Author Report for: Liu ZNo contact information in database for Liu Z
Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y and Sang Z <1 more author(s)> Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y, Dong W, Sang Z (- 1) Ref: J Enzyme Inhib Med Chem, 38:2169682, 2023 : PubMed ESTHER: Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682 PubMedSearch: Chen 2023 J.Enzyme.Inhib.Med.Chem 38 2169682 PubMedID: 36688444 Abstract A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The insvitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC(50) values of 1.3 microM and 0.81 microM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1beta and NO. In addition, compound 3f presented significant neuroprotective effect on Abeta(25-35)-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes insvitro and plasma. Furthermore, compound 3f could improve AlCl(3)-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD. Title: Structure-Directed Discovery of Potent Soluble Epoxide Hydrolase Inhibitors for the Treatment of Inflammatory Diseases 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: Simple and novel icariin-loaded pro-glycymicelles as a functional food: physicochemical characteristics, in vitro biological activities, and in vivo experimental hyperlipidemia prevention evaluations Cui Q, Wang C, Zhou L, Wei Y, Liu Z, Wu X Ref: Food Funct, :, 2023 : PubMed ESTHER: Cui_2023_Food.Funct__ PubMedSearch: Cui 2023 Food.Funct PubMedID: 37853783 Abstract A novel functional food for hyperlipidemia named icariin (ICA) pro-glycymicelles (ICA-PGs) using glycyrrhizin as a phytonanomaterial was easily prepared with improved storage, pH, and salt stabilities. ICA-PGs can easily dissolve in water to self-assemble into a clear glycymicelle solution with high ICA encapsulation efficiency. The ICA in ICA-PGs exhibits significantly increased aqueous solubility, faster in vitro release, and higher bioaccessibility than bare ICA. The ICA-PGs exhibited improved in vitro activities including antioxidant, anti-alpha-glucosidase, anti-lipase, and anti-cholesterol esterase activities. The ICA-PG also demonstrated improved antioxidant activity in cells. In vivo evaluation confirmed that the ICA-PG demonstrated a significant protective effect against experimental hyperlipidemia in mice, exhibiting decreasing levels of triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) in the serum, and restoring the hepatic morphology to the normal state. These results indicated that the ICA-PG could improve in vitro/in vivo profiles of ICA, providing a new concept and a promising functional food for hyperlipidemia. Title: In vivo visualization of enantioselective targeting of amyloid and improvement of cognitive function by clickable chiral metallohelices Du Z, Liu C, Liu Z, Song H, Scott P, Du X, Ren J, Qu X Ref: Chem Sci, 14:506, 2023 : PubMed ESTHER: Du_2023_Chem.Sci_14_506 PubMedSearch: Du 2023 Chem.Sci 14 506 PubMedID: 36741518 Abstract The pathogenesis of Alzheimer's disease (AD) is closely related to several contributing factors, especially amyloid-beta (Abeta) aggregation. Bioorthogonal reactions provide a general, facile, and robust route for the localization and derivatization of Abeta-targeted agents. Herein, a pair of chiral alkyne-containing metallohelices (A and deltaA) were demonstrated to enantioselectively target and modulate Abeta aggregation, which has been monitored in triple-transgenic AD model mice and proved to improve cognitive function. Compared with its enantiomer deltaA, A performed better in blocking Abeta fibrillation, relieving Abeta-triggered toxicity, and recovering memory deficits in vivo. Moreover, clickable A could act as a functional module for subsequent visualization and versatile modification of amyloid via bioorthogonal reaction. As a proof-of-concept, thioflavin T, tacrine, and magnetic nanoparticles were conjugated with A to realize Abeta photo-oxygenation, acetylcholinesterase inhibition, and Abeta clearance, respectively. This proof-of-principle work provided new insights into the biolabeling and bioconjugation of multifunctional metallosupramolecules through click reactions for AD therapy. Title: Dissecting the HGT network of carbon metabolic genes in soil-borne microbiota Li L, Liu Y, Xiao Q, Xiao Z, Meng D, Yang Z, Deng W, Yin H, Liu Z Ref: Front Microbiol, 14:1173748, 2023 : PubMed ESTHER: Li_2023_Front.Microbiol_14_1173748 PubMedSearch: Li 2023 Front.Microbiol 14 1173748 PubMedID: 37485539 Abstract The microbiota inhabiting soil plays a significant role in essential life-supporting element cycles. Here, we investigated the occurrence of horizontal gene transfer (HGT) and established the HGT network of carbon metabolic genes in 764 soil-borne microbiota genomes. Our study sheds light on the crucial role of HGT components in microbiological diversification that could have far-reaching implications in understanding how these microbial communities adapt to changing environments, ultimately impacting agricultural practices. In the overall HGT network of carbon metabolic genes in soil-borne microbiota, a total of 6,770 nodes and 3,812 edges are present. Among these nodes, phyla Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes are predominant. Regarding specific classes, Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacteroidia, Actinomycetia, Betaproteobacteria, and Clostridia are dominant. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional assignments of glycosyltransferase (18.5%), glycolysis/gluconeogenesis (8.8%), carbohydrate-related transporter (7.9%), fatty acid biosynthesis (6.5%), benzoate degradation (3.1%) and butanoate metabolism (3.0%) are primarily identified. Glycosyltransferase involved in cell wall biosynthesis, glycosylation, and primary/secondary metabolism (with 363 HGT entries), ranks first overwhelmingly in the list of most frequently identified carbon metabolic HGT enzymes, followed by pimeloyl-ACP methyl ester carboxylesterase, alcohol dehydrogenase, and 3-oxoacyl-ACP reductase. Such HGT events mainly occur in the peripheral functions of the carbon metabolic pathway instead of the core section. The inter-microbe HGT genetic traits in soil-borne microbiota genetic sequences that we recognized, as well as their involvement in the metabolism and regulation processes of carbon organic, suggest a pervasive and substantial effect of HGT on the evolution of microbes. Title: The Conformational Transitions and Dynamics of Burkholderia cepacia Lipase Regulated by Water-Oil Interfaces Liang K, Dong W, Gao J, Liu Z, Zhou R, Shu Z, Duan M Ref: J Chem Inf Model, :, 2023 : PubMed ESTHER: Liang_2023_J.Chem.Inf.Model__ PubMedSearch: Liang 2023 J.Chem.Inf.Model PubMedID: 37307245 Abstract Structural dynamics and conformational transitions are crucial for the activities of enzymes. As one of the most widely used industrial biocatalysts, lipase could be activated by the water-oil interfaces. The interface activations were believed to be dominated by the close-to-open transitions of the lid subdomains. However, the detailed mechanism and the roles of structure transitions are still under debate. In this study, the dynamic structures and conformational transitions of Burkholderia cepacia lipase (LipA) were investigated by combining all-atom molecular dynamics simulations, enhanced sampling simulation, and spectrophotometric assay experiments. The conformational transitions between the lid-open and lid-closed states of LipA in aqueous solution are directly observed by the computational simulation methods. The interactions between the hydrophobic residues on the two lid-subdomains are the driven forces for the LipA closing. Meanwhile, the hydrophobic environment provided by the oil interfaces would separate the interactions between the lid-subdomains and promote the structure opening of LipA. Moreover, our studies demonstrate the opening of the lids structure is insufficient to initiate the interfacial activation, providing explanations for the inability of interfacial activation of many lipases with lid structures. Title: The transcription factor CREB3-2 regulated neutral lipase gene expression in ovary of Nilaparvata lugens Lin X, Zhang H, Gao H, Yuan X, Liu Z Ref: Pestic Biochem Physiol, 196:105632, 2023 : PubMed ESTHER: Lin_2023_Pestic.Biochem.Physiol_196_105632 PubMedSearch: Lin 2023 Pestic.Biochem.Physiol 196 105632 PubMedID: 37945264 Abstract The cyclic AMP-responsive element-binding protein 3 (CREB3) members have unique regulatory roles in cellular lipid metabolism as transcription factors. Two CREB3 proteins in Nilaparvata lugens were identified and analyzed. In ovary, when silencing NlCREB3-2, triacylglycerol (TAG) content dramatically increased but glycerol and free fatty acid (FFA) significantly decreased, which implicated that NlCREB3-2 was involved in the lipase-related TAG metabolism. In N. lugens, five neutral lipases with complete features for TAG hydrolytic activity and high expression in ovary were focused. Among them, the expression levels of three neutral lipase genes were significantly down-regulated by NlCREB3-2 RNAi. The direct regulation of NlCREB3-2 towards the three neutral lipase genes was evidenced by the dual-luciferase reporter assay. After jointly silencing three neutral lipase genes, TAG and glycerol contents displayed similar changes as NlCREB3-2 RNAi. The study proved that NlCREB3-2 participated in TAG metabolism in ovary via the direct activation towards the ovary-specific neutral lipase genes. Title: Transcriptomics and Selection Pressure Analysis Reveals the Influence Mechanism of PLIN1 Protein on the Development of Small Size in Min Pigs Liu Q, Yu L, Zhang Z, Chang Y, Liu Z, Xu C Ref: Int J Mol Sci, 24:, 2023 : PubMed ESTHER: Liu_2023_Int.J.Mol.Sci_24_ PubMedSearch: Liu 2023 Int.J.Mol.Sci 24 PubMedID: 36835359 Abstract Body size is an important biological phenotypic trait that has attracted substantial attention. Small domestic pigs can serve as excellent animal models for biomedicine and also help meet sacrificial culture needs in human societies. Although the mechanisms underlying vertebral development regulating body size variation in domestic pigs during the embryonic period have been well described, few studies have examined the genetic basis of body size variation in post embryonic developmental stages. In this study, seven candidate genes-PLIN1, LIPE, PNPLA1, SCD, FABP5, KRT10 and IVL-significantly associated with body size were identified in Min pigs, on the basis of weighted gene co-expression network analysis (WGCNA), and most of their functions were found to be associated with lipid deposition. Six candidate genes except for IVL were found to have been subjected to purifying selection. PLIN1 had the lowest omega value (0.139) and showed heterogeneous selective pressure among domestic pig lineages with different body sizes (p < 0.05). These results suggested that PLIN1 is an important genetic factor regulating lipid deposition and consequently affecting body size variation in pigs. The culture of whole pig sacrifice in Manchu during the Qing Dynasty in China might have contributed to the strong artificial domestication and selection of Hebao pigs. Title: IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL Liu CZ, Liu XB, Sun J, Yu CQ, Yao JC, Liu Z, Hao JC Ref: BMC Cancer, 23:626, 2023 : PubMed ESTHER: Liu_2023_BMC.Cancer_23_626 PubMedSearch: Liu 2023 BMC.Cancer 23 626 PubMedID: 37403022 Gene_locus related to this paper: human-MGLL Abstract BACKGROUND: CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14(+)CXCR2(+) monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function. METHODS: Flow cytometry was used to analyze the proportion of the CD14(+)CXCR2(+) subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14(+)CXCR2(+) monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression. RESULTS: A decrease in the proportion of the CD14(+)CXCR2(+) monocyte subset was observed in HCC patients compared with healthy controls. CXCR2(+) monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2(+) monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression. CONCLUSIONS: Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor. Title: Design of carboxymethylcellulose-conjugated polymeric prodrug micelles for enhanced in vivo performance of docetaxel Liu Z, Liu Y, Liu H, Lv R, Liu B, Zhao L, Yin T, Zhang Y, He H and Gao S <3 more author(s)> Liu Z, Liu Y, Liu H, Lv R, Liu B, Zhao L, Yin T, Zhang Y, He H, Gou J, Tang X, Yang L, Gao S (- 3) Ref: Int J Biol Macromol, :127690, 2023 : PubMed ESTHER: Liu_2023_Int.J.Biol.Macromol__127690 PubMedSearch: Liu 2023 Int.J.Biol.Macromol 127690 PubMedID: 37898254 Abstract Docetaxel (DTX) has become one of the most important cytotoxic drugs to treat cancer; nevertheless, its poor hydrophilicity and non-specific distribution of DTX lead to detrimental side effects. In this article, we devised carboxymethylcellulose (CMC)-conjugated polymeric prodrug micelles (mPEG-CMC-DTX PMs) for DTX delivery. The ester-bonded polymeric prodrug, mPEG-CMC-DTX, was synthesized and exhibited the capacity for self-assembling into polymeric micelles. The CMC is profusely substituted and acetylated to promote the coupling rate of DTX. Covalent binding of DTX and CMC through an ester bond can be hydrolyzed to dissociate the bond under the action of esterase in the tumor. The mPEG-CMC-DTX PMs displayed promoted drug loading (>50 %, wt), commendable stability, and sustained release behavior in vitro. The gradual release of the