinal degeneration and diabetic retinopathy. Photoreceptor degeneration and subsequent retinal vasoregression, characterized by pericyte loss and acellular capillary formation in the absence diabetes, are also seen in transgenic rats expressing the polycystic kidney disease (PKD) gene. Activated Muller glia contributes to retinal vasodegeneration, at least in part via the expression of the soluble epoxide hydrolase (sEH). Given that an increase in sEH expression triggered vascular destabilization in diabetes, and that vasoregression is similar in diabetic mice and PKD rats, the aim of the present study was to determine whether sEH inhibition could prevent retinal vasoregression in the PKD rat. Methods: One-month old male homozygous transgenic PKD rats were randomly allocated to receive vehicle or a sEH inhibitor (sEH-I; Sar5399, 30 mg/kg) for four weeks. Wild-type Sprague-Dawley (SD) littermates received vehicle as controls. Retinal sEH expression and activity were measured by Western blotting and LC-MS, and vasoregression was quantified in retinal digestion preparations. Microglial activation and immune response cytokines were assessed by immunofluorescence and quantitative PCR, respectively. 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) mediated Notch signaling, microglial activation and migration were assessed in vivo and in vitro. Results: This study demonstrates that sEH expression and activity were increased in PKD retinae, which led to elevated production of 19,20-DHDP and the depression of Notch signaling. The latter changes elicited pericyte loss and the recruitment of CD11b(+)/CD74(+) microglia to the perivascular region. Microglial activation increased the expression of immune-response cytokines, and reduced levels of Notch3 and delta-like ligand 4 (Dll4). Treatment with Sar5399 decreased 19,20-DHDP generation and increased Notch3 expression. Sar5399 also prevented vasoregression by reducing pericyte loss and suppressed microglial activation as well as the expression of immune-response cytokines. Mechanistically, the activation of Notch signaling by Dll4 maintained a quiescent microglial cell phenotype, i.e. reduced both the surface presentation of CD74 and microglial migration. In contrast, in retinal explants, 19,20-DHDP and Notch inhibition both promoted CD74 expression and reversed the Dll4-induced decrease in migration. Conclusions: Our data indicate that 19,20-DHDP-induced alterations in Notch-signaling result in microglia activation and pericyte loss and contribute to retinal vasoregression in polycystic kidney disease. Moreover, sEH inhibition can ameliorate vasoregression through reduced activity of inflammatory microglia. sEH inhibition is thus an attractive new therapeutic approach to prevent retinal vasoregression. Title: ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis Liu G, Ruan Y, Zhang J, Wang X, Wu W, He P, Wang J, Xiong J, Cheng Y and Jian R <3 more author(s)> Liu G, Ruan Y, Zhang J, Wang X, Wu W, He P, Wang J, Xiong J, Cheng Y, Liu L, Yang Y, Tian Y, Jian R (- 3) Ref: Front Cell Developmental Biology, 8:570, 2020 : PubMed ESTHER: Liu_2020_Front.Cell.Dev.Biol_8_570 PubMedSearch: Liu 2020 Front.Cell.Dev.Biol 8 570 PubMedID: 32733886 Gene_locus related to this paper: human-ABHD11 Abstract Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3beta/beta-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function. Title: Cadmium exposure alters expression of protective enzymes and protein processing genes in venom glands of the wolf spider Pardosa pseudoannulata Lv B, Yang HL, Peng YD, Wang J, Zeng Z, Li N, Tang YE, Wang Z, Song QS Ref: Environ Pollut, 268:115847, 2020 : PubMed ESTHER: Lv_2020_Environ.Pollut_268_115847 PubMedSearch: Lv 2020 Environ.Pollut 268 115847 PubMedID: 33130443 Abstract Cadmium (Cd) pollution is currently the most serious type of heavy metal pollution throughout the world. Previous studies have shown that Cd elevates the mortality of paddy field spiders, but the lethal mechanism remains to be explored profoundly. In the present study, we measured the activities of protective enzymes (acetylcholinesterase, glutathione peroxidase, phenol oxidase) and a heavy metal chelating protein (metallothionein) in the pond wolf spider Pardosa pseudoannulata after Cd exposure. The results indicated that Cd initially increased the enzyme activities and protein concentration of the spider after 10- and 20-day exposure before inhibiting them at 30-day exposure. Further analysis showed that the enzyme activities in the cephalothorax were inhibited to some extent. Since the cephalothorax region contains important venom glands, we performed transcriptome sequencing (RNA-seq) analysis of the venom glands collected from the spiders after long-term Cd exposure. RNA-seq yielded a total of 2826 differentially expressed genes (DEGs), and most of the DEGs were annotated into the process of protein synthesis, processing and degradation. Furthermore, a mass of genes involved in protein recognition and endoplasmic reticulum (ER) -associated protein degradation were down-regulated. The reduction of protease activities supports the view that protein synthesis and degradation in organelles and cytoplasm were dramatically inhibited. Collectively, our outcomes illustrate that Cd poses adverse effects on the expression of protective enzymes and protein, which potentially down-regulates the immune function in the venom glands of the spiders via the alteration of protein processing and degradation in the ER. Title: Donepezil promotes neurogenesis via Src signaling pathway in a rat model of chronic cerebral hypoperfusion Man J, Cui K, Fu X, Zhang D, Lu Z, Gao Y, Yu L, Li N, Wang J Ref: Brain Research, 1736:146782, 2020 : PubMed ESTHER: Man_2020_Brain.Res_1736_146782 PubMedSearch: Man 2020 Brain.Res 1736 146782 PubMedID: 32184165 Abstract Donepezil, a selective acetylcholinesterase (AchE) inhibitor, enhances stroke-induced neurogenesis within subventricular zone (SVZ). Src/Pyk-2 is one of the downstream pathways of acetylcholine receptors (AchRs), and has been shown to participate in the activation of fibroblast growth factor receptor (FGFR)/epidermal growth factor receptor (EGFR) signaling in cancer cells. In this study, we investigated whether donepezil could promote SVZ neurogenesis in chronic cerebral hypoperfusion (CCH) injury via Src signaling pathway. In the bilateral carotid artery occlusion (2VO) rat model, we observed more nestin/5-bromo-2'-deoxyuridine (BrdU)-positive cells and doublecortin (DCX)/BrdU-positive cells in the SVZ than that in the sham group. Further, donepezil obviously improved neurologic function after 2VO, induced the greater number of SVZ proliferative NSCs and neuroblasts, and elevated levels of Src, p-FGFR1, p-EGFR, p-Akt and p-Raf in ipsilateral SVZ. Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. These results suggest that donepezil could upregulate Src signaling pathway to enhance CCH-induced SVZ neurogenesis. Title: Structurally various sorbicillinoids from the deep-sea sediment derived fungus Penicillium sp. SCSIO06871 Pang X, Zhou X, Lin X, Yang B, Tian X, Wang J, Xu S, Liu Y Ref: Bioorg Chem, 107:104600, 2020 : PubMed ESTHER: Pang_2020_Bioorg.Chem_107_104600 PubMedSearch: Pang 2020 Bioorg.Chem 107 104600 PubMedID: 33453645 Abstract Two new hybrid sorbicillinoids (1 and 5), three new bisorbicillinoids (2-4), and three monomeric sorbicillinoids (6-8), along with eighteen known sorbicillinoids (9-26) were isolated from cultures of the deep-sea sediment derived fungus Penicillium sp. SCSIO06871. Their structures and absolute configurations were elucidated based upon the extensive spectroscopic analysis, X-ray crystallography analysis and the comparison of the experimental and calculated ECD data. Bisorbicillpyrone A (4) is the first example of bisorbicillinoid containing an alpha-pyrone derivative unit. All of the isolated compounds were evaluated for their antibacterial, antifungal and enzyme inhibitory activities against alpha-glycosidase and acetylcholinesterase (AChE) in vitro. Compound 6 displayed more potent inhibitory activity against alpha-glycosidase than acarbose with IC(50) value of 36.0 microM and compounds 4, 12, 18, 22, 23 exhibited moderate inhibitory activity with IC(50) values ranging from 115.8 to 208.5 microM. Compounds 10 and 22 showed weak enzyme inhibitory activities against AChE with 55.1% and 51.1% inhibitions at concentration of 50 microg/mL, respectively. Besides, compounds 11 and 12 exhibited significant antibacterial activities against Staphylococcus aureus with MIC values of 10.0 and 5.0 microg/mL, respectively. The hypothetical biosynthetic pathway of the isolated sorbicillinoids with three different structural types was discussed. Title: Urethane attenuates early neuropathology of diisopropylfluorophosphate-induced status epilepticus in rats Rojas A, Wang J, Glover A, Dingledine R Ref: Neurobiol Dis, :104863, 2020 : PubMed ESTHER: Rojas_2020_Neurobiol.Dis__104863 PubMedSearch: Rojas 2020 Neurobiol.Dis 104863 PubMedID: 32283202 Abstract Seizures can be evident within minutes of exposure to an organophosphorus (OP) agent and often progress to status epilepticus (SE) resulting in a high mortality if left untreated. Effective medical countermeasures are necessary to sustain patients suffering from OP poisoning and to mitigate the ensuing brain injury. Here, the hypothesis was tested that a single subanesthetic dose of urethane prevents neuropathology measured 24h following diisopropylfluorophosphate (DFP)-induced SE. Adult Sprague-Dawley rats were injected with DFP to induce SE. During SE rats displayed increased neuronal activity in the hippocampus and an upregulation of immediate early genes as well as pro-inflammatory mediators. In additional experiments rats were administered diazepam (10mg/kg, ip) or urethane (0.8g/kg, sc) 1h after DFP-induced SE and compared to rats that experienced uninterrupted SE. Cortical electroencephalography (EEG) and power analysis strengthen the conclusion that urethane effectively terminates SE and prevents the overnight return of seizure activity. Neurodegeneration in limbic brain regions and the seizure-induced upregulation of key inflammatory mediators present 24h after DFP-induced SE were strongly attenuated by administration of urethane. A trivial explanation for these beneficial effects, that urethane simply reactivates acetylcholinesterase, has been ruled out. These findings indicate that, by contrast to rats administered diazepam or rats that experience uninterrupted SE, the early neuropathology after SE is prevented by subanesthetic urethane, which terminates rather than interrupts, SE. Title: Identification and Functional Study of Chitin Metabolism and Detoxification-Related Genes in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae) Based on Transcriptome Analysis Shao ZM, Li YJ, Zhang XR, Chu J, Ma JH, Liu ZX, Wang J, Sheng S, Wu FA Ref: Int J Mol Sci, 21:, 2020 : PubMed ESTHER: Shao_2020_Int.J.Mol.Sci_21_ PubMedSearch: Shao 2020 Int.J.Mol.Sci 21 PubMedID: 32164390 Abstract Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a serious pest in the sericulture industry, which has caused damage and losses in recent years. With the widespread use of insecticides, the insecticide resistance of G. pyloalis has becomes increasingly apparent. In order to find other effective methods to control G. pyloalis, this study performed a transcriptome analysis of the midgut, integument, and whole larvae. Transcriptome data were annotated with KEGG and GO, and they have been shown to be of high quality by RT-qPCR. The different significant categories of differentially expressed genes between the midgut and the integument suggested that the transcriptome data could be used for next analysis. With the exception of Dda9 (GpCDA5), 19 genes were involved in chitin metabolism, most of which had close protein-protein interactions. Among them, the expression levels of 11 genes, including GpCHSA, GpCDA1, GpCDA2, GpCDA4, GPCHT1, GPCHT2a, GPCHT3a, GPCHT7, GpTre1, GpTre2, and GpRtv were higher in the integument than in the midgut, while the expression levels of the last eight genes, including GpCHSB, GpCDA5, GpCHT2b, GpCHT3b, GpCHT-h, GpPAGM, GpNAGK, and GpUAP, were higher in the midgut than in the integument. Moreover, 282 detoxification-related genes were identified and can be divided into 10 categories, including cytochrome P450, glutathione S-transferase, carboxylesterase, nicotinic acetylcholine receptor, aquaporin, chloride channel, methoprene-tolerant, serine protease inhibitor, sodium channel, and calcium channel. In order to further study the function of chitin metabolism-related genes, dsRNA injection knocked down the expression of GpCDA1 and GpCHT3a, resulting in the significant downregulation of its downstream genes. These results provide an overview of chitin metabolism and detoxification of G. pyloalis and lay the foundation for the effective control of this pest in the sericulture industry. Title: Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z and Du G <3 more author(s)> Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z, Wang Y, Li L, Liu A, Du G (- 3) Ref: Front Pharmacol, 11:595254, 2020 : PubMed ESTHER: Shen_2020_Front.Pharmacol_11_595254 PubMedSearch: Shen 2020 Front.Pharmacol 11 595254 PubMedID: 33390981 Abstract Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD. Title: Structural optimization of pyrazolo[1,5-a]pyrimidine derivatives as potent and highly selective DPP-4 inhibitors Shen J, Deng X, Sun R, Tavallaie MS, Wang J, Cai Q, Lam C, Lei S, Fu L, Jiang F Ref: Eur Journal of Medicinal Chemistry, 208:112850, 2020 : PubMed ESTHER: Shen_2020_Eur.J.Med.Chem_208_112850 PubMedSearch: Shen 2020 Eur.J.Med.Chem 208 112850 PubMedID: 32987315 Abstract Our previous discovery of pyrazolo [1,5-a]pyrimidin-7(4H)-one scaffold-based DPP-4 inhibitors yielded two potent compounds b2 (IC(50) = 79 nM) and d1 (IC(50) = 49 nM) but characterized by cytotoxicity. Herein, with scaffold hopping and fragment-based drug design strategies, highly potent and selective pyrazolo [1,5-a]pyrimidine DPP-4 inhibitors were found featured by reduced or diminished cytotoxicity. Specifically, c24 (IC(50) = 2 nM) exhibits a 25 to 40-fold increase of inhibitory activity respect to those of b2 and d1, respectively, 2-fold from Alogliptin (IC(50) = 4 nM), and remarkable selectivity over DPP-8 and DPP-9 (>2000 fold). Further docking studies confirmed that the pyrazolo [1,5-a]pyrimidine core interacts with the S1 pocket whereas its substituted aromatic ring interacts with the sub-S1 pocket. The interactive mode in this case resembles that of Alogliptin and Trelagliptin. Further in vivo IPGTT assays in diabetic mice demonstrated that c24 effectively reduces glucose excursion by 48% at the dose of 10 mg/kg, suggesting that c24 is worthy of further development as a potent anti-diabetes agent. Title: In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease Song X, Wang T, Guo L, Jin Y, Wang J, Yin G, Jiang K, Wang L, Huang H, Zeng L Ref: Evid Based Complement Alternat Med, 2020:2804849, 2020 : PubMed ESTHER: Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849 PubMedSearch: Song 2020 Evid.Based.Complement.Alternat.Med 2020 2804849 PubMedID: 32148536 Abstract Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD. Title: A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC) Sun Y, Wang J, Hao K Ref: Molecules, 25:, 2020 : PubMed ESTHER: Sun_2020_Molecules_25_ PubMedSearch: Sun 2020 Molecules 25 PubMedID: 32397338 Abstract Gemcitabine (dFdC) demonstrates significant effectiveness against solid tumors in vitro and in vivo; however, its clinical application is limited because it tends to easily undergo deamination metabolism. Therefore, we synthesized 4-N-carbobenzoxy-gemcitabine (Cbz-dFdC) as a lead prodrug and conducted a detailed pharmacokinetic, metabolic, and pharmacodynamic evaluation. After intragastric Cbz-dFdC administration, the Cmax of Cbz-dFdC and dFdC was 451.1 +/- 106.7 and 1656.3 +/- 431.5 ng/mL, respectively. The Tmax of Cbz-dFdC and dFdC was 2 and 4 h, respectively. After intragastric administration of Cbz-dFdC, this compound was mainly distributed in the intestine due to low carboxylesterase-1 (CES1) activity. Cbz-dFdC is activated by CES1 in both humans and rats. The enzyme kinetic curves were well fitted by the Michaelis-Menten equation in rats' blood, plasma, and tissue homogenates and S9 of the liver and kidney, as well as human liver S9 and CES1 recombinase. The pharmacodynamic results showed that the Cbz-dFdC have a good antitumor effect in the HepG2 cell and in tumor-bearing mice, respectively. In general, Cbz-dFdC has good pharmaceutical characteristics and is therefore a good candidate for a potential prodrug. Title: Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease Syal C, Kosaraju J, Hamilton L, Aumont A, Chu A, Sarma SN, Thomas J, Seegobin M, Dilworth FJ and Wang J <5 more author(s)> Syal C, Kosaraju J, Hamilton L, Aumont A, Chu A, Sarma SN, Thomas J, Seegobin M, Dilworth FJ, He L, Wondisford FE, Zimmermann R, Parent M, Fernandes K, Wang J (- 5) Ref: Theranostics, 10:6337, 2020 : PubMed ESTHER: Syal_2020_Theranostics_10_6337 PubMedSearch: Syal 2020 Theranostics 10 6337 PubMedID: 32483456 Abstract Rationale: Monoacylglycerol lipase (Mgll), a hydrolase that breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG) to produce arachidonic acid (ARA), is a potential target for neurodegenerative diseases, such as Alzheimer's disease (AD). Increasing evidence shows that impairment of adult neurogenesis by perturbed lipid metabolism predisposes patients to AD. However, it remains unknown what causes aberrant expression of Mgll in AD and how Mgll-regulated lipid metabolism impacts adult neurogenesis, thus predisposing to AD during aging. Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce beta-amyloid accumulation. Methods: Mgll expression was assessed in both human AD patient post-mortem hippocampal tissues and 3xTg-AD mouse model. In addition, we used both the 3xTg-AD animal model and the CbpS436A genetic knock-in mouse model to identify that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway, involving atypical protein kinase C (aPKC)-stimulated Ser436 phosphorylation of histone acetyltransferase CBP through biochemical methods. Furthermore, we performed in vivo adult neurogenesis assay with BrdU/EdU labelling and Morris water maze task in both animal models following pharmacological treatments to show the key role of Mgll in metformin-corrected neurogenesis and spatial memory deficits of AD through reactivating the aPKC-CBP pathway. Finally, we performed in vitro adult neurosphere assays using both animal models to study the role of the aPKC-CBP mediated Mgll repression in determining adult neural stem/progenitor cell (NPC) fate. Results: Here, we demonstrate that aging-dependent induction of Mgll is observed in the 3xTg-AD model and human AD patient post-mortem hippocampal tissues. Importantly, we discover that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway. The accumulation of Mgll in the 3xTg-AD mice reduces the genesis of newborn neurons and perturbs spatial memory. However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD. In addition, we reveal that elevated Mgll levels in cultured adult NPCs from both 3xTg-AD and CbpS436A animal models are responsible for their NPC neuronal differentiation deficits. Conclusion: Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory. Title: Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis Tu L, Su P, Zhang Z, Gao L, Wang J, Hu T, Zhou J, Zhang Y, Zhao Y and Gao W <9 more author(s)> Tu L, Su P, Zhang Z, Gao L, Wang J, Hu T, Zhou J, Zhang Y, Zhao Y, Liu Y, Song Y, Tong Y, Lu Y, Yang J, Xu C, Jia M, Peters RJ, Huang L, Gao W (- 9) Ref: Nat Commun, 11:971, 2020 : PubMed ESTHER: Tu_2020_Nat.Commun_11_971 PubMedSearch: Tu 2020 Nat.Commun 11 971 PubMedID: 32080175 Gene_locus related to this paper: triwf-a0a7j7c8l4 Abstract Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction. Title: Monitoring insecticide resistance and diagnostics of resistance mechanisms in Bemisia tabaci Mediterranean (Q biotype) in China Wang R, Che W, Wang J, Luo C Ref: Pestic Biochem Physiol, 163:117, 2020 : PubMed ESTHER: Wang_2020_Pestic.Biochem.Physiol_163_117 PubMedSearch: Wang 2020 Pestic.Biochem.Physiol 163 117 PubMedID: 31973847 Abstract Bemisia tabaci is one of notorious agricultural insect pests in China, and the strategies of management largely depend on application of insecticides. In order to assess levels of resistance in field populations of B. tabaci to six insecticides including abamectin, cyantraniliprole, pymetrozine, imidacloprid, chlorpyrifos and bifenthrin, we monitored the susceptibility to all tested insecticides in five field populations across China and the results indicated that field populations of B. tabaci have developed various levels of resistance to each chemical agent. Furthermore, para-type voltage gated sodium channel mutations (L925I and T929V) and acetylcholinesterase ace1 mutation (F331W) were confirmed, and expression levels of CYP6CM1, CYP4C64, GSTd7 and ABCG3 were detected for investigating mechanisms of imidacloprid resistance in the five field-collected populations. The results showed that, in all tested populations, frequencies of F331W were 100%, and the frequencies of the L925I and T929V were in the range of 28.5 to 47.0% and 11.0 to 53.5%, respectively. Moreover, CYP6CM1 and CYP4C64 were significantly overexpressed in two tested populations, respectively, and GSTd7 was significantly overexpressed in one population. No overexpression of ABCG3 was observed in all the populations. Above results provided valuable insight into the current status of insecticide resistance and could be contributed to design strategies of management for B. tabaci. Title: Insight into the Functional Diversification of Lipases in the Endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae) by Genome-scale Annotation and Expression Analysis Wang J, Song J, Fang Q, Yao H, Wang F, Song Q, Ye G Ref: Insects, 11:, 2020 : PubMed ESTHER: Wang_2020_Insects_11_ PubMedSearch: Wang 2020 Insects 11 PubMedID: 32260574 Abstract Lipases play essential roles in digestion, transport, and processing of dietary lipids in insects. For parasitoid wasps with a unique life cycle, lipase functions could be multitudinous in particular. Pteromalus puparum is a pupal endoparasitoid of butterflies. The female adult deposits eggs into its host, along with multifunctional venom, and the developing larvae consume host as its main nutrition source. Parasitoid lipases are known to participate in the food digestion process, but the mechanism remains unclear. P. puparum genome and transcriptome data were interrogated. Multiple alignments and phylogenetic trees were constructed. We annotated a total of 64 predicted lipase genes belonging to five lipase families and suggested that eight venom and four salivary lipases could determine host nutrition environment post-parasitization. Many putative venom lipases were found with incomplete catalytic triads, relatively long beta9 loops, and short lids. Data analysis reveals the loss of catalytic activities and weak triacylglycerol (TAG) hydrolytic activities of lipases in venom. Phylogenetic trees indicate various predicted functions of lipases in P. puparum. Our information enriches the database of parasitoid lipases and the knowledge of their functional diversification, providing novel insight into how parasitoid wasps manipulate host lipid storage by using venom lipases. Title: Silicon-mediated multiple interactions: Simultaneous induction of rice defense and inhibition of larval performance and insecticide tolerance of Chilo suppressalis by sodium silicate Wang J, Xue R, Ju X, Yan H, Gao Z, Esmail Abdalla Elzaki M, Hu L, Zeng R, Song Y Ref: Ecol Evol, 10:4816, 2020 : PubMed ESTHER: Wang_2020_Ecol.Evol_10_4816 PubMedSearch: Wang 2020 Ecol.Evol 10 4816 PubMedID: 32551063 Abstract The rice striped stem borer (SSB, Chilo suppressalis) is one of the most destructive pests of rice plants. Si-mediated rice defense against various pests has been widely reported, and sodium silicate (SS) has been used as an effective source of silicon for application to plants. However, there is quite limited information about the direct effects of Si application on herbivorous insects. SSB larval performance and their insecticide tolerance were examined after they had been reared either on rice plants cultivated in nutrient solution containing 0.5 and 2.0 mM SS or on artificial diets with 0.1% and 0.5% SS. SS amendment in either rice culture medium or artificial diets significantly suppressed the enzymatic activities of acetylcholinesterase, glutathione S-transferases, and levels of cytochrome P450 protein in the midgut of C. suppressalis larvae. Larvae fed on diets containing SS showed lower insecticide tolerance. Additionally, RNA-seq analysis showed that SS-mediated larval insecticide tolerance was closely associated with fatty acid biosynthesis and pyruvate metabolism pathways. Our results suggest that Si not only enhances plant resistance against insect herbivore, but also impairs the insect's capacity to detoxify the insecticides. This should be considered as another important aspect in Si-mediated plant-insect interaction and may provide a novel approach of pest management. Title: Evaluation of modes of action of pesticides to Daphnia magna based on QSAR, excess toxicity and critical body residues Wang J, Yang Y, Huang Y, Zhang X, Qin WC, Wen Y, Zhao YH Ref: Ecotoxicology & Environmental Safety, 203:111046, 2020 : PubMed ESTHER: Wang_2020_Ecotoxicol.Environ.Saf_203_111046 PubMedSearch: Wang 2020 Ecotoxicol.Environ.Saf 203 111046 PubMedID: 32888614 Abstract Agricultural pesticides serve as effective controls of unwanted weeds and pests. However, these same chemicals can exert toxic effects in non-target organisms. To determine chemical modes of action, the toxicity ratio (TR) and critical body residues (CBRs) of 57 pesticides were calculated for Daphnia magna. Results showed that the CBR values of inert compounds were close to a constant while the CBR values of pesticides