prodrug amplified the selectivity of cytotoxicity between normal cells and tumor cells, mitigating the systemic toxicity of mPEG-CMC-DTX PMs and enabling dose intensification. Notably, mPEG-CMC-DTX PMs demonstrated a superior antitumor efficacy and low systemic toxicity due to the elevated tolerance dosage (even at 40 mg/kg DTX). In summation, mPEG-CMC-DTX PMs harmonized the antitumor efficacy and toxicity of DTX. In essence, innovative perspectives for the rational design of CMC-conjugated polymeric prodrug micelles for the delivery of potently toxic drugs were proffered. Title: Discovery of quinazolin-4(3H)-one derivatives as novel AChE inhibitors with anti-inflammatory activities Lv L, Maimaitiming M, Huang Y, Yang J, Chen S, Sun Y, Zhang X, Li X, Xue C and Liu Z <2 more author(s)> Lv L, Maimaitiming M, Huang Y, Yang J, Chen S, Sun Y, Zhang X, Li X, Xue C, Wang P, Wang CY, Liu Z (- 2) Ref: Eur Journal of Medicinal Chemistry, 254:115346, 2023 : PubMed ESTHER: Lv_2023_Eur.J.Med.Chem_254_115346 PubMedSearch: Lv 2023 Eur.J.Med.Chem 254 115346 PubMedID: 37043994 Abstract A series of quinazolin-4(3H)-one derivatives was designed through scaffold-hopping strategy and synthesized as novel multifunctional anti-AD agents demonstrating both cholinesterase inhibition and anti-inflammatory activities. Their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were evaluated, and the enzyme kinetics study as well as detailed binding mode via molecular docking were performed for selected compounds. MR2938 (B12) displayed promising AChE inhibitory activity with an IC(50) value of 5.04 microM and suppressed NO production obviously (IC(50) = 3.29 microM). Besides, it was able to decrease the mRNA levels of pro-inflammatory cytokines IL-1beta, TNF-alpha, IL-6 and CCL2 at 1.25 microM. Further mechanism study suggested that MR2938 suppressed the neuroinflammation through blocking MAPK/JNK and NF-kappaB signaling pathways. All these results indicate that MR2938 is a good starting point to develop multifunctional anti-AD lead compounds. Title: Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN Ma Q, Liu Z, Wang T, Zhao P, Liu M, Wang Y, Zhao W, Yuan Y, Li S Ref: Int J Mol Sci, 24:, 2023 : PubMed ESTHER: Ma_2023_Int.J.Mol.Sci_24_ PubMedSearch: Ma 2023 Int.J.Mol.Sci 24 PubMedID: 38003694 Abstract Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes. Title: Alzheimer's Disease; Mechanism, Mutations, and Applications of Nano-Medicine Maisam M, Khan MT, Lodhi MS, Mou K, Liu Z, Wei D Ref: Front Biosci (Landmark Ed), 28:258, 2023 : PubMed ESTHER: Maisam_2023_Front.Biosci.(Landmark.Ed)_28_258 PubMedSearch: Maisam 2023 Front.Biosci.(Landmark.Ed) 28 258 PubMedID: 37919079 Abstract BACKGROUND: In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most widely accepted concept, the production and aggregation of beta-amyloid (Abeta) peptides play a critical role in AD. As a result, therapeutic intervention with these processes is the focus of intense research. The Abeta peptide is cleaved by the alpha-secretase, beta-secretase, and gamma-secretase enzymes in a region near the pathogenic amyloid precursor protein (APP) and mutations occurring site. METHODS: In the current review, a complete picture of the risk factors behind AD has been investigated. Mutations involved in AD progression have also been screened in various studies. RESULTS: Most of the mutations in the amyloid precursor protein (APP) can lead to the accumulation of APP oligomers in the brain, leading to AD. Several point mutations in APP can cause familial AD (FAD), including the Swedish mutation (K>M670/671N>L) and the A673>V mutation. The pathogenic A673>V mutation and Swedish mutation (M670>K/N671>L) are present in the same region of amyloid precursor protein (APP). However, the A673>T mutation has been shown to confer protection against AD. CONCLUSION: More investigations are needed from geographically distinct regions on mutations associated with AD development and applications of nanomedicines for better management of the disease burden in the future. Nanotechnology-produced metal nanoparticles (NPs) have gotten much attention because of their wide range of uses in the medicinal and agricultural industries. Nanomedicine containing potential phytochemicals, including GX-50 and curcumin conjugated with NPs, maybe a potential candidate for treating AD. Title: Monoacylglycerol lipase regulates macrophage polarization and cancer progression in uveal melanoma and pan-cancer Tan Y, Pan J, Deng Z, Chen T, Xia J, Liu Z, Zou C, Qin B Ref: Front Immunol, 14:1161960, 2023 : PubMed ESTHER: Tan_2023_Front.Immunol_14_1161960 PubMedSearch: Tan 2023 Front.Immunol 14 1161960 PubMedID: 37033945 Abstract BACKGROUND: Although lipid metabolism has been proven to play a key role in the development of cancer, its significance in uveal melanoma (UM) has not yet been elucidated in the available literature. METHODS: To identify the expression patterns of lipid metabolism in 80 UM patients from the TCGA database, 47 genes involved in lipid metabolism were analyzed. Consensus clustering revealed two distinct molecular groups. ESTIMATE, TIMER, and ssGSEA analyses were done to identify the differences between the two subgroups in tumor microenvironment (TME) and immune state. Using Cox regression and Lasso regression analysis, a risk model based on differentially expressed genes (DEGs) was developed. To validate the expression of monoacylglycerol lipase (MGLL) and immune infiltration in diverse malignancies, a pan-cancer cohort from the UCSC database was utilized. Next, a single-cell sequencing analysis on UM patients from the GEO data was used to characterize the lipid metabolism in TME and the role of MGLL in UM. Finally, in vitro investigations were utilized to study the involvement of MGLL in UM. RESULTS: Two molecular subgroups of UM patients have considerably varied survival rates. The majority of DEGs between the two subgroups were associated with immune-related pathways. Low immune scores, high tumor purity, a low number of immune infiltrating cells, and a comparatively low immunological state were associated with a more favorable prognosis. An examination of GO and KEGG data demonstrated that the risk model based on genes involved with lipid metabolism can accurately predict survival in patients with UM. It has been demonstrated that MGLL, a crucial gene in this paradigm, promotes the proliferation, invasion, and migration of UM cells. In addition, we discovered that MGLL is strongly expressed in macrophages, specifically M2 macrophages, which may play a function in the M2 polarization of macrophages and M2 macrophage activation in cancer cells. CONCLUSION: This study demonstrates that the risk model based on lipid metabolism may be useful for predicting the prognosis of patients with UM. By promoting macrophage M2 polarization, MGLL contributes to the evolution of malignancy in UM, suggesting that it may be a therapeutic target for UM. 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: Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors Yu D, Yang C, Liu Y, Lu T, Li L, Chen G, Liu Z, Li Y Ref: Sci Rep, 13:4877, 2023 : PubMed ESTHER: Yu_2023_Sci.Rep_13_4877 PubMedSearch: Yu 2023 Sci.Rep 13 4877 PubMedID: 36966194 Abstract Alzheimer's disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC(50) values of 3.94 microM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor. Title: Improving efficiency and reducing enzyme inactivation during lipase-mediated epoxidation of alpha-pinene in a double-phase reaction system Yu L, Zou C, Li Q, Liu Z, Liu Y, Tang A Ref: Bioprocess Biosyst Eng, :, 2023 : PubMed ESTHER: Yu_2023_Bioprocess.Biosyst.Eng__ PubMedSearch: Yu 2023 Bioprocess.Biosyst.Eng PubMedID: 37470869 Abstract Chemoenzymatic epoxidation of olefin mediated by lipase is a green and environmentally friendly alternative process. However, the mass transfer barrier and lipase deactivation caused by the traditional organic-water biphasic reaction system have always been the focus of researchers' attention. To overcome these issues, we investigated the effects of reaction temperature and two important substrates (H(2)O(2) and acyl donor) on the epoxidation reaction and interfacial mass transfer. As a result, we determined the optimal reaction conditions: a temperature of 30 degreesC, 30 wt-% H(2)O(2) as the oxygen source, and 1 M lauric acid as the oxygen carrier. Additionally, by simulating the conditions of shaking flask reactions, we designed a batch reactor and added a metal mesh to effectively block the direct contact between high-concentration hydrogen peroxide and the enzyme. Under these optimal conditions, the epoxidation reaction was carried out for 5 h, and the product yield reached a maximum of 93.2%. Furthermore, after seven repetitive experiments, the lipase still maintained a relative activity of 51.2%. Title: A High-Density Raman Photometry for Tracking and Quantifying of AchE Activity in The Brain of Freely Moving Animals with Network Zhang Z, Liu Z, Wu P, Guo X, Luo X, Yang Y, Chen J, Tian Y Ref: Adv Sci (Weinh), :e2301004, 2023 : PubMed ESTHER: Zhang_2023_Adv.Sci.(Weinh)__e2301004 PubMedSearch: Zhang 2023 Adv.Sci.(Weinh) e2301004 PubMedID: 37635166 Abstract A high-density Raman photometry based on a dual-recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free-moving animals with network. A series of 5-ethynyl-1,2,3,3-tetramethyl-based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2-(4-((4-(dimethylamino)benzoyl)oxy)styryl)-5-ethynyl-1,3,3-trimethyl-3H-indol-1-ium (ET-5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high-density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO. Title: Smartphone-based colorimetric sensor array using gold nanoparticles for rapid distinguishment of multiple pesticides in real samples Zhao T, Liang X, Guo X, Yang X, Guo J, Zhou X, Huang X, Zhang W, Wang Y and Zhou H <2 more author(s)> Zhao T, Liang X, Guo X, Yang X, Guo J, Zhou X, Huang X, Zhang W, Wang Y, Liu Z, Jiang Z, Zhou H (- 2) Ref: Food Chem, 404:134768, 2023 : PubMed ESTHER: Zhao_2023_Food.Chem_404_134768 PubMedSearch: Zhao 2023 Food.Chem 404 134768 PubMedID: 36444090 Abstract A simple, sensitive method for pesticide distinguishment based on a colorimetric sensor array using diverse gold nanoparticles (AuNPs) at room temperature is presented in this study. Acetylcholinesterase (AChE) hydrolysis ability was influenced by different pesticides and produced different concentrations of thiocholine by hydrolyzing acetylthiocholine iodide (ATCh). Thiocholine could be easily linked to the AuNPs through an Aus-sS covalent bond, and AuNPs underwent aggregation, resulting in a visible color change due to alteration of surface plasmon resonance properties. Based on these results, we successfully distinguished eight pesticides (glyphosate, thiram, imidacloprid, tribenuron methyl, nicosulfuron, thifensulfuron methyl, dichlorprop, and fenoprop) utilizing five different AuNPs by colorimetric assay. The limit of detection (LOD) of this visual method for all pesticides was less than 1.5x 10(-7) M, which was more sensitive than the U.S. Environmental Protection Agency regulations specify (1.18s-s3.91x10(-6) M). This method was further improved by combining a portable smartphone device with a color picking application using (color name AR) and RGB (red, green, blue) values. The method was successfully applied to pesticide residue distinguishment in real samples by linear discriminant analysis (LDA). Title: Design, synthesis and biological evaluation of salicylanilides as novel allosteric inhibitors of human pancreatic lipase Zhao Y, Zhang M, Hou X, Han J, Qin X, Yang Y, Song Y, Liu Z, Zhang Y and Ge G <6 more author(s)> Zhao Y, Zhang M, Hou X, Han J, Qin X, Yang Y, Song Y, Liu Z, Zhang Y, Xu Z, Jia Q, Li Y, Chen K, Li B, Zhu W, Ge G (- 6) Ref: Bioorganic & Medicinal Chemistry, 91:117413, 2023 : PubMed ESTHER: Zhao_2023_Bioorg.Med.Chem_91_117413 PubMedSearch: Zhao 2023 Bioorg.Med.Chem 91 117413 PubMedID: 37490786 Abstract Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC(50) values of 1.86 microM and 1.63 microM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the k(i) value of 1.67 microM and 1.70 microM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs. Title: Neuroligin-1 plays an important role in methamphetamine-induced hippocampal synaptic plasticity Cao C, Wang L, Zhang J, Liu Z, Li M, Xie S, Chen G, Xu X Ref: Toxicol Lett, 361:1, 2022 : PubMed ESTHER: Cao_2022_Toxicol.Lett_361_1 PubMedSearch: Cao 2022 Toxicol.Lett 361 1 PubMedID: 35331841 Abstract The neurotoxic effects of methamphetamine (METH) include not only neuronal apoptosis and autophagy, but also lead to substance use disorder and have become increasingly prominent. Studies suggest that synaptic plasticity may be the structural basis of METH-induced neurological impairment. Neuroligins are postsynaptic adhesion molecules involved in the regulation of synaptic organization and function. Animal studies have shown that neuroligin (NLG)- 1 is involved in memory formation; however, its role in METH-induced neurotoxicity is not clear. In the present study, we used 1 mM METH in vitro; mice in the acute and subacute exposure groups received intraperitoneal injections of 30 mg/kg METH (1 injection) or 15 mg/kg METH (8 separate injections at 12-h intervals). We found that the expression of NLG-1, Synapsin-1, and postsynaptic density-95 were increased after METH exposure. We further observed that METH-induced inhibition of long-term potentiation and spatial memory loss could be alleviated when mice were pretreated with NLG-1 small interfering RNA. Therefore, our study provides evidence that NLG-1 is involved in METH-induced hippocampal synaptic plasticity and may be a potential target for the treatment of METH-induced neurotoxicity. Title: Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain Du F, Cao R, Chen L, Sun J, Shi Y, Fu Y, Hammock BD, Zheng Z, Liu Z, Chen G Ref: Acta Pharm Sin B, 12:1377, 2022 : PubMed ESTHER: Du_2022_Acta.Pharm.Sin.B_12_1377 PubMedSearch: Du 2022 Acta.Pharm.Sin.B 12 1377 PubMedID: 35530144 Inhibitor(s) related to this paper: EC5026 Abstract Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (+/-)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain. Title: N-Benzyl Benzamide Derivatives as Selective Sub-Nanomolar Butyrylcholinesterase Inhibitors for Possible Treatment in Advanced Alzheimer's Disease Du C, Wang L, Guan Q, Yang H, Chen T, Liu Y, Li Q, Lyu W, Lu X and Sun H <6 more author(s)> Du C, Wang L, Guan Q, Yang H, Chen T, Liu Y, Li Q, Lyu W, Lu X, Chen Y, Liu H, Feng F, Liu W, Liu Z, Li W, Sun H (- 6) Ref: Journal of Medicinal Chemistry, :, 2022 : PubMed ESTHER: Du_2022_J.Med.Chem__ PubMedSearch: Du 2022 J.Med.Chem PubMedID: 35969197 Inhibitor(s) related to this paper: S11-1014 Abstract Herein, we report a series of selective sub-nanomolar inhibitors against butyrylcholinesterase (BChE). These compounds, bearing a novel N-benzyl benzamide scaffold, inhibited BChE with IC(50) from picomolar to nanomolar. The inhibitory activity was confirmed by the surface plasmon resonance assay, showing a sub-nanomolar K(D) value, which revealed that the compounds exert the inhibitory effect through directly binding to BChE. Several compounds showed neuroprotective effects verified by the oxidative damage model. Furthermore, the safety of S11-1014 and S11-1033 was demonstrated by the in vivo acute toxicity test. In the behavior study, 0.5 mg/kg S11-1014 or S11-1033 exhibited a marked therapeutic effect, which was almost equal to the treatment with 1 mg/kg rivastigmine, against the cognitive impairment induced by Abeta(1-42). The pharmacokinetics studies characterized the metabolic stability of S11-1014. Thus, N-benzyl benzamide inhibitors are promising compounds with drug-like properties for improving cognitive dysfunction, providing a potential strategy for the treatment of Alzheimer's disease. Title: An efficient strategy based on two-stage chromatography and in vitro evaluation for rapid screening and isolation of acetylcholinesterase inhibitors from Scutellaria baicalensis Georgi Hou W, Liu C, Li S, Zhang Y, Jin Y, Li X, Liu Z, Niu H, Xia J Ref: J Sep Sci, :, 2022 : PubMed ESTHER: Hou_2022_J.Sep.Sci__ PubMedSearch: Hou 2022 J.Sep.Sci PubMedID: 34990521 Inhibitor(s) related to this paper: Oroxylin-A Abstract The extraction of Scutellaria baicalensis Georgi was investigated using the response surface methodology-genetic algorithm mathematical regression model, and the extraction variables were optimized to maximize the flavonoid yield. Furthermore, a simple and efficient ultrafiltration-liquid chromatography-mass spectrometry and molecular docking methods was developed for the rapid screening and identification of acetylcholinesterase inhibitors present in Scutellaria baicalensis Georgi. Subsequently, four major chemical constituents, namely baicalein, norwogonin, wogonin, and oroxylin A, were identified as potent acetylcholinesterase inhibitors. This novel approach, involving the use of ultrafiltration-liquid chromatography-mass spectrometry and molecular docking methods combined with stepwise flow rate counter-current chromatography and semi-preparative high-performance liquid chromatography, could potentially provide a powerful tool for the screening and extraction of acetylcholinesterase inhibitors from complex matrices and be a useful platform for the production of bioactive and nutraceutical ingredients. This article is protected by copyright. All rights reserved. Title: Structure-guided preparation of functional oil rich in 1,3-diacylglycerols and linoleic acid from Camellia oil by combi-lipase Huang C, Lin Z, Zhang Y, Liu Z, Tang X, Li C, Lin L, Huang W, Ye Y Ref: J Sci Food Agric, :, 2022 : PubMed ESTHER: Huang_2022_J.Sci.Food.Agric__ PubMedSearch: Huang 2022 J.Sci.Food.Agric PubMedID: 35810339 Abstract BACKGROUND: The diacylglycerols (DAG) enriched oil has been attracting attention on nutritional benefits and biological functions, but its various free fatty acids (FFA) composition and unclear relationship between substrate and yield make it difficult to be identified and qualified to produce. In this research, the linoleic acid-enriched diacylglycerols (LA-DAG) was synthesized and enriched from Camellia oil by the esterification process using the combi-lipase Lipozyme TL IM/RM IM systems. RESULTS: The relationship between the FFA compositions and the DAG species productivity was revealed. Results showed that heterogeneous FFA with a major constituent (more than 50%) exhibited higher DAG productivity and inhibited TAG productivity than homogeneous constituents. The joint characterization by HPLC-ELSD, GC-MS and UPLC-HESI-MS/MS identified that DAG components contained dilinoleic acid acyl glyceride, linoleyl-oleyl glyceride, and dioleic acid acyl glyceride in esterification products. Under the optimum conditions, 60.4% 1,3-DAG and 61.3% LA-DAG in the crude product at 1 h reaction were obtained, and further purified to 81.7% LA-DAG and 94.7% DAG by the silica column chromatography. CONCLUSION: This research provides a guideline for identification of DAG species, and a structure-guided preparing method of the DAG enriched oils by the cost-effective combi-lipase. This article is protected by copyright. All rights reserved. Title: [Characterization of Humicola insolens cutinase-tachystatin A2 fusion protein and its application in treatment of recycled paper stickies] Li G, Liu Z, Zhang Y, Wu J Ref: Sheng Wu Gong Cheng Xue Bao, 38:207, 2022 : PubMed ESTHER: Li_2022_Sheng.Wu.Gong.Cheng.Xue.Bao_38_207 PubMedSearch: Li 2022 Sheng.Wu.Gong.Cheng.Xue.Bao 38 207 PubMedID: 35142131 Abstract With the decrease of forest timber resources, the recycling of waste paper has received increasing attention. However, the stickies produced in the process of waste paper recycling may negatively affect the production of recycled paper. The biological decomposition of stickies, which has the advantages of high efficiency, high specificity and pollution-free, is achieved mainly through the enzymatic cleavage of the ester bond in the stickies components to prevent flocculation. Cutinase is a serine esterase that can degrade some components of the stickies. Previous research indicated that the anchor peptide tachystatin A2 (TA2) is able to bind polyurethane. In this study, the cutinase HiC derived from Humicola insolens was used to construct a fusion protein HiC-TA2 by megaprimer PCR of the whole plasmid (MEGAWHOP). The enzymatic properties and the degradation efficiency of the fusion protein on poly(ethyl acrylate) (PEA), a model substrate of stickies component, were determined. The results showed that the degradation efficiency, the size decrease of PEA particle, and the amount of ethanol produced by HiC-TA2 were 1.5 times, 6.8 times, and 1.4 times of that by HiC, respectively. These results demonstrated that TA2 improved the degradation efficiency of HiC on PEA. This study provides a useful reference for biological decomposition of stickies produced in the process of recycled paper production. Title: Multiple acetylcholinesterases in Pardosa pseudoannulata brain worked collaboratively to provide protection from organophosphorus insecticides Lin X, Zhang Y, Yang B, Zhang L, Chen Y, Liu Z Ref: Ecotoxicology & Environmental Safety, 248:114301, 2022 : PubMed ESTHER: Lin_2022_Ecotoxicol.Environ.Saf_248_114301 PubMedSearch: Lin 2022 Ecotoxicol.Environ.Saf 248 114301 PubMedID: 36410143 Gene_locus related to this paper: 9arac-KU501290, 9arac-KU501289, 9arac-KU501288, 9arac-KU501287, 9arac-v5qqc6, 9arac-v5qqr1 Abstract Acetylcholinesterase (AChE) is an essential neurotransmitter hydrolase in nervous systems of animals and its number varies among species. So far, five AChEs have been identified in the natural enemy Pardosa pseudoannulata. Here we found that Ppace1, Ppace2 and Ppace5 were highly expressed in the spider brain, among which the mRNA level of Ppace5, but not Ppace1 and Ppace2, could be up-regulated by organophosphorus insecticides at their sublethal concentrations. In spider brain, the treatment by organophosphorus insecticides at the sublethal concentrations could increase total AChE activity, although high concentrations inhibited the activity. The activity that increased from the sublethal concentration pretreatment could compensate for the activity inhibition due to subsequent application of organophosphorus insecticides at lethal concentrations, and consequently reduce the mortality of spiders. PpAChE1 and PpAChE2 were highly sensitive to organophosphorus insecticides, and their activities would be strongly inhibited by the insecticides. In contrast, PpAChE5 displayed relative insensitivity towards organophosphorus insecticides, but with the highest catalytic efficiency for ACh. That meant the up-regulation of Ppace5 under insecticide exposure was important for maintaining AChE activity in spider brain, when PpAChE1 and PpAChE2 were inhibited by organophosphorus insecticides. The study demonstrated that multiple AChEs in the spider brain worked collaboratively, with part members for maintaining AChE activity and other members responding to organophosphorus inhibition, to provide protection from organophosphorus insecticides. In fields, high concentration insecticides are often applied when ineffective controls of insect pests occur due to relative-low concentration of insecticides in last round application. This application pattern of organophosphorus insecticides provides more chances for P. pseudoannulata to survive and controlling insect pests as a natural enemy. Title: Light-Addressable Paper-Based Photoelectrochemical Analytical Device with Tunable Detection Throughput for On-Site Biosensing Liu M, Yang J, Wang J, Liu Z, Hu C Ref: Analytical Chemistry, 94:583, 2022 : PubMed ESTHER: Liu_2022_Anal.Chem_94_583 PubMedSearch: Liu 2022 Anal.Chem 94 583 PubMedID: 34978797 Abstract Development of biosensing systems resembling optical 96-well plates using portable single-channel electrochemical analyzers is usually a great challenge. Herein, a light-addressable paper-based photoelectrochemical (PEC) analytical device suitable for on-site high-throughput biosensing is reported. This device consists of a solar cell-type single-channel PEC system with plenty of separated detection zones. Each zone contains a silver nanowires/fullerene-Congo red (AgNWs/C(60)-CR) disc working electrode and a AgNWs ring reference/counter electrode, which can be massively produced by a simple filtration and laser cutting method. Taking advantage of the sensitive photocurrent response of thiocholine (TCl) on AgNWs/C(60)-CR, an acetylcholinesterase (AChE)-based PEC biosensing system with tunable detection throughput for the on-site screening of ultratrace organophosphorus pesticides (OPs) was established. Title: Discovery of novel 3-butyl-6-benzyloxyphthalide Mannich base derivatives as multifunctional agents against Alzheimer's disease Liu Z, Shi Y, Zhang X, Yu G, Li J, Cong S, Deng Y Ref: Bioorganic & Medicinal Chemistry, 58:116660, 2022 : PubMed ESTHER: Liu_2022_Bioorg.Med.Chem_58_116660 PubMedSearch: Liu 2022 Bioorg.Med.Chem 58 116660 PubMedID: 35183029 Inhibitor(s) related to this paper: 3-butyl-6-benzyloxyphthalide-Mannich-base-7d Abstract Based on the multitarget-directed ligands strategy, a series of 3-butyl-6-benzyloxyphthalide Mannich base derivatives were designed, synthesized and identified for Alzheimer's disease (AD). Biological activity studies demonstrated that the designed hybrids showed multitarget activities toward AD. Among them, compound 7d was the most potent agent with excellent inhibitory activities on EeAChE (IC(50) = 0.087 microM), HuAChE (IC(50) = 0.041 microM) and MAO-B (IC(50) = 0.30 microM). Furthermore, molecular docking studies were conducted to investigate the interaction mode with enzymes. Besides, 7d also possessed good effects of Cu(2+) chelation, ameliorate oxidative stress, and anti-neuroinflammation, desirable BBB permeability and eligible drug-like properties. Altogether, the multifunctional profiles of 7d prove that it deserves further investigation as a novel drug candidate for AD treatment. Title: Cucurbitacin B exerts neuroprotection in a murine Alzheimer's disease model by modulating oxidative stress, inflammation, and neurotransmitter levels Liu Z, Kumar M, Kabra A Ref: Front Biosci (Landmark Ed), 27:71, 2022 : PubMed ESTHER: Liu_2022_Front.Biosci.(Landmark.Ed)_27_71 PubMedSearch: Liu 2022 Front.Biosci.