varied over a wider range. Although herbicides are categorized as specifically-acting compounds to plants, herbicides did not exhibit excess toxicity to Daphnia magna and were categorized as inert compounds with an average logTR = 0.41, which was less than a threshold of one. Conversely, fungicides and insecticides exhibited strong potential for toxic effects to Daphnia magna with an average logTR >2. Many of these chemicals act via disruption of the nervous, respiratory, or reproductive system, with high ligand-receptor binding activity which leads to higher toxicity for Daphnia magna. Molecular docking using acetylcholinesterase revealed that fungicides and insecticides bind more easily with the biological macromolecule when compared with inert compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the toxicity of fungicides was mainly dependent upon the heat of formation and polar surface area, while the toxicity of insecticides was more related to hydrogen-bond properties. This comprehensive analysis reveals that there are specific differences in toxic mechanisms between fungicides and insecticides. These results are useful for determining relative risk associated with pesticide exposure to aquatic crustaceans, such as Daphnia magna. Title: miR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer Wang H, Hu H, Luo Z, Liu S, Wu W, Zhu M, Wang J, Liu Y, Lu Z Ref: Bioscience Reports, 40:, 2020 : PubMed ESTHER: Wang_2020_Biosci.Rep_40_ PubMedSearch: Wang 2020 Biosci.Rep 40 PubMedID: 32816024 Abstract The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 are identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells. Title: Experimental determination of the bioluminescence resonance energy transfer (BRET) Frster distances of NanoBRET and red-shifted BRET pairs Weihs F, Wang J, Pfleger KDG, Dacres H Ref: Anal Chim Acta X, 6:100059, 2020 : PubMed ESTHER: Weihs_2020_Anal.Chim.Acta.X_6_100059 PubMedSearch: Weihs 2020 Anal.Chim.Acta.X 6 100059 PubMedID: 33392495 Abstract Bioluminescence Resonance Energy Transfer (BRET) is widely applied to study protein-protein interactions, as well as increasingly to monitor both ligand binding and molecular rearrangements. The Forster distance (R(0)) describes the physical distance between the two chromophores at which 50% of the maximal energy transfer occurs and it depends on the choice of RET components. R(0) can be experimentally determined using flexible peptide linkers of known lengths to separate the two chromophores. Knowledge of the R(0) helps to inform on the choice of BRET system. For example, we have previously shown that BRET(2) exhibits the largest R(0) to date for any genetically encoded RET pair, which may be advantageous for investigating large macromolecular complexes if its issues of low and fast-decaying bioluminescence signal can be accommodated. In this study we have determined R(0) for a range of bright and red-shifted BRET pairs, including NanoBRET with tetramethylrhodamine (TMR), non-chloro TOM (NCT), mCherry or Venus as acceptor, and BRET(6), a red-shifted BRET(2)-like system. This study revealed R(0) values of 6.15 nm and 6.94 nm for NanoBRET using TMR or NCT as acceptor ligands, respectively. R(0) was 5.43 nm for NanoLuc-mCherry, 5.59 nm for NanoLuc-Venus and 5.47 nm for BRET(6). This extends the palette of available BRET Forster distances, to give researchers a better-informed choice when considering BRET systems and points towards NanoBRET with NCT as a good alternative to BRET(2) as an analysis tool for large macromolecular complexes. Title: Identification, characterization and expression analyses of cholinesterases genes in Yesso scallop (Patinopecten yessoensis) reveal molecular function allocation in responses to ocean acidification Xing Q, Liao H, Peng C, Zheng G, Yang Z, Wang J, Lu W, Huang X, Bao Z Ref: Aquat Toxicol, 231:105736, 2020 : PubMed ESTHER: Xing_2020_Aquat.Toxicol_231_105736 PubMedSearch: Xing 2020 Aquat.Toxicol 231 105736 PubMedID: 33422860 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210ptr6, mizye-a0a210ptv1, mizye-a0a210ptq0, mizye-P021348901.2 Abstract Cholinesterases are key enzymes in central and peripheral cholinergic nerve system functioning on nerve impulse transmission in animals. Though cholinesterases have been identified in most vertebrates, the knowledge about the variable numbers and multiple functions of the genes is still quite meagre in invertebrates, especially in scallops. In this study, the complete cholinesterase (ChE) family members have been systematically characterized in Yesso scallop (Patinopecten yessoensis) via whole-genome scanning through in silico analysis. Ten ChE family members in the genome of Yesso scallop (designated PyChEs) were identified and potentially acted to be the largest number of ChE in the reported species to date. Phylogenetic and protein structural analyses were performed to determine the identities and evolutionary relationships of these genes. The expression profiles of PyChEs were determined in all developmental stages, in healthy adult tissues, and in mantles under low pH stress (pH 6.5 and 7.5). Spatiotemporal expression suggested the ubiquitous functional roles of PyChEs in all stages of development, as well as general and tissue-specific functions in scallop tissues. Regulation expressions revealed diverse up- and down-regulated expression patterns at most time points, suggesting different functional specialization of gene superfamily members in response to ocean acidification (OA). Evidences in gene number, phylogenetic relationships and expression patterns of PyChEs revealed that functional innovations and differentiations after gene duplication may result in altered functional constraints among PyChEs gene clusters. Collectively, our results provide the potential clues that the selection pressures coming from the environment were the potential inducement leading to function allocation of ChE family members in scallop. Title: In Situ Assessment of Donghu Lake China Using Rare Minnow (Gobiocypris rarus) Xiong X, Qiu N, Su L, Hou M, Xu C, Xiong Y, Dong X, Song Z, Wang J Ref: Archives of Environmental Contamination & Toxicology, 79:246, 2020 : PubMed ESTHER: Xiong_2020_Arch.Environ.Contam.Toxicol_79_246 PubMedSearch: Xiong 2020 Arch.Environ.Contam.Toxicol 79 246 PubMedID: 32607658 Abstract In this work, rare minnow (Gobiocypris rarus) was applied as a sentinel organism and set in cages at control and test sampling sites in Donghu Lake for 4 weeks in March, June, September, and December 2016 to assess the biological toxicity of in situ water. Sampling for active biomonitoring and physicochemical variables was performed weekly. The control was obtained from the outdoor pool of the Institute of Hydrobiology, China. Superoxide dismutase, lipoperoxidation, metallothioneins, acetylcholinesterase activity, and Vtg mRNA expression were determined as biomarkers during the field exposure period. Survival and growth also were monitored to evaluate the overall physiological condition of the fish. The seasonal changes of organic pollutants and trace metals (As, Hg, Cr, Cu, Zn, Cd, Pb) in surface water were determined. The integrated biomarker response (IBR) index was applied to summarize biomarker responses and correlate stress levels with concentrations of organic pollutants and trace metals in the surface water. Results indicated that complex pollution by persistent organic pollutants and heavy metals was present in Donghu Lake and that the in situ exposed organisms were stressed. Moreover, the complex pollution of Donghu Lake in summer and autumn was more serious than that in spring and winter. Active biomonitoring combined with IBR analysis enabled good discrimination among different exposure seasons. The proposed protocol with caged rare minnow revealed marked biological effects caused by the investigated Lake and a useful approach that can easily be extended to monitor water pollution. Title: An enzyme inhibition-based lab-in-a-syringe device for point-of-need determination of pesticides Yang L, Wang J, Qu L, Liu Z, Jiang L Ref: Analyst, :, 2020 : PubMed ESTHER: Yang_2020_Analyst__ PubMedSearch: Yang 2020 Analyst PubMedID: 32319482 Abstract An enzyme inhibition-based lab-in-a-syringe (EI-LIS) device was developed by integrating a 1-naphthol-linked bi-enzymatic reaction (sensor core) into the LIS (sensor device) for point-of-need monitoring of pesticide residues. The integration relies on the rational design of two reaction pads. The conjugate pad is a polyester fiber membrane loaded with plant-esterase, an alternative to acetylcholinesterase. Besides pesticide capture, plant-esterase also mediates the hydrolysis of 1-naphthyl acetate, generating 1-naphthol. The detection pad is an agarose gel entrapping oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) from Fe(iii) meso-tetra(N-methyl-4-pyridyl) porphyrin (FeTMPyP4)-catalyzed TMB oxidation. Both pads were embedded into their cartridges and then connected to a syringe. Under syringe pumping, 1-naphthol vertically flowed from the conjugate to the detection cartridge, linking the two pads. If plant-esterase was intact, 1-naphthol would reduce oxTMB, causing a color change of the detection pad from blue to colorless. If the plant-esterase activity was inhibited by pesticides, less 1-naphthol was produced, and the blue color of the detection pad would be partially or wholly retained. The deeper the blue color, the greater the pesticide concentration. This chromogenic pattern is responsible for a highly sensitive readout (detection limits of dichlorvos: 0.1 nM with the naked eye and 0.07 nM with a spectrometer). Title: Sequencing of Transcriptome and Small RNA Revealed the Xenobiotic Metabolism-Related Genes and Potential Regulatory miRNA in Asian Tramp Snail Yang Q, Yang W, Shang F, Ding B, Niu J, Wang J Ref: Front Genet, 11:595166, 2020 : PubMed ESTHER: Yang_2020_Front.Genet_11_595166 PubMedSearch: Yang 2020 Front.Genet 11 595166 PubMedID: 33519897 Abstract The Asian tramp snail, Bradybaena similaris (Ferusssac), is an invasive land snail species and has been a rising agricultural pest in south of China. As a pest, it also plays a role in transmission of Angiostrongylus cantonensis. However, present studies on this species are rare and the molecular information is limited. For this purpose, we sequenced the transcriptome and small RNA of B. similaris collected from citrus orchards. In total, 89,747 unigenes with an N50 size of 1287 bp and an average length of 817 bp were generated from -8.9 Gb transcriptome and 31 Mb clean reads were generated from -36 Mb small RNA library. To demonstrate the usefulness of these two datasets, we analyzed a series of genes associated with xenobiotic metabolism and core RNAi machinery. Analysis of the transcripts resulted in annotation of 126 putative genes encoding cytochrome P450 monooxygenases (CYP, 45), carboxyl/cholinesterases (CCE, 13), glutathione-S-transferases (GST, 24), and ATP-binding cassette transporters (ABC, 44). Analysis of the small RNA detected 42 miRNAs. In addition, four genes involved in small RNA pathways (miRNA, piRNA, and siRNA) were identified, and a total of 430 genes that can be targeted by miRNAs were predicted. Moreover, we found that a few miRNAs could target certain genes involved in xenobiotic metabolism. Therefore, we believe that these two datasets and the characterization of the identified/predicted genes will facilitate the molecular study of this species as well as other land snails with agricultural importance. Title: Self-assembly of lipase hybrid nanoflowers with bifunctional Ca(2+) for improved activity and stability Zhang Y, Sun W, Elfeky NM, Wang Y, Zhao D, Zhou H, Wang J, Bao Y Ref: Enzyme Microb Technol, 132:109408, 2020 : PubMed ESTHER: Zhang_2020_Enzyme.Microb.Technol_132_109408 PubMedSearch: Zhang 2020 Enzyme.Microb.Technol 132 109408 PubMedID: 31731973 Gene_locus related to this paper: 9gamm-a0a1b1ijp3 Abstract Lipase ZC12, a cold-adapted lipase derived from Psychrobacter sp. ZY124, can be effectively activated by Ca(2+). Inspired by this significant property, we developed a novel immobilized lipase ZC12/Ca3(PO4)2 hybrid nanoflowers (LHNs). The LHNs have been characterized as a regular hierarchical flowerlike structure nanoflowers by scanning electron microscopy (SEM). Compared with free lipase ZC12, the LHNs exerted enhanced enzymatic activity of 206% and 2.31-fold in kcat/Km value, especially high specific activity at low temperature. After 7 successive cycles, the LHNs could still maintain its initial activity, demonstrating superior durability than the free lipase ZC12. Meanwhile, its stability basically kept unchanged in a wide range of temperature and pH. Finally, fructose laurate was transformed by the LHNs with 57.39% conversion rate which is twice as much as the free lipase. To sum up, these results validated that LHNs could emerge as an efficient immobilized lipase and possess the promising potential for practical applications. Title: Effect of Massa Medicata Fermentata on the Gut Microbiota of Dyspepsia Mice Based on 16S rRNA Technique Zhang X, Zhang H, Huang Q, Sun J, Yao R, Wang J Ref: Evid Based Complement Alternat Med, 2020:7643528, 2020 : PubMed ESTHER: Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_7643528 PubMedSearch: Zhang 2020 Evid.Based.Complement.Alternat.Med 2020 7643528 PubMedID: 33029172 Abstract Massa Medicata Fermentata (MMF) is a traditional Chinese medicine (TCM) for treating indigestion and its related disorders. This study analyzes the effect of MMF on intestinal microorganisms in dyspepsia mice based on 16S rRNA technology. We take a dyspepsia model caused by a high-protein, high-calorie, high-fat diet. The 60 specific-pathogen free Kunming (SPF KM) mice were randomly divided into a model group (n=12), an MMF group (LSQ group, n=12), a Jianweixiaoshi group (JWXS group, n=12), a domperidone group (DP group, n=12), and a blank group (n=12). On the seventh day of administration, mice were fasted and deprived of water. After 24 h, take the second feces of stress defecation in mice under strict aseptic conditions and quickly transfer them to a sterile cryotube. This study comprehensively evaluates the alpha-diversity, beta-diversity, flora abundance and composition of each group of mice's intestinal microorganisms, and their correlation with functional dyspepsia based on the 16S rRNA gene sequencing technology. After modeling, some dyspepsia reactions, proximal gastric relaxation reduction, and intestinal microflora changes were noted. Dyspepsia mice showed dyspepsia reactions and proximal gastric relaxation reduction, characterized by a significant decrease of contents of gastrin (P < 0.01) and cholinesterase (P < 0.01). MMF can improve dyspepsia symptoms and promote proximal gastric relaxation. Significant intestinal flora disorders were found in dyspepsia mice, including downregulation of Bacteroidetes, Lactobacillus, and Prevotellaceae and upregulation of Proteobacteria, Verrucomicrobia, Epsilonbacteraeota, Firmicutes, Lachnospiraceae NK4A136 group, and Lachnospiraceae. MMF could alleviate intestinal microflora disturbance, and the regulation effect of MMF on Bacteroidetes, Verrucomicrobia, and Epsilonbacteraeota was more reliable than that of Jianweixiaoshi tables and domperidone. The intestinal microflora may be correlated with the promoted digestion of MMF. Title: Monoacylglycerol Lipase Knockdown Inhibits Cell Proliferation and Metastasis in Lung Adenocarcinoma Zhang H, Guo W, Zhang F, Li R, Zhou Y, Shao F, Feng X, Tan F, Wang J and He J <2 more author(s)> Zhang H, Guo W, Zhang F, Li R, Zhou Y, Shao F, Feng X, Tan F, Wang J, Gao S, Gao Y, He J (- 2) Ref: Front Oncol, 10:559568, 2020 : PubMed ESTHER: Zhang_2020_Front.Oncol_10_559568 PubMedSearch: Zhang 2020 Front.Oncol 10 559568 PubMedID: 33363004 Abstract Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, has emerged as an important regulator of tumor progression. In this study, we aimed to characterize the role of MGLL in the development of lung adenocarcinoma (LUAD). To this end, we used tissue microarrays to evaluate the expression of MGLL in LUAD tissue and assessed whether the levels of this protein are correlated with clinicopathological characteristics of LUAD. We found that the expression of MGLL is higher in LUAD samples than that in adjacent non-tumor tissues. In addition, elevated MGLL expression was found to be associated with advanced tumor progression and poor prognosis in LUAD patients. Functional studies further demonstrated that stable short hairpin RNA (shRNA)-mediated knockdown of MGLL inhibits tumor proliferation and metastasis, both in vitro and in vivo, and mechanistically, our data indicate that MGLL regulates Cyclin D1 and Cyclin B1 in LUAD cells. Moreover, we found that knockdown of MGLL suppresses the expression of matrix metalloproteinase 14 (MMP14) in A549 and H322 cells, and in clinical samples, expression of MMP14 is significantly correlated with MGLL expression. Taken together, our results indicate that MGLL plays an oncogenic role in LUAD progression and metastasis and may serve as a potential biomarker for disease prognosis and as a target for the development of personalized therapies. Title: Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities Zhao J, Li K, Wang Y, Li D, Wang Q, Xie S, Wang J, Zuo Z Ref: J Ethnopharmacol, :113711, 2020 : PubMed ESTHER: Zhao_2020_J.Ethnopharmacol__113711 PubMedSearch: Zhao 2020 J.Ethnopharmacol 113711 PubMedID: 33352242 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure. Title: Discovery of Aryl Formyl Piperidine Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase Inhibitors Zhi Z, Zhang W, Yao J, Shang Y, Hao Q, Liu Z, Ren Y, Li J, Zhang G, Wang J Ref: Journal of Medicinal Chemistry, :, 2020 : PubMed ESTHER: Zhi_2020_J.Med.Chem__ PubMedSearch: Zhi 2020 J.Med.Chem PubMedID: 32429662 Abstract Most of the current MAGL inhibitors function by an irreversible mechanism of action, causing a series of side effects. Herein, starting from irreversible inhibitors, 25 compounds were synthesized and evaluated in vitro for MAGL inhibition, among which, compound 36 showed the most potent inhibitory activity (IC50 = 15 nM).Crucially, docking studies demonstrated that the m-chlorine-substituted aniline fragment occupied a hydrophobic sub-pocket enclosed by side chains of Val191, Tyr194, Val270, and Lys273, which creatively identify a new key anchoring point for the development of new MAGL inhibitors. Furthermore, in vivo evaluation innovatively revealed that this reversible inhibitor 36 significantly displayed the depressive-like behaviors induced by reserpine. To the best of our knowledge, this is the first time that reversible inhibitors of MAGL were developed to support MAGL as a potential therapeutic target for depression. Title: HFIP-Functionalized Co3 O4 Micro-Nano-Octahedra/rGO as a Double-Layer Sensing Material for Chemical Warfare Agents Alali KT, Liu J, Chen R, Liu Q, Zhang H, Li J, Hou J, Li R, Wang J Ref: Chemistry, 25:11892, 2019 : PubMed ESTHER: Alali_2019_Chemistry_25_11892 PubMedSearch: Alali 2019 Chemistry 25 11892 PubMedID: 31309626 Abstract Semiconductor metal oxides (SMO)-based gas-sensing materials suffer from insufficient detection of a specific target gas. Reliable selectivity, high sensitivity, and rapid response-recovery times under various working conditions are the main requirements for optimal gas sensors. Chemical warfare agents (CWA) such as sarin are fatal inhibitors of acetylcholinesterase in the nerve system. So, sensing materials with high sensitivity and selectivity toward CWA are urgently needed. Herein, micro-nano octahedral Co3 O4 functionalized with hexafluoroisopropanol (HFIP) were deposited on a layer of reduced graphene oxide (rGO) as a double-layer sensing materials. The Co3 O4 micro-nano octahedra were synthesized by direct growth from electrospun fiber templates calcined in ambient air. The double-layer rGO/Co3 O4 -HFIP sensing materials presented high selectivity toward DMMP (sarin agent simulant, dimethyl methyl phosphonate) versus rGO/Co3 O4 and Co3 O4 sensors after the exposure to various gases owing to hydrogen bonding between the DMMP molecules and Co3 O4 -HFIP. The rGO/Co3 O4 -HFIP sensors showed high stability with a response signal around 11.8 toward 0.5 ppm DMMP at 125 degrees C, and more than 75 % of the initial response was maintained under a saturated humid environment (85 % relative humidity). These results prove that these double-layer inorganic-organic composite sensing materials are excellent candidates to serve as optimal gas-sensing materials. Title: Rapid colorimetric determination of the pesticides carbofuran and dichlorvos by exploiting their inhibitory effect on the aggregation of peroxidase-mimicking platinum nanoparticles Cao J, Wang M, She Y, El-Aty AMA, Hacimuftuoglu A, Wang J, Yan M, Hong S, Lao S, Wang Y Ref: Mikrochim Acta, 186:390, 2019 : PubMed ESTHER: Cao_2019_Mikrochim.Acta_186_390 PubMedSearch: Cao 2019 Mikrochim.Acta 186 390 PubMedID: 31152243 Abstract A novel and highly sensitive enzyme inhibition assay was developed for the rapid detection of the organophosphate pesticide dichlorvos and the carbamate pesticide carbofuran. It achieves signal amplification by the secondary catalysis of platinum nanoparticles. Acetylcholinesterase (AChE) is capable of catalyzing the hydrolysis of acetylthiocholine to form thiocholine. Thiocholine causes the aggregation of citrate-capped platinum nanoparticles which then lose their peroxidase-mimicking properties. After addition of pesticides, the activity of AChE is inhibited, less thiocholine is produced, less aggregation occurs, and the peroxidase-mimetic properties are increasingly retained. In the presence of tetramethylbenzidine and H2O2, a deep blue coloration with an absorption maximum at 650 nm will be formed. The assay was applied to the determination of dichlorvos and carbofuran, and detection limits of 2.3 mug.L(-1) and 1.4 mug.L(-1) were obtained, respectively. Recovery experiments with spiked tap water and pears gave satisfactory relative standard deviations. Graphical abstract The blue product formed by platinum nanoparticle-catalyzed oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) by H2O2 is reduced if acetylthiocholine (ATCh) is hydrolyzed by acetylcholinesterase (AChE) to form thiocholine. However, if AChE is inhibited by pesticides, color formation will recover. Title: Plant allelochemicals affect tolerance of polyphagous lepidopteran pest Helicoverpa armigera (Hubner) against insecticides Chen S, Elzaki MEA, Ding C, Li ZF, Wang J, Zeng RS, Song YY Ref: Pestic Biochem Physiol, 154:32, 2019 : PubMed ESTHER: Chen_2019_Pestic.Biochem.Physiol_154_32 PubMedSearch: Chen 2019 Pestic.Biochem.Physiol 154 32 PubMedID: 30765054 Abstract Cotton bollworm, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae), is a polyphagous lepidopteran pest distributed worldwide with a broad spectrum of host plants. However, the mechanism of H. armigera adaptation to various insecticides and defensive allelochemicals in its host plants is not fully understood. Therefore, this study examined the influence of consumption of plant allelochemicals on larval tolerance to methomyl and chlorpyrifos insecticides in H. armigera and its possible mechanism. Twelve plant allelochemicals were screened to evaluate their effects on larval sensitivity to methomyl. Of which flavone, coumarin, DIMBOA (2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one) and visnagin significantly reduced larval sensitivity to methomyl. Application of cytochrome P450 inhibitor piperonyl butoxide (PBO) significantly increased the mortality of methomyl-treated larvae. In contrast, PBO addition significantly decreased the mortality of chlorpyrifos-treated larvae. Moreover, allelochemical consumption enhanced the activities of glutathione S-transferase, carboxylesterase, cytochrome P450 and acetylcholinesterase in the midgut and fat body. The qRT-PCR analysis confirms that P450 genes, CYP6B2, CYP6B6 and CYP6B7 were induced by the four allelochemicals in the midguts and the fat bodies. In conclusion, the generalist H. armigera can take benefit of plant allelochemicals from its host plants to elaborate its defense against insecticides. Title: Design, synthesis and biological Evaluation of Dual acetyl cholinesterase and beta-secretase inhibitors in treatment for alzheimer's Disease Deng Y, Jiang Y, Zhao X, Wang J Ref: Pak J Pharm Sci, 32:2091, 2019 : PubMed ESTHER: Deng_2019_Pak.J.Pharm.Sci_32_2091 PubMedSearch: Deng 2019 Pak.J.Pharm.Sci 32 2091 PubMedID: 31813875 Abstract With the recent research advances in molecular biology and technology multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in this work to develop muilti-functional agents, which can mainly serve as dual beta-secretase (BACE 1) and Acetylcholinesterase (AChE) inhibitors. Series of new compounds were designed, synthesized and evaluated in this work, from which we identified 2-((4-(1,3-dioxoisoindolin-2-yl)benzyl)amino)-2-oxoethyl-2-(4-methoxyphenyl)aceta te (1h) as a new dual cholinesterase and beta-secretase inhibitor without toxicity. Title: Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer's Disease Based on Systems Biology Guo S, Wang J, Wang Y, Zhang Y, Bi K, Zhang Z, Li Q Ref: Oxid Med Cell Longev, 2019:1707218, 2019 : PubMed ESTHER: Guo_2019_Oxid.Med.Cell.Longev_2019_1707218 PubMedSearch: Guo 2019 Oxid.Med.Cell.Longev 2019 1707218 PubMedID: 31976026 Abstract Kai-Xin-San (KXS), a classical Chinese traditional prescription, was widely applied in the treatment of Alzheimer's disease (AD), while its functional mechanisms still remain unclear. By using systems biology approaches at animal, cellular, and molecular levels, the improvement of KXS on cognitive impairment was achieved by inhibiting abnormal acetylcholinesterase. The function on the nerve skeleton was performed by regulating the Tau phosphorylation pathway. Its antioxidant, anti-inflammatory, and antiapoptotic effects by modulating the aberrant upregulation of ROS, proinflammatory factors, and apoptosis-related proteins in the brain were studied to reveal the synergistic therapeutic efficacy of