(Landmark.Ed) 27 71 PubMedID: 35227014 Abstract BACKGROUND: Alzheimer's disease (AD) type dementia encompasses diverse cognitive deficits marked by free radicals and pro-inflammatory cytokines mediated progressive neurodegeneration and vascular damage including the blood-brain barrier. Subsequently, an imbalance in neurotransmitters, excitotoxicity, and synaptic loss provide impetus to AD pathogenesis and perpetuate brain dysfunctions. Cucurbitacin possesses several biological properties and has shown potential in cancer, diabetes, and brain disorders. In this study, neuroprotective effects of cucurbitacin B (CuB) were investigated using the intracerebroventricular streptozotocin (STZ-ICV) AD prototype. METHODS: Wistar rats (adult males) were injected STZ-ICV (3 mg/kg) bilaterally on day(s) 1 and 3. Rats were treated with CuB (25, 50 mg/kg, i.p.) or donepezil (1 mg/kg, i.p.) for 28 days daily starting from day 1. Behavioral tests viz. locomotor activity, motor coordination, and memory functions were conducted at different time intervals. After behavioral tests, biochemical markers of oxidative mutilation, inflammatory cell demise, and neurotransmitters were assessed in the whole brain. RESULTS: CuB attenuated STZ-ICV-induced decrease in spatial memory in novel object recognition task and long-term memory in passive avoidance test. CuB diminished protein carbonyls, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, and enhanced antioxidants in the brain of rats inoculated with STZ-ICV. A decline in inflammatory and cell death biomarkers was observed in rats treated with CuB and STZ-ICV. In neurotransmitter analysis, a decrease in acetylcholinesterase activity and glutamate levels indicated an increase in cholinergic and attenuation of excitatory transmission in the brain. GABA (gamma-aminobutyric acid) levels were enhanced by CuB treatment in the STZ-ICV rat model. Histomorphometry analysis disclosed that CuB treatment caused an increase in viable neuron density in the cortex and hippocampus of rats against STZ-ICV neurotoxicity. CONCLUSIONS: It can be inferred that CuB can afford a decline in AD symptoms. CuB protects neurons against STZ-ICV toxicity that improved memory functions in rats. Title: Enhancement of PET biodegradation by anchor peptide-cutinase fusion protein Liu Z, Zhang Y, Wu J Ref: Enzyme Microb Technol, 156:110004, 2022 : PubMed ESTHER: Liu_2022_Enzyme.Microb.Technol_156_110004 PubMedSearch: Liu 2022 Enzyme.Microb.Technol 156 110004 PubMedID: 35217214 Gene_locus related to this paper: thefu-q6a0i3 Abstract With the increasing production of polyethylene terephthalate (PET) plastic products, the problem of PET waste has become a serious threat to ecosystem. PET enzymatic biodegradation, due to its environmental friendliness and sustainability, has gradually attracted attention. As a multifunctional hydrolase, cutinase (EC 3.1.1.74) can not only degrade fatty acid esters, soluble synthetic esters, and emulsified triglycerides, but also exhibit potential for PET degradation. In order to enhance the PET degradation activity of cutinase, we functionally screened several PET binding domains, e.g. carbohydrate binding module, anchor peptide, and hydrophobin, that promote the absorption of enzyme to PET substrate, selected Dermaseptin SI (DSI) and fused it onto the N-terminus of Thermobifida fusca cutinase mutant D204C/E253C (Tfuc2), and finally achieved the PET degradation rate up to 57.9% at 70 degreesC for 96 h, which was 22.7-fold of that of Tfuc2 itself. These results indicate that the fusion of PET binding domain is a promising strategy to enhance PET enzymatic degradation. Title: Enhanced biodegradation activity towards poly(ethyl acrylate) and poly(vinyl acetate) by anchor peptide assistant targeting Liu Z, Li G, Zhang F, Wu J Ref: J Biotechnol, :, 2022 : PubMed ESTHER: Liu_2022_J.Biotechnol__ PubMedSearch: Liu 2022 J.Biotechnol PubMedID: 35292345 Abstract The paper industry is one of the most important basic raw material pillar industries. With the decrease of forest wood resources, the recycling of wastepaper has drawn increasingly attention. However, the stickies generated in the process of wastepaper recycling will flocculate and deposite in the pulp, resulting in production accidents and inferior product quality. The biological enzymatic method, with the advantages of high efficiency, specificity, and pollution-free, can prevent the flocculation of the stickies by enzymatically hydrolyzing the ester bond of the stickies components. Previous studies have demonstrated that cutinase (EC 3.1.1.74) had the ability to degrade polyester components of stickies. Meanwhile, relevant studies have shown that anchor peptides possessed the ability to bind polyester. Herein, the cutinase from Humicola insolens (HiC) was fused with Escherichia coli anchor peptide OMP25, the enzymatic properties of the fusion protein HiC-OMP25 and its degradation efficiency of the stickies model substrate, poly(ethyl acrylate) (PEA) and poly(vinyl acetate) (PVAc), as well as stickies sediment were determined. All of the results demonstrated that OMP25 efficiently enhanced the degradation ability of HiC. Title: The juvenile hormone epoxide hydrolase homolog in Penaeus vannamei plays immune-related functions Liu Z, Huang Z, Zheng X, Zheng Z, Yao D, Zhang Y, Aweya JJ Ref: Dev Comp Immunol, 132:104410, 2022 : PubMed ESTHER: Liu_2022_Dev.Comp.Immunol_132_104410 PubMedSearch: Liu 2022 Dev.Comp.Immunol 132 104410 PubMedID: 35398160 Gene_locus related to this paper: penva-a0a3r7m6s0 Abstract Juvenile hormone epoxide hydrolase (JHEH) participates in the degradation of juvenile hormone and also involved in the development and molting process in insects. Here, the JHEH homolog in Pennaus vannamei was cloned and found to consist of a full-length cDNA of 2543 bp and an open reading frame (ORF) of 1386 bp. Transcripts of PvJHEH1 were expressed in most tissues of healthy shrimp with the highest found in the hepatopancreas and lowest in hemocytes. Both Gram-negative (Vibrio parahaemolyticus) and Gram-positive (Streptococcus iniae) bacteria induced PvJHEH1 expression in shrimp hemocytes and hepatopancreas, suggesting the involvement of PvJHEH1 in P. vannamei immune responses. Moreover, the mRNA levels of ecdysone inducible nuclear transcription factor PvE75 and crustacean hyperglycemic hormone (PvCHH), two endocrine-related genes with roles in shrimp innate immune response, decreased significantly in shrimp hemocytes after PvJHEH1 knockdown. Shrimp survival was also affected after PvJHEH1 knockdown followed by V. parahaemolyticus challenge, indicating that JHEH1 plays an essential role in shrimp survival during bacterial infection. Title: Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress Liu X, Viswanadhapalli S, Kumar S, Lee TK, Moore A, Ma S, Chen L, Hsieh M, Li M and Raj GV <19 more author(s)> Liu X, Viswanadhapalli S, Kumar S, Lee TK, Moore A, Ma S, Chen L, Hsieh M, Li M, Sareddy GR, Parra K, Blatt EB, Reese TC, Zhao Y, Chang A, Yan H, Xu Z, Pratap UP, Liu Z, Roggero CM, Tan Z, Weintraub ST, Peng Y, Tekmal RR, Arteaga CL, Lippincott-Schwartz J, Vadlamudi RK, Ahn JM, Raj GV (- 19) Ref: Nat Cancer, :, 2022 : PubMed ESTHER: Liu_2022_Nat.Cancer__ PubMedSearch: Liu 2022 Nat.Cancer PubMedID: 35654861 Gene_locus related to this paper: human-LIPA Inhibitor(s) related to this paper: ERX-41 Abstract Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death. Title: Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction Liu Z, Yang N, Dong J, Tian W, Chang L, Ma J, Guo J, Tan J, Dong A and Tang B <27 more author(s)> Liu Z, Yang N, Dong J, Tian W, Chang L, Ma J, Guo J, Tan J, Dong A, He K, Zhou J, Cinar R, Wu J, Salinas AG, Sun L, Kumar M, Sullivan BT, Oldham BB, Pitz V, Makarious MB, Ding J, Kung J, Xie C, Hawes SL, Wang L, Wang T, Chan P, Zhang Z, Le W, Chen S, Lovinger DM, Blauwendraat C, Singleton AB, Cui G, Li Y, Cai H, Tang B (- 27) Ref: Nat Commun, 13:3490, 2022 : PubMed ESTHER: Liu_2022_Nat.Commun_13_3490 PubMedSearch: Liu 2022 Nat.Commun 13 3490 PubMedID: 35715418 Gene_locus related to this paper: human-DAGLB, mouse-DGLB Abstract Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism. Title: Biological evaluation, molecular modeling and dynamics simulation of phenanthrenes isolated from Bletilla striata as butyrylcholinesterase inhibitors Liu Y, Tu Y, Kang Y, Zhu C, Wu C, Chen G, Liu Z, Li Y Ref: Sci Rep, 12:13649, 2022 : PubMed ESTHER: Liu_2022_Sci.Rep_12_13649 PubMedSearch: Liu 2022 Sci.Rep 12 13649 PubMedID: 35953511 Abstract As part of our continuous studies on natural cholinesterase inhibitors from plant kingdom, the 95% ethanol extract from tubers of Bletilla striata showed promising butyrylcholinesterase (BChE) inhibition (IC(50) = 8.6 microg/mL). The extracts with different polarities (petroleum ether, ethyl acetate, n-butanol, and water) were prepared and evaluated for their inhibition of cholinesterases. The most active ethyl acetate extract was subjected to a bioassay-guided isolation and afforded twenty-two bibenzyls and phenanthrenes (1-22). All isolates were further evaluated for their BChE inhibition activity, and five phenanthrenes presented promising capacity (IC(50) < 10 microM). Further kinetic studies indicated their modes of inhibition. Compounds 6, 8, and 14 were found to be mixed-type inhibitors, while compounds 10 and 12 could be classified as non-competitive inhibitors. The potential interaction mechanism of them with BChE was demonstrated by molecular docking and molecular dynamics simulation, showing that they could interact with catalytic active site and peripheral anionic site of BChE. These natural phenanthrenes provide new scaffold for the further design and optimization, with the aim to discover new selective BChE inhibitors for the treatment of AD. Title: Synthesis, insecticidal activity, and mode of action of novel imidazopyridine mesoionic derivatives containing an amido group Liu Z, Song R, Zhang D, Wu R, Liu T, Wu Z, Zhang J, Hu D Ref: Pest Manag Sci, :, 2022 : PubMed ESTHER: Liu_2022_Pest.Manag.Sci__ PubMedSearch: Liu 2022 Pest.Manag.Sci PubMedID: 36054072 Abstract BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC(50) values of 10.5 and 2.09 microg mL(-1) , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the alpha4 and beta1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. 2022 Society of Chemical Industry. Title: Molecular Mechanisms Underlying Metabolic Resistance to Cyflumetofen and Bifenthrin in Tetranychus urticae Koch on Cowpea Liu Z, Wu F, Liang W, Zhou L, Huang J Ref: Int J Mol Sci, 23:16220, 2022 : PubMed ESTHER: Liu_2022_Int.J.Mol.Sci_23_16220 PubMedSearch: Liu 2022 Int.J.Mol.Sci 23 16220 PubMedID: 36555861 Abstract Tetranychus urticae Koch (T. urticae) is one of the most tremendous herbivores due to its polyphagous characteristics, and is resistant to most acaricides. In this study, enzyme-linked immunosorbent assay (ELISA), transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) were carried out to analyze the mechanisms of T. urticae metabolic resistance to cyflumetofen and bifenthrin on cowpea. The enzyme activity of UDP-glucuronosyltransferases (UGTs) and carboxylesterases (CarEs) in the cyflumetofen-resistant (R_cfm) strain significantly decreased, while that of cytochrome P450 monooxygenases (P450s) significantly increased. Meanwhile, the activities of glutathione-S-transferases (GSTs), CarEs and P450s in the bifenthrin-resistant (R_bft) strain were significantly higher than those in the susceptible strain (Lab_SS). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, in the R_cfm mite strain, two carboxyl/cholinesterase (CCE) genes and two P450 genes were upregulated and one gene was downregulated, namely CYP392E7; in the R_bft mite strain, eleven CCE, nine UGT, two P450, four GST and three ABC genes were upregulated, while four CCE and three P450 genes were downregulated. Additionally, 94 differentially expressed genes (DEGs) were common to the two resistant groups. Specifically, TuCCE46 and TuCCE70 were upregulated in both resistant groups. Furthermore, the qRT-PCR validation data were consistent with those from the transcriptome sequencing analysis. Specifically, TuCCE46 (3.37-fold) was significantly upregulated in the R_cfm strain, while in the R_bft strain, TeturUGT22 (5.29-fold), teturUGT58p (1.74-fold), CYP392A11 (2.89-fold) and TuGSTd15 (5.12-fold) were significantly upregulated and TuCCE01 (0.13-fold) and CYP392A2p (0.07-fold) were significantly downregulated. Our study indicates that TuCCE46 might play the most important role in resistance to cyflumetofen, and TuCCE01, teturUGT58p, teturUGT22, CYP392A11, TuGSTd15, TuGSTm09 and TuABCG-13 were prominent in the resistance to bifenthrin. These findings provide further insight into the critical genes involved in the metabolic resistance of T. urticae to cyflumetofen and bifenthrin. Title: Transport, Stability, and In Vivo Hypoglycemic Effect of a Broccoli-Derived DPP-IV Inhibitory Peptide VPLVM Pei J, Liu Z, Pan D, Zhao Y, Dang Y, Gao X Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Pei_2022_J.Agric.Food.Chem__ PubMedSearch: Pei 2022 J.Agric.Food.Chem PubMedID: 35436096 Abstract Diabetes is a major metabolic disease that requires long-term pharmacotherapy. Bioactive peptides have unique advantages such as higher potency, selectivity, and safety over small molecules and have achieved great success in the treatment of diabetes. We previously isolated a dipeptidyl peptidase-IV (DPP-IV) inhibitory peptide VPLVM with IC(50) = 99.68 microM from the protein hydrolysates of broccoli stems and leaves. Here, we evaluated the interaction with DPP-IV, transport, stability, and in vivo hypoglycemic effects of VPLVM. VPLVM interacted closely and steadily with DPP-IV at S1 and S2 pockets. VPLVM had a good gastrointestinal enzyme resistance and was transported through the Caco-2 cell monolayer via paracellular diffusion and by the PepT1 with a P(app) of 6.96 x 10(-7) cm/s. VPLVM has a t(1/2) of 12.56 +/- 0.41 min in vitro plasma stability. In the oral glucose tolerance test, VPLVM showed an excellent hypoglycemic effect at 30 min after administration. VPLVM has potential as a candidate for the treatment of hyperglycemia. Title: Development of novel 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives as balanced multifunctional agents against Alzheimer's disease Shi Y, Zhang H, Song Q, Yu G, Liu Z, Zhong F, Tan Z, Liu X, Deng Y Ref: Eur Journal of Medicinal Chemistry, 230:114098, 2022 : PubMed ESTHER: Shi_2022_Eur.J.Med.Chem_230_114098 PubMedSearch: Shi 2022 Eur.J.Med.Chem 230 114098 PubMedID: 35026532 Abstract Based on multitarget-directed ligands approach, through two rounds of screening, a series of 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives were designed, synthesized and evaluated as innovative multifunctional agents against Alzheimer's disease. In vitro biological assays indicated that most of the hybrids were endowed with great AChE inhibitory activity, excellent antioxidant activity and moderate Abeta(1-42) aggregation inhibition. Taken both efficacy and balance into account, 12a was identified as the optimal multifunctional ligand with significant inhibition of AChE (EeAChE, IC(50) = 0.20 microM; HuAChE, IC(50) = 37.02 nM) and anti-Abeta activity (IC(50) = 1.92 microM for self-induced Abeta(1-42) aggregation; IC(50) = 1.80 microM for disaggregation of Abeta(1-42) fibrils; IC(50) = 2.18 microM for Cu(2+)-induced Abeta(1-42) aggregation; IC(50) = 1.17 microM for disaggregation of Cu(2+)-induced Abeta(1-42) fibrils; 81.7% for HuAChE-induced Abeta(1-40) aggregation). Moreover, it was equipped with the potential to serve as antioxidant (3.03 Trolox equivalents), metals chelator and anti-neuroinflammation agent for synergetic treatment. Finally, in vivo study demonstrated that 12a, with suitable BBB permeability (log BB = -0.61), could efficaciously ameliorate cognitive dysfunction on scopolamine-treated mice by regulating cholinergic system and oxidative stress simultaneously. Altogether, these results highlight the potential of 12a as an innovative balanced multifunctional candidate for Alzheimer's disease treatment. Title: Sensitive detection of organophosphorus pesticides based on the localized surface plasmon resonance and fluorescence dual-signal readout Wang K, Li Q, Wang Y, Wu Y, Liu Z, Liu S Ref: Anal Chim Acta, 1235:340536, 2022 : PubMed ESTHER: Wang_2022_Anal.Chim.Acta_1235_340536 PubMedSearch: Wang 2022 Anal.Chim.Acta 1235 340536 PubMedID: 36368824 Abstract In this work, a dual-signal visual biosensor was designed for organophosphorus pesticides (OPs) detection using DNA functionalized Ag/Au bimetallic nanoparticles (Ag/Au NPs) as multifunctional nanoprobe. The dual-signal detection strategy was based on the inhibition of enzyme-induced H(2)O(2) generation by OPs in the detection solution containing acetylcholinesterase (AChE), choline oxidase (CHO), acetylcholine (ACh) and nanoprobe. H(2)O(2) produced by enzyme-catalyzed reaction could trigger the etching of Ag and dissociation of carboxyfluorescein (FAM)-labeled aptamer from the nanoprobe, resulting in significant localized surface plasmon resonance (LPRR) and fluorescence (FL) signal responses. In the presence of OPs, AChE activity was inhibited to disrupt the enzymatic generation of H(2)O(2), which allowed to simultaneous quantitative measure OPs through the LSPR peak shifts and FL intensity variations of the nanoprobe. The LSPR/FL dual-signal biosensor showed great selectivity and sensitivity for OPs detection. In addition, two distinct colour changes were visually observed to match the LSPR/FL spectra signal responses, which was a feasible means for visual analysis of OPs. Consequently, the work provided a dual-signal visual biosensor via the combination of multifunctional nanoprobe, and had significant potential to monitor pesticide residue with high anti-interference capability and detection accuracy. Title: Rapid Mining of Novel alpha-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS Xu J, Liu Z, Feng Z, Ren Y, Liu H, Wang Y Ref: Mar Drugs, 20:, 2022 : PubMed ESTHER: Xu_2022_Mar.Drugs_20_ PubMedSearch: Xu 2022 Mar.Drugs 20 PubMedID: 35323488 Abstract A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10-16) along with four known related compounds (17-20) were obtained directly from the crude extract of strain HO1518. Compounds 10-13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous alpha-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs. Title: Effects of urea application on the reproduction of Pardosa pseudoannulata: Field and laboratory studies Yang Z, Wang Y, Wang K, Zhang Y, Yu N, Liu Z Ref: Chemosphere, 301:134697, 2022 : PubMed ESTHER: Yang_2022_Chemosphere_301_134697 PubMedSearch: Yang 2022 Chemosphere 301 134697 PubMedID: 35513078 Abstract As an important chemical fertilizer, urea can greatly increase crop yields, but it also has negative effects on beneficial arthropods in the agricultural field, such as spiders. Here, we reported that urea application reduced the reproductive performance in Pardosa pseudoannulata, a dominant species of spider in rice fields, which preys on a range of insect pests, based on both field and laboratory studies. In a field test, urea application significantly reduced the egg production of adult and subadult females collected from the urea-treated fields. A laboratory test was set up to further evaluate the impact of urea application on P. pseudoannulata reproduction. In consistent with field test results, the spiders treated by urea for 14 d and 28 d had lower reproduction ability than their control counterparts, with regard to the mating rate, egg production, and egg hatchability. The transcriptomic sequencing of individuals treated by urea for 28 d showed that urea application caused a number of differentially expressed transcripts with several downregulated unigenes related to basic enzymes and several upregulated unigenes involved in stress resistance. The knockdown of a metalloproteinase gene caused a significant decrease in egg production, and the silencing of a carboxylesterase gene significantly reduced both the egg production and egg hatchability. Taken together, the present study found that urea application reduced P. pseudoannulata reproduction ability and the negative impact partially resulted from the downregulation of certain basic enzyme genes. The study provided a fresh view of fertilizers on beneficial arthropods with great potential in the protection of P. pseudoannulata in fields. Title: Acetylcholinesterase-Cu(3)(PO(4))(2) hybrid nanoflowers for electrochemical detection of dichlorvos using square-wave voltammetry Yang L, Zhang X, Li M, Qu L, Liu Z Ref: Anal Methods, :, 2022 : PubMed ESTHER: Yang_2022_Anal.Methods__ PubMedSearch: Yang 2022 Anal.Methods PubMedID: 36169013 Abstract Immobilization of enzymes is one of the key steps in the development of high-performance enzymatic electrochemical biosensors, and various nanostructured materials have been designed and developed to achieve this goal. Herein, hybrid nanoflowers (HNFs) were synthesized using acetylcholinesterase (AChE) as an organic component and copper phosphate (Cu(3)(PO(4))(2)) as an inorganic component. These AChE-Cu(3)(PO(4))(2) HNFs exhibit a three-dimensional hierarchical flower-like structure, which not only has a large specific surface area but also promotes the affinity between AChE and its substrate with better catalytic activity. Not only that, the surface modification of the glassy carbon electrode (GCE) by the joint use of gold nanoparticles (AuNPs) and graphene oxide (GO) extended the electroactive area. Using square-wave voltammetry (SWV), the as-prepared biosensor (i.e., AChE-Cu(3)(PO(4))(2) HNF/AuNP/GO/GCE) demonstrated superior sensing performance in the detection of dichlorvos. The detection limit is as low as 0.07 pM, and the linear detection range can range from 0.5 pM to 10 microM. In addition, the biosensor was feasible in real agricultural samples with satisfactory recoveries (98.65% to 103.43%). The reported biosensor provides an alternative tool for the direct measurements of AChE activity and its inhibition. Besides organophosphorus pesticides represented by dichlorvos, this biosensor has the potential to detect other AChE inhibitors, such as carbamate pesticides, drugs for Alzheimer's disease, etc., thus having broader applications in food safety and drug screening. Title: Populus euphratica Phospholipase Ddelta Increases Salt Tolerance by Regulating K(+)/Na(+) and ROS Homeostasis in Arabidopsis Zhang Y, Yao J, Yin K, Liu Z, Deng C, Liu J, Hou S, Zhang H, Yu D and Chen S <2 more author(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 (- 2) Ref: Int J Mol Sci, 23:4911, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_23_4911 PubMedSearch: Zhang 2022 Int.J.Mol.Sci 23 4911 PubMedID: 35563299 Abstract Phospholipase Dalpha (PLDalpha), which produces signaling molecules phosphatidic acid (PA), has been shown to play a critical role in plants adapting to salt environments. However, it is unclear whether phospholipase Ddelta (PLDdelta) can mediate the salt response in higher plants. PePLDdelta was isolated from salt-resistant Populus euphratica and transferred to Arabidopsis thaliana to testify the salt tolerance of transgenic plants. The NaCl treatment (130 mM) reduced the root growth and whole-plant fresh weight of wild-type (WT) A. thaliana, vector controls (VC) and PePLDdelta-overexpressed lines, although a less pronounced effect was observed in transgenic plants. Under salt treatment, PePLDdelta-transgenic Arabidopsis exhibited lower electrolyte leakage, malondialdehyde content and H(2)O(2) levels than WT and VC, resulting from the activated antioxidant enzymes and upregulated transcripts of genes encoding superoxide dismutase, ascorbic acid peroxidase and peroxidase. In addition, PePLDdelta-overexpressed plants increased the transcription of genes encoding the plasma membrane Na(+)/H(+) antiporter (AtSOS1) and H(+)-ATPase (AtAHA2), which enabled transgenic plants to proceed with Na(+) extrusion and reduce K(+) loss under salinity. The capacity to regulate reactive oxygen species (ROS) and K(+)/Na(+) homeostasis was associated with the abundance of specific PA species in plants overexpressing PePLDdelta. PePLDdelta-transgenic plants retained a typically higher abundance of PA species, 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2), 36:5 (18:2-18:3) and 36:6 (18:3-18:3), under control and saline conditions. It is noteworthy that PA species 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2) and 36:5 (18:2-18:3) markedly increased in response to NaCl in transgenic plants. In conclusion, we suppose that PePLDdelta-derived PA enhanced the salinity tolerance by regulating ROS and K(+)/Na(+) homeostasis in Arabidopsis. Title: Role of epoxyeicosatrienoic acids in cardiovascular diseases and cardiotoxicity of drugs Zhang Y, Gao L, Yao B, Huang S, Liu J, Liu Z, Wang X Ref: Life Sciences, 310:121122, 2022 : PubMed ESTHER: Zhang_2022_Life.Sci_310_121122 PubMedSearch: Zhang 2022 Life.Sci 310 121122 PubMedID: 36309225 Abstract Epoxyeicosatrienoic acids (EETs) are important endogenous substances that affect heart function in human body. Animal models of cytochrome P450 (CYP) and soluble epoxide hydrolase (sEH) related cardiovascular diseases (CVD) have revealed the physiological effects of EETs, mainly including vascular function regulation, angiogenesis, myocardial fibrosis, myocardial hypertrophy, and cardiovascular inflammation. At the same time, clinical studies have found that most of the substrates and inhibitors of CYP2J2 affect the content of EETs, resulting in cardiotoxicity of drugs. Therefore, the regulation of CYP and sEH enzymes on EETs points out the direction for exploring EET-mediated cardiac protection. The metabolic pathway of EETs is not only an important target for the development of new drugs for CVD but also an important factor in preventing drug cardiotoxicity. The development and clinical application of sEH inhibitors and EETs analogues provide broad prospects for the treatment of CVD. Title: Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster Zhu K, Li M, Wu H, Zhang D, Dong L, Wu Q, Chen Y, Xie J, Lu P and Hua W <13 more author(s)> Zhu K, Li M, Wu H, Zhang D, Dong L, Wu Q, Chen Y, Xie J, Lu P, Guo G, Zhang H, Zhang P, Li B, Li W, Wang Q, Zhu J, Hu W, Guo L, Wang R, Yuan C, Li H, Liu Z, Hua W (- 13) Ref: Theor Appl Genet, :, 2022 : PubMed ESTHER: Zhu_2022_Theor.Appl.Genet__ PubMedSearch: Zhu 2022 Theor.Appl.Genet PubMedID: 35006335 Abstract Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars. Title: Analysis of virulence proteins in pathogenic Acinetobacter baumannii to provide early warning of zoonotic risk Zou D, Chang J, Lu S, Xu J, Hu P, Zhang K, Sun X, Guo W, Li Y and Ren H <1 more author(s)> Zou D, Chang J, Lu S, Xu J, Hu P, Zhang K, Sun X, Guo W, Li Y, Liu Z, Ren H (- 1) Ref: Microbiol Res, 266:127222, 2022 : PubMed ESTHER: Zou_2022_Microbiol.Res_266_127222 PubMedSearch: Zou 2022 Microbiol.Res 266 127222 PubMedID: 36306681 Gene_locus related to this paper: aciba-YdeN Abstract Acinetobacter baumannii is a ubiquitous opportunistic pathogen usually with low virulence. In recent years, reports of increased pathogenicity of A. baumannii in livestock due to the migratory behaviour of wildlife have attracted public health attention. Our previous study reported that an A. baumannii strain isolated from dead chicks, CCGGD201101, showed enhanced pathogenicity, but the mechanism for increased virulence is not understood. Here, to screen potential virulence factors, the proteomes of the isolated strain CCGGD201101 and the standard strain ATCC19606 of A. baumannii were compared, and the possible virulence-enhancing mechanisms were further analysed. The 50 % lethal dose (LD(50)) values of CCGGD201101 and standard strain ATCC19606 in ICR mice were determined to verify their bacterial toxicity. 