KXS. Then, formula dismantling in vitro indicated that ginseng was the principal herb, whereas three other herbs served adjuvant roles to achieve the best effect. After that, the in vivo analysis of components into plasma and brain of AD rats showed that 8 of 23 components in blood and 4 of 10 components in brain were from ginseng, respectively, further verifying the principal status of ginseng and the synergistic effects of the formula. Thus, the anti-AD effects of KXS were achieved by multitargets and multichannels. The systems biology approaches presented here provide a novel way in traditional herbal medicine research. Title: Lycopodium alkaloids from Huperzia serrata Jiang F, Qi B, Ding N, Yang H, Jia F, Luo Y, Wang J, Liu X, Wang X and Shi S <1 more author(s)> Jiang F, Qi B, Ding N, Yang H, Jia F, Luo Y, Wang J, Liu X, Wang X, Tu P, Shi S (- 1) Ref: Fitoterapia, :104277, 2019 : PubMed ESTHER: Jiang_2019_Fitoterapia__104277 PubMedSearch: Jiang 2019 Fitoterapia 104277 PubMedID: 31351127 Abstract Five new Lycopodium alkaloids, huperzine Y1 (1), huperzine Y2 (2), huperzine Y3 (3), (+)-huperzine Z (4a) and (-)-huperzine Z (4b) as well as ten known alkaloids (5-14) were isolated from Huperzia serrata. The structures of the new compounds were established using extensive spectroscopic (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Compounds 4a and 4b were a pair of enantiomers successfully separated by chiral HPLC resolution. Compounds 2 and 3 indicated inhibitory activities against acetylcholinesterase with IC50 value of 57.1+/-1.6 and 32.7+/-1.0 muMu, respectively. However, no compound showed inhibitory effect on butyrocholinesterase at the concentration of 100 muMu. Title: Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes Li S, Qin C, Cui S, Xu H, Wu F, Wang J, Su M, Fang X, Li D and Li H <8 more author(s)> Li S, Qin C, Cui S, Xu H, Wu F, Wang J, Su M, Fang X, Li D, Jiao Q, Zhang M, Xia C, Zhu L, Wang R, Li J, Jiang H, Zhao Z, Li H (- 8) Ref: Journal of Medicinal Chemistry, 62:2348, 2019 : PubMed ESTHER: Li_2019_J.Med.Chem_62_2348 PubMedSearch: Li 2019 J.Med.Chem 62 2348 PubMedID: 30694668 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: HL2 Abstract Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level. Title: Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity Lin Y, Wang Y, Lv J, Wang N, Wang J, Li M Ref: Int J Nanomedicine, 14:5817, 2019 : PubMed ESTHER: Lin_2019_Int.J.Nanomedicine_14_5817 PubMedSearch: Lin 2019 Int.J.Nanomedicine 14 5817 PubMedID: 31440049 Abstract Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment. Title: Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model Meriwether D, Sulaiman D, Volpe C, Dorfman A, Grijalva V, Dorreh N, Solorzano-Vargas RS, Wang J, O'Connor E and Reddy ST <8 more author(s)> Meriwether D, Sulaiman D, Volpe C, Dorfman A, Grijalva V, Dorreh N, Solorzano-Vargas RS, Wang J, O'Connor E, Papesh J, Larauche M, Trost H, Palgunachari MN, Anantharamaiah GM, Herschman HR, Martin MG, Fogelman AM, Reddy ST (- 8) Ref: J Clinical Investigation, 129:3670, 2019 : PubMed ESTHER: Meriwether_2019_J.Clin.Invest_129_3670 PubMedSearch: Meriwether 2019 J.Clin.Invest 129 3670 PubMedID: 31184596 Abstract Cyclooxygenase 2 (Cox2) total knockout and myeloid knockout (MKO) mice develop Crohn's-like intestinal inflammation when fed cholate-containing high fat diet (CCHF). We demonstrated that CCHF impaired intestinal barrier function and increased translocation of endotoxin, initiating TLR/MyD88-dependent inflammation in Cox2 KO but not WT mice. Cox2 MKO increased pro-inflammatory mediators in LPS-activated macrophages, and in the intestinal tissue and plasma upon CCHF challenge. Cox2 MKO also reduced inflammation resolving lipoxin A4 (LXA4) in intestinal tissue, while administration of an LXA4 analog rescued disease in Cox2 MKO mice fed CCHF. The apolipoprotein A-I (APOA1) mimetic 4F mitigated disease in both the Cox2 MKO/CCHF and piroxicam-accelerated Il10-/- models of inflammatory bowel disease (IBD) and reduced elevated levels of pro-inflammatory mediators in tissue and plasma. APOA1 mimetic Tg6F therapy was also effective in reducing intestinal inflammation in the Cox2 MKO/CCHF model. We further demonstrated that APOA1 mimetic peptides: i) inhibited LPS and oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphatidylcholine (oxPAPC) dependent pro-inflammatory responses in human macrophages and intestinal epithelium; and ii) directly cleared pro-inflammatory lipids from mouse intestinal tissue and plasma. Our results support a causal role for pro-inflammatory and inflammation resolving lipids in IBD pathology and a translational potential for APOA1 mimetic peptides for the treatment of IBD. Title: Molecular footprints of inshore aquatic adaptation in Indo-Pacific humpback dolphin (Sousa chinensis) Ming Y, Jian J, Yu F, Yu X, Wang J, Liu W Ref: Genomics, 111:1034, 2019 : PubMed ESTHER: Ming_2019_Genomics_111_1034 PubMedSearch: Ming 2019 Genomics 111 1034 PubMedID: 30031902 Gene_locus related to this paper: delle-a0a2y9mw48 Abstract The Indo-Pacific humpback dolphin, Sousa chinensis, being a member of cetaceans, had fully adapted to inshore waters. As a threatened marine mammal, little molecular information available for understanding the genetic basis of ecological adaptation. We firstly sequenced and obtained the draft genome map of S. chinensis. Phylogenetic analysis in this study, based on the single copy orthologous genes of the draft genome, is consistent with traditional phylogenetic classification. The comparative genomic analysis indicated that S. chinensis had 494 species-specific gene families, which involved immune, DNA repair and sensory systems associated with the potential adaption mechanism. We also identified the expansion and positive selection genes in S. chinensis lineage to investigate the potential adaptation mechanism. Our study provided the potential insight into the molecular bases of ecological adaptation in Indo-Pacific humpback dolphin and will be also valuable for future understanding the ecological adaptation and evolution of cetaceans at the genomic level. Title: Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica Qi B, Yang W, Ding N, Luo Y, Jia F, Liu X, Wang J, Wang X, Tu P, Shi S Ref: J Nat Med, 73:769, 2019 : PubMed ESTHER: Qi_2019_J.Nat.Med_73_769 PubMedSearch: Qi 2019 J.Nat.Med 73 769 PubMedID: 31209724 Abstract Six new pyrrole 2-carbaldehyde derived alkaloids, dahurines A-F (1-6), along with five known ones (7-11) and butyl 2-pyrrolidone-5-carboxylate (12) were isolated from the roots of Angelica dahurica. Their structures were determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Although compounds 7 and 8 have been chemically synthesized, they were obtained from natural materials for the first time. Compounds 2, 3, 4, 10, and 11 exhibited acetylcholinesterase inhibitory activity with IC50 values in the range of 47.5-52.5 muM. Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica. Title: A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition Rojas A, Ganesh T, Wang W, Wang J, Dingledine R Ref: Neurobiol Dis, :104399, 2019 : PubMed ESTHER: Rojas_2019_Neurobiol.Dis__104399 PubMedSearch: Rojas 2019 Neurobiol.Dis 104399 PubMedID: 30818067 Abstract This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2-4h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies. Title: Thiocholine-triggered reaction in personal glucose meters for portable quantitative detection of organophosphorus pesticide Tang W, Yang J, Wang F, Wang J, Li Z Ref: Anal Chim Acta, 1060:97, 2019 : PubMed ESTHER: Tang_2019_Anal.Chim.Acta_1060_97 PubMedSearch: Tang 2019 Anal.Chim.Acta 1060 97 PubMedID: 30902336 Abstract A portable and user-friendly method using personal glucose meters for on-site quantitative detection of organophosphorus pesticide (OP) was developed. The inhibition of organophosphorus compounds on acetylcholinesterase (AChE) leads to reduced yields of thiocholine formed by the enzymatic hydrolysis of acetylthiocholine chloride. Ferricyanide ([Fe(CN)6](3-)), the mediator used in glucose test strips for electron transfer to the electrode, can be rapidly reduced to ferrocyanide ([Fe(CN)6](4-)) by thiocholine. This reaction enables direct measurement of thiocholine by personal glucose meters in the same way as measuring the glucose in blood, offering an interesting choice to quantify OP. After incubation of AChE for 30min and enzymatic reaction of 10min, the yield of thiocholine was measured by a personal glucose meter, achieving detection limit of 5mugL(-1) for paraoxon. The proposed method was successfully applied to the detection in apples and cucumbers, presenting promising potential for on-site OP detection in food samples. Title: High-level expression of Thermomyces dupontii thermo-alkaline lipase in Pichia pastoris under the control of different promoters Wang J, Zhang T, Li Y, Li L, Wang Y, Yang B Ref: 3 Biotech, 9:33, 2019 : PubMed ESTHER: Wang_2019_3.Biotech_9_33 PubMedSearch: Wang 2019 3.Biotech 9 33 PubMedID: 30622871 Abstract In this study, 15 methanol-inducible and 9 constitutive promoters were used to drive the expression of Thermomyces dupontii lipase (TDL) in Pichia pastoris. Of the 15 methanol-inducible promoters, formaldehyde dehydrogenase promoter (PFLD1) showed the highest efficiency in driving lipase production, followed by alcohol oxidase 1 (PAOX1) and dihydroxyacetone synthase (PDAS1) promoters. The maximum lipase activity of transformants with PFLD1, PAOX1 and PDAS1 promoters in 5-l bioreactor was 27,076, 24,159 and 22,342 U/ml, respectively. For the nine constitutive promoters, glycosyl phosphatidyl inositol-anchored protein promoter (PGCW14) produced the highest amount of lipases in a medium containing glucose or glycerol as the only carbon source, followed by mitochondrial alcohol dehydrogenase isozyme (P0472) and glyceraldehyde-3-phosphate dehydrogenase (PGAP) promoters. The maximum lipase yields in 5-l bioreactors under the control of PGCW14, P0472 and PGAP promoters were 17,353, 15,046 and 14,276 U/ml, respectively. The result of this study not only identifies a few highly efficient promoters for the heterologous expression of TDL in P. pastoris, but also casts some insight into the optimization of protein production in heterologous systems. Title: Enhancing the atypical esterase promiscuity of the gamma-lactamase Sspg from Sulfolobus solfataricus by substrate screening Wang J, Zhao H, Zhao G, Chen D, Tao Y, Wu S Ref: Applied Microbiology & Biotechnology, 103:4077, 2019 : PubMed ESTHER: Wang_2019_Appl.Microbiol.Biotechnol_103_4077 PubMedSearch: Wang 2019 Appl.Microbiol.Biotechnol 103 4077 PubMedID: 30955078 Abstract Promiscuous enzymes can be modified by protein engineering, which enables the catalysis of non-native substrates. gamma-lactamase Sspg from Sulfolobus solfataricus is an enzyme with high activity, high stability, and pronounced tolerance of high concentrations of the gamma-lactam substrate. These characteristics suggest Sspg as a robust enzymatic catalyst for the preparation of optically pure gamma-lactam. This study investigated the modification of this enzyme to expand its application toward resolving chiral esters. gamma-Lactamase-esterase conversion was performed by employing a three-step method: initial sequence alignment, followed by substrate screening, and protein engineering based on the obtained substrate-enzyme docking results. This process of fine-tuning of chemical groups on substrates has been termed "substrate screening." Steric hindrance and chemical reactivity of the substrate are major concerns during this step, since both are determining factors for the enzyme-substrate interaction. By employing this three-step method, gamma-lactamase Sspg was successfully converted into an esterase with high enantioselectivity towards phenylglycidate substrates (E value > 300). However, since both wild-type Sspg and Sspg mutants did not hydrolyze para-nitrophenyl substrates (pNPs), this esterase activity was termed "atypical esterase activity." The gamma-lactamase activity and stability of the Sspg mutants were not severely compromised. The proposed method can be applied to find novel multi-functional enzyme catalysts within existing enzyme pools. Title: Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure Wang J, Dai M, Cao Q, Yu Q, Luo Q, Shu L, Zhang Y, Bao M Ref: Basic Res Cardiol, 114:41, 2019 : PubMed ESTHER: Wang_2019_Basic.Res.Cardiol_114_41 PubMedSearch: Wang 2019 Basic.Res.Cardiol 114 41 PubMedID: 31502080 Abstract Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS. Title: Exosomes Released from Rabies Virus-Infected Cells May be Involved in the Infection Process Wang J, Wu F, Liu C, Dai W, Teng Y, Su W, Kong W, Gao F, Cai L and Jiang C <1 more author(s)> Wang J, Wu F, Liu C, Dai W, Teng Y, Su W, Kong W, Gao F, Cai L, Hou A, Jiang C (- 1) Ref: Virol Sin, 34:59, 2019 : PubMed ESTHER: Wang_2019_Virol.Sin_34_59 PubMedSearch: Wang 2019 Virol.Sin 34 59 PubMedID: 30725320 Abstract Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated. In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies. Title: Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats Wang K, Chen Q, Wu N, Li Y, Zhang R, Wang J, Gong D, Zou X, Liu C, Chen J Ref: Front Pharmacol, 10:1003, 2019 : PubMed ESTHER: Wang_2019_Front.Pharmacol_10_1003 PubMedSearch: Wang 2019 Front.Pharmacol 10 1003 PubMedID: 31551793 Inhibitor(s) related to this paper: Berberine Abstract Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and beta-Amyloid (Abeta) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Abeta formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Abeta deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats. Title: Musa balbisiana genome reveals subgenome evolution and functional divergence Wang Z, Miao H, Liu J, Xu B, Yao X, Xu C, Zhao S, Fang X, Jia C and Jin Z <30 more author(s)> Wang Z, Miao H, Liu J, Xu B, Yao X, Xu C, Zhao S, Fang X, Jia C, Wang J, Zhang J, Li J, Xu Y, Ma W, Wu Z, Yu L, Yang Y, Liu C, Guo Y, Sun S, Baurens FC, Martin G, Salmon F, Garsmeur O, Yahiaoui N, Hervouet C, Rouard M, Laboureau N, Habas R, Ricci S, Peng M, Guo A, Xie J, Li Y, Ding Z, Yan Y, Tie W, D'Hont A, Hu W, Jin Z (- 30) Ref: Nat Plants, 5:810, 2019 : PubMed ESTHER: Wang_2019_Nat.Plants_5_810 PubMedSearch: Wang 2019 Nat.Plants 5 810 PubMedID: 31308504 Gene_locus related to this paper: musam-m0tuu7, musam-a0a804kav5 Abstract Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars. Title: Electropolymerization-Induced Positively Charged Phenothiazine Polymer Photoelectrode for Highly Sensitive Photoelectrochemical Biosensing Wang J, Lv W, Wu J, Li H, Li F Ref: Analytical Chemistry, 91:13831, 2019 : PubMed ESTHER: Wang_2019_Anal.Chem_91_13831 PubMedSearch: Wang 2019 Anal.Chem 91 13831 PubMedID: 31560517 Abstract Exploring the fabrication of an electrode with high photoelectric conversion efficiency and abundant functional groups for ideal photoelectrochemical (PEC) sensor development is highly urgent but faces a significant challenge. Herein we report an electropolymerization strategy for the preparation of phenothiazine polymeric film on an indium tin oxide (ITO) surface (PPT/ITO), within only a few seconds, and monomers. The fabricated PPT/ITO electrode possessed excellent stability and abundant quaternary ammonium salt groups for developing a highly sensitive PEC sensor through electrostatic binding with negatively charged materials. In this context, a CdS QDs-functionalized PPT/ITO electrode (CdS/PPT/ITO) was proposed and applied to the analysis of chlorpyrifos, used as a model target organophosphorous pesticide (OP). The thiocholine generated from acetylcholinesterase (AChE)-induced catalyzed hydrolysis of acetylthiocholine (ATCh) efficiently directed CdS QDs away from PPT/ITO via electrostatic repulsion, subsequently decreasing PEC current, whereas chlorpyrifos prohibited the generation of thiocholine through inhibiting AChE activity. As compared to the case where chlorpyrifos is absent, significantly enhanced PEC current is determined and is proportional to chlorpyrifos amounts. Thus, the developed CdS/PPT/ITO-based PEC sensor achieved excellent chlorpyrifos biosensing with improved sensitivity down to approximately ng/mL level with good specificity. We envision the proposed strategy will provide a new path to conveniently fabricate photoelectrodes possessing high performance, which will have more useful applications in PEC sensing. Title: Mori Ramulus (Chin.Ph.)-the Dried Twigs of Morus alba L./Part 1: Discovery of Two Novel Coumarin Glycosides from the Anti-Hyperuricemic Ethanol Extract Yao J, He H, Xue J, Wang J, Jin H, Wu J, Hu J, Wang R, Kuchta K Ref: Molecules, 24:, 2019 : PubMed ESTHER: Yao_2019_Molecules_24_ PubMedSearch: Yao 2019 Molecules 24 PubMedID: 30754654 Abstract In Traditional Chinese Medicine (TCM), Mori ramulus (Chin.Ph.)-the dried twigs of Morus alba L.-is extensively used as an antirheumatic agent and also finds additional use in asthma therapy. As a pathological high xanthine oxidase (XO, EC 1.1.3.22) activity is strongly correlated to hyperuricemy and gout, standard anti-hyperuremic therapy typically involves XO inhibitors like allopurinol, which often cause adverse effects by inhibiting other enzymes involved in purine metabolism. Mori ramulus may therefore be a promissing source for the development of new antirheumatic therapeutics with less side effects. Coumarins, one of the dominant groups of bioactive constituents of M. alba, have been demonstrated to possess anti-inflammatory, antiplatelet aggregation, antitumor, and acetylcholinesterase (AChE) inhibitory activities. The combination of HPLC (DAD) and Q-TOF technique could give excellent separating and good structural characterization abilities which make it suitable to analyze complex multi-herbal extracts in TCM. The aim of this study was to develop a HPLC (DAD)/ESI-Q-TOF-MS/MS method for the identification and profiling of pharmacologically active coumarin glycosides in Mori ramulus refined extracts for used in TCM. This HPLC (DAD)/ESI-Q-TOF-MS/MS method provided a rapid and accurate method for identification of coumarin glycosides-including new natural products described here for the first time-in the crude extract of M. alba L. In the course of this project, two novel natural products moriramulosid A (umbelliferone-6-beta-d-apiofuranosyl-(1-->6)-beta-d-glucopyranoside) and moriramulosid B (6-[[6-O-(6-deoxy-alpha-l-mannopyranosyl)-beta-d-glucopyranosyl]oxy]-2H-1-benzopy ran-1-one) were newly discovered and the known natural product Scopolin was identified in M. alba L. for the first time. Title: Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice Zhang J, Wang J, Zhou GS, Tan YJ, Tao HJ, Chen JQ, Pu ZJ, Ma JY, She W and Duan JA <6 more author(s)> Zhang J, Wang J, Zhou GS, Tan YJ, Tao HJ, Chen JQ, Pu ZJ, Ma JY, She W, Kang A, Zhu Y, Liu P, Zhu ZH, Shi XQ, Tang YP, Duan JA (- 6) Ref: Oxid Med Cell Longev, 2019:8636835, 2019 : PubMed ESTHER: Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835 PubMedSearch: Zhang 2019 Oxid.Med.Cell.Longev 2019 8636835 PubMedID: 30911351 Abstract Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication. Title: Treatment Effects of Jinlingzi Powder and Its Extractive Components on Gastric Ulcer Induced by Acetic Acid in Rats Zhao X, Li J, Meng Y, Cao M, Wang J Ref: Evid Based Complement Alternat Med, 2019:7365841, 2019 : PubMed ESTHER: Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841 PubMedSearch: Zhao 2019 Evid.Based.Complement.Alternat.Med 2019 7365841 PubMedID: 30719066 Abstract Jinlingzi powder comprises Melia toosendan Sieb. et Zucc. and Corydalis yanhusuo (Y.H. Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu and is usually applied in clinic as traditional Chinese medicine for pain. The present study aims to investigate the therapeutic actions of Jinlingzi powder and its extracted components and theirs treatment mechanism on the acetic acid induced-gastric ulcer in rats. The gastric ulcer model was induced by the administration of acetic acid in rats (84 male). Jinlingzi powder water decoction, its polysaccharide, and nonalkaloid and alkaloid components were used to investigate the therapeutic actions on the acetic acid induced-gastric ulcer by measuring the related pharmacy and pharmacodynamic factors, including ulcer index, ulcer area, ulcer healing rate, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), neurotensin (NT), platelet activating factor (PAF), thromboxane B2 (TXB2), and vascular endothelial growth factor (VEGF) in rat serum, acetylcholinesterase (AChE) in brain tissue, prostaglandin E2 (PGE2), and basic fibroblast growth factor (bFGF) in gastric tissue. Among the various groups, Jinlingzi powder and the nonalkaloid components caused significant changes in IL-8, TNF-alpha, NT, PAF TXB2, and VEGF values in the serum. The AChE content in the rats' brain tissue was also reduced after using Jinlingzi powder and the nonalkaloid components. Additionally, Jinlingzi powder and the nonalkaloid components considerably affect the amount of PGE2 and bFGF in a rat's stomach tissue. Therefore, Jinlingzi powder and the nonalkaloid components can effectively inhibit neutral neutrophil activation, prevent capillaries thrombosis, and protect gastric mucosa. Thus, the nonalkaloid components of the Jinlingzi powder play a key role in the treatment of gastric ulcer. Title: Biodegradation of mycotoxin fumonisin B1 by a novel bacterial consortium SAAS79 Zhao Z, Zhang Y, Gong A, Liu N, Chen S, Zhao X, Li X, Chen L, Zhou C, Wang J Ref: Applied Microbiology & Biotechnology, 103:7129, 2019 : PubMed ESTHER: Zhao_2019_Appl.Microbiol.Biotechnol_103_7129 PubMedSearch: Zhao 2019 Appl.Microbiol.Biotechnol 103 7129 PubMedID: 31230101 Abstract Fumonisin B1 (FB1) contamination in cereals and cereal products remains an important aspect of food safety because of its wide distribution and the potential health hazard. However, only a few microorganisms have been reported to effectively degrade FB1. In this present study, a bacterial consortium SAAS79 with highly FB1-degrading activity was isolated from the spent mushroom compost. The combination of antibiotic-driven selection and 16S rDNA sequencing identified the Pseudomonas genus as the key FB1-degrading member. The microbial consortium could degrade more than 90% of 10 microg/mL FB1 after incubation for 24 h at pH of 5-7 and temperature of 28-35 degreesC. The enzymes from the intracellular space were proved to be responsible for FB1 degradation, which eliminated about 90% of 10 microg/mL FB1 in 3 h. Besides, liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) analysis identified two degradation products of FB1, and their toxicity on the monkey kidney cells (MARC-145) was significantly lower (p < 0.05) compared with the parent FB1. Overall, the consortium SAAS79 and its crude enzymes may be a potential choice for the decontamination of FB1 in the feed and food industry. Also, the bacterial consortium provides a new source of genes for the development of enzymatic detoxification agent. Title: Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice Chen H, Wu X, Gu X, Zhou Y, Ye L, Zhang K, Pan H, Wang J, Wei H and Han YF <5 more author(s)> Chen H, Wu X, Gu X, Zhou Y, Ye L, Zhang K, Pan H, Wang J, Wei H, Zhu B, Naman CB, Mak SH, Carlier PR, Cui W, Han YF (- 5) Ref: Front Cell Neurosci, 12:396, 2018 : PubMed ESTHER: Chen_2018_Front.Cell.Neurosci_12_396 PubMedSearch: Chen 2018 Front.Cell.Neurosci 12 396 PubMedID: 30483056 Inhibitor(s) related to this paper: Hupyridone Abstract Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD. Title: Induction of hepatic miR-34a by perfluorooctanoic acid regulates metabolism-related genes in mice Cui R, Li C, Wang J, Dai J Ref: Environ Pollut, 244:270, 2018 : PubMed ESTHER: Cui_2018_Environ.Pollut_244_270 PubMedSearch: Cui 2018 Environ.Pollut 244 270 PubMedID: 30342367 Abstract Perfluorooctanoic acid (PFOA) is a widespread organic pollutant with various toxicological impacts on the liver. Members of the miR-34 family are P53-targeted growth suppressors. We found that PFOA exposure (5mg/kg/d PFOA for 28d) resulted in a significant increase of miR-34a in the livers of mice but had no effect on either miR-34b or miR-34c. We knocked out miR-34a in mice to explore the role of elevated miR-34a in PFOA-induced liver toxicity. Compared with the corresponding untreated control, significant increases in liver weight as well as serum alanine transaminase, aspartate aminotransferase, and cholinesterase levels were observed in miR-34a(-/-) and wild-type mice after PFOA exposure. Hepatic cells showed similar swelling in both miR-34a(-/-) and wild-type mice after PFOA treatment. Hepatic RNA-sequencing (RNA-seq) showed that PFOA led to significant alteration in lipid metabolism genes, especially those involved in the peroxisome proliferator-activated receptor pathway, in both wild-type and miR-34a null mice. With or without PFOA treatment, relatively fewer genes were altered in miR-34a(-/-) livers compared to wild-type livers. Among the changed genes by miR-34a, the most dominant were metabolism-related genes, such as Fabp3, Cyp7a1, and Apoa4. Our in vivo study indicated that miR-34a mainly exerts a metabolic regulation role, rather than the pro-apoptosis and cell cycle arrest role reported previously by many in vitro studies. In addition, although hepatic P53 was unchanged, the active type of P53 (acetylated P53 (acetyl-p53, Lys379)) was markedly altered under PFOA treatment. Therefore, the increase in acetylated P53 may have activated the transcription of miR-34a in mouse livers after PFOA treatment. Title: Surrogating and redirection of pyrazolo[1,5-a]pyrimidin-7(4H)-one core, a novel class of potent and selective DPP-4 inhibitors Deng X, Shen J, Zhu H, Xiao J, Sun R, Xie F, Lam C, Wang J, Qiao Y and Jiang F <5 more author(s)> Deng X, Shen J, Zhu H, Xiao J, Sun R, Xie F, Lam C, Wang J, Qiao Y, Tavallaie MS, Hu Y, Du Y, Li J, Fu L, Jiang F (- 5) Ref: Bioorganic & Medicinal Chemistry, 26:903, 2018 : PubMed ESTHER: Deng_2018_Bioorg.Med.Chem_26_903 PubMedSearch: Deng 2018 Bioorg.Med.Chem 26 903 PubMedID: 29373269 Abstract The initial focus on characterizing novel pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as DPP-4 inhibitors, led to a potent and selective inhibitor compound b2. This ligand exhibits potent in vitro DPP-4 inhibitory activity (IC(50): 80 nM), while maintaining other key cellular parameters such as high selectivity, low cytotoxicity and good cell viability. Subsequent optimization of b2 based on docking analysis and structure-based drug design knowledge resulted in d1. Compound d1 has nearly 2-fold increase of inhibitory activity (IC(50): 49 nM) and over 1000-fold selectivity against DPP-8 and DPP-9. Further in vivo IPGTT assays showed that compound b2 effectively reduce glucose excursion by 34% at the dose of 10 mg/kg in diabetic mice. Herein we report the optimization and design of a potent and highly selective series of pyrazolo[1,5-a]pyrimidin-7(4H)-one DPP-4 inhibitors. Title: Delivering the Acetylcholine Neurotransmitter by Nanodrugs as an Effective Treatment for Alzheimer's Disease Fan L, Wang J, Meng F, Luo Y, Sui X, Zhao B, Li W, Quan D, Yang J, Wang Y Ref: J Biomed Nanotechnol, 14:2066, 2018 : PubMed ESTHER: Fan_2018_J.Biomed.Nanotechnol_14_2066 PubMedSearch: Fan 2018 J.Biomed.Nanotechnol 14 2066 PubMedID: 30305214 Abstract The current clinical symptomatic therapy for Alzheimer's disease involves increasing acetylcholine levels in the brain by inhibiting acetylcholinesterase. However, the effectiveness of acetylcholinesterase inhibitors decreases as the disease progresses, leading to many side effects including over-inhibition of other enzymes and hepatic injury. Herein, we investigate the effects of the direct delivery of a low-dose of acetylcholine via human serum albumin nanoparticles to brain. This novel nanodrug improved both spatial learning and memory capability, whereas it reduced oxidative damage in mice. More importantly, damage to the liver or interference with the inherent neurotransmitter generation due to supplementation were almost absent. Our study is the first to demonstrate that supplementation of acetylcholine-loaded nanoparticles might offer a better therapeutic option in the ease of Alzheimer's disease. Title: Comparative proteomic analysis of Ulva prolifera response to high temperature stress Fan M, Sun X, Liao Z, Wang J, Li Y, Xu N Ref: Proteome Sci, 16:17, 2018 : PubMed ESTHER: Fan_2018_Proteome.Sci_16_17 PubMedSearch: Fan 2018 Proteome.Sci 16 17 PubMedID: 30386183 Abstract Background: Ulva prolifera belongs to green macroalgae and is the dominant species of green tide. It is distributed worldwide and is therefore subject to high-temperature stress during the growth process. However, the adaptation mechanisms of the response of U. prolifera to high temperatures have not been clearly investigated yet. Methods: In this study, isobaric tags for relative and absolute quantitation (iTRAQ) labelling was applied in combination with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to conduct comparative proteomic analysis of the response of U. prolifera to high-temperature stress and to elucidate the involvement of this response in adaptation mechanisms. Differentially expressed proteins (DEPs) of U. prolifera under high temperature (denote UpHT) compared with the control (UpC) were identified. Bioinformatic analyses including GO analysis, pathway analysis, and pathway enrichment analysis was performed to analyse the key metabolic pathways that underlie the thermal tolerance mechanism through protein networks. Quantitative real-time PCR and western blot were performed to validate selected proteins. Results: In the present study, 1223 DEPs were identified under high temperature compared with the control, which included 790 up-regulated and 433 down-regulated proteins. The high-temperature stimulus mainly induced the expression of glutathione S-transferase, heat shock protein, ascorbate peroxidase, manganese superoxide dismutase, ubiquitin-related protein, lhcSR, rubisco activase, serine/threonine protein kinase 2, adenylate kinase, Ca(2+)-dependent protein kinase (CDPK), disease resistance protein EDS1, metacaspase type II, NDPK2a, 26S proteasome regulatory subunit, ubiquinone oxidoreductase, ATP synthase subunit, SnRK2s, and cytochrome P450. The down-regulated proteins were photosynthesis-related proteins, glutathione reductase, catalase-peroxidase, thioredoxin, thioredoxin peroxidase, PP2C, and carbon fixation-related proteins. Furthermore, biological index analysis indicated that protein content and SOD activity decreased; the value of Fv/Fm dropped to the lowest point after culture for 96 h. However, APX activity and MDA content increased under high temperature. Conclusion: The present study implied an increase in proteins that were associated with the stress response, oxidative phosphorylation, the cytokinin signal transduction pathway, the abscisic acid signal transduction pathway, and the glutathione metabolism pathway. Proteins that were associated with photosynthesis, carbon fixation in photosynthesis organisms, and the photosynthesis antenna protein pathway were decreased. These pathways played a pivotal role in high temperature regulation. These novel proteins provide a good starting point for further research into their functions using genetic or other approaches. These findings significantly improve the understanding of the molecular mechanisms involved in the tolerance of algae to high-temperature stress. Title: Excellent Degradation Performance of a Versatile Phthalic Acid Esters-Degrading Bacterium and Catalytic Mechanism of Monoalkyl Phthalate Hydrolase Fan S, Wang J, Yan Y, Jia Y Ref: Int J Mol Sci, 19:, 2018 : PubMed ESTHER: Fan_2018_Int.J.Mol.Sci_19_ PubMedSearch: Fan 2018 Int.J.Mol.Sci 19 PubMedID: 30231475 Gene_locus related to this paper: 9acto-q2mhh5 Abstract Despites lots of characterized microorganisms that are capable of degrading phthalic acid esters (PAEs), there are few isolated strains with high activity towards PAEs under a broad range of environmental conditions. In this study, Gordonia sp. YC-JH1 had advantages over its counterparts in terms of di(2-ethylhexyl) phthalate (DEHP) degradation performance. It possessed an excellent degradation ability in the range of 20(-)50 degrees C, pH 5.0(-)12.0, or 0(-)8% NaCl with the optimal degradation condition 40 degrees C and pH 10.0. Therefore, strain YC-JH1 appeared suitable for bioremediation application at various conditions. Metabolites analysis revealed that DEHP was sequentially hydrolyzed by strain YC-JH1 to mono(2-ethylhexyl) phthalate (MEHP) and phthalic acid (PA). The hydrolase MphG1 from strain YC-JH1 hydrolyzed monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-n-hexyl phthalate (MHP), and MEHP to PA. According to molecular docking and molecular dynamics simulation between MphG1 and monoalkyl phthalates (MAPs), some key residues were detected, including the catalytic triad (S125-H291-D259) and the residues R126 and F54 potentially binding substrates. The mutation of these residues accounted for the reduced activity. Together, the mechanism of MphG1 catalyzing MAPs was elucidated, and would shed insights into catalytic mechanism of more hydrolases. Title: A novel chlorpyrifos hydrolase CPD from Paracoccus sp. TRP: Molecular cloning, characterization and catalytic mechanism Fan S, Li K, Yan Y, Wang J, Qiao C, Yang T, Jia Y, Zhao B Ref: Electronic Journal of Biotechnology, 31:10, 2018 : PubMed ESTHER: Fan_2018_Electron.J.Biotechnol_31_10 PubMedSearch: Fan 2018 Electron.J.Biotechnol 31 10 Gene_locus related to this paper: 9rhob-a0a1x7ll67 Abstract Background: Biodegradation is a reliable approach for efficiently eliminating persistent pollutants such as chlorpyrifos. Despite many bacteria or fungi isolated from contaminated environment and capable of degrading chlorpyrifos, limited enzymes responsible for its degradation have been identified, let alone the catalytic mechanism of the enzymes. Results: In present study, the gene cpd encoding a chlorpyrifos hydrolase was cloned by analysis of genomic sequence of Paracoccus sp. TRP. Phylogenetic analysis and BLAST indicated that CPD was a novel member of organophosphate hydrolases. The purified CPD enzyme, with conserved catalytic triad (Ser155-Asp251-His281) and motif Gly-Asp-Ser-Ala-Gly, was significantly inhibited by PMSF, a serine modifier. Molecular docking between CPD and chlorpyrifos showed that Ser155 was adjacent to chlorpyrifos, which indicated that Ser155 may be the active amino acid involved in chlorpyrifos degradation. This speculation was confirmed by site-directed mutagenesis of Ser155Ala accounting for the decreased activity of CPD towards chlorpyrifos. According to the key role of Ser155 in chlorpyrifos degradation and molecular docking conformation, the nucleophilic catalytic mechanism for chlorpyrifos degradation by CPD was proposed. Conclusion: The novel enzyme CPD was capable of hydrolyze chlorpyrifos and Ser155 played key role during degradation of chlorpyrifos. Title: CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells Feng X, Zhang D, Li X, Ma S, Zhang C, Wang J, Li Y, Liang L, Zhang P and Wang W <7 more author(s)> Feng X, Zhang D, Li X, Ma S, Zhang C, Wang J, Li Y, Liang L, Zhang P, Qu Y, Zhang Z, Yang Z, Xiang Y, Zhang W, Wang S, Shao W, Wang W (- 7) Ref: Biomed Pharmacother, 107:1496, 2018 : PubMed ESTHER: Feng_2018_Biomed.Pharmacother_107_1496 PubMedSearch: Feng 2018 Biomed.Pharmacother 107 1496 PubMedID: 30257367 Abstract CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC. Title: A Verticillium dahliae Extracellular Cutinase Modulates Plant Immune Responses Gui YJ, Zhang WQ, Zhang DD, Zhou L, Short DPG, Wang J, Ma XF, Li TG, Kong ZQ and Dai XF <5 more author(s)> Gui YJ, Zhang WQ, Zhang DD, Zhou L, Short DPG, Wang J, Ma XF, Li TG, Kong ZQ, Wang BL, Wang D, Li NY, Subbarao KV, Chen JY, Dai XF (- 5) Ref: Mol Plant Microbe Interact, 31:260, 2018 : PubMed ESTHER: Gui_2018_Mol.Plant.Microbe.Interact_31_260 PubMedSearch: Gui 2018 Mol.Plant.Microbe.Interact 31 260 PubMedID: 29068240 Abstract Cutinases have been implicated as important enzymes during the process of fungal infection of aerial plant organs. The function of cutinases in the disease cycle of fungal pathogens that invade plants through the roots has been less studied. Here, functional analysis of 13 cutinase (carbohydrate esterase family 5 domain-containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen Verticillium dahliae Vd991 was performed. Significant sequence divergence in cutinase family members was observed in the genome of V. dahliae Vd991. Functional analyses demonstrated that only VdCUT11, as purified protein, induced cell death and triggered defense responses in Nicotiana benthamiana, cotton, and tomato plants. Virus-induced gene silencing showed that VdCUT11 induces plant defense responses in Nicotiana benthamania in a BAK1 and SOBIR-dependent manner. Furthermore, coinfiltration assays revealed that the carbohydrate-binding module family 1 protein (VdCBM1) suppressed VdCUT11-induced cell death and other defense responses in N. benthamiana. Targeted deletion of VdCUT11 in V. dahliae significantly compromised virulence on cotton plants. The cutinase VdCUT11 is an important secreted enzyme and virulence factor that elicits plant defense responses in the absence of VdCBM1. Title: Xuebijing injection induces anti-inflammatory-like effects and downregulates the expression of TLR4 and NF-kappaB in lung injury caused by dichlorvos poisoning He F, Wang J, Liu Y, Wang X, Cai N, Wu C, Gao Q Ref: Biomed Pharmacother, 106:1404, 2018 : PubMed ESTHER: He_2018_Biomed.Pharmacother_106_1404 PubMedSearch: He 2018 Biomed.Pharmacother 106 1404 PubMedID: 30119213 Abstract BACKGROUND: The mechanism in lung injury caused by acute organophosphate pesticide poisoning (AOPP) and an effective treatment remains unclear. We aim to clarify how the inflammatory lung injury caused by AOPP might be modulated by Xuebijing (XBJ) injection. METHODS: AOPP-induced lung injury model was induced by dichlorvos (DDVP) subcutaneous administration in rats and XBJ injection was administered by intraperitoneal injection after DDVP challenge. The effects of XBJ injection were assessed by lung histopathological analysis and lung injury scores, lung wet-to-dry weight ratios (WDR) and oxygenation, differential immune cell count in bronchoalveolar lavage fluid (BALF), IL-6 and TNF-alpha levels in blood, the levels of TLR4 and NF-kappaB proteins in lung tissue and blood acetylcholinesterase (AChE) activity. RESULTS: DDVP administration resulted in damage of lung histopathology and lower PaO2/FiO2 ratios (P < 0.05), which were notably attenuated by XBJ injection (P < 0.05). Total cell, macrophage, and neutrophils count in BALF and TNF-alpha and IL-6 levels in blood were significantly increased after DDVP exposure (P < 0.05), which were notably ameliorated by XBJ injection (P < 0.05). TLR4 and NF-kappaB protein in lung tissue expression after DDVP challenge were markedly increased (P < 0.05), and they were substantially downregulated by XBJ injection (P < 0.05). In addition, blood AChE activity was significantly decreased by DDVP administration (P < 0.05), however, there was no significant improvement after XBJ injection. CONCLUSION: XBJ injection prevents DDVP poisoning induced lung injury by attenuating the inflammatory response. The protective effect appears to be mediated through downregulation of the TLR4 and NF-kappaB expression. Title: Asperversins A and B, Two Novel Meroterpenoids with an Unusual 5/6/6/6 Ring from the Marine-Derived Fungus Aspergillus versicolor Li H, Sun W, Deng M, Qi C, Chen C, Zhu H, Luo Z, Wang J, Xue Y, Zhang Y Ref: Mar Drugs, 16:, 2018 : PubMed ESTHER: Li_2018_Mar.Drugs_16_ PubMedSearch: Li 2018 Mar.Drugs 16 PubMedID: 29882867 Abstract Asperversins A (1) and B (2), two novel meroterpenoids featuring an uncommon 5/6/6/6 ring system, along with five new analogues (3(-)7) and a known compound asperdemin (8), were obtained from the marine-derived fungus Aspergillus versicolor. Their structures and absolute configurations were confirmed by extensive spectroscopic analyses, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculation. All new compounds were tested for their acetylcholinesterase enzyme (AChE) inhibitory activities and cytotoxic activities, of which compound 7 displayed moderate inhibitory activity against the AChE with an IC50 value of 13.6 μM. Title: Biosynthetic and antimicrobial potential of actinobacteria isolated from bulrush rhizospheres habitat in Zhalong Wetland, China Li Y, Li Q, Gao J, Wang J, Luo Y, Fan X, Gu P Ref: Arch Microbiol, 200:695, 2018 : PubMed ESTHER: Li_2018_Arch.Microbiol_200_695 PubMedSearch: Li 2018 Arch.Microbiol 200 695 PubMedID: 29368168 Gene_locus related to this paper: 9actn-a0a2s3y543 Abstract The wetland ecosystem is known to possess unique vegetation and serves multiple functions within the environment. In this study, bacterial bioprospecting of bulrush rhizospheres in the Zhalong Wetland, China, was performed using comprehensive methods, including strain isolation and phylogenetic analysis, PCR detection of biosynthetic gene clusters, assessment of antimicrobial activity, metabolite profiling and genome analysis. A total of 27 actinobacterial strains were isolated, and their biosynthetic gene clusters (NRPS, PKS-I and PKS-II) were investigated; all of the tested strains had at least one of the three aforementioned biosynthetic gene clusters. Furthermore, fermentation broth extracts produced by these strains showed antimicrobial activities against certain pathogens, and ten of the extracts exhibited broad-spectrum antimicrobial activity. Liquid chromatography-mass spectrometry (LC-MS) analysis indicated chemical diversity of secondary metabolites from these extracts. Among these strains, ZLSD-24 generated the largest amounts and types of secondary metabolites. Subsequent genome analysis showed that 41 secondary metabolite biosynthetic gene clusters were present in the strain ZLSD-24, which was in accordance with the LC-MS data. Taken together, the results of this study reveal that bulrush rhizosphere habitat in the Zhalong wetland is a promising source of novel natural products. Title: High expression of NDRG3 associates with unfavorable overall survival in non-small cell lung cancer Luo X, Hou N, Chen X, Xu Z, Xu J, Wang L, Yang S, Liu S, Xu L and Fan W <3 more author(s)> Luo X, Hou N, Chen X, Xu Z, Xu J, Wang L, Yang S, Liu S, Xu L, Chen Y, Xiong L, Wang J, Fan W (- 3) Ref: Cancer Biomark, 21:461, 2018 : PubMed ESTHER: Luo_2018_Cancer.Biomark_21_461 PubMedSearch: Luo 2018 Cancer.Biomark 21 461 PubMedID: 29171988 Abstract BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p= 0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis. Title: Detection of vapor-phase organophosphate threats using wearable conformable integrated epidermal and textile wireless biosensor systems Mishra RK, Martin A, Nakagawa T, Barfidokht A, Lu X, Sempionatto JR, Lyu KM, Karajic A, Musameh MM and Wang J <1 more author(s)> Mishra RK, Martin A, Nakagawa T, Barfidokht A, Lu X, Sempionatto JR, Lyu KM, Karajic A, Musameh MM, Kyratzis IL, Wang J (- 1) Ref: Biosensors & Bioelectronics, 101:227, 2018 : PubMed ESTHER: Mishra_2018_Biosens.Bioelectron_101_227 PubMedSearch: Mishra 2018 Biosens.Bioelectron 101 227 PubMedID: 29096360 Abstract Flexible epidermal tattoo and textile-based electrochemical biosensors have been developed for vapor-phase detection of organophosphorus (OP) nerve agents. These new wearable sensors, based on stretchable organophosphorus hydrolase (OPH) enzyme electrodes, are coupled with a fully integrated conformal flexible electronic interface that offers rapid and selective square-wave voltammetric detection of OP vapor threats and wireless data transmission to a mobile device. The epidermal tattoo and textile sensors display a good reproducibility (with RSD of 2.5% and 4.2%, respectively), along with good discrimination against potential interferences and linearity over the 90-300mg/L range, with a sensitivity of 10.7microAcm3mg-1 (R2 = 0.983) and detection limit of 12mg/L in terms of OP air density. Stress-enduring inks, used for printing the electrode transducers, ensure resilience against mechanical deformations associated with textile and skin-based on-body sensing operations. Theoretical simulations are used to estimate the OP air density over the sensor surface. These fully integrated wearable wireless tattoo and textile-based nerve-agent vapor biosensor systems offer considerable promise for rapid warning regarding personal exposure to OP nerve-agent vapors in variety of decentralized security applications. Title: New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus Qi C, Qiao Y, Gao W, Liu M, Zhou Q, Chen C, Lai Y, Xue Y, Zhang J and Zhang Y <5 more author(s)> Qi C, Qiao Y, Gao W, Liu M, Zhou Q, Chen C, Lai Y, Xue Y, Zhang J, Li D, Wang J, Zhu H, Hu Z, Zhou Y, Zhang Y (- 5) Ref: Org Biomol Chem, 16:9046, 2018 : PubMed ESTHER: Qi_2018_Org.Biomol.Chem_16_9046 PubMedSearch: Qi 2018 Org.Biomol.Chem 16 9046 PubMedID: 30430177 Abstract Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease. Title: Carboxylesterase and UDP-glucuronosyltransferases mediated metabolism of irinotecan: In vitro and in vivo insights from quantitative ultra-performance liquid chromatography-mass spectrometry analysis Qin Y, Kang A, Zhou G, Wang H, Wei W, Cao Y, Chen Y, Wang J, Shi Y and Jiang J <1 more author(s)> Qin Y, Kang A, Zhou G, Wang H, Wei W, Cao Y, Chen Y, Wang J, Shi Y, Tang Y, Jiang J (- 1) Ref: Biomedical Chromatography, :e4320, 2018 : PubMed ESTHER: Qin_2018_Biomed.Chromatogr__e4320 PubMedSearch: Qin 2018 Biomed.Chromatogr e4320 PubMedID: 29920713 Abstract Carboxylesterase and UDP-glucuronosyltransferases mediated metabolism of irinotecan (CPT-11) has long been proposed to be responsible for its anti-tumor activity and toxicity, like delayed-onset diarrhea. However, recent studies failed to gain more comprehensive in vivo and in vitro pharmacokinetic profiles of irinotecan. Herein, we choose rat plasma, human liver microsomes and immortalized HepG2 cell as experimental subjects to describes an sensitive and versatile UHPLC-MS/MS method for simultaneously quantify CPT-11 and its metabolites, including SN-38 and SN-38G. Meanwhile, we have adopted the method to investigate the pharmacokinetic or metabolism behavior of CPT-11 in the above biological samples. Calibration curves for all bio-matrices showed desirable linearity (r(2) >0.99). The intra-day and inter-day precision (RSD, %) were within 15 % and the excellent accuracy (RE, %) was between 2.96% and 14.12%. In addition, the specificity, matrix effect and extraction recovery were all meet the requirements of biological sample analysis. We have successfully applied this method to investigating pharmacokinetic of irinotecan in different biological samples, which mediated by carboxylesterase and UDP-glucuronosyltransferases. And this method could be emplyed in monitoring the metabolic status and clinical efficacy of irinotecan in the future. Title: Post-exposure treatment with the oxime RS194B rapidly reactivates and reverses advanced symptoms of lethal inhaled paraoxon in macaques Rosenberg YJ, Wang J, Ooms T, Rajendran N, Mao L, Jiang X, Lees J, Urban L, Romper J and Taylor P <2 more author(s)> Rosenberg YJ, Wang J, Ooms T, Rajendran N, Mao L, Jiang X, Lees J, Urban L, Romper J, Sepulveda Y, Shyong YJ, Taylor P (- 2) Ref: Toxicol Lett, 293:229, 2017 : PubMed ESTHER: Rosenberg_2018_Toxicol.Lett_293_229 PubMedSearch: Rosenberg 2018 Toxicol.Lett 293 229 PubMedID: 29129799 Abstract Fatalities from organophosphate (OP) insecticide result from both occupational and deliberate exposure; significantly impacting human health. Like nerve agents, insecticides are neurotoxins which target and inhibit acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with a pyridinium aldoximes e.g. pralidoxime, to reactivate the OP-inhibited AChE. However, commonly used oximes inefficiently cross the blood brain barrier and are rapidly cleared and their benefit is debated. Recent findings have demonstrated the ability of a novel zwitterionic, centrally acting, brain penetrating oxime (RS194B) to reverse severe symptoms and rapidly reactivate sarin-inhibited AChE in macaques but has not been tested following OP pesticide poisoning. The severe symptoms following a lethal dose of inhaled paraoxon (100ug/kg), which mimicked those in insecticide poisoned individuals, were rapidly reversed in macaques by post-exposure IM administration of 80mg/kg of RS194B. This occurred with a concomitant reactivation of AChE to 40-100% in <1hr and BChE (40% in 8hr). These findings will be used to develop a macaque model with RS194B as a post-exposure treatment for insecticide poisoning and generate efficacy data for approval under the FDA Animal rule. Title: Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas Sun H, Lee P, Yan C, Gao N, Wang J, Fan X, Yu FS Ref: Diabetes, 67:1162, 2018 : PubMed ESTHER: Sun_2018_Diabetes_67_1162 PubMedSearch: Sun 2018 Diabetes 67 1162 PubMedID: 29615440 Abstract EPHX2 (encoding soluble epoxide hydrolase [sEH]) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and profibrinolytic effectors, into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, was markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type 2 and mouse type 1 (streptozotocin [STZ] induced) and/or type 2 diabetes. Ephx2 depletion had no detectable effects on STZ-induced hyperglycemia but prevented the development of tear deficiency. Ephx2(-/-) mice showed an acceleration of hyperglycemia-delayed epithelium wound healing. Moreover, inhibition of sEH increased the rate of epithelium wound closure and restored hyperglycemia-suppressed STAT3 activation and heme oxygenase-1 (HO-1) expression in the diabetic corneas. Treatment of diabetic corneas with cobalt protoporphyrin, a well-known HO-1 inducer, restored wound-induced HO-1 upregulation and accelerated delayed wound healing. Finally, Ephx2 depletion enhanced sensory innervation and regeneration in diabetic corneas at 1 month after epithelial debridement. Our data suggest that increased sEH activity may be a contributing factor for diabetic corneal complications; targeting sEH pharmacologically or supplementing EETs may represent a new, adjunctive therapy for treating diabetic keratopathy. Title: Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II) Wang J, Wang C, Wu Z, Li X, Xu S, Liu J, Lan Q, Zhu Z, Xu J Ref: Chemical Biology Drug Des, 91:756, 2018 : PubMed ESTHER: Wang_2018_Chem.Biol.Drug.Des_91_756 PubMedSearch: Wang 2018 Chem.Biol.Drug.Des 91 756 PubMedID: 29112799 Abstract A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC50 value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti-Alzheimer's disease agents. Title: Neuroprotective effect of berberine agonist against impairment of learning and memory skills in severe traumatic brain injury via Sirt1/p38 MAPK expression Wang J, Zhang Y Ref: Mol Med Rep, 17:6881, 2018 : PubMed ESTHER: Wang_2018_Mol.Med.Rep_17_6881 PubMedSearch: Wang 2018 Mol.Med.Rep 17 6881 PubMedID: 29512719 Inhibitor(s) related to this paper: Berberine Abstract Berberine has multiple clinical applications, including the treatment of tumors, diabetes, cardiovascular diseases, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemic injuries, mental diseases, Alzheimer's disease and osteoporosis. In the present study, the neuroprotective effect of berberine agonist rescue learning and memory in severe traumatic brain injury (TBI), and the possible mechanism underlying these observations was explored. The protective effect of berberine agonist significantly recovered learning and memory skills, attenuated brain edema and inhibited matrix metalloproteinase3 and 9 protein expression in mice with severe TBI. Berberine agonist significantly reduced inflammation, oxidative stress and apoptosis levels in mice with severe TBI. Berberine agonist promoted choline acetyltransferase activity and inhibited the activity of acetylcholinesterase. Collectively, results of the present study revealed that the neuroprotective effect of berberine agonist rescues learning and memory skills in severe TBI. Title: Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane Wang J, Tang X, Li Y, Zhang R, Zhu L, Chen J, Sun Y, Zhang Q, Wang W Ref: Phys Chem Chem Phys, 20:20540, 2018 : PubMed ESTHER: Wang_2018_Phys.Chem.Chem.Phys_20_20540 PubMedSearch: Wang 2018 Phys.Chem.Chem.Phys 20 20540 PubMedID: 30051124 Abstract The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts. Title: Assessment of novel azaanthraquinone derivatives as potent multi-target inhibitors of inflammation and amyloid-beta aggregation in Alzheimer's disease Wang J, Li W, Qin J, Wang L, Wei S, Tang H Ref: Bioorg Chem, 83:477, 2018 : PubMed ESTHER: Wang_2018_Bioorg.Chem_83_477 PubMedSearch: Wang 2018 Bioorg.Chem 83 477 PubMedID: 30448726 Abstract A series of 6-substituted azaanthraquinone derivatives have been designed, synthesized, and their anti-inflammatory activities, antiaggregation effects on beta-amyloid proteins, anticholinesterase and neuroprotective activity were tested. The new derivatives strongly suppressed NO and iNOS production and modulate the production of cytokines by decreasing TNF-a, IL-1beta and IL-6 formation in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Meanwhile, the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Abeta aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human b-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Abeta42 secretion levels. Moreover, the derivatives exhibited moderate inhibitory potency toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Further investigations indicated that compound 7b could attenuate H2O2-induced neurotoxicity toward SH-SY5Y neuroblastoma cells and half of the synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Taken together, azaanthraquinone derivatives targeting multiple pathogenetic factors deserves further investigation for prevention and treatment of AD. Title: Correlation Between Liver Stiffness Measured by Shear Wave Elastography and Child-Pugh Classification Wang J, Wang Q, Yu G, She Q, Zhang W, Zhang J Ref: Journal of Ultrasound in Medicine, 37:2191, 2018 : PubMed ESTHER: Wang_2018_J.Ultrasound.Med_37_2191 PubMedSearch: Wang 2018 J.Ultrasound.Med 37 2191 PubMedID: 29476558 Abstract OBJECTIVES: To explore the association between liver stiffness and the Child-Pugh classification of liver function by shear wave elastography (SWE). METHODS: A total of 116 patients with liver cirrhosis were divided into 3 groups according to the Child-Pugh classification prospectively. Conventional ultrasound imaging and SWE were performed for all patients. The associations of liver stiffness measured by SWE with ultrasound measurements, serum biochemical indicators, and the Child-Pugh classification were analyzed. Receiver operating characteristic curves were analyzed and compared to determine the ability of liver stiffness to diagnose cirrhosis. RESULTS: Liver stiffness measured by SWE increased with an increasing Child-Pugh classification, internal diameter of the hepatic portal and splenic veins, spleen thickness, spleen length, total bilirubin level, and prothrombin time, which were positively correlated with the Child-Pugh classification (all P < .05). The albumin level and liver stiffness showed higher areas under the curve in comparison with other parameters for evaluating the Child-Pugh classification. Albumin and cholinesterase levels were negatively correlated with the Child-Pugh classification (P < .05). All of these indicators were significantly different between each pair of groups (all P < .05), except for the internal diameter of the hepatic portal vein, prothrombin time, and total bilirubin, and cholinesterase levels between groups B and C (P > 0.05) and the thickness and length of spleen and internal diameter of the splenic vein between groups A and B (P > 0.05). There were no differences among the groups for alanine aminotransferase, aspartate aminotransferase, and globulin levels. CONCLUSIONS: Liver stiffness measured by SWE was correlated with the Child-Pugh classification, and it may be able to help evaluate liver function in patients with cirrhosis. Title: [Effect of enteral nutrition tolerance assessment standardized process management on ventilator associated pneumonia and prognosis in patients with tracheotomy and long-term mechanical ventilation in intensive care unit] Wang C, Wang J, Wang B, Jing X, Huang Y Ref: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 30:1173, 2018 : PubMed ESTHER: Wang_2018_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_30_1173 PubMedSearch: Wang 2018 Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue 30 1173 PubMedID: 30592953 Abstract OBJECTIVE: To investigate the effect of enteral nutrition (EN) tolerance assessment standardized process management on nosocomial infection and prognosis in patients with tracheotomy and long-term mechanical ventilation (MV) in intensive care unit (ICU). METHODS: A prospective cohort study was conducted. Forty-six patients who required long-term MV due to tracheotomy admitted to ICU of Changzhou First People's Hospital from January 2015 to December 2017 were enrolled. Taking the standardized process management of EN tolerance assessment from June 30th, 2016 as the time spot, patients admitted from January 1st, 2015 to June 30th, 2016 were taken as the control group (25 cases) and patients admitted from July 1st, 2016 to December 31st, 2017 as the observation group (21 cases). The two groups were all given conventional EN treatment and conventional symptomatic supportive treatment. Patients in the observation group was given the EN tolerance standardized process management, and received the nutritional risk screening score. While the control group was given a conventional EN management protocol (nurses routinely reported to the doctor and then gave further action). The nutritional support related indicators within 30 days of treatment (including serum albumin, serum pre-albumin, serum cholinesterase), the EN feeding tolerance index (the average amount of gastrointestinal motility drugs used within 30 days, the average EN interruption time per patient, and the incidence of gastrointestinal bleeding) and the prognosis-related indicators [including the incidence of ventilator-associated pneumonia (VAP), the monthly average hospitalization cost, the proportion of drugs, and the ratio of antibiotics to drugs] were compared. RESULTS: Compared with the control group, serum albumin, pre-albumin and cholinesterase were significantly increased in the observation group [albumin (g/L): 32.86+/-4.83 vs. 28.16+/-3.62, pre-albumin (mg/L): 186.42+/-62.84 vs. 163.26+/-73.49, cholinesterase (U/L): 3 482.34+/-369.92 vs. 2 986.86+/-491.49, all P < 0.05], the average use of gastrointestinal motility drugs was significantly reduced (mg: 11.20+/-3.86 vs. 15.23+/-5.68, P < 0.05), the average EN interruption time was significantly longer in each patient (hours: 6.38+/-3.59 vs. 4.96+/-2.28, P < 0.05), and the incidence of gastrointestinal bleeding was significantly decreased (19.04% vs. 24.00%, P < 0.05), the incidence of VAP was significantly decreased (18.64% vs. 21.36%, P < 0.05), and the antibiotics accounted for a significant decrease (62.43% vs. 76.59%, P < 0.05), but there was no significant difference in the proportion of drugs and monthly average hospitalization expenses [drug ratio: 36.88% vs. 38.42%, monthly average hospitalization cost (ten thousand yuan): 4.36+/-0.57 vs. 4.39+/-0.49, both P > 0.05]. CONCLUSIONS: For the patients with tracheotomy and long-term MV of ICU, the enteral nutrition tolerance assessment standardized process management can improve the nutritional status, reduce the incidence of nosocomial infections, and improve the prognosis of the patients. Title: Recovery of respiratory function and autonomic diaphragm movement following unilateral recurrent laryngeal nerve to phrenic nerve anastomosis in rabbits Wen J, Han Y, Guo S, Yang M, Li L, Sun G, Wang J, Hu F, Liang J and Tan J <3 more author(s)> Wen J, Han Y, Guo S, Yang M, Li L, Sun G, Wang J, Hu F, Liang J, Wei L, Zhou Q, Zhang W, Tan J (- 3) Ref: Journal of Neurosurgery Spine, :1, 2018 : PubMed ESTHER: Wen_2018_J.Neurosurg.Spine__1 PubMedSearch: Wen 2018 J.Neurosurg.Spine 1 PubMedID: 29979142 Abstract OBJECTIVE Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). The authors' previous study suggested that vagus nerve (VN) and phrenic nerve (PN) anastomosis could partially improve respiratory function in rabbits that had been subjected to PN transection. As a branch of the VN and a motor fiber-dominated nerve, the recurrent laryngeal nerve (RLN) seems a better choice to anastomose with the PN for respiratory function restoration after upper cervical SCI. This study was designed to determine whether RLN-PN anastomosis could restore the respiratory function after upper cervical SCI in rabbits. METHODS Twelve male New Zealand rabbits were randomly divided into 3 groups: 1) sham group (no injury), 2) transection group (right RLN and PN were transected), and 3) bridge group (transected right RLN and PN were immediately anastomosed). Spontaneous discharges of the RLN and PN were compared using a bio-signal collection system. RLN and PN cross sections were stained for acetylcholinesterase (AChE), and the numbers of motor fibers were compared. Three months after the initial surgical procedures, the movement of the diaphragm was assessed using a digital subtraction angiography (DSA) system, and discharges from the right diaphragm muscle were recorded. Toluidine blue staining, electron microscopy, and staining for AChE were used to assess whether motor fibers from the RLN regenerated into the PN, and sections of diaphragm were examined after AChE staining to assess the motor endplates. RESULTS Both the RLN and PN exhibited highly rhythmic discharges, synchronized with respiration, and most fibers in the RLN and PN were found to be motor fibers. Numerous myelinated fibers were observed in anastomosed PN using toluidine blue staining and electron microscopy. Staining for AChE showed that those regenerated fibers had typical characteristics of motor fibers, and motor endplates with typical morphological characteristics were observed in the diaphragm. Reestablished rhythmic contraction of the hemidiaphragm was directly observed using the DSA system, and rhythmic spontaneous discharge was recorded from the reinnervated hemidiaphragm using the bio-signal collection system. CONCLUSIONS Motor fibers from the RLN could regenerate into the PN after end-to-end anastomosis and reinnervate the denervated hemidiaphragm in rabbits. Those regenerated motor fibers restored rhythmic and autonomic movement of the paralyzed diaphragm. These results suggest that the RLN is an optimal donor nerve to anastomose with the PN in order to reestablish the autonomic movement of paralyzed diaphragms after high-level SCI. Title: miR-29 contributes to normal endothelial function and can restore it in cardiometabolic disorders Widlansky ME, Jensen DM, Wang J, Liu Y, Geurts AM, Kriegel AJ, Liu P, Ying R, Zhang G and Liang M <7 more author(s)> Widlansky ME, Jensen DM, Wang J, Liu Y, Geurts AM, Kriegel AJ, Liu P, Ying R, Zhang G, Casati M, Chu C, Malik M, Branum A, Tanner MJ, Tyagi S, Usa K, Liang M (- 7) Ref: EMBO Mol Med, 10:, 2018 : PubMed ESTHER: Widlansky_2018_EMBO.Mol.Med_10_ PubMedSearch: Widlansky 2018 EMBO.Mol.Med 10 PubMedID: 29374012 Abstract We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR-29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients. Intraluminal delivery of miR-29a-3p or miR-29b-3p mimics restored normal endothelium-dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD Intraluminal delivery of anti-miR-29b-3p in arterioles from non-DM human subjects or rats or targeted mutation of Mir29b-1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR-29b-3p mimic increased, while anti-miR-29b-3p or Mir29b-1/a gene mutation decreased, nitric oxide levels in arterioles. The mutation of Mir29b-1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1. Lypla1 was a direct target of miR-29 and could abrogate the effect of miR-29 in promoting nitric oxide production. Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b-1/a mutant rats or treated with anti-miR-29b-3p. These findings indicate miR-29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders. Title: An iridium complex-based probe for photoluminescence lifetime imaging of human carboxylesterase 2 in living cells Yan Z, Wang J, Zhang Y, Zhang S, Qiao J, Zhang X Ref: Chem Commun (Camb), 54:9027, 2018 : PubMed ESTHER: Yan_2018_Chem.Commun.(Camb)_54_9027 PubMedSearch: Yan 2018 Chem.Commun.(Camb) 54 9027 PubMedID: 30047956 Abstract A novel photoluminescence lifetime probe (Ir-TB) has been developed for the detection and imaging of hCE2 in living cells. A large lifetime increase by around 300 ns after the enzymatic reaction makes it an ideal tool to distinguish hCE2-hydrolyzed probes from those non-hydrolyzed ones via PLIM for the first time. Title: One-step methodology for the direct covalent capture of GPCRs from complex matrices onto solid surfaces based on the bioorthogonal reaction between haloalkane dehalogenase and chloroalkanes Zeng K, Li Q, Wang J, Yin G, Zhang Y, Xiao C, Fan T, Zhao X, Zheng X Ref: Chem Sci, 9:446, 2018 : PubMed ESTHER: Zeng_2018_Chem.Sci_9_446 PubMedSearch: Zeng 2018 Chem.Sci 9 446 PubMedID: 29629116 Abstract Protein immobilization techniques play an important role in the development of assays for disease diagnosis and drug discovery. However, many of these approaches are not applicable to transmembrane proteins. G protein-coupled receptors (GPCRs) are the largest protein superfamily encoded by the human genome and are targeted by a quarter of all prescription drugs. GPCRs are highly dynamic and sensitive to changes in the ambient environment, and current immobilization methodologies are not suitable for GPCRs. We used haloalkane dehalogenase (Halo) as an immobilization tag fused to the beta2-adrenoceptor (beta2-AR), angiotensin II type 1 (AT1) and angiotensin II type 2 (AT2) receptors. The engineered Halo-tag covalently binds to a specific substrate chloroalkane through Asp 106 in the catalytic pocket. The Halo-tagged GPCRs were expressed in Escherichia coli at a suitable yield. Accordingly, we loaded cell lysate containing Halo-tagged GPCRs onto a macroporous silica gel coated with chloroalkane. Morphological characterization indicated a homogeneous monolayer of immobilized Halo-tagged GPCRs on the silica gel surface. The immobilized receptors proved to be surrounded by specific bound phospholipids including PG C18:1/C18:1. We observed a radio-ligand binding ability and ligand-induced conformational changes in the immobilized GPCRs, suggesting the preservation of bioactivity. This method is a one-step approach for the specific immobilization of GPCRs from cell lysates and validates that immobilized receptors retain canonical ligand binding capacity. Our immobilization strategy circumvents labor-intensive purification procedures and minimizes loss of activity. The immobilized receptors can be applied to high-throughput drug and interaction partner screening for GPCRs. Title: Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors Zhang Q, Hu Y, Wu D, Ma S, Wang J, Rao J, Xu L, Xu H, Shao H and Wang S <1 more author(s)> Zhang Q, Hu Y, Wu D, Ma S, Wang J, Rao J, Xu L, Xu H, Shao H, Guo Z, Wang S (- 1) Ref: Talanta, 183:258, 2018 : PubMed ESTHER: Zhang_2018_Talanta_183_258 PubMedSearch: Zhang 2018 Talanta 183 258 PubMedID: 29567174 Abstract A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H2O2), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H2O2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H2O2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC50 of donepezil and tacrine were estimated to be 1.4nM and 3.5nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity. Title: Pharmacological Basis for the Use of Evodiamine in Alzheimer's Disease: Antioxidation and Antiapoptosis Zhang Y, Wang J, Wang C, Li Z, Liu X, Zhang J, Lu J, Wang D Ref: Int J Mol Sci, 19:, 2018 : PubMed ESTHER: Zhang_2018_Int.J.Mol.Sci_19_ PubMedSearch: Zhang 2018 Int.J.Mol.Sci 19 PubMedID: 29883380 Inhibitor(s) related to this paper: Evodiamine Abstract Evodiamine (Evo), a major alkaloid compound isolated from the dry unripened fruit of Evodia fructus, has a wide range of pharmacological activities. The present study sought to explore the neuroprotective effects of Evo in l-glutamate (l-Glu)-induced apoptosis of HT22 cells, and in a d-galactose and aluminum trichloride-developed Alzheimer’s disease (AD) mouse model. Evo significantly enhanced cell viability, inhibited the accumulation of reactive oxygen species, ameliorated mitochondrial function, increased the B-cell lymphoma-2 protein content, and inhibited the high expression levels of Bax, Bad, and cleaved-caspase-3 and -8 in l-Glu-induced HT22 cells. Evo also enhanced the phosphorylation activities of protein kinase B and the mammalian target of rapamycin in the l-Glu-induced HT22 cells. In the AD mouse model, Evo reduced the aimless and chaotic movements, reduced the time spent in the central area in the open field test, and decreased the escape latency time in the Morris water maze test. Evo reduced the deposition of amyloid beta 42 (Aβ42) in the brain, and increased the serum level of Aβ42, but showed no significant effects on Aβ40. In addition, six weeks of Evo administration significantly suppressed oxidative stress by modulating the related enzyme levels. In the central cholinergic system of AD mice, Evo significantly increased the serum levels of acetylcholine and choline acetyltransferase and decreased the level of acetylcholinesterase in the serum, hypothalamus, and brain. Our results provide experimental evidence that Evo can serve as a neuroprotective candidate for the prevention and/or treatment of neurodegenerative diseases. Title: Prolonged neuromuscular block associated with cholinesterase deficiency Zhang C, Cao H, Wan ZG, Wang J Ref: Medicine (Baltimore), 97:e13714, 2018 : PubMed ESTHER: Zhang_2018_Medicine.(Baltimore)_97_e13714 PubMedSearch: Zhang 2018 Medicine.(Baltimore) 97 e13714 PubMedID: 30593143 Abstract RATIONALE: Hereditary genetic mutations may cause congenital cholinesterase deficiency. When succinylcholine and mivacurium are applied on cholinesterase-deficient patients during general anesthesia, prolonged postoperative asphyxia occurs, which is an uncommon but very serious complication. PATIENT CONCERNS: A previously healthy 30-year-old female presented prolonged spontaneous breathing recovery after general anesthesia. DIAGNOSES: After the patient's postoperative spontaneous breathing recovery delayed, the plasma cholinesterase was found to be 27 U/L, which was far below the normal level (4000 U/L to 13500 U/L). This patient had no disease that can cause plasma cholinesterase deficiency and was therefore diagnosed as congenital cholinesterase deficiency. INTERVENTIONS AND OUTCOMES: The patient was sent to the intensive care unit (ICU) intubated for mechanical ventilator support, and on the next day the tracheal tube was removed without any complications when her spontaneous respiration resumed. LESSONS: Cholinesterase is an enzyme secreted by the liver involved in many physiological processes in human body. Plasma cholinesterase commonly contains acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). When succinylcholine and mivacurium are applied on patients with cholinesterase-deficiency during general anesthesia, prolonged postoperative asphyxia occurs, which is an uncommon but very serious complication. Lately, new evidences have suggested that hereditary genetic mutations may be responsible for congenital cholinesterase deficiency. Title: Azetidine and Piperidine Carbamates as Efficient, Covalent Inhibitors of Monoacylglycerol Lipase Butler CR, Beck EM, Harris A, Huang Z, McAllister LA, Am Ende CW, Fennell K, Foley TL, Fonseca K and Brodney MA <12 more author(s)> Butler CR, Beck EM, Harris A, Huang Z, McAllister LA, Am Ende CW, Fennell K, Foley TL, Fonseca K, Hawrylik SJ, Johnson DS, Knafels JD, Mente S, Noell GS, Pandit J, Phillips TB, Piro JR, Rogers BN, Samad TA, Wang J, Wan S, Brodney MA (- 12) Ref: Journal of Medicinal Chemistry, 60:9860, 2017 : PubMed ESTHER: Butler_2017_J.Med.Chem_60_9860 PubMedSearch: Butler 2017 J.Med.Chem 60 9860 PubMedID: 29148769 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: 6AX1-cp3 Abstract Monoacylglycerol lipase (MAGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the CNS. MAGL catalyzes the conversion of 2-AG to arachidonic acid (AA), a precursor to the proinflammatory eicosannoids such as prostaglandins. Herein we describe highly efficient MAGL inhibitors, identified through a parallel medicinal chemistry approach that highlighted the improved efficiency of azetidine and piperidine-derived carbamates. The discovery and optimization of 3-substituted azetidine carbamate irreversible inhibitors of MAGL were aided by the generation of inhibitor-bound MAGL crystal structures. Compound 6, a highly efficient and selective MAGL inhibitor against recombinant enzyme and in a cellular context, was tested in vivo and shown to elevate central 2-AG levels at a 10 mg/kg dose. Title: Loss of ABHD5 promotes the aggressiveness of prostate cancer cells Chen G, Zhou G, Aras S, He Z, Lucas S, Podgorski I, Skar W, Granneman JG, Wang J Ref: Sci Rep, 7:13021, 2017 : PubMed ESTHER: Chen_2017_Sci.Rep_7_13021 PubMedSearch: Chen 2017 Sci.Rep 7 13021 PubMedID: 29026202 Gene_locus related to this paper: human-ABHD5 Abstract The accumulation of neutral lipids in intracellular lipid droplets has been associated with the formation and progression of many cancers, including prostate cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator of intracellular neutral lipids that has been recently identified as a tumor suppressor in colorectal cancer, yet its potential role in PCa has not been investigated. Through mining publicly accessible PCa gene expression datasets, we found that ABHD5 gene expression is markedly decreased in metastatic castration-resistant PCa (mCRPC) samples. We further demonstrated that RNAi-mediated ABHD5 silencing promotes, whereas ectopic ABHD5 overexpression inhibits, the invasion and proliferation of PCa cells. Mechanistically, we found that ABHD5 knockdown induces epithelial to mesenchymal transition, increasing aerobic glycolysis by upregulating the glycolytic enzymes hexokinase 2 and phosphofrucokinase, while decreasing mitochondrial respiration by downregulating respiratory chain complexes I and III. Interestingly, knockdown of ATGL, the best-known molecular target of ABHD5, impeded the proliferation and invasion, suggesting an ATGL-independent role of ABHD5 in modulating PCa aggressiveness. Collectively, these results provide evidence that ABHD5 acts as a metabolic tumor suppressor in PCa that prevents EMT and the Warburg effect, and indicates that ABHD5 is a potential therapeutic target against mCRPC, the deadly aggressive PCa. Title: Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset Chen Z, Bao L, Chen C, Zou T, Xue Y, Li F, Lv Q, Gu S, Gao X and Jin Q <3 more author(s)> Chen Z, Bao L, Chen C, Zou T, Xue Y, Li F, Lv Q, Gu S, Gao X, Cui S, Wang J, Qin C, Jin Q (- 3) Ref: J Infect Dis, 215:1807, 2017 : PubMed ESTHER: Chen_2017_J.Infect.Dis_215_1807 PubMedSearch: Chen 2017 J.Infect.Dis 215 1807 PubMedID: 28472421 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings. Title: Tris(1,3-dichloro-2-propyl) phosphate disrupts axonal growth, cholinergic system and motor behavior in early life zebrafish Cheng R, Jia Y, Dai L, Liu C, Wang J, Li G, Yu L Ref: Aquat Toxicol, 192:7, 2017 : PubMed ESTHER: Cheng_2017_Aquat.Toxicol_192_7 PubMedSearch: Cheng 2017 Aquat.Toxicol 192 7 PubMedID: 28898785 Abstract Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) could have neurotoxic effects and alter motor behaviors in zebrafish (Danio rerio) larvae, however, the underlying mechanisms are still unknown. In this study, zebrafish embryos were subjected to waterborne exposure of TDCIPP at 100, 300, 600, 900mug/L from 2 to 120-h post-fertilization (hpf). Behavioral measurements indicate that TDCIPP exposure significantly elevated spontaneous movement, and altered swimming behavior response of larvae to both light and dark stimulation. Interestingly, in accordance with these motor effects, TDCIPP significantly decreased expression of the neuron-specific GFP in transgenic (HuC-GFP) zebrafish larvae as well as decreased expression of the neural marker genes elavl3 and ngn1, inhibited the axonal growth of the secondary motoneurons and altered the expressions of axon-related genes (alpha1-tubulin, shha and netrin2) in zebrafish larvae. Furthermore, TDCIPP exposure at 900mug/L significantly increased the activity of acetylcholinesterase (AChE) enzyme, and decreased the total acetylcholine (ACh) concentration. Our data indicate that the alteration in motor neuron and inhibition of cholinergic system could together lead to the TDCIPP induced motor behavior alterations in zebrafish larvae. Title: Lighting-up breast cancer cells by a near-infrared fluorescent probe based on KIAA1363 enzyme-targeting Fan J, Guo S, Wang S, Kang Y, Yao Q, Wang J, Gao X, Wang H, Du J, Peng X Ref: Chem Commun (Camb), 53:4857, 2017 : PubMed ESTHER: Fan_2017_Chem.Commun.(Camb)_53_4857 PubMedSearch: Fan 2017 Chem.Commun.