2D fluorescence difference gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) and quantitative real-time PCR (RTqPCR) were applied to screen and identify differentially expressed proteins or genes that may be related to virulence enhancement. Bioinformatics analyses based on proteinprotein interaction (PPI) networks were used to explore the function of potential virulence proteins. The pathogenicity of potential virulence factors was assessed by phylogenetic analyses and an animal infection model. The results showed that the LD(50) of CCGGD201101 for mice was 1.186 x 10(6) CFU/mL, and the virulence was increased by 180.5-fold compared to ATCC19606. Forty-seven protein spots were significantly upregulated for the A. baumannii CCGGD201101 strain (fold change <=1.5, p < 0.05). In total, 14 upregulated proteins were identified using proteomic analysis, and the mRNA expression levels of these proteins were nearly identical, with few exceptions. According to the PPI network and phylogenetic analyses, the I78 family peptidase inhibitor, 3-oxoacyl-ACP reductase FabG, and glycine zipper were screened as being closely related to the pathogenicity of bacteria. Furthermore, the I78 overexpression strains exhibited higher lethality in mouse infection models, which indicated that the I78 family peptidase inhibitor was a potential new virulence factor to enhance the pathogenicity of the A. baumannii CCGGD201101 strain. The present study helped us to better understand the mechanisms of virulence enhancement and provided a scientific basis for establishing an early warning system for enhanced virulence of A. baumannii from animals. Title: Novel 3-benzylidene/benzylphthalide Mannich base derivatives as potential multifunctional agents for the treatment of Alzheimer's disease Cao Z, Song Q, Yu G, Liu Z, Cong S, Tan Z, Deng Y Ref: Bioorganic & Medicinal Chemistry, 35:116074, 2021 : PubMed ESTHER: Cao_2021_Bioorg.Med.Chem_35_116074 PubMedSearch: Cao 2021 Bioorg.Med.Chem 35 116074 PubMedID: 33640707 Abstract To discover novel multifunctional agents for the treatment of Alzheimer's disease, a series of 3-benzylidene/benzylphthalide Mannich base derivatives were designed, synthesized and evaluated. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound (Z)-13c raised particular interest because of its excellent multifunctional bioactivities. It displayed excellent EeAChE and HuAChE inhibition (IC(50) = 9.18 x 10(-5) and 6.16 x 10(-4) microM, respectively), good MAO-B inhibitory activity (IC(50) = 5.88 microM) and high antioxidant activity (ORAC =2.05 Trolox equivalents). Additionally, it also exhibited good antiplatelet aggregation activity, moderate self- and Cu(2+)-induced Abeta(1-42) aggregation inhibitory potency, disaggregation ability on Abeta(1-42) fibrils, biometal chelating ability, appropriate BBB permeability and significant neuroprotective effect. Furthermore, (Z)-13c can also ameliorate the learning and memory impairment induced by scopolamine in mice. These multifunctional properties highlight compound (Z)-13c as a promising candidate for further development of multifunctional drug against AD. Title: Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis Du F, Sun W, Morisseau C, Hammock BD, Bao X, Liu Q, Wang C, Zhang T, Yang H and Chen G <3 more author(s)> Du F, Sun W, Morisseau C, Hammock BD, Bao X, Liu Q, Wang C, Zhang T, Yang H, Zhou J, Xiao W, Liu Z, Chen G (- 3) Ref: Eur Journal of Medicinal Chemistry, 223:113678, 2021 : PubMed ESTHER: Du_2021_Eur.J.Med.Chem_223_113678 PubMedSearch: Du 2021 Eur.J.Med.Chem 223 113678 PubMedID: 34218083 Inhibitor(s) related to this paper: B401 Abstract Sepsis, a systemic inflammatory response, caused by pathogenic factors including microorganisms, has high mortality and limited therapeutic approaches. Herein, a new soluble epoxide hydrolase (sEH) inhibitor series comprising a phenyl ring connected to a memantyl moiety via a urea or amide linkage has been designed. A preferential urea pharmacophore that improved the binding properties of the compounds was identified for those series via biochemical assay in vitro and in vivo studies. Molecular docking displayed that 3,5-dimethyl on the adamantyl group in B401 could make van der Waals interactions with residues at a hydrophobic pocket of sEH active site, which might indirectly explain the subnanomolar level activities of memantyl urea derivatives in vitro better than AR-9281. Among them, compound B401 significantly improved the inhibition potency with human and murine sEH IC(50) values as 0.4 nM and 0.5 nM, respectively. Although the median survival time of C57BL/6 mice in LPS-induced sepsis model was slightly increased, the survival rate did not reach significant efficacy. Based on safety profile, metabolic stability, pharmacokinetic and in vivo efficacy, B401 demonstrated the proof of potential for this class of memantyl urea-based sEH inhibitors as therapeutic agents in sepsis. Title: Improving the catalytic efficiency and substrate affinity of a novel esterase from marine Klebsiella aerogenes by random and site-directed mutation Gao H, Zhu R, Li Z, Wang W, Liu Z, Hu N Ref: World J Microbiol Biotechnol, 37:106, 2021 : PubMed ESTHER: Gao_2021_World.J.Microbiol.Biotechnol_37_106 PubMedSearch: Gao 2021 World.J.Microbiol.Biotechnol 37 106 PubMedID: 34037848 Abstract A novel esterase (EstKa) from marine Klebsiella aerogenes was characterized with hydrolytic activity against p-nitrophenyl caprylate (pNPC, C(8)) under optimum conditions (50 degreesC and pH 8.5). After two rounds of mutagenesis, two highly potential mutants (I6E9 and L7B11) were obtained with prominent activity, substrate affinity and thermostability. I6E9 (L90Q/P96T) and L7B11 (A37S/Q100L/S133G/R138C/Q156R) were 1.56- and 1.65-fold higher than EstKa in relative catalytic efficiency. The influence of each amino acid on enzyme activity was explored by site-directed mutation. The mutants Pro96Thr and Gln156Arg showed 1.29- and 1.48-fold increase in catalytic efficiency (Kcat/Km) and 54.4 and 36.2% decrease in substrate affinity (Km), respectively. The compound mutant Pro96Thr/Gln156Arg exhibited 68.9% decrease in Km and 1.41-fold increase in Kcat/Km relative to EstKa. Homology model structure analysis revealed that the replacement of Gln by hydrophilic Arg on the esterase surface improved the microenvironment stability and the activity. The replacement of Pro by Thr enabled the esterase enzyme to retain 90% relative activity after 3 h incubation at 45 degreesC. Structural analysis confirmed that the formation of a hydrogen bond leads to a notable increase of catalytic efficiency under high temperature conditions. Title: The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis Li Y, Fang R, Liu Z, Jiang L, Zhang J, Li H, Liu C, Li F Ref: Chemosphere, 263:128238, 2021 : PubMed ESTHER: Li_2021_Chemosphere_263_128238 PubMedSearch: Li 2021 Chemosphere 263 128238 PubMedID: 33297185 Abstract Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions. Title: Biological detoxification of fumonisin by a novel carboxylesterase from Sphingomonadales bacterium and its biochemical characterization Li Z, Wang Y, Liu Z, Jin S, Pan K, Liu H, Liu T, Li X, Zhang C and Zhang T <3 more author(s)> Li Z, Wang Y, Liu Z, Jin S, Pan K, Liu H, Liu T, Li X, Zhang C, Luo X, Song Y, Zhao J, Zhang T (- 3) Ref: Int J Biol Macromol, 169:18, 2021 : PubMed ESTHER: Li_2021_Int.J.Biol.Macromol_169_18 PubMedSearch: Li 2021 Int.J.Biol.Macromol 169 18 PubMedID: 33309671 Gene_locus related to this paper: 9sphn-a0a101vlk1 Abstract Fumonisins have posed hazardous threat to human and animal health worldwide. Enzymatic degradation is a desirable detoxification approach but is severely hindered by serious shortage of detoxification enzymes. After mining enzymes by bioinformatics analysis, a novel carboxylesterase FumDSB from Sphingomonadales bacterium was expressed in Escherichia coli, and confirmed to catalyze fumonisin B1 to produce hydrolyzed fumonisin B1 by liquid chromatography mass spectrometry for the first time. FumDSB showed high sequence novelty, sharing only ~34% sequence identity with three reported fumonisin detoxification carboxylesterases. Besides, FumDSB displayed its high degrading activity at 30-40 degreesC within a broad pH range from 6.0 to 9.0, which is perfectly suitable to be used in animal physiological condition. It also exhibited excellent pH stability and moderate thermostability. This study provides a FB1 detoxification carboxylesterase which could be further used as a potential food and feed additive. Title: Construction and characterization of CRISPR/Cas9 knockout rat model of carboxylesterase 2a gene Liu J, Shang X, Huang S, Xu Y, Lu J, Zhang Y, Liu Z, Wang X Ref: Molecular Pharmacology, :, 2021 : PubMed ESTHER: Liu_2021_Mol.Pharmacol__2 PubMedSearch: Liu 2021 Mol.Pharmacol 2 PubMedID: 34503976 Gene_locus related to this paper: ratno-LOC246252 Abstract Carboxylesterase 2 (CES2), an important metabolic enzyme, plays a critical role in drug biotransformation and lipid metabolism. Although CES2 is very important, few animal models have been generated to study its properties and functions. Rat Ces2 is similar to human CES2A-CES3A-CES4A gene cluster, with highly similar gene structure, function and substrate. In this report, CRISPR/Cas9 technology was firstly used to knock out rat Ces2a, a main subtype of Ces2 mostly distributed in liver and intestine. This model showed the absence of CES2A protein expression in liver. Further pharmacokinetic studies of diltiazem, a typical substrate of CES2A, confirmed the loss of function of CES2A both in vivo and in vitro. At the same time, the expression of CES2C and CES2J protein in liver decreased significantly. The body and liver weight of Ces2a knockout rats also increased, but the food intake did not change. Moreover, the deficiency of Ces2a led to obesity, insulin resistance and liver fat accumulation, which are consistent with the symptoms of nonalcoholic fatty liver disease (NAFLD). Therefore, this rat model is not only a powerful tool to study drug metabolism mediated by CES2, but also a good disease model to study NAFLD. Significance Statement Human CES2 plays a key role in the first-pass hydrolysis metabolism of most oral prodrugs as well as lipid metabolism. In this study, CRISPR/Cas9 technology was used to knock out Ces2a gene in rats for the first time. This model can be used not only in the study of drug metabolism and pharmacokinetics, but also as a disease model of NAFLD and other metabolic disorder. Title: Blood-Brain Barrier Permeable and NO-Releasing Multifunctional Nanoparticles for Alzheimer's Disease Treatment: Targeting NO/cGMP/CREB Signaling Pathways Liu Z, Liu Q, Zhang B, Fang L, Gou S Ref: Journal of Medicinal Chemistry, 64:13853, 2021 : PubMed ESTHER: Liu_2021_J.Med.Chem_64_13853 PubMedSearch: Liu 2021 J.Med.Chem 64 13853 PubMedID: 34517696 Abstract The development of novel therapeutic strategies for combating Alzheimer's disease (AD) is challenging but imperative. Multifunctional nanoparticles are promising tools for regulating complex pathological dysfunctions for AD treatment. Herein, we constructed multifunctional nanoparticles consisting of regadenoson (Reg), nitric oxide (NO) donor, and YC-1 in a single molecular entity that can spontaneously self-assemble into nanoparticles and load donepezil to yield Reg-nanoparticles (Reg-NPs). The Reg moiety enabled the Reg-NPs to effectively regulate tight junction-associated proteins in the blood-brain barrier, thus facilitating the permeation of donepezil through the barrier and its accumulation in the brain. Moreover, the released NO and YC-1 activated the NO/cGMP/CREB signaling pathway by stimulating soluble guanylyl cyclase and inhibiting phosphodiesterase activity, which finally reduced cytotoxicity induced by aggregated Abeta in the neurons and was beneficial for synaptic plasticity and memory formation. Title: The Mechanisms of Cucurbitacin E as a Neuroprotective and Memory-Enhancing Agent in a Cerebral Hypoperfusion Rat Model: Attenuation of Oxidative Stress, Inflammation, and Excitotoxicity Liu Z, Kumar M, Devi S, Kabra A Ref: Front Pharmacol, 12:794933, 2021 : PubMed ESTHER: Liu_2021_Front.Pharmacol_12_794933 PubMedSearch: Liu 2021 Front.Pharmacol 12 794933 PubMedID: 34955861 Abstract Impaired cerebral hemodynamic autoregulation, vasoconstriction, and cardiovascular and metabolic dysfunctions cause cerebral hypoperfusion (CH) that triggers pro-oxidative and inflammatory events. The sequences linked to ion-channelopathies and calcium and glutamatergic excitotoxicity mechanisms resulting in widespread brain damage and neurobehavioral deficits, including memory, neurological, and sensorimotor functions. The vasodilatory, anti-inflammatory, and antioxidant activities of cucurbitacin E (CuE) can alleviate CH-induced neurobehavioral impairments. In the present study, the neuroprotective effects of CuE were explored in a rat model of CH. Wistar rats were subjected to permanent bilateral common carotid artery occlusion to induce CH on day 1 and administered CuE (0.25, 0.5 mg/kg) and/or Bay-K8644 (calcium agonist, 0.5 mg/kg) for 28 days. CH caused impairment of neurological, sensorimotor, and memory functions that were ameliorated by CuE. CuE attenuated CH-triggered lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, protein carbonyls, tumor necrosis factor-alpha, nuclear factor-kappaB, myeloperoxidase activity, inducible nitric oxide synthase, and matrix metalloproteinase-9 levels in brain resulting in a decrease in cell death biomarkers (lactate dehydrogenase and caspase-3). CuE decreased acetylcholinesterase activity, glutamate, and increased gamma-aminobutyric acid levels in the brain. An increase in brain antioxidants was observed in CuE-treated rats subjected to CH. CuE has the potential to alleviate pathogenesis of CH and protect neurological, sensorimotor, and memory functions against CH. Title: A distal regulatory strategy of enzymes: from local to global conformational dynamics Peng X, Lu C, Pang J, Liu Z, Lu D Ref: Phys Chem Chem Phys, :, 2021 : PubMed ESTHER: Peng_2021_Phys.Chem.Chem.Phys__ PubMedSearch: Peng 2021 Phys.Chem.Chem.Phys PubMedID: 34585687 Abstract Modulating the distribution of various states in protein ensembles through distal sites may be promising in the evolution of enzymes in desired directions. However, the prediction of distal mutation hotspots that stabilize the favoured states from a computational perspective remains challenging. Here, we presented a strategy based on molecular dynamics (MD) and Markov state models (MSM) to predict distal mutation sites. Extensive MD combined with MSM was applied to determine the principally distributed metastable states interconverting at a slow timescale. Then, molecular docking was used to classify these states into active states and inactive ones. Distal mutation hotspots were targeted based on comparing the conformational features between active and inactive states, where mutations destabilize the inactive states and show little influence on the active state. The proposed strategy was used to explore the highly dynamic MHETase, which shows a potential application in the biodegradation of poly(ethylene terephthalate) (PET). Seven principally populated interrelated metastable states were identified, and the atomistic picture of their conformational changes was unveiled. Several residues at distal positions were found to adopt more H-bond occupancies in inactive states than active states, making them potential mutation hotspots for stabilizing the favoured conformations. In addition, the detailed mechanism revealed the significance of calcium ions at a distance from the catalytic centre in reshaping the free energy landscape. This study deepens the understanding of the conformational dynamics of alpha/beta hydrolases containing a lid domain and advances the study of enzymatic plastic degradation. Title: Enhancing Therapeutic Efficacy of Donepezil by Combined Therapy: A Comprehensive Review Rong X, Jiang L, Qu M, Hassan SSU, Liu Z Ref: Curr Pharm Des, 27:332, 2021 : PubMed ESTHER: Rong_2021_Curr.Pharm.Des_27_332 PubMedSearch: Rong 2021 Curr.Pharm.Des 27 332 PubMedID: 33100197 Abstract Combination therapy involving different therapeutic strategies mostly provides more rapid and effective results as compared to monotherapy in diverse areas of clinical practice. The most worldwide famous acetylcholinesterase inhibitor (AChEIs) donepezil for its dominant role in Alzheimer's disease (AD) has also attracted the attention of many pharmaceuticals due to its promising pharmacological potencies such as neuroprotective, muscle relaxant, and sleep inducer. Recently, a combination of donepezil with other agents has displayed better desirable results in managing several disorders, including the most common Alzheimer's disease (AD). This study involves all the data regarding the therapeutic effect of donepezil in its combination with other agents and explains its therapeutic targets and mode of action. Furthermore, this review also puts light on the current status of donepezil with other agents in clinical trials. The combination therapy of donepezil with symptomatic relief drugs and disease-modifying agents opens a new road for treating multiple pathological disorders. To the best of our knowledge, this is the first report encircling all the pharmacologic effects of donepezil in its combination therapy with other agents and their current status in clinical trials. Title: Multi-target drug design of anti-Alzheimer's disease based on tacrine Tian S, Huang Z, Meng Q, Liu Z Ref: Mini Rev Med Chem, :, 2021 : PubMed ESTHER: Tian_2021_Mini.Rev.Med.Chem__ PubMedSearch: Tian 2021 Mini.Rev.Med.Chem PubMedID: 33583371 Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease with concealed onset, which is characterized by damage of cholinergic system, deposition and accumulation of beta-amyloid protein (Abeta) and Neurofibrillary tangles. Because cholinergic system plays a key role in the process of brain memory, cholinergic system has become one of the important targets in anti-AD research. In view of the complicated pathological characteristics of AD, the multi-target directed ligands (MTDLs) that can act on multiple targetsis considered to be an effective treatment strategy at present. Tacrine, as the first acetylcholinesterase (AChE) inhibitor, has been discontinued because of its hepatotoxicity, but its core structure is simple and easy to modify. By using tacrine to target the catalytic active site (CAS), the tacrine-based MTDLs can act on both CAS and peripheral anion site (PAS) of AChE so as to serve as a dual-site AChE inhibitor. Additionally, the tacrine-based MTDLs can also be designed on the basis of other theories of AD, for example, introducing functional moieties to modulate the formation of beta-amyloid (Abeta), oxidation resistance or metal chelation. In this paper, the research progress of tacrine-based MTDLs is summarized. Title: [Serum C-reactive protein, cholinesterase and prealbumin are correlated with prognosis of severe coronavirus disease 2019 patients] Wang H, Hu L, Bai GQ, Liu Z, Yu GG, Wang W, Sun L Ref: Zhonghua Nei Ke Za Zhi, 60:134, 2021 : PubMed ESTHER: Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134 PubMedSearch: Wang 2021 Zhonghua.Nei.Ke.Za.Zhi 60 134 PubMedID: 33503724 Abstract Objective: To retrospectively analyze the relationship between serum C-reactive protein (CRP), serum cholinesterase (ChE), prealbumin (PA) and mortality in severe patients with coronavirus disease 2019 (COVID-19). Methods: During the period from January 29 to March 30, 2020, a total of 344 COVID-19 patients were admitted to west branch of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. One-hundred and ninety-two patients were diagnosed with common type and excluded, and 34 patients were transferred to LeiShenShan or other medical units. The remaining 118 patients were severe cases, and 18 cases were excluded due to incomplete data. A total of 100 severe COVID-19 patients were finally collected. According to the outcome, the patients were divided into death group (37 cases) and survival group(63 cases), and the levels of serum CRP, ChE and PA were compared. Statistical analysis were performed by SPSS25.0. Results: There were 53 male patients in this study. The level of CRP in death group was significantly more elevated compare to the survival group [(95.72+/-39.56) mg/L vs. (22.21+/-20.75) mg/L, P<0.01]. On the contrary, serum ChE in death group was remarkably decreased [(5 082+/-1 566) U/L vs. (7 075+/-1 680) U/L, P<0.01]. Also, serum PA in death group was significantly lower [(86.18+/-47.94) mg/L vs. (167.40+/-57.82) mg/L, P<0.01]. Univariate analysis showed that CRP and PA had an impact on the survival of critical patients, but multivariate Cox regression analysis suggested that CRP was the independent factor affecting the survival of critical patients. Conclusions: CRP is generally elevated in severe patients with COVID-19, and serum ChE and PA accordingly decrease. CRP and PA have influence on patients' survival, but only CRP demonstrates predictive value for prognosis in critical patients with COVID-19. Title: Design, synthesis, and in vitro evaluation of 4-aminoalkyl-1(2H)-phthalazinones as potential multifunctional anti-Alzheimer's disease agents Ye C, Xu R, Cao Z, Song Q, Yu G, Shi Y, Liu Z, Liu X, Deng Y Ref: Bioorg Chem, 111:104895, 2021 : PubMed ESTHER: Ye_2021_Bioorg.Chem_111_104895 PubMedSearch: Ye 2021 Bioorg.Chem 111 104895 PubMedID: 33887586 Abstract A series of 4-aminoalkyl-1(2H)-phthalazinone derivatives was designed and synthesized as potential multifunctional agents for Alzheimer's disease (AD) treatment. In vitro biological assay results demonstrated that most synthesized compounds exhibited significant AChE inhibition, moderate to high MAOs inhibitory potencies and good anti-platelet aggregation abilities. Among them, compound 15b exhibited the highest inhibitory potencies towards MAO-B and MAO-A (IC(50) = 0.7 microM and 6.4 microM respectively), moderate inhibition towards AChE (IC(50) = 8.2 microM), and good activities against self- and Cu(2+)-induced Abeta(1-42) aggregation and platelet aggregation. Moreover, 15b also displayed antioxidant capacity, neuroprotective potency, anti-neuroinflammation and BBB permeability. These excellent results indicated that compound 15b could be worthy of further studies to be considered as a promising multifunctional candidate for the treatment of AD. Title: Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease Zhang P, Wang Z, Mou C, Zou J, Xie Y, Liu Z, Benjamin Naman C, Mao Y, Wei J and Cui W <11 more author(s)> Zhang P, Wang Z, Mou C, Zou J, Xie Y, Liu Z, Benjamin Naman C, Mao Y, Wei J, Huang X, Dong J, Yang M, Wang N, Jin H, Liu F, Lin D, Liu H, Zhou F, He S, Zhang B, Cui W (- 11) Ref: Bioorg Chem, 116:105387, 2021 : PubMed ESTHER: Zhang_2021_Bioorg.Chem_116_105387 PubMedSearch: Zhang 2021 Bioorg.Chem 116 105387 PubMedID: 34628225 Inhibitor(s) related to this paper: Tacrine-dipicolylamine-13a Abstract Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an beta-amyloid (Abeta) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Abeta(1-42) aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Abeta(1-42) pentamers. Moreover, 13a effectively attenuated Abeta(1-42) oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD. Title: Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis Cai Y, Cai X, Wang Q, Wang P, Zhang Y, Cai C, Xu Y, Wang K, Zhou Z and Liu F <25 more author(s)> Cai Y, Cai X, Wang Q, Wang P, Zhang Y, Cai C, Xu Y, Wang K, Zhou Z, Wang C, Geng S, Li B, Dong Q, Hou Y, Wang H, Ai P, Liu Z, Yi F, Sun M, An G, Cheng J, Shi Q, Xie Y, Shi X, Chang Y, Huang F, Chen Y, Hong S, Mi L, Sun Q, Zhang L, Zhou B, Peng R, Zhang X, Liu F (- 25) Ref: Plant Biotechnol J, 18:814, 2020 : PubMed ESTHER: Cai_2020_Plant.Biotechnol.J_18_814 PubMedSearch: Cai 2020 Plant.Biotechnol.J 18 814 PubMedID: 31479566 Gene_locus related to this paper: gosra-a0a0d2pzd7 Abstract The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes. Title: Expression Profiling of Plant Cell Wall-Degrading Enzyme Genes in Eucryptorrhynchus scrobiculatus Midgut Gao P, Liu Z, Wen J Ref: Front Physiol, 11:1111, 2020 : PubMed ESTHER: Gao_2020_Front.Physiol_11_1111 PubMedSearch: Gao 2020 Front.Physiol 11 1111 PubMedID: 33013475 Abstract In China, the wood-boring weevil Eucryptorrhynchus scrobiculatus damages and eventually kills the tree of heaven Ailanthus altissima. To feed and digest the cell wall of A. altissima, E. scrobiculatus requires plant cell wall-degrading enzymes (PCWDEs). In the present study, we used next-generation sequencing to analyze the midgut transcriptome of E. scrobiculatus. Using three midgut transcriptomes, we assembled 21,491 unigenes from 167,714,100 clean reads. We identified 25 putative PCWDEs, including 11 cellulases and 14 pectinases. We constructed phylogenetic trees with a maximum likelihood algorithm to elucidate the relationships between sequences of the PCWDE protein families and speculate the functions of the PCWDE genes in E. scrobiculatus. The expression patterns of 17 enzymes in the midgut transcriptome were analyzed in various tissues by quantitative real-time PCR (RT-qPCR). The relative expression levels of 12 genes in the midgut and two genes in the proboscis were significantly higher than those in the other tissues. The proboscis and midgut are the digestive organs of insects, and the high expression level indirectly indicates that these genes are related to digestion. The present study has enabled us to understand the types and numbers of the PCWDEs of E. scrobiculatus and will be helpful for research regarding other weevils' PCWDEs in the future. Title: Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer's Diseases Guo Y, Yang H, Huang Z, Tian S, Li Q, Du C, Chen T, Liu Y, Sun H, Liu Z Ref: Molecules, 25:, 2020 : PubMed ESTHER: Guo_2020_Molecules_25_ PubMedSearch: Guo 2020 Molecules 25 PubMedID: 31979317 Abstract A series of novel compounds 6a-h, 8i-1, 10s-v, and 16a-d were synthesized and evaluated, together with the known analogs 11a-f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 muM) and BChE (eqBChE IC50 = 0.28 muM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer's disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD. Title: (+/-)-Dievodialetins A-G: Seven pairs of enantiomeric coumarin dimers with anti-acetylcholinesterase activity from the roots of Evodia lepta Merr Huang GY, Cui H, Lu XY, Zhang LD, Ding XY, Wu