(Camb) 53 4857 PubMedID: 28421217 Gene_locus related to this paper: human-NCEH1 Abstract The first NIR KIAA1363-targeting probe, NB-AX, specifically and instantly featured an "off-on" switch upon gradual addition of KIAA1363 over all kinds of other biomolecules, and its detection limit was initially calculated to be 0.58 mug mL(-1) (3delta/k). The probe was also able to be used in ultrafast distinguishing of breast cancer cells from normal cells in fluorescence imaging and applied in tissue imaging and tumor imaging in vivo. Title: Characterization of the Polymyxin D Synthetase Biosynthetic Cluster and Product Profile of Paenibacillus polymyxa ATCC 10401 Galea CA, Han M, Zhu Y, Roberts K, Wang J, Thompson PE, L J, Velkov T Ref: Journal of Natural Products, 80:1264, 2017 : PubMed ESTHER: Galea_2017_J.Nat.Prod_80_1264 PubMedSearch: Galea 2017 J.Nat.Prod 80 1264 PubMedID: 28463513 Abstract The increasing prevalence of polymyxin-resistant bacteria has stimulated the search for improved polymyxin lipopeptides. Here we describe the sequence and product profile for polymyxin D nonribosomal peptide synthetase from Paenibacillus polymyxa ATCC 10401. The polymyxin D synthase gene cluster comprised five genes that encoded ABC transporters (pmxC and pmxD) and enzymes responsible for the biosynthesis of polymyxin D (pmxA, pmxB, and pmxE). Unlike polymyxins B and E, polymyxin D contains d-Ser at position 3 as opposed to l-alpha,gamma-diaminobutyric acid and has an l-Thr at position 7 rather than l-Leu. Module 3 of pmxE harbored an auxiliary epimerization domain that catalyzes the conversion of l-Ser to the d-form. Structural modeling suggested that the adenylation domains of module 3 in PmxE and modules 6 and 7 in PmxA could bind amino acids with larger side chains than their preferred substrate. Feeding individual amino acids into the culture media not only affected production of polymyxins D1 and D2 but also led to the incorporation of different amino acids at positions 3, 6, and 7 of polymyxin D. Interestingly, the unnatural polymyxin analogues did not show antibiotic activity against a panel of Gram-negative clinical isolates, while the natural polymyxins D1 and D2 exhibited excellent in vitro antibacterial activity and were efficacious against Klebsiella pneumoniae and Acinetobacter baumannii in a mouse blood infection model. The results demonstrate the excellent antibacterial activity of these unusual d-Ser3 polymxyins and underscore the possibility of incorporating alternate amino acids at positions 3, 6, and 7 of polymyxin D via manipulation of the polymyxin nonribosomal biosynthetic machinery. Title: A nematicidal tannin from Punica granatum L. rind and its physiological effect on pine wood nematode (Bursaphelenchus xylophilus) Guo Q, Du G, Qi H, Zhang Y, Yue T, Wang J, Li R Ref: Pestic Biochem Physiol, 135:64, 2017 : PubMed ESTHER: Guo_2017_Pestic.Biochem.Physiol_135_64 PubMedSearch: Guo 2017 Pestic.Biochem.Physiol 135 64 PubMedID: 28043333 Abstract The ethanol extract of Punica granatum L. rind was tested to show significant nematicidal activity against pine wood nematode. Three nematicidal compounds were obtained from the ethanol extract by bioassay-guided fractionation and identified as punicalagin 1, punicalin 2, and corilagin 3 by mass and nuclear magnetic resonance spectral data analysis. Punicalagin 1 was most active against PWN among the purified compounds with the LC50 value of 307.08muM in 72h. According to the enzyme assays in vitro, punicalagin 1 could inhibit the activity of acetylcholinesterase, amylase and cellulase from PWN with IC50 value of 0.60mM, 0.96mM and 1.24mM, respectively. The morphological structures of PWNs treated by punicalagin 1 were greatly changed. These physiological effects of punicalagin 1 on PWN may helpful to elucidate its nematicidal mechanism. Title: A reference gene set for sex pheromone biosynthesis and degradation genes from the diamondback moth, Plutella xylostella, based on genome and transcriptome digital gene expression analyses He P, Zhang YF, Hong DY, Wang J, Wang XL, Zuo LH, Tang XF, Xu WM, He M Ref: BMC Genomics, 18:219, 2017 : PubMed ESTHER: He_2017_BMC.Genomics_18_219 PubMedSearch: He 2017 BMC.Genomics 18 219 PubMedID: 28249567 Gene_locus related to this paper: pluxy-CCE016a, pluxy-CCE016c Abstract BACKGROUND: Female moths synthesize species-specific sex pheromone components and release them to attract male moths, which depend on precise sex pheromone chemosensory system to locate females. Two types of genes involved in the sex pheromone biosynthesis and degradation pathways play essential roles in this important moth behavior. To understand the function of genes in the sex pheromone pathway, this study investigated the genome-wide and digital gene expression of sex pheromone biosynthesis and degradation genes in various adult tissues in the diamondback moth (DBM), Plutella xylostella, which is a notorious vegetable pest worldwide. Title: Association between Lipoprotein Lipase Polymorphism and the Risk of Stroke: A Meta-analysis He T, Wang J, Deng WS, Sun P Ref: J Stroke Cerebrovasc Dis, 26:2570, 2017 : PubMed ESTHER: He_2017_J.Stroke.Cerebrovasc.Dis_26_2570 PubMedSearch: He 2017 J.Stroke.Cerebrovasc.Dis 26 2570 PubMedID: 28687421 Abstract BACKGROUND: Several studies have studied the relationship between lipoprotein lipase (LPL) HindIII gene polymorphism and stroke susceptibility. However, the conclusions remain controversial. To clarify the association of LPL gene HindIII polymorphism and stroke susceptibility, we therefore conducted a comprehensive meta-analysis. MATERIALS AND Title: Simulation of Deepwater Horizon oil plume reveals substrate specialization within a complex community of hydrocarbon degraders Hu P, Dubinsky EA, Probst AJ, Wang J, Sieber CMK, Tom LM, Gardinali PR, Banfield JF, Atlas RM, Andersen GL Ref: Proc Natl Acad Sci U S A, 114:7432, 2017 : PubMed ESTHER: Hu_2017_Proc.Natl.Acad.Sci.U.S.A_114_7432 PubMedSearch: Hu 2017 Proc.Natl.Acad.Sci.U.S.A 114 7432 PubMedID: 28652349 Gene_locus related to this paper: 9gamm-a0a1y5gx26, 9gamm-a0a1z7ys35, 9gamm-a0a1z7yxg3, 9gamm-a0a1y5fvt2, 9gamm-a0a1y5gtm5, 9flao-a0a1z7zjx1 Abstract The Deepwater Horizon (DWH) accident released an estimated 4.1 million barrels of oil and 10(10) mol of natural gas into the Gulf of Mexico, forming deep-sea plumes of dispersed oil droplets and dissolved gases that were largely degraded by bacteria. During the course of this 3-mo disaster a series of different bacterial taxa were enriched in succession within deep plumes, but the metabolic capabilities of the different populations that controlled degradation rates of crude oil components are poorly understood. We experimentally reproduced dispersed plumes of fine oil droplets in Gulf of Mexico seawater and successfully replicated the enrichment and succession of the principal oil-degrading bacteria observed during the DWH event. We recovered near-complete genomes, whose phylogeny matched those of the principal biodegrading taxa observed in the field, including the DWH Oceanospirillales (now identified as a Bermanella species), multiple species of Colwellia, Cycloclasticus, and other members of Gammaproteobacteria, Flavobacteria, and Rhodobacteria. Metabolic pathway analysis, combined with hydrocarbon compositional analysis and species abundance data, revealed substrate specialization that explained the successional pattern of oil-degrading bacteria. The fastest-growing bacteria used short-chain alkanes. The analyses also uncovered potential cooperative and competitive relationships, even among close relatives. We conclude that patterns of microbial succession following deep ocean hydrocarbon blowouts are predictable and primarily driven by the availability of liquid petroleum hydrocarbons rather than natural gases. Title: Enzymatic synthesis of lysophosphatidylcholine with n-3 polyunsaturated fatty acid from sn-glycero-3-phosphatidylcholine in a solvent-free system Liu Y, Zhang Q, Guo Y, Liu J, Xu J, Li Z, Wang J, Wang Y, Xue C Ref: Food Chem, 226:165, 2017 : PubMed ESTHER: Liu_2017_Food.Chem_226_165 PubMedSearch: Liu 2017 Food.Chem 226 165 PubMedID: 28254008 Abstract The n-3 polyunsaturated fatty acids (PUFA)-rich lysophosphatidylcholine (LPC) was successfully synthesized by Thermomyces lanuginosus lipase (TL IM)-catalyzed esterification of glycerylphosphorylcholine (GPC) and n-3 PUFA-rich fatty acids in a solvent-free system. Effects of reaction temperature, enzyme loading and substrate mole ratio on the yield of LPC and incorporation of n-3 PUFA were evaluated. The acyl-specificities of five enzymes were tested for direct esterification of n-3 PUFA, and Lipozyme TL IM was found to be more effective than others for production of LPC with n-3 PUFA. Substrate mole ratio and reaction temperature, however, had no significant effect on the incorporation. The maximal yield of LPC was obtained under the following conditions: temperature 45 degC, enzyme loading 15% by weight and substrate mole ratio (GPC/n-3 PUFA) 1:20. Furthermore, the composition of products were further investigated in the study. The 1-acyl-sn-glycero-3-lysophosphatidylcholine (2-LPC) was predominant in the mixtures at early stages of reaction, whereas less increment of 2-acyl-sn-glycero-3-lysophosphatidylcholine (1-LPC) and PC was observed at later stages. Title: Characterization of the Fifth Putative Acetylcholinesterase in the Wolf Spider, Pardosa pseudoannulata Meng X, Xu X, Bao H, Wang J, Liu Z Ref: Molecules, 22:, 2017 : PubMed ESTHER: Meng_2017_Molecules_22_ PubMedSearch: Meng 2017 Molecules 22 PubMedID: 28696352 Gene_locus related to this paper: 9arac-KU501289 Abstract Background: Acetylcholinesterase (AChE) is an important neurotransmitter hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is various among invertebrate species, with different functions including the 'classical' role in terminating synaptic transmission and other 'non-classical' roles. Methods: Using rapid amplification of cDNA ends (RACE) technology, a new putative AChE-encoding gene was cloned from Pardosa pseudoannulata, an important predatory natural enemy. Sequence analysis and in vitro expression were employed to determine the structural features and biochemical properties of this putative AChE. Results: The cloned AChE contained the most conserved motifs of AChEs family and was clearly clustered with Arachnida AChEs. Determination of biochemical properties revealed that the recombinant enzyme had the obvious preference for the substrate ATC (acetylthiocholine iodide) versus BTC (butyrylthiocholine iodide). The AChE was highly sensitive to AChE-specific inhibitor BW284C51, but not butyrylcholinesterase-specific inhibitor tetraisopropyl pyrophosphoramide (ISO-OMPA). Based on these results, we concluded that a new AChE was identified from P. pseudoannulata and denoted as PpAChE5. Conclusion: Here we report the identification of a new AChE from P. pseudoannulata and increased the AChE number to five in this species. Although PpAChE5 had the biggest Vmax value among five identified AChEs, it showed relatively low affinity with ATC. Similar sensitivity to test insecticides indicated that this AChE might serve as the target for both organophosphorus and carbamate insecticides. Title: Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells Pan H, Zhang X, Jiang H, Jiang X, Wang L, Qi Q, Bi Y, Wang J, Shi Q, Li R Ref: Sci Rep, 7:44440, 2017 : PubMed ESTHER: Pan_2017_Sci.Rep_7_44440 PubMedSearch: Pan 2017 Sci.Rep 7 44440 PubMedID: 28290521 Abstract The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3(+/-) germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse. Title: ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice Wang J, Fu X, Zhang D, Yu L, Li N, Lu Z, Gao Y, Wang M, Liu X and Yan B <2 more author(s)> Wang J, Fu X, Zhang D, Yu L, Li N, Lu Z, Gao Y, Wang M, Liu X, Zhou C, Han W, Yan B (- 2) Ref: Behavioural Brain Research, 316:145, 2017 : PubMed ESTHER: Wang_2017_Behav.Brain.Res_316_145 PubMedSearch: Wang 2017 Behav.Brain.Res 316 145 PubMedID: 27609645 Abstract The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT+ neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated-neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-alpha, IFN-gamma, or TGF-beta on day 7 after MCAO. We conclude that ChAT+ neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke. Title: Novel cinnamamide-dibenzylamine hybrids: Potent neurogenic agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for Alzheimer's disease Wang J, Cai P, Yang XL, Li F, Wu JJ, Kong LY, Wang XB Ref: Eur Journal of Medicinal Chemistry, 139:68, 2017 : PubMed ESTHER: Wang_2017_Eur.J.Med.Chem_139_68 PubMedSearch: Wang 2017 Eur.J.Med.Chem 139 68 PubMedID: 28800459 Abstract By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a novel series of cinnamamide-dibenzylamine hybrids have been designed, synthesized, and evaluated biologically. In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit ChEs, strong potency inhibitory of self-induced beta-amyloid (Abeta) aggregation and to act as potential antioxidants and biometal chelators. A Lineweaver-Burk plot and molecular modeling study showed that compound 7f targeted both the CAS and PAS of AChE. In addition, compound 7f could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Overall, all of these outstanding in vitro results in combination with promising in vivo outcomes highlighted derivative 7f as the lead structure worthy of further investigation. Title: Scallop genome provides insights into evolution of bilaterian karyotype and development Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B and Bao Z <42 more author(s)> Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B, Zhang L, Hu X, Sun X, Wang J, Zhao C, Wang Y, Wang D, Huang X, Wang R, Lv J, Li Y, Zhang Z, Liu B, Lu W, Hui Y, Liang J, Zhou Z, Hou R, Li X, Liu Y, Li H, Ning X, Lin Y, Zhao L, Xing Q, Dou J, Mao J, Guo H, Dou H, Li T, Mu C, Jiang W, Fu Q, Fu X, Miao Y, Liu J, Yu Q, Li R, Liao H, Kong Y, Jiang Z, Chourrout D, Bao Z (- 42) Ref: Nat Ecol Evol, 1:120, 2017 : PubMed ESTHER: Wang_2017_Nat.Ecol.Evol_1_120 PubMedSearch: Wang 2017 Nat.Ecol.Evol 1 120 PubMedID: 28812685 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210ped6, mizye-a0a210q4h5, mizye-a0a210q4h9, mizye-a0a210q4j1, mizye-a0a210qf86, mizye-a0a210q332, mizye-a0a210pqn0, mizye-a0a210q7t5, mizye-a0a210pij5, mizye-a0a210qyk8, mizye-a0a210pwl7, mizye-a0a210q8u5, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210pek1, mizye-a0a210pul3, mizye-a0a210pum3, mizye-a0a210ptr6, mizye-a0a210ptq5, mizye-a0a210ptc4.1, mizye-a0a210ptc4.2, mizye-a0a210ptv1, mizye-a0a210ptv7, mizye-a0a210qgl6, mizye-a0a210qg90, mizye-a0a210ptq0, mizye-a0a210qg72, mizye-a0a210ptb1, mizye-a0a210pjd3, mizye-a0a210qg92, mizye-a0a210q8v2, mizye-a0a210qg93, mizye-a0a210q160.1, mizye-a0a210q160.2, mizye-a0a210qes4, mizye-a0a210pk25, mizye-a0a210q1b8, mizye-a0a210q110, mizye-a0a210r503, mizye-P021348901.1, mizye-P021348901.2 Abstract Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology. Title: Increased Expression of NDRG3 in Mouse Uterus During Embryo Implantation and in Mouse Endometrial Stromal Cells During In Vitro Decidualization Yang Q, Zhang X, Shi Y, He YP, Sun ZG, Shi HJ, Wang J Ref: Reprod Sci, :1933719117737843, 2017 : PubMed ESTHER: Yang_2017_Reprod.Sci__1933719117737843 PubMedSearch: Yang 2017 Reprod.Sci 1933719117737843 PubMedID: 29096585 Gene_locus related to this paper: human-NDRG3, mouse-ndr3 Abstract Decidualization is an indispensable event in the embryo implantation process, but its underlying molecular mechanisms remain elusive. In this study, we showed that in mice, the uterine expression of N-myc downstream-regulated gene 3 (NDRG3), a member of the alpha/beta hydrolase superfamily, was induced by estradiol and progesterone. During the embryo implantation process, uterine Ndrg3 expression was remarkably upregulated, and its expression level at implantation sites (IS) was significantly higher than that at inter-IS. Increased uterine expression of Ndrg3 was associated with artificial decidualization and the activation of delayed implantation. The in vitro decidualization of mouse endometrial stromal cells (ESCs) induced by estradiol and progesterone was also accompanied by increased Ndrg3 expression, and downregulated Ndrg3 expression in ESCs effectively inhibited decidualization. miR-290b-5p was identified as an upstream regulator of Ndrg3, and the uterine expression level of miR-290b-5p was decreased during the implantation process. Furthermore, overexpression of miR-290b-5p in mouse ESCs inhibited their in vitro decidualization. Taken together, these data suggested that Ndrg3 might play an important role in embryo implantation by regulating decidualization potentially via the estrogen/progesterone/miR-290b-5p pathway. Title: Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3 Yao Y, Wang W, Jing L, Wang Y, Li M, Hou X, Wang J, Peng T, Teng J, Jia Y Ref: Neurochem Res, 42:446, 2017 : PubMed ESTHER: Yao_2017_Neurochem.Res_42_446 PubMedSearch: Yao 2017 Neurochem.Res 42 446 PubMedID: 27812761 Abstract microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identified let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dual-color fluorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke. Title: Identification of lysophospholipase protein from Spiroplasma eriocheiris and verification of its function Zhu H, Liu P, Du J, Wang J, Jing Y, Zhang J, Gu W, Wang W, Meng Q Ref: Microbiology, 163:175, 2017 : PubMed ESTHER: Zhu_2017_Microbiology_163_175 PubMedSearch: Zhu 2017 Microbiology 163 175 PubMedID: 27926815 Gene_locus related to this paper: 9molu-a0a0h3xm88 Abstract Spiroplasma eriocheiris is known to cause tremor disease in the Chinese mitten crab Eriocheir sinensis; however, the molecular characterization of this pathogen is still unclear. S. eriocheiris has the ability to invade and survive within mouse 3T6 cells. The invasion process may require causing damage to the host cell membrane by chemical, physical or enzymatic means. In this study, we systematically characterized a novel lysophospholipase (lysoPL) of S. eriocheiris TDA-040725-5T. The gene that encodes lysoPL in S. eriocheiris (SE-LysoPL) was cloned, sequenced and expressed in Escherichia coli BL21 (DE3). Enzymatic assays revealed that the purified recombinant SE-LysoPL hydrolysed long-chain acyl esterases at pH 7 and 30 degrees C. SE-LysoPL was detected in the membrane and cytoplasmic protein fractions using the SE-LysoPL antibody in Western blot. The virulence ability of S. eriocheiris was effectively reduced at the early stage of infection (m.o.i.=100) by the SE-LysoPL antibody neutralization test. To the best of our knowledge, this is the first study to identify and characterize a gene from S. eriocheiris encoding a protein exhibiting lysoPL and esterase activities. Our findings indicate that SE-LysoPL plays important roles in the pathogenicity of S. eriocheiris. Title: Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo Chen HW, He XH, Yuan R, Wei BJ, Chen Z, Dong JX, Wang J Ref: Fitoterapia, 110:142, 2016 : PubMed ESTHER: Chen_2016_Fitoterapia_110_142 PubMedSearch: Chen 2016 Fitoterapia 110 142 PubMedID: 26976216 Abstract Acetylcholinesterase Inhibitor (AchEI) is the most extensive in all anti-dementia drugs. The extracts and isolated compounds from the Valeriana genus have shown anti-dementia bioactivity. Four new sesquiterpenoids (1-4) and a new monoterpenoid (5) were isolated from the root of Valeriana officinalis var. latiofolia. The acetylcholinesterase (AchE) inhibitory activity of isolates was evaluated by modified Ellman method in vitro. Learning and memory ability of compound 4 on mice was evaluated by the Morris water maze. The contents of acetylcholine (Ach), acetylcholine transferase (ChAT) and AchE in mice brains were determined by colorimetry. The results showed IC50 of compound 4 was 0.161muM in vitro. Compared with the normal group, the learning and memory ability of mice and the contents of Ach and ChAT decreased in model group mice (P<0.01), while the AchE increased (P<0.01). Compared with the model group, Ach and ChAT in the positive control group, the high-dose group and the medium-dose group increased (P<0.01), while the AchE decreased (P<0.01). Compound 4 can improve the learning and memory abilities of APPswe/PSDeltaE9 double-transgenic mice, and the mechanism may be related to the regulation of the relative enzyme in the cholinergic system. Title: 18F-FNDP for PET Imaging of Soluble Epoxide Hydrolase Horti AG, Wang Y, Minn I, Lan X, Wang J, Koehler RC, Alkayed NJ, Dannals RF, Pomper MG Ref: J Nucl Med, 57:1817, 2016 : PubMed ESTHER: Horti_2016_J.Nucl.Med_57_1817 PubMedSearch: Horti 2016 J.Nucl.Med 57 1817 PubMedID: 27417650 Abstract Soluble epoxide hydrolase (sEH) is a bifunctional enzyme located within cytosol and peroxisomes that converts epoxides to the corresponding diols and hydrolyzes phosphate monoesters. It serves to inactivate epoxyeicosatrienoic acids (EETs), which are generated in the brain to couple neuronal activity and cerebral blood flow in normal and pathologic states. Altered regulation of sEH was observed previously in various neuropathologic disorders including vascular dementia and stroke. Inhibitors of sEH are pursued as agents to mitigate neuronal damage after stroke. We developed N-(3,3-diphenylpropyl)-6-18F-fluoronicotinamide (18F-FNDP), which proved highly specific for imaging of sEH in the mouse and nonhuman primate brain with PET. Title: Postconditioning with sevoflurane ameliorates spatial learning and memory deficit after hemorrhage shock and resuscitation in rats Hu X, Wang J, Zhang Q, Duan X, Chen Z, Zhang Y Ref: J Surg Res, 206:307, 2016 : PubMed ESTHER: Hu_2016_J.Surg.Res_206_307 PubMedSearch: Hu 2016 J.Surg.Res 206 307 PubMedID: 27884324 Abstract BACKGROUND: Severe hemorrhage shock and resuscitation are a systemic ischemia-reperfusion phenomenon which can induce learning and memory deficit in human and rats. Sevoflurane postconditioning has been proved to offer neuroprotection under different setting of cerebral ischemia-reperfusion in rats. The aim of this study was to investigate whether sevoflurane postconditioning could improve spatial learning and memory ability after hemorrhage shock and resuscitation in rats. Title: Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism Hu X, Chen R, Fu C, Fan X, Wang J, Qian J, Yi S, Li C, Luo J and Shen Y <9 more author(s)> Hu X, Chen R, Fu C, Fan X, Wang J, Qian J, Yi S, Li C, Luo J, Su J, Zhang S, Xie B, Zheng H, Lai Y, Chen Y, Li H, Gu X, Chen S, Shen Y (- 9) Ref: Mol Cell Endocrinol, 423:60, 2016 : PubMed ESTHER: Hu_2016_Mol.Cell.Endocrinol_423_60 PubMedSearch: Hu 2016 Mol.Cell.Endocrinol 423 60 PubMedID: 26777470 Gene_locus related to this paper: human-TG Abstract Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic variants including six truncating variants and 16 missense variants of unknown significance (VUS). Seven patients carried homozygous pathogenic variants, and three patients carried homozygous or compound heterozygous VUS. 48 out of 382 patients carried one of 18 heterozygous VUS which is significantly more often than their occurrences in control cohort (P < 0.0001). Unique to Asian population, the c.274+2T>G variant is the most common pathogenic variant with an allele frequency of 0.021. The prevalence of CH due to TG gene defect in Chinese population was estimated to be approximately 1/101,000. Our study uncovered ethnicity specific TG mutation spectrum and frequency. Title: Phomopsichin A-D; Four New Chromone Derivatives from Mangrove Endophytic Fungus Phomopsis sp. 33 Huang M, Li J, Liu L, Yin S, Wang J, Lin Y Ref: Mar Drugs, 14:, 2016 : PubMed ESTHER: Huang_2016_Mar.Drugs_14_ PubMedSearch: Huang 2016 Mar.Drugs 14 PubMedID: 27879655 Abstract Four new chromone derivatives, phomopsichins A-D (1-4), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction or theoretical calculations of electronic circular dichroism (ECD). They feature a tricyclic framework, in which a dihydropyran ring is fused with the chromone ring. Compounds 1-5 showed weak inhibitory activities on acetylcholinesterase as well as alpha-glucosidase, weak radical scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak antimicrobial activities. Compounds 1-4 showed no cytotoxic activity against MDA-MB-435 breast cancer cells. Their other bioactivities are worthy of further study, considering their unique molecular structures. Title: Novel Selective Butyrylcholinesterase Inhibitors Incorporating Antioxidant Functionalities as Potential Bimodal Therapeutics for Alzheimer's Disease Jones M, Wang J, Harmon S, Kling B, Heilmann J, Gilmer JF Ref: Molecules, 21:, 2016 : PubMed ESTHER: Jones_2016_Molecules_21_ PubMedSearch: Jones 2016 Molecules 21 PubMedID: 27534722 Abstract Isosorbide-2-carbamates-5-aryl esters are highly potent and very selective butyrylcholinesterase inhibitors. The objective of the present work was to address the hypothesis that the isosorbide-aryl-5-ester group could be replaced with an antioxidant functionality while maintaining inhibitor effects and selectivity. We successfully incorporated ferulic acid or lipoic acid groups producing potent selective inhibitors of butyrylcholinesterase (BuChE). The hybrid compounds were non-toxic to the murine hippocampal cell line HT-22 and lipoate esters were neuroprotective at 10 and 25 microM when the cells were challenged with glutamate (5 mM) in a similar manner to the positive control quercetin. The benzyl carbamate 7a was a potent inhibitor of BuChE (IC50 150 nM) and it was effective in reducing glutamate toxicity to neuronal cells at >5 microM. Representative compounds exhibited an antioxidant effect in the oxygen radical absorbance capacity assay as the lipoate 7d was not active, whereas the ferulate 8a showed a weak, but significant, activity with 0.635 +/- 0.020 Trolox Equivalent. Title: Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer's disease Li F, Wang ZM, Wu JJ, Wang J, Xie SS, Lan JS, Xu W, Kong LY, Wang XB Ref: J Enzyme Inhib Med Chem, :1, 2016 : PubMed ESTHER: Li_2016_J.Enzyme.Inhib.Med.Chem__1 PubMedSearch: Li 2016 J.Enzyme.Inhib.Med.Chem 1 PubMedID: 27384289 Abstract In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of donepezil-like compounds were designed, synthesized and evaluated. In vitro studies showed that most of the designed compounds displayed potent inhibitory activities toward AChE, BuChE, MAO-B and MAO-A. Among them, w18 was a promising agent with balanced activities, which exhibited a moderate cholinesterase inhibition (IC50, 0.220 muM for eeAChE; 1.23 muM for eqBuChE; 0.454 muM for hAChE) and an acceptable inhibitory activity against monoamine oxidases (IC50, 3.14 muM for MAO-B; 13.4 muM for MAO-A). Moreover, w18 could also be a metal-chelator, and able to cross the blood-brain barrier with low cell toxicity on PC12 cells. Taken together, these results suggested that w18 might be a promising multitargeted compound for AD treatment. Title: Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes Li S, Xu H, Cui S, Wu F, Zhang Y, Su M, Gong Y, Qiu S, Jiao Q and Li H <13 more author(s)> Li S, Xu H, Cui S, Wu F, Zhang Y, Su M, Gong Y, Qiu S, Jiao Q, Qin C, Shan J, Zhang M, Wang J, Yin Q, Xu M, Liu X, Wang R, Zhu L, Li J, Xu Y, Jiang H, Zhao Z, Li H (- 13) Ref: Journal of Medicinal Chemistry, 59:6772, 2016 : PubMed ESTHER: Li_2016_J.Med.Chem_59_6772 PubMedSearch: Li 2016 J.Med.Chem 59 6772 PubMedID: 27396490 Gene_locus related to this paper: human-DPP4 Abstract Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented. Title: Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro Lin J, Huang L, Yu J, Xiang S, Wang J, Zhang J, Yan X, Cui W, He S, Wang Q Ref: Mar Drugs, 14:, 2016 : PubMed ESTHER: Lin_2016_Mar.Drugs_14_ PubMedSearch: Lin 2016 Mar.Drugs 14 PubMedID: 27023569 Abstract Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 muM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer's disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression. Title: Arsenicitalea aurantiaca gen. nov., sp. nov., a new member of the family Hyphomicrobiaceae, isolated from high-arsenic sediment Mu Y, Zhou L, Zeng XC, Liu L, Pan Y, Chen X, Wang J, Li S, Li WJ, Wang Y Ref: Int J Syst Evol Microbiol, 66:5478, 2016 : PubMed ESTHER: Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478 PubMedSearch: Mu 2016 Int.J.Syst.Evol.Microbiol 66 5478 PubMedID: 27902179 Gene_locus related to this paper: 9rhiz-a0a433xfq5 Abstract A novel arsenic-resistant bacterium, designated 42-50T, was isolated from the high-arsenic sediment of Jianghan Plain, Hubei Province, China. Phylogenetic and biochemical analysis indicated that this bacterium represents the first species of a novel genus belonging to the family Hyphomicrobiaceae. The 16S rRNA gene of strain 42-50T shares 96.3-94.2, 96.3, 96.2 and 94.9-93.8 % sequence identities to those of species from the genera Devosia, Youhaiella, Paradevosia and Pelagibacterium, respectively. The major cellular fatty acids are C16 : 0, C18 : 0, C18 : 1omega7c 11-methyl and summed feature 8 (comprising C18 : 1omega7c and C18 : 1omega6c). The predominant polar lipids are diphosphatidylglycerol, phosphatidylglycerol and two unidentified glycolipids. The predominant respiratory quinone is ubiquinone-10 (Q-10). The DNA G+C content of strain 42-50T is 73.7 mol%. The distinct phylogenetic lineage and unique cellular fatty acids suggest that strain 42-50T represents a novel species of a new genus affiliated with the family Hyphomicrobiaceae, for which the name Arsenicitalea aurantiaca gen. nov., sp. nov. is proposed. The type strain is 42-50T (=CCTCC AB 2014325T=KCTC 42825T). Title: Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations Wang D, Jin H, Wang J, Guan S, Zhang Z, Han W Ref: J Biomol Struct Dyn, 34:749, 2016 : PubMed ESTHER: Wang_2016_J.Biomol.Struct.Dyn_34_749 PubMedSearch: Wang 2016 J.Biomol.Struct.Dyn 34 749 PubMedID: 26155973 Gene_locus related to this paper: aerpe-APE1547 Inhibitor(s) related to this paper: Chlorpyrifos Abstract Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family. Title: Three new sesquiterpenoids from agarwood of Aquilaria crassna Wang HN, Dong WH, Huang SZ, Li W, Kong FD, Wang H, Wang J, Mei WL, Dai HF Ref: Fitoterapia, 114:7, 2016 : PubMed ESTHER: Wang_2016_Fitoterapia_114_7 PubMedSearch: Wang 2016 Fitoterapia 114 7 PubMedID: 27502285 Abstract Three new sesquiterpenoids (1-3), together with two known ones were isolated from the EtOAc extract of agarwood originating from Aquilaria crassna. The new compounds were elucidated on the basis of spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). Compounds 1-5 were isolated from agarwood of A. crassna for the first time. In the acetylcholinesterase inhibition experiment of 2-5, compound 3 showed acetylcholinesterase inhibition activity (IR 42.9+/-0.6%). Compound 5 expressed antibacterial activities against Staphylococcus aureus and Ralstonia solanacearum with diameter of the inhibition zones of 12.35+/-0.11mm and 16.90+/-0.09mm, respectively. Title: ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials Wang J, Logovinsky V, Hendrix SB, Stanworth SH, Perdomo C, Xu L, Dhadda S, Do I, Rabe M and Satlin A <2 more author(s)> Wang J, Logovinsky V, Hendrix SB, Stanworth SH, Perdomo C, Xu L, Dhadda S, Do I, Rabe M, Luthman J, Cummings J, Satlin A (- 2) Ref: Journal of Neurology Neurosurg Psychiatry, 87:993, 2016 : PubMed ESTHER: Wang_2016_J.Neurol.Neurosurg.Psychiatry_87_993 PubMedSearch: Wang 2016 J.Neurol.Neurosurg.Psychiatry 87 993 PubMedID: 27010616 Abstract BACKGROUND: Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials. Title: Synthesis and evaluation of multi-target-directed ligands for the treatment of Alzheimer's disease based on the fusion of donepezil and melatonin Wang J, Wang ZM, Li XM, Li F, Wu JJ, Kong LY, Wang XB Ref: Bioorganic & Medicinal Chemistry, 24:4324, 2016 : PubMed ESTHER: Wang_2016_Bioorg.Med.Chem_24_4324 PubMedSearch: Wang 2016 Bioorg.Med.Chem 24 4324 PubMedID: 27460699 Inhibitor(s) related to this paper: Donepezil-Melatonin-4u Abstract A novel series of compounds obtained by fusing the acetylcholinesterase (AChE) inhibitor donepezil and the antioxidant melatonin were designed as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (eqBuChE and hBuChE), and beta-amyloid (Abeta) aggregation, and to act as potential antioxidants and biometal chelators. Especially, 4u displayed a good inhibition of AChE (IC50 value of 193nM for eeAChE and 273nM for hAChE), strong inhibition of BuChE (IC50 value of 73nM for eqBuChE and 56nM for hBuChE), moderate inhibition of Abeta aggregation (56.3% at 20muM) and good antioxidant activity (3.28trolox equivalent by ORAC assay). Molecular modeling studies in combination with kinetic analysis revealed that 4u was a mixed-type inhibitor, binding simultaneously to catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4u could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results strongly indicated the hybridization approach is an efficient strategy to identify novel scaffolds with desired bioactivities, and further optimization of 4u may be helpful to develop more potent lead compound for AD treatment. Title: Downregulated expression of microRNA-124 in pediatric intestinal failure patients modulates macrophages activation by inhibiting STAT3 and AChE Xiao YT, Wang J, Lu W, Cao Y, Cai W Ref: Cell Death Dis, 7:e2521, 2016 : PubMed ESTHER: Xiao_2016_Cell.Death.Dis_7_e2521 PubMedSearch: Xiao 2016 Cell.Death.Dis 7 e2521 PubMedID: 27977009 Abstract Intestinal inflammation plays a critical role in the pathogenesis of intestinal failure (IF). The macrophages are essential to maintain the intestinal homeostasis. However, the underlying mechanisms of intestinal macrophages activation remain poorly understood. Since microRNAs (miRNAs) have pivotal roles in regulation of immune responses, here we aimed to investigate the role of miR-124 in the activation of intestinal macrophages. In this study, we showed that the intestinal macrophages increased in pediatric IF patients and resulted in the induction of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). The miRNA fluorescence in situ hybridization analysis showed that the expression of miR-124 significantly reduced in intestinal macrophages in IF patients. Overexpression of miR-124 was sufficient to inhibit intestinal macrophages activation by attenuating production of IL-6 and TNF-alpha. Further studies showed that miR-124 could directly target the 3'-untranslated region of both signal transducer and activator of transcription 3 (STAT3) and acetylcholinesterase (AChE) mRNAs, and suppress their protein expressions. The AChE potentially negates the cholinergic anti-inflammatory signal by hydrolyzing the acetylcholine. We here showed that intestinal macrophages increasingly expressed the AChE and STAT3 in IF patients when compared with controls. The inhibitors against to STAT3 and AChE significantly suppressed the lipopolysaccharides-induced IL-6 and TNF-alpha production in macrophages. Taken together, these findings highlight an important role for miR-124 in the regulation of intestinal macrophages activation, and suggest a potential application of miR-124 in pediatric IF treatment regarding as suppressing intestinal inflammation. Title: Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease Xie SS, Lan JS, Wang X, Wang ZM, Jiang N, Li F, Wu JJ, Wang J, Kong LY Ref: Bioorganic & Medicinal Chemistry, 24:1528, 2016 : PubMed ESTHER: Xie_2016_Bioorg.Med.Chem_24_1528 PubMedSearch: Xie 2016 Bioorg.Med.Chem 24 1528 PubMedID: 26917219 Abstract Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87muM and 0.93muM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37muM for hAChE; 1.98muM for hBuChE; 2.62muM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. Title: Synthesis and evaluation of donepezil-ferulic acid hybrids as multi-target-directed ligands against Alzheimer's disease Xu W, Wang XB, Wang ZM, Wu JJ, Li F, Wang J, Kong LY Ref: Medchemcomm, 7:990, 2016 : PubMed ESTHER: Xu_2016_Medchemcomm_7_990 PubMedSearch: Xu 2016 Medchemcomm 7 990 Abstract A novel family of donepezilferulic acid hybrids were designed, synthesized and biologically evaluated as multi-target-directed ligands against Alzheimer's disease by fusing a fragment of donepezil and ferulic acid. The in vitro assay indicated that some of these molecules exhibited potent cholinesterase inhibitory activities, outstanding radical scavenging activities and good neuroprotective effects on PC12 cells, and could penetrate into the central nervous system. Compound 5c especially showed moderate acetylcholinesterase inhibitory activity (IC50 values of 0.398 M for electric eel acetylcholinesterase) and butyrylcholinesterase inhibitory activity (IC50 = 0.976 microM for equine serum butyrylcholinesterase). It also showed significant antioxidant activity (1.78 trolox equivalents by the ABTS method, IC50 values of 24.9 microM by the DPPH method). The kinetic study and molecular docking indicated that compound 5c interacted with both the peripheral anionic site and the catalytic binding site of acetylcholinesterase. Overall, these results indicated that compound 5c is a promising drug candidate with balanced properties for the treatment of Alzheimer's disease. Title: Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg) with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by Engineering the Substrate Entrance Tunnel Yan X, Wang J, Sun Y, Zhu J, Wu S Ref: Applied Environmental Microbiology, 82:6748, 2016 : PubMed ESTHER: Yan_2016_Appl.Environ.Microbiol_82_6748 PubMedSearch: Yan 2016 Appl.Environ.Microbiol 82 6748 PubMedID: 27613682 Gene_locus related to this paper: 9mico-e3svs0 Abstract Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical alpha/beta fold hydrolase, was previously reported to have both gamma-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from Pseudomonas fluorescens, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any gamma-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of alpha/beta fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies. Title: Design, synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells Yao D, Wang J, Wang G, Jiang Y, Shang L, Zhao Y, Huang J, Yang S, Yu Y Ref: Bioorg Chem, 68:112, 2016 : PubMed ESTHER: Yao_2016_Bioorg.Chem_68_112 PubMedSearch: Yao 2016 Bioorg.Chem 68 112 PubMedID: 27479541 Abstract A novel series of coumarin derivatives were designed, synthesized and investigated for inhibition of cholinesterase, including acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE). This biological study showed that these compounds containing piperazine ring had significant inhibition activities on AChE rather than BuChE. Further study suggested that 9x, as one of this kind of structure derivative, showed the strongest inhibition activity on AChE with an IC50 value of 34nM. Moreover, molecular docking, flow cytometry (FCM), and western blot assay suggested that 9x could induce cytoprotective autophagy to attenuate H2O2-induced cell death in human neuroblastoma SH-SY5Y cells. These findings highlight a new approach for the development of a novel potential neuroprotective compound targeting AChE with autophagy-inducing activity in future Alzheimer's disease (AD) therapy. Title: Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities Zhan G, Zhou J, Liu R, Liu T, Guo G, Wang J, Xiang M, Xue Y, Luo Z and Yao G <1 more author(s)> Zhan G, Zhou J, Liu R, Liu T, Guo G, Wang J, Xiang M, Xue Y, Luo Z, Zhang Y, Yao G (- 1) Ref: Journal of Natural Products, 79:760, 2016 : PubMed ESTHER: Zhan_2016_J.Nat.Prod_79_760 PubMedSearch: Zhan 2016 J.Nat.Prod 79 760 PubMedID: 26913788 Abstract Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 muM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 muM. Title: Single point mutations enhance activity of cis-epoxysuccinate hydrolase Zhang C, Pan H, Yao L, Bao W, Wang J, Xie Z, Zhang J Ref: Biotechnol Lett, 38:1301, 2016 : PubMed ESTHER: Zhang_2016_Biotechnol.Lett_38_1301 PubMedSearch: Zhang 2016 Biotechnol.Lett 38 1301 PubMedID: 27259723 Abstract OBJECTIVES: To enhance activity of cis-epoxysuccinate hydrolase from Klebsiella sp. BK-58 for converting cis-epoxysuccinate to tartrate. Title: Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora Zhang L, Zhou Z, Guo Q, Fokkens L, Miskei M, Pocsi I, Zhang W, Chen M, Wang L and Lin M <12 more author(s)> Zhang L, Zhou Z, Guo Q, Fokkens L, Miskei M, Pocsi I, Zhang W, Chen M, Wang L, Sun Y, Donzelli BG, Gibson DM, Nelson DR, Luo JG, Rep M, Liu H, Yang S, Wang J, Krasnoff SB, Xu Y, Molnar I, Lin M (- 12) Ref: Sci Rep, 6:23122, 2016 : PubMed ESTHER: Zhang_2016_Sci.Rep_6_23122 PubMedSearch: Zhang 2016 Sci.Rep 6 23122 PubMedID: 26975455 Gene_locus related to this paper: 9hypo-a0a151ga75, 9hypo-a0a151gbh5, 9hypo-a0a151gd50, 9hypo-a0a151ggb9, 9hypo-a0a151gjd5, 9hypo-a0a151gtv2, 9hypo-a0a151gxh2, 9hypo-a0a151gaw8, 9hypo-a0a151gia2 Abstract Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle. Title: Monoacylglycerol Lipase: A Novel Potential Therapeutic Target and Prognostic Indicator for Hepatocellular Carcinoma Zhang J, Liu Z, Lian Z, Liao R, Chen Y, Qin Y, Wang J, Jiang Q, Wang X, Gong J Ref: Sci Rep, 6:35784, 2016 : PubMed ESTHER: Zhang_2016_Sci.Rep_6_35784 PubMedSearch: Zhang 2016 Sci.Rep 6 35784 PubMedID: 27767105 Abstract Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed. MAGL levels in HCC samples were closely linked to the degree of malignancy and patient prognosis. RNA interference, specific pharmacological inhibitor JZL-184 and gene knock-in of MAGL were utilized to investigate the effects of MAGL on HCC cell proliferation, apoptosis, and invasion. MAGL played important roles in both proliferation and invasion of HCC cells through mechanisms that involved prostaglandin E2 (PGE2) and lysophosphatidic acid (LPA). JZL-184 administration significantly inhibited tumor growth in mice. Furthermore, we confirmed that promoter methylation of large tumor suppressor kinase 1 (LATS1) resulted in dysfunction of the Hippo signal pathway, which induced overexpression of MAGL in HCC. These results indicate that MAGL could be a potentially novel therapeutic target and prognostic indicator for HCC. Title: Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T and Chen X <19 more author(s)> Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T, Ding Y, Nie L, Li Q, Dong WR, Jiang L, Sun B, Zhang X, Li M, Zhang HQ, Xie S, Zhu Y, Jiang X, Wang X, Mu P, Chen W, Yue Z, Wang Z, Wang J, Shao JZ, Chen X (- 19) Ref: PLoS Genet, 11:e1005118, 2015 : PubMed ESTHER: Ao_2015_PLoS.Genet_11_E1005118 PubMedSearch: Ao 2015 PLoS.Genet 11 E1005118 PubMedID: 25835551 Gene_locus related to this paper: larcr-a0a0f8ay25, larcr-a0a0f8cf53, larcr-a0a0f8cir1, larcr-a0a0f8d1j2, larcr-a0a0f8alq6, larcr-a0a0f8bdu4, larcr-a0a0f8abw1, larcr-a0a0f8ahh1, larcr-a0a0f8avc6, larcr-a0a0f8al93, larcr-a0a0f8aed8, larcr-a0a0f7ir14, larcr-a0a0f8aje8, larcr-k9lsm3, larcr-a0a0f8but5, larcr-a0a0f8af44 Abstract The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea. Title: Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP Competitive Inhibitor Fang P, Han H, Wang J, Chen K, Chen X, Guo M Ref: Chemical Biology, 22:734, 2015 : PubMed ESTHER: Fang_2015_Chem.Biol_22_734 PubMedSearch: Fang 2015 Chem.Biol 22 734 PubMedID: 26074468 Gene_locus related to this paper: clacd-cla3 Abstract Pharmaceutical inhibitors of aminoacyl-tRNA synthetases demand high species and family specificity. The antimalarial ATP-mimetic cladosporin selectively inhibits Plasmodium falciparum LysRS (PfLysRS). How the binding to a universal ATP site achieves the specificity is unknown. Here we report three crystal structures of cladosporin with human LysRS, PfLysRS, and a Pf-like human LysRS mutant. In all three structures, cladosporin occupies the class defining ATP-binding pocket, replacing the adenosine portion of ATP. Three residues holding the methyltetrahydropyran moiety of cladosporin are critical for the specificity of cladosporin against LysRS over other class II tRNA synthetase families. The species-exclusive inhibition of PfLysRS is linked to a structural divergence beyond the active site that mounts a lysine-specific stabilizing response to binding cladosporin. These analyses reveal that inherent divergence of tRNA synthetase structural assembly may allow for highly specific inhibition even through the otherwise universal substrate binding pocket and highlight the potential for structure-driven drug development. Title: Next generation digital PCR measurement of hepatitis B virus copy number in formalin-fixed paraffin-embedded hepatocellular carcinoma tissue Huang JT, Liu YJ, Wang J, Xu ZG, Yang Y, Shen F, Liu XH, Zhou X, Liu SM Ref: Clinical Chemistry, 61:290, 2015 : PubMed ESTHER: Huang_2015_Clin.Chem_61_290 PubMedSearch: Huang 2015 Clin.Chem 61 290 PubMedID: 25361948 Abstract BACKGROUND: Hepatocellular carcinoma (HCC) is strongly associated with hepatitis B virus (HBV) infection. False-negative results are common in routine serological tests and quantitative real-time PCR because of HBV surface antigen (HBsAg) variation and low HBV copy number. Droplet digital PCR (ddPCR), a next generation digital PCR, is a novel, sensitive, and specific platform that can be used to improve HBV detection. Title: Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology Jia J, Yang X, Wu Z, Zhang Q, Lin Z, Guo H, Lin CS, Wang J, Wang Y Ref: Biomed Res Int, 2015:497462, 2015 : PubMed ESTHER: Jia_2015_Biomed.Res.Int_2015_497462 PubMedSearch: Jia 2015 Biomed.Res.Int 2015 497462 PubMedID: 26366414 Abstract Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production. Title: Esterification degree of fructose laurate exerted by Candida antarctica lipase B in organic solvents Li L, Ji F, Wang J, Li Y, Bao Y Ref: Enzyme Microb Technol, 69:46, 2015 : PubMed ESTHER: Li_2015_Enzyme.Microb.Technol_69_46 PubMedSearch: Li 2015 Enzyme.Microb.Technol 69 46 PubMedID: 25640724 Abstract Sugar esters of fatty acids have many applications as biocompatible and biodegradable emulsifiers, which are determined by their degrees of esterification (DE). Direct esterification of fructose with lauric acid in organic media used commercial immobilized Candida antarctica lipase B (CALB) was investigated for DE. Significant difference of DE was observed between 2-methyl-2-butanol (2M2B) and methyl ethyl ketone (MEK), as di-ester/mono-ester molar ratio of 1.05:1 in 2M2B and 2.79:1 in MEK. Fourier transform infrared (FTIR) spectra showed that the secondary structure of the enzyme binding mono-ester presented distinct difference in 2M2B and MEK. Contents of beta-turn and antiparallel beta-sheet of CALB in 2M2B were 26.9% and 16.2%, respectively, but 19.1% and 13.2% in MEK. To understand the relationship between the conformational changes and differences of DE, mono-ester and fatty acid were directly employed for synthesis of di-ester. The maximum initial velocity of di-ester synthesis in MEK was 0.59mmolg(enzyme)(-1)h(-1), which was 2.19-fold as greater as that in 2M2B, indicating that CALB conformation in MEK was preferred for the synthesis of di-ester. These results demonstrated that the conformation of CALB binding mono-ester affected by organic solvents essentially determined DE. Title: Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients Li Z, Yu Z, Zhang J, Wang J, Sun C, Wang P Ref: Eur Neurol, 74:86, 2015 : PubMed ESTHER: Li_2015_Eur.Neurol_74_86 PubMedSearch: Li 2015 Eur.Neurol 74 86 PubMedID: 26288230 Abstract BACKGROUND: The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. SUBJECTS AND Title: Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies Li X, Fan D, Zhang W, Liu G, Zhang L, Zhao L, Fang X, Chen L, Dong Y and Wang W <14 more author(s)> Li X, Fan D, Zhang W, Liu G, Zhang L, Zhao L, Fang X, Chen L, Dong Y, Chen Y, Ding Y, Zhao R, Feng M, Zhu Y, Feng Y, Jiang X, Zhu D, Xiang H, Feng X, Li S, Wang J, Zhang G, Kronforst MR, Wang W (- 14) Ref: Nat Commun, 6:8212, 2015 : PubMed ESTHER: Li_2015_Nat.Commun_6_8212 PubMedSearch: Li 2015 Nat.Commun 6 8212 PubMedID: 26354079 Gene_locus related to this paper: papxu-a0a194pj15, papxu-a0a194q254, papma-a0a194rdx2, papxu-a0a194q858, papxu-a0a194pyl3, papxu-a0a194q337, papma-a0a194r1p9, papma-a0a194r6h1, papxu-a0a194q1w8, papma-a0a194ql80, papma-a0a0n1ipl3, papma-a0a194qm14 Abstract Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system. Title: Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X and Yu S <30 more author(s)> Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X, Wu J, Liang X, Huang G, Percy RG, Liu K, Yang W, Chen W, Du X, Shi C, Yuan Y, Ye W, Liu X, Zhang X, Liu W, Wei H, Wei S, Zhu S, Zhang H, Sun F, Wang X, Liang J, Wang J, He Q, Huang L, Cui J, Song G, Wang K, Xu X, Yu JZ, Zhu Y, Yu S (- 30) Ref: Nat Biotechnol, 33:524, 2015 : PubMed ESTHER: Li_2015_Nat.Biotechnol_33_524 PubMedSearch: Li 2015 Nat.Biotechnol 33 524 PubMedID: 25893780 Gene_locus related to this paper: gosra-a0a0d2rxs2, gosra-a0a0d2tng2, gosra-a0a0d2twz7, goshi-a0a1u8hr03, gosra-a0a0d2vdc5, goshi-a0a1u8ljh5, gosra-a0a0d2vj24, goshi-a0a1u8pxd3, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8mt09, goshi-a0a1u8kis4, goshi-a0a1u8ibk3, goshi-a0a1u8ieg2, goshi-a0a1u8iki6, goshi-a0a1u8jvp4, goshi-a0a1u8jw35, gosra-a0a0d2pzd7 Abstract Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum. Title: Efficient mono-acylation of fructose by lipase-catalyzed esterification in ionic liquid co-solvents Li L, Ji F, Wang J, Jiang B, Li Y, Bao Y Ref: Carbohydr Res, 416:51, 2015 : PubMed ESTHER: Li_2015_Carbohydr.Res_416_51 PubMedSearch: Li 2015 Carbohydr.Res 416 51 PubMedID: 26343327 Abstract Fructose monoesters are eco-friendly nonionic surfactants in various applications. Selective preparation of mono-acylated fructose is challenging due to the multiple hydroxyl sites available for acylation both chemically and enzymatically. Ionic liquids (ILs) have profound impacts not only on the reaction media but also on the catalytic properties of enzymes in the acylation process. In this study, utilizing an IL co-solvent system, selective synthesis of mono-acylated fructose with lauric acid catalyzed by immobilized Candida antarctica lipase B (CALB) was investigated. The imidazolium-based ILs selected as co-solvents with 2-methyl-2-butanol (2M2B) markedly improved the ratios of monolauroyl fructose in the presence of 60% [BMIM][TfO] (v/v) and 20% [BMIM][BF4] (v/v), in which the mono-acylated fructose was 85% and 78% respectively. Based on a Ping-Pong Bi-Bi model, a kinetic equation was fitted, by which the kinetic parameters revealed that the affinity between fructose and acyl-enzyme intermediate was enhanced. The inhibition effect of fructose on free enzyme was weakened in the presence of IL co-solvents. The conformation of CALB binding substrates also changed in the co-solvent system as demonstrated by Fourier transform infrared spectra. These results demonstrated that the variation of CALB kinetic characteristics was a crucial factor for the selectivity of mono-acylation in ILs/2M2B co-solvents. Title: APA-style human milk fat analogue from silkworm pupae oil: Enzymatic production and improving storage stability using alkyl caffeates Liu X, Wang X, Pang N, Zhu W, Zhao X, Wang F, Wu F, Wang J Ref: Sci Rep, 5:17909, 2015 : PubMed ESTHER: Liu_2015_Sci.Rep_5_17909 PubMedSearch: Liu 2015 Sci.Rep 5 17909 PubMedID: 26643045 Abstract Silkworm pupae oil derived from reeling waste is a rich source of alpha-linolenic acid (ALA), which has multipal applications. ALAs were added in sn-1, 3 positions in a triacylglycerol (TAG) to produce an APA-human milk fat analogues (APA-HMFAs, A: alpha-linolenic acid, P: palmitic acid). The optimum condition is that tripalmitin to free fatty acids of 1:12 (mole ratio) at 65 degreeC for 48 h using lipase Lipozyme RM IM. Results show that, the major TAG species that comprised APA-HMFAs were rich in ALA and palmitic acid, which contained 64.52% total unsaturated fatty acids (UFAs) and 97.05% PA at the sn-2 position. The melting point of APA was -27.5 degreeC which is much lower than tripalmitin (40.5 degreeC) indicating more plastic character. In addition, the practical application of alkyl caffeates as liposoluble antioxidants in APA was developed. Alkyl caffeate showed a superior IC50 (1.25-1.66 g/mL) compared to butyl hydroxy anisd (1.67 g/mL) and L-ascorbic acid-6-palmitate (L-AP) (1.87 g/mL) in DPPH analysis. The addition of ethyl caffeate to oil achieved a higher UFAs content (73.58%) at high temperatures. Overall, APA was obtained from silkworm pupae oil successfully, and the addition of caffeates extended storage ranges for APA-HMFAs. Title: Production of Structured Triacylglycerols Containing Palmitic Acids at sn-2 Position and Docosahexaenoic Acids at sn-1, 3 Positions Liu Y, Guo Y, Sun Z, Jie X, Li Z, Wang J, Wang Y, Xue C Ref: J Oleo Sci, 64:1227, 2015 : PubMed ESTHER: Liu_2015_J.Oleo.Sci_64_1227 PubMedSearch: Liu 2015 J.Oleo.Sci 64 1227 PubMedID: 26521813 Abstract Docosahexaenoic acid supplementation has been shown well-established health benefits that justify their use as functional ingredients in healthy foods and nutraceutical products. Structured