JJ, Duan LX, Zhang SJ, Liu Z, Zhang RR Ref: Phytochemistry, 182:112597, 2020 : PubMed ESTHER: Huang_2020_Phytochemistry_182_112597 PubMedSearch: Huang 2020 Phytochemistry 182 112597 PubMedID: 33341030 Abstract Seven pairs of undescribed enantiomeric bis-coumarins, (+/-)-dievodialetins A-G, were separated from the roots of Evodia lepta Merr. Two coumarin nuclei were linked via a 1,4-dimethyl4-vinylcyclohexene moiety in (+/-)-dievodialetins C-G. The structures of the undescribed compounds, including their absolute configurations were elucidated by spectroscopic analyses, X-ray diffraction, and computational calculations. In the biosynthetic pathways, these bis-coumarins were presumably derived from the precursors demethylsuberosin and 3-(3-methylbut-2-enyl)umbelliferone via a [4 + 2] Diels-Alder reaction. Besides, all compounds exhibited neuroprotective effects by inhibiting acetylcholinesterase (AChE) activity with IC(50) values ranging from 7.3 to 12.1 nM and they also suppressed oxidative stress (MDA and SOD) and neuroinflammation (IL-1beta and IL-6). Title: Antioxidative enzyme activities in the Rhodeinae sinensis Gunther and Macrobrachium nipponense and multi-endpoint assessment under tonalide exposure Li W, Wang S, Li J, Wang X, Cui L, Chen J, Liu Z Ref: Ecotoxicology & Environmental Safety, 199:110751, 2020 : PubMed ESTHER: Li_2020_Ecotoxicol.Environ.Saf_199_110751 PubMedSearch: Li 2020 Ecotoxicol.Environ.Saf 199 110751 PubMedID: 32446104 Abstract Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 mug/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 mug/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 mug/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 mug/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 mug/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 mug/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 mug/L and 0.000395 mug/L, respectively, which were significantly lower than the PNEC of 2.636 mug/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment. Title: Widespread Multiple Insecticide Resistance in the Major Dengue Vector Aedes albopictus in Hainan Province, China Li Y, Zhou G, Zhong D, Wang X, Hemming-Schroeder E, David RE, Lee MC, Zhong S, Yi G and Yan G <2 more author(s)> Li Y, Zhou G, Zhong D, Wang X, Hemming-Schroeder E, David RE, Lee MC, Zhong S, Yi G, Liu Z, Cui G, Yan G (- 2) Ref: Pest Manag Sci, 77:1945, 2020 : PubMed ESTHER: Li_2020_Pest.Manag.Sci_77_1945 PubMedSearch: Li 2020 Pest.Manag.Sci 77 1945 PubMedID: 33301644 Abstract BACKGROUND: Aedes albopictus is a highly invasive mosquito and has become a potential vector of dengue, chikungunya and Zika viruses. Insecticide-based mosquito interventions are the main tools for vector-borne disease control. However, mosquito resistance to insecticides is a major threat to effective prevention and control. Five Ae. albopictus populations across Hainan Province, China were investigated for susceptibility to multiple insecticides and resistance mechanisms. RESULTS: Larval bioassays indicated that resistance to pyrethroids was common in all larval populations. Adult bioassays revealed all populations were either resistant or highly resistant to at least 4 of the 6 synthetic insecticides (deltamethrin, permethrin, cyfluthrin, propoxur, malathion, and DDT) tested. Pre-exposure of mosquitoes to the synergistic agent piperonyl butoxide (PBO) increased mosquito mortality by 2.4-43.3% in bioassays to DDT, malathion, and permethrin and rendered mosquito sensitive to deltamethrin, cyfluthrin, and propoxur. The frequency of knockdown resistance (kdr) mutations (F1534S and F1534C) ranged from 69.8% to 89.3% and from 38.1% to 87.0% in field resistant and sensitive populations, respectively. F1534S mutation was significantly associated with pyrethroid resistance. No mutation was detected in acetylcholinesterase (ace-1) gene in the two examined populations. CONCLUSION: This study provides evidence of widespread resistance to multiple insecticides in Ae. albopictus in Hainan Province, China. Both kdr mutations and metabolic detoxification were the potential causes of insecticide resistance for Ae. albopictus. Our findings highlight the need for insecticide resistance management and mosquito control measures that do not entirely depend on synthetic insecticides. Title: Acetylcholinesterase-catalyzed silver deposition for ultrasensitive electrochemical biosensing of organophosphorus pesticides Liu Z, Xia X, Zhou G, Ge L, Li F Ref: Analyst, :, 2020 : PubMed ESTHER: Liu_2020_Analyst__ PubMedSearch: Liu 2020 Analyst PubMedID: 32031197 Abstract Herein, an electrochemical biosensing platform with acetylcholinesterase (AChE)-catalyzed silver deposition was developed for the ultrasensitive detection of organophosphorus pesticides (OPs). The biosensing mechanism is based on the fact that AChE can catalyze the rapid hydrolysis of indoxyl acetate to form hydroxyindole, which in turn reduces silver ions to metallic silver, resulting in the deposition of silver on the gold electrode. Upon sweeping positive voltages on the gold electrode using linear sweep voltammetry (LSV), the deposited silver on the gold electrode surface undergoes a rapid electrochemical oxidation reaction. Due to its lower oxidation potential under facile conditions with a relatively sharp peak, a small amount of deposited silver generated from AChE-catalysis could result in a significant change in the LSV response. In the presence of OPs, the AChE-catalyzed hydrolysis of indoxyl acetate is blocked, and then the silver deposition on the gold electrode declines, leading to a remarkable decrease in the LSV response and, thus producing a large signal output for the ultrasensitive detection of chlorpyrifos, a proof-of-concept OP in this work. The change in the LSV peak current intensity is linearly correlated with the logarithmic value of the chlorpyrifos concentration ranging from 10 pM to 10 nM with a low detection limit of 4.0 pM. To the best of our knowledge, this is the first example of a biosensing platform for ultrasensitive OP assay using AChE-controlled silver deposition to enhance the output of electronic signals. Title: GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine Liu Z, Qin G, Mana L, Dong Y, Huang S, Wang Y, Wu Y, Shi J, Tian J, Wang P Ref: Brain Behav, :e01602, 2020 : PubMed ESTHER: Liu_2020_Brain.Behav__e01602 PubMedSearch: Liu 2020 Brain.Behav e01602 PubMedID: 32174034 Abstract BACKGROUND: Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. METHODS: Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC-MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step-down passive-avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T-SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. RESULTS: After one-half or 1 month of intragastric administration, GAPT can ameliorate scopolamine-induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine-treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. CONCLUSIONS: GAPT can improve the learning and memory ability of scopolamine-induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury. Title: ROS-responsive and multifunctional anti-Alzheimer prodrugs: Tacrine-ibuprofen hybrids via a phenyl boronate linker Liu Z, Zhang B, Xia S, Fang L, Gou S Ref: Eur Journal of Medicinal Chemistry, :112997, 2020 : PubMed ESTHER: Liu_2020_Eur.J.Med.Chem__112997 PubMedSearch: Liu 2020 Eur.J.Med.Chem 112997 PubMedID: 33189440 Abstract Current drugs available in clinic for Alzheimer's disease (AD) treatment can only alleviate disease symptoms without clearly curing or delaying the process of AD. And some AD drugs failed in Phase III clinical trials are only focused on targeting amyloid-beta (Abeta). Therefore, an alternative strategy in AD drug design is meaningful to be involved in the multiple pathogenic factors which can affect each other at multiple levels. Herein, we report a series of ROS-responsive prodrugs based on multi-target-directed ligands (MTDLs) approach, which can specifically release tacrine derivatives and ibuprofen under oxidation of ROS and show acetylcholinesterase (AChE)-inhibiting, neuron-protective and anti-inflammatory effects in extracellular or intracellular assays. Related biological study illustrated that compound 22 was able to permeate blood-brain-barrier (BBB) showing little hepatotoxicity in comparison to tacrine. Besides, 22 hinted a therapeutic clue in AD-treatment by regulating proinflammatory factors (IL-1beta and TNF-alpha) and apoptosis related proteins (Bax, Bcl-2 and cleaved caspase-3). Further spatial memory assays in Abeta-induced AD model showed that 22 enhanced the ability of learning and memory. Our study proves that the strategy of ROS-responsive prodrugs has promise for AD treatments in future and offers a way for AD drug development. Title: Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model Lu C, Peng X, Lu D, Liu Z Ref: ACS Omega, 5:9806, 2020 : PubMed ESTHER: Lu_2020_ACS.Omega_5_9806 PubMedSearch: Lu 2020 ACS.Omega 5 9806 PubMedID: 32391467 Gene_locus related to this paper: canar-LipB Abstract Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme-substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. Candida antarctica lipase B (CALB) is extensively used for producing various chemicals because of its rich catalytic mechanisms, broad substrate spectrum, thermal stability, and tolerance to organic solvents. In this study, an all-atom molecular dynamics (MD) combined with Markov-state models (MSMs) implemented in pyEMMA was proposed to simulate diffusion pathways of 4-nitrophenyl ester (4NPE), a commonly used substrate, from the surface into the active site of CALB. Six important metastable conformations of CALB were identified in the diffusion process, including a closed state. An induced-fit mechanism incorporating multiple pathways with molecular information was proposed, which might find unprecedented applications for the rational design of lipase for green catalysis. Title: Single-Cell Profiling and SCOPE-Seq Reveal Lineage Dynamics of Adult Ventricular-Subventricular Zone Neurogenesis and NOTUM as a Key Regulator Mizrak D, Bayin NS, Yuan J, Liu Z, Suciu RM, Niphakis MJ, Ngo N, Lum KM, Cravatt BF and Sims PA <1 more author(s)> Mizrak D, Bayin NS, Yuan J, Liu Z, Suciu RM, Niphakis MJ, Ngo N, Lum KM, Cravatt BF, Joyner AL, Sims PA (- 1) Ref: Cell Rep, 31:107805, 2020 : PubMed ESTHER: Mizrak_2020_Cell.Rep_31_107805 PubMedSearch: Mizrak 2020 Cell.Rep 31 107805 PubMedID: 32579931 Gene_locus related to this paper: human-NOTUM Inhibitor(s) related to this paper: ABC99 Abstract In the adult ventricular-subventricular zone (V-SVZ), neural stem cells (NSCs) generate new olfactory bulb (OB) neurons and glia throughout life. To map adult neuronal lineage progression, we profiled >56,000 V-SVZ and OB cells by single-cell RNA sequencing (scRNA-seq). Our analyses reveal the molecular diversity of OB neurons, including fate-mapped neurons, lineage progression dynamics, and an NSC intermediate enriched for Notum, which encodes a secreted WNT antagonist. SCOPE-seq technology, which links live-cell imaging with scRNA-seq, uncovers cell-size transitions during NSC differentiation and preferential NOTUM binding to proliferating neuronal precursors. Consistently, application of NOTUM protein in slice cultures and pharmacological inhibition of NOTUM in slice cultures and in vivo demonstrated that NOTUM negatively regulates V-SVZ proliferation. Timely, context-dependent neurogenesis demands adaptive signaling among neighboring progenitors. Our findings highlight a critical regulatory state during NSC activation marked by NOTUM, which attenuates WNT-stimulated proliferation in NSC progeny. Title: Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer's disease Mo J, Chen T, Yang H, Guo Y, Li Q, Qiao Y, Lin H, Feng F, Liu W and Sun H <2 more author(s)> Mo J, Chen T, Yang H, Guo Y, Li Q, Qiao Y, Lin H, Feng F, Liu W, Chen Y, Liu Z, Sun H (- 2) Ref: J Enzyme Inhib Med Chem, 35:330, 2020 : PubMed ESTHER: Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330 PubMedSearch: Mo 2020 J.Enzyme.Inhib.Med.Chem 35 330 PubMedID: 31856607 Abstract Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer's disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 +/- 0.11 microM; 15j, eqBChE IC50 = 0.16 +/- 0.04 microM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD. Title: Irinotecan-mediated diarrhea is mainly correlated with intestinal exposure to SN-38: Critical role of gut Ugt Sun R, Zhu L, Li L, Song W, Gong X, Qi X, Wang Y, Ghose R, Gao S and Liu Z <1 more author(s)> Sun R, Zhu L, Li L, Song W, Gong X, Qi X, Wang Y, Ghose R, Gao S, Hu M, Liu Z (- 1) Ref: Toxicol Appl Pharmacol, :115032, 2020 : PubMed ESTHER: Sun_2020_Toxicol.Appl.Pharmacol__115032 PubMedSearch: Sun 2020 Toxicol.Appl.Pharmacol 115032 PubMedID: 32387182 Inhibitor(s) related to this paper: SN-38 Abstract BACKGROUND AND PURPOSE: Irinotecan-induced diarrhea (IID) results from intestinal damages by its active metabolite SN-38. Alleviation of these damages has focused on lowering luminal SN-38 concentrations. However, it is unclear if the enteric bioavailability of SN-38 is mostly dependent on luminal SN-38 concentrations. EXPERIMENTAL APPROACH: Irinotecan (50mg/kg, i.p. once daily for 6days) was administered to female wildtype FVB, Mdr1a (-/-), Mrp2 (-/-) and Bcrp1 (-/-) mice for pharmacokinetic (PK), toxicokinetic (TK) and biodistribution studies. Plasma PK/TK profiles and tissues drug distribution were determined after first