triacylglycerols rich in 1,3-docosahexenoyl-2-palmitoyl-sn-glycerol were produced from algal oil (Schizochytrium sp) which was prepared by a two-step process. Novozym 435 lipase was used to produce tripalmitin. Tripalmitin was then used to produce the final structured triacylglycerol (STAG) through interesterification reactions using Lipozyme RM IM. The optimum conditions for the enzymatic reaction were a mole ratio of tripalmitin/fatty acid ethyl esters 1:9, 60 degC, 10% enzyme load (wt % of substrates), 10 h; the enzymatic product contained 51.6% palmitic acid (PA), 30.13% docosahexaenoic acid (DHA, C22:6 n-3) and 5.33% docosapentanoic acid (DPA, C22:5 n-3), 12.15% oleic acid (OLA). This STAG can be used as a functional ingredient in dietary supplementation to provide the benefits of DHA. Title: Baicalein alters PI3K/Akt/GSK3beta signaling pathway in rats with diabetes-associated cognitive deficits Qi Z, Xu Y, Liang Z, Li S, Wang J, Wei Y, Dong B Ref: Int J Clin Exp Med, 8:1993, 2015 : PubMed ESTHER: Qi_2015_Int.J.Clin.Exp.Med_8_1993 PubMedSearch: Qi 2015 Int.J.Clin.Exp.Med 8 1993 PubMedID: 25932128 Abstract Our present investigation focused on assessing the neuroprotective potential of baicalein (BAC) against diabetes-associated cognitive deficit (DACD) using a diabetic model and further figure out the potential molecular mechanisms. Diabetic rat model was established by streptozotocin (STZ). Vehicle or BAC by the doses of 2 and 4 mg/kg was intraperitoneally injected once a day for seven consecutive weeks. Memory function was evaluated by Morris water maze test and avoidance passive test. The activities of acetylcholinesterase (AChE), choline acetylase (ChAT), caspase-9 and caspase-3 in STZ-induced diabetic rats' hippocampus were detected via responsive commercial kits. Western blot assay were used to determine the protein levels of phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-Akt (p-Akt), and phospho-glycogen synthase kinase-3beta (p-GSK3beta). Our results showed that BAC remarkably increased body weight and ChAT activity, decreased blood glucose level and AChE activity as well as improved cognitive deficits in diabetic rats. Additionally, it was also found that treatment with BAC to diabetes obviously stimulated the p-PI3K and p-Akt and inhibited the level of p-GSK3beta. Furthermore, the neuronal apoptosis was also prevented after BAC treatment by decreasing caspase-9 and caspase-3 activities in diabetic rats' hippocampus. It is concluded that BAC exerted beneficial effects against DACD in rats and its neuroprotection might be linked with activating PI3K and Akt phosphorylation accompanied with suppressing the phosphorylated level of GSK3beta. These results hint that BAC is likely to be served as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as DACD. Title: Transcriptomic and proteomic analysis of pre-diapause and non-diapause eggs of migratory locust, Locusta migratoria L. (Orthoptera: Acridoidea) Tu X, Wang J, Hao K, Whitman DW, Fan Y, Cao G, Zhang Z Ref: Sci Rep, 5:11402, 2015 : PubMed ESTHER: Tu_2015_Sci.Rep_5_11402 PubMedSearch: Tu 2015 Sci.Rep 5 11402 PubMedID: 26091374 Abstract Low temperature induces diapause in locusts. However, the physiological processes and initiation mechanism of diapause are not well understood. To understand the molecular basis of diapause, 'omics' analyses were performed to examine the differences between diapause and non-diapause eggs at both transcriptional and translational levels. Results indicated that a total of 62,241 mRNAs and 212 proteins were differentially expressed. Among them, 116 transcripts had concurrent transcription and translation profiles. Up-regulated genes related to diapause included glutathiones-S-transferase et al., and down-regulated genes including juvenile hormone esterase-like protein et al. KEGG analysis mapped 7,243 and 99 differentially expressed genes and proteins, to 83 and 25 pathways, respectively. Correlation enriched pathways indicated that there were nine identical pathways related to diapause. Gene Ontology analysis placed these genes and proteins into three categories, and a higher proportion of genes related to metabolism was up-regulated than down-regulated. Furthermore, three up-regulated pathways were linked to cryoprotection. This study demonstrates the applicability of high-throughput omics tools to identify molecules linked to diapause in the locust. In addition, it reveals cellular metabolism in diapause eggs is more active than in non-diapause eggs, and up-regulated enzymes may play roles in cryoprotection and storing energy for diapause and post-diapause stages. Title: Pharmacological treatment of neuropsychiatric symptoms in Alzheimer's disease: a systematic review and meta-analysis Wang J, Yu JT, Wang HF, Meng XF, Wang C, Tan CC, Tan L Ref: Journal of Neurology Neurosurg Psychiatry, 86:101, 2015 : PubMed ESTHER: Wang_2015_J.Neurol.Neurosurg.Psychiatry_86_101 PubMedSearch: Wang 2015 J.Neurol.Neurosurg.Psychiatry 86 101 PubMedID: 24876182 Abstract BACKGROUND: A wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms, which are common in Alzheimer's disease (AD), but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting. OBJECTIVES: To quantify the efficacy and safety of pharmacological treatment on neuropsychiatric symptoms in AD patients. Title: Butyrylcholinesterase K Variant and Alzheimer's Disease Risk: A Meta-Analysis Wang Z, Jiang Y, Wang X, Du Y, Xiao D, Deng Y, Wang J Ref: Med Sci Monit, 21:1408, 2015 : PubMed ESTHER: Wang_2015_Med.Sci.Monit_21_1408 PubMedSearch: Wang 2015 Med.Sci.Monit 21 1408 PubMedID: 25978873 Abstract Background Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. Material and Methods We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE epsilon4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE epsilon4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). Conclusions The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk. Title: Abundance and significance of neuroligin-1 and glutamate in Hirschsprung's disease Wang J, Du H, Mou YR, Niu JY, Zhang WT, Yang HC, Li AW Ref: World J Gastroenterol, 21:7172, 2015 : PubMed ESTHER: Wang_2015_World.J.Gastroenterol_21_7172 PubMedSearch: Wang 2015 World.J.Gastroenterol 21 7172 PubMedID: 26109803 Abstract AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate (Glu) in Hirschsprung's disease (HSCR). Title: Microfluidic Device for Coulometric Detection of Organophosphate Pesticides Wang J, Satake T, Suzuki H Ref: Anal Sci, 31:591, 2015 : PubMed ESTHER: Wang_2015_Anal.Sci_31_591 PubMedSearch: Wang 2015 Anal.Sci 31 591 PubMedID: 26165279 Abstract A microdevice for coulometric detection of organophosphate pesticides (OPs) was fabricated based on the measurement of the inhibition of an enzyme, acetylcholinesterase (AChE), by OPs. Thiocholine (TCh) produced in the enzymatic reaction of AChE with acetylthiocholine (ATCh) as a substrate was oxidized on a microelectrode array formed in a main flow channel. Volumes of plugs of necessary solutions were measured using a structure consisting of a row of rhombuses formed in an auxiliary flow channel. The plugs were merged and solution components were mixed at a T-junction formed with the main and auxiliary flow channels. A linear relationship was confirmed between the generated charge and the logarithm of the OP (malathion) concentration in a concentration range between 10(-6) and 10(-3) M with a correlation coefficient of 0.951. The lower limit of detection was 412 nM. Title: Organelle-Specific Nitric Oxide Detection in Living Cells via HaloTag Protein Labeling Wang J, Zhao Y, Wang C, Zhu Q, Du Z, Hu A, Yang Y Ref: PLoS ONE, 10:e0123986, 2015 : PubMed ESTHER: Wang_2015_PLoS.One_10_e0123986 PubMedSearch: Wang 2015 PLoS.One 10 e0123986 PubMedID: 25923693 Abstract Nitric oxide (NO) is a membrane-permeable signaling molecule that is constantly produced, transferred, and consumed in vivo. NO participates and plays important roles in multiple biological processes. However, spatiotemporal imaging of NO in living cells is challenging. To fill the gap in currently used techniques, we exploited the versatility of HaloTag technology and synthesized a novel organelle-targetable fluorescent probe called HTDAF-2DA. We demonstrate the utility of the probe by monitoring subcellular NO dynamics. The developed strategy enables precise determination of local NO function. Title: From microalgae oil to produce novel structured triacylglycerols enriched with unsaturated fatty acids Wang J, Wang XD, Zhao XY, Liu X, Dong T, Wu FA Ref: Bioresour Technol, 184:405, 2015 : PubMed ESTHER: Wang_2015_Bioresour.Technol_184_405 PubMedSearch: Wang 2015 Bioresour.Technol 184 405 PubMedID: 25451776 Abstract Novel structured triacylglycerols (STAGs) enriched with unsaturated fatty acids (UFAs) and low palmitic acid (PA) content were firstly synthesized from Schizochytrium sp. oil and oleic acid (OA) via solvent-free acidolysis catalyzed by Lipozyme RM IM. The results indicated that, the PA content decreased from 24.49% to 6.95%, while the UFAs content increased from 70.20% to 90.9% at the sn-1,3 positions in the STAGs under the optimal condition (i.e., lipase load of 7%, molar ratio of microalgae oil TAGs to OA of 1:3, and temperature of 65 degreeC). The lipase Lipozyme RM IM could be reused 16 times without significant loss of activity. The improved plastic and storage ranges of STAGs are useful for infant formula formulations, by which a possible method is blending of this product and 1,3-dioleoyl-2-palmitoylglycerol enriched fats and minor lipids based on the corresponding chemical compositions of human milk fat. Title: A ratiometric fluorescent system for carboxylesterase detection with AIE dots as FRET donors Wu Y, Huang S, Zeng F, Wang J, Yu C, Huang J, Xie H, Wu S Ref: Chem Commun (Camb), 51:12791, 2015 : PubMed ESTHER: Wu_2015_Chem.Commun.(Camb)_51_12791 PubMedSearch: Wu 2015 Chem.Commun.(Camb) 51 12791 PubMedID: 26165151 Abstract A ratiometric fluorescent system for CaE detection with AIE dots as the FRET donors was designed. Upon enzymatic reaction, electrostatic interaction between the cationic TPE-N(+) dots and the enzymatic reaction product - the negatively charged fluorescein molecules - allows the FRET process to proceed, thus affording the ratiometric fluorescence CaE assay. Title: Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis Yan YL, Chen X, Liang HJ, Wang J, Li TJ, Li RL, Li S, Qin X Ref: Dis Esophagus, 28:164, 2015 : PubMed ESTHER: Yan_2015_Dis.Esophagus_28_164 PubMedSearch: Yan 2015 Dis.Esophagus 28 164 PubMedID: 25714851 Abstract The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk. Title: Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y and Wan P <17 more author(s)> Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y, Li W, Chen Y, Zhang Y, Ai D, Zhao J, Shang C, Ma Y, Wu B, Wang M, Gao L, Sun D, Zhang P, Guo F, Wang W, Wang J, Varshney RK, Ling HQ, Wan P (- 17) Ref: Proc Natl Acad Sci U S A, 112:13213, 2015 : PubMed ESTHER: Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213 PubMedSearch: Yang 2015 Proc.Natl.Acad.Sci.U.S.A 112 13213 PubMedID: 26460024 Gene_locus related to this paper: phaan-a0a0l9ttq5, phaan-a0a0l9vh69, phaan-a0a0l9vh89, phaan-a0a0s3tc53, vigrr-a0a1s3v914, phaan-a0a0s3s998, phaan-a0a0s3siv8, phaan-a0a0l9uys5, phaan-a0a0s3rp07, phaan-a0a0s3rbq0, vigrr-a0a1s3tul4, phaan-a0a0s3smk7, phaan-a0a0s3slm9, phaan-a0a0l9ujf5, phaan-a0a0l9til9, phaan-a0a0l9uqr2, phaan-a0a0l9v1m8, phaan-a0a0l9uc60, phaan-a0a0l9ucr8 Abstract Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean. Title: Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury Zhang J, Yong Y, Li X, Hu Y, Wang J, Wang YQ, Song W, Chen WT, Xie J and Song JG <6 more author(s)> Zhang J, Yong Y, Li X, Hu Y, Wang J, Wang YQ, Song W, Chen WT, Xie J, Chen XM, Lv X, Hou LL, Wang K, Zhou J, Wang XR, Song JG (- 6) Ref: Sci Rep, 5:15503, 2015 : PubMed ESTHER: Zhang_2015_Sci.Rep_5_15503 PubMedSearch: Zhang 2015 Sci.Rep 5 15503 PubMedID: 26499847 Abstract Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a alpha7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion. Title: Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents Zhang X, Wang J, Hong C, Luo W, Wang C Ref: Acta Pharm Sin B, 5:67, 2015 : PubMed ESTHER: Zhang_2015_Acta.Pharm.Sin.B_5_67 PubMedSearch: Zhang 2015 Acta.Pharm.Sin.B 5 67 PubMedID: 26579427 Abstract A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 2.75 mumol/L, which was better than that of rivastigmine (5.60 mumol/L). Lineweaver-Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10 mumol/L. Title: Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr-/- mice Bie J, Wang J, Yuan Q, Kakiyama G, Ghosh SS, Ghosh S Ref: J Lipid Res, 55:729, 2014 : PubMed ESTHER: Bie_2014_J.Lipid.Res_55_729 PubMedSearch: Bie 2014 J.Lipid.Res 55 729 PubMedID: 24563511 Abstract The liver plays a central role in the final elimination of cholesterol from the body either as bile acids or as free cholesterol (FC), and lipoprotein-derived cholesterol is the major source of total biliary cholesterol. HDL is the major lipoprotein responsible for removal and transport of cholesterol, mainly as cholesteryl esters (CEs), from the peripheral tissues to the liver. While HDL-FC is rapidly secreted into bile, the fate of HDL-CE remains unclear. We have earlier demonstrated the role of human CE hydrolase (CEH, CES1) in hepatic hydrolysis of HDL-CE and increasing bile acid synthesis, a process dependent on scavenger receptor BI expression. In the present study, we examined the hypothesis that by enhancing the elimination of HDL-CE into bile/feces, liver-specific transgenic expression of CEH will be anti-atherogenic. Increased CEH expression in the liver significantly increased the flux of HDL-CE to bile acids. In the LDLR(-/-) background, this enhanced elimination of cholesterol led to attenuation of diet-induced atherosclerosis with a consistent increase in fecal sterol secretion primarily as bile acids. Taken together with the observed reduction in atherosclerosis by increasing macrophage CEH-mediated cholesterol efflux, these studies establish CEH as an important regulator in enhancing cholesterol elimination and also as an anti-atherogenic target. Title: Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle Chen S, Zhang G, Shao C, Huang Q, Liu G, Zhang P, Song W, An N, Chalopin D and Wang J <34 more author(s)> Chen S, Zhang G, Shao C, Huang Q, Liu G, Zhang P, Song W, An N, Chalopin D, Volff JN, Hong Y, Li Q, Sha Z, Zhou H, Xie M, Yu Q, Liu Y, Xiang H, Wang N, Wu K, Yang C, Zhou Q, Liao X, Yang L, Hu Q, Zhang J, Meng L, Jin L, Tian Y, Lian J, Yang J, Miao G, Liu S, Liang Z, Yan F, Li Y, Sun B, Zhang H, Zhu Y, Du M, Zhao Y, Schartl M, Tang Q, Wang J (- 34) Ref: Nat Genet, 46:253, 2014 : PubMed ESTHER: Chen_2014_Nat.Genet_46_253 PubMedSearch: Chen 2014 Nat.Genet 46 253 PubMedID: 24487278 Gene_locus related to this paper: cynse-a0a3p8wch2, cynse-a0a3p8vd14, cynse-a0a3p8w747, cynse-a0a3p8wq40, cynse-a0a3p8wul3, cynse-a0a3p8vqr4, cynse-a0a3p8vmz4 Abstract Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'. Title: Investigation of a new acetogen isolated from an enrichment of the tammar wallaby forestomach Gagen EJ, Wang J, Padmanabha J, Liu J, de Carvalho IP, Webb RI, Al Jassim R, Morrison M, Denman SE, McSweeney CS Ref: BMC Microbiol, 14:314, 2014 : PubMed ESTHER: Gagen_2014_BMC.Microbiol_14_314 PubMedSearch: Gagen 2014 BMC.Microbiol 14 314 PubMedID: 25495654 Gene_locus related to this paper: 9firm-a0a0d0sh39 Abstract BACKGROUND: Forestomach fermentation in Australian marsupials such as wallabies and kangaroos, though analogous to rumen fermentation, results in lower methane emissions. Insights into hydrogenotrophy in these systems could help in devising strategies to reduce ruminal methanogenesis. Reductive acetogenesis may be a significant hydrogen sink in these systems and previous molecular analyses have revealed a novel diversity of putative acetogens in the tammar wallaby forestomach. Title: The adverse effects of phoxim exposure in the midgut of silkworm, Bombyx mori Gu Z, Zhou Y, Xie Y, Li F, Ma L, Sun S, Wu Y, Wang B, Wang J and Li B <2 more author(s)> Gu Z, Zhou Y, Xie Y, Li F, Ma L, Sun S, Wu Y, Wang B, Wang J, Hong F, Shen W, Li B (- 2) Ref: Chemosphere, 96:33, 2014 : PubMed ESTHER: Gu_2014_Chemosphere_96_33 PubMedSearch: Gu 2014 Chemosphere 96 33 PubMedID: 23899924 Abstract The silkworm is an important economic insect. Poisoning of silkworms by organophosphate pesticides causes tremendous loss to the sericulture. In this study, Solexa sequencing technology was performed to profile the gene expression changes in the midgut of silkworms in response to 24h of phoxim exposure and the impact on detoxification, apoptosis and immune defense were addressed. The results showed that 254 genes displayed at least 2.0-fold changes in expression levels, with 148 genes up-regulated and 106 genes down-regulated. Cytochrome P450 played an important role in detoxification. Histopathology examination and transmission electron microscope revealed swollen mitochondria and disappearance of the cristae of mitochondria, which are the important features in insect apoptotic cells. Cytochrome C release from mitochondria into the cytoplasm was confirmed. In addition, the Toll and immune deficiency (IMD) signal pathways were all inhibited using qRT-PCR. Our results could help better understand the impact of phoxim exposure on silkworm. Title: Genome and transcriptome analysis of the fungal pathogen Fusarium oxysporum f. sp. cubense causing banana vascular wilt disease Guo L, Han L, Yang L, Zeng H, Fan D, Zhu Y, Feng Y, Wang G, Peng C and Huang J <9 more author(s)> Guo L, Han L, Yang L, Zeng H, Fan D, Zhu Y, Feng Y, Wang G, Peng C, Jiang X, Zhou D, Ni P, Liang C, Liu L, Wang J, Mao C, Fang X, Peng M, Huang J (- 9) Ref: PLoS ONE, 9:e95543, 2014 : PubMed ESTHER: Guo_2014_PLoS.ONE_9_E95543 PubMedSearch: Guo 2014 PLoS.ONE 9 E95543 PubMedID: 24743270 Gene_locus related to this paper: fusox-w9hvf0, fusox-x0d9n6 Abstract BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced. METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana. Title: Eucommia ulmoides Oliv.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine He X, Wang J, Li M, Hao D, Yang Y, Zhang C, He R, Tao R Ref: J Ethnopharmacol, 151:78, 2014 : PubMed ESTHER: He_2014_J.Ethnopharmacol_151_78 PubMedSearch: He 2014 J.Ethnopharmacol 151 78 PubMedID: 24296089 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. (Family Eucommiaceae), also known as Du-zhong (Chinese: ), Tuchong (in Japanese), is the sole species of the genus Eucommia. The leaf, stem, and bark as well as staminate flower of Eucommia ulmoides have been traditionally used to cure many diseases in China, Japan, Korea, among others. The aim of this review is to comprehensively outline the botanical description, ethnopharmacology, phytochemistry, biological activities, and toxicology of Eucommia ulmoides and to discuss possible trends for further study of Eucommia ulmoides. MATERIALS AND Title: Complete Genome Sequence of the p-Nitrophenol-Degrading Bacterium Pseudomonas putida DLL-E4 Hu X, Wang J, Wang F, Chen Q, Huang Y, Cui Z Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Hu_2014_Genome.Announc_2_e00596 PubMedSearch: Hu 2014 Genome.Announc 2 e00596 PubMedID: 24948765 Gene_locus related to this paper: psepu-q9wwz4, psepu-a0a059uyg1 Abstract The first complete genome sequence of a p-nitrophenol (PNP)-degrading bacterium is reported here. Pseudomonas putida DLL-E4, a Gram-negative bacterium isolated from methyl-parathion-polluted soil, can utilize PNP as the sole carbon and nitrogen source. P. putida DLL-E4 has a 6,484,062 bp circular chromosome that contains 5,894 genes, with a G+C content of 62.46%. Title: Genome and transcriptome of the porcine whipworm Trichuris suis Jex AR, Nejsum P, Schwarz EM, Hu L, Young ND, Hall RS, Korhonen PK, Liao S, Thamsborg S and Gasser RB <7 more author(s)> Jex AR, Nejsum P, Schwarz EM, Hu L, Young ND, Hall RS, Korhonen PK, Liao S, Thamsborg S, Xia J, Xu P, Wang S, Scheerlinck JP, Hofmann A, Sternberg PW, Wang J, Gasser RB (- 7) Ref: Nat Genet, 46:701, 2014 : PubMed ESTHER: Jex_2014_Nat.Genet_46_701 PubMedSearch: Jex 2014 Nat.Genet 46 701 PubMedID: 24929829 Gene_locus related to this paper: 9bila-a0a085nui3, 9bila-a0a085mx66, 9bila-a0a085lsb8, 9bila-a0a085mja7, 9bila-a0a085ly55, 9bila-a0a085nlc5, 9bila-a0a085nb82, 9bila-a0a085n057, 9bila-a0a085mjs6 Abstract Trichuris (whipworm) infects 1 billion people worldwide and causes a disease (trichuriasis) that results in major socioeconomic losses in both humans and pigs. Trichuriasis relates to an inflammation of the large intestine manifested in bloody diarrhea, and chronic disease can cause malnourishment and stunting in children. Paradoxically, Trichuris of pigs has shown substantial promise as a treatment for human autoimmune disorders, including inflammatory bowel disease (IBD) and multiple sclerosis. Here we report whole-genome sequencing at approximately 140-fold coverage of adult male and female T. suis and approximately 80-Mb draft assemblies. We explore stage-, sex- and tissue-specific transcription of mRNAs and small noncoding RNAs. Title: Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors Ji X, Su M, Wang J, Deng G, Deng S, Li Z, Tang C, Li J, Zhao L and Liu H <1 more author(s)> Ji X, Su M, Wang J, Deng G, Deng S, Li Z, Tang C, Li J, Zhao L, Jiang H, Liu H (- 1) Ref: Eur Journal of Medicinal Chemistry, 75C:111, 2014 : PubMed ESTHER: Ji_2014_Eur.J.Med.Chem_75C_111 PubMedSearch: Ji 2014 Eur.J.Med.Chem 75C 111 PubMedID: 24531224 Abstract A series of novel hetero-aromatic moieties substituted alpha-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure-activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004-113.6 muM). Moreover, compounds 6h (IC50 = 0.004 muM) and 6n (IC50 = 0.01 muM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t1/2 = 1.45 h; compound 6n, F% = 16.8%, t1/2 = 3.64 h). Title: Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors Ji X, Xia C, Wang J, Su M, Zhang L, Dong T, Li Z, Wan X, Li J and Liu H <3 more author(s)> Ji X, Xia C, Wang J, Su M, Zhang L, Dong T, Li Z, Wan X, Li J, Zhao L, Gao Z, Jiang H, Liu H (- 3) Ref: Eur Journal of Medicinal Chemistry, 86:242, 2014 : PubMed ESTHER: Ji_2014_Eur.J.Med.Chem_86_242 PubMedSearch: Ji 2014 Eur.J.Med.Chem 86 242 PubMedID: 25164763 Abstract Based on the previous work in our group and the principle of computer-aided drug design, a series of novel beta-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 8l had moderate DPP4 inhibitory activity (IC50 = 0.05 muM) and good oral bioavailability (F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC50 = 0.01 muM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles (F = 22.8%, t1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9. Title: Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for alpha4beta2alpha5 nicotinic acetylcholine receptors Jin Z, Khan P, Shin Y, Wang J, Lin L, Cameron MD, Lindstrom JM, Kenny PJ, Kamenecka TM Ref: Bioorganic & Medicinal Chemistry Lett, 24:674, 2014 : PubMed ESTHER: Jin_2014_Bioorg.Med.Chem.Lett_24_674 PubMedSearch: Jin 2014 Bioorg.Med.Chem.Lett 24 674 PubMedID: 24365158 Abstract The design and synthesis of a series of substituted heteroaromatic alpha4beta2alpha5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2-yl)benzonitrile (5k) and 3,3'-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered. Title: Hyphomonas beringensis sp. nov. and Hyphomonas chukchiensis sp. nov., isolated from surface seawater of the Bering Sea and Chukchi Sea Li C, Lai Q, Li G, Dong C, Wang J, Liao Y, Shao Z Ref: Antonie Van Leeuwenhoek, 106:657, 2014 : PubMed ESTHER: Li_2014_Antonie.Van.Leeuwenhoek_106_657 PubMedSearch: Li 2014 Antonie.Van.Leeuwenhoek 106 657 PubMedID: 25070064 Gene_locus related to this paper: 9rhob-a0a059fvx5, 9rhob-a0a062ve25, 9rhob-a0a059e3y9, 9rhob-a0a062tww8, 9rhob-a0a062u829, 9rhob-a0a059e1b7, 9rhob-a0a059g4l9, 9rhob-a0a059f7b2, 9rhob-a0a069e8d0, 9rhob-a0a059g313, 9rhob-a0a059g3u2, 9rhob-a0a059fuw7, 9rhob-a0a062ui03, 9rhob-a0a059fgt4, 9rhob-a0a059dz53, 9rhob-a0a069e7i5, 9rhob-a0a059fgq3, 9rhob-a0a069e822, 9rhob-a0a062vhu5, 9rhob-a0a062uj80, 9rhob-a0a062udx1, 9rhob-a0a059eck3, 9rhob-a0a062u513, 9rhob-a0a062vh83, 9rhob-a0a062u677, 9rhob-a0a069e9p2, 9rhob-a0a062ui16, 9rhob-a0a059g4x1, 9rhob-a0a062u908, 9rhob-a0a062uqj8, 9rhob-a0a062u917, 9rhob-a0a059fty9, 9rhob-a0a062uq79, 9rhob-a0a059g214, 9rhob-a0a062uez6, 9rhob-a0a062v9r9, 9rhob-a0a059g243, 9rhob-a0a059fbn4, 9rhob-a0a069e4q5, 9rhob-a0a069e8h3, 9rhob-a0a059dyu6, 9rhob-a0a059fva5, 9rhob-a0a059g4g8, 9rhob-a0a059f9m8, 9rhob-a0a062vgs9 Abstract Two Gram-negative, non-spore-forming, oval to pear shaped motile strains, designated 25B14_1(T) and BH-BN04-4(T), isolated from surface seawater from the Bering Sea and Chukchi Sea, respectively, were subjected to polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strains 25B14_1(T) and BH-BN04-4(T) clustered together with Hyphomonas atlanticus 22II1-22F38(T) and Hyphomonas oceanitis DSM 5155(T), respectively, within genus Hyphomonas. Based on whole genome sequence analysis, the calculated DDH and ANIm values between strain 25B14_1(T) and BH-BN04-4(T) are 18.8 and 83.19% respectively. The calculated DDH values of strain 25B14_1(T) and BH-BN04-4(T) with seven type strains ranged from 18.2 to 19.9% and from 18.4 to 40.4%, respectively. The ANIm values of strain 25B14_1(T) and BH-BN04-4(T) with seven type strains ranged from 83.00 to 84.67% and from 83.14 to 90.58%, respectively. Both isolates were found to contain Q-11 as the predominant respiratory quinone. The major fatty acids of strain 25B14_1(T) were identified as C(16:0), C(17:0), C(18:1)omega7c-methyl and Summed Feature 8 (C(18:1)omega6c/omega7c as defined by MIDI), while in the case of strain BH-BN04-4(T) they were identified as C(16:0), C(18:1)omega7c-methyl and Summed Feature 8 (C(18:1)omega6c/omega7c). The G+C contents of 25B14_1(T) and BH-BN04-4(T) were determined to be 58.4 and 61.0 mol%, respectively. The combined phenotypic and genotypic data show that the two isolates each represent novel species of the genus Hyphomonas, for which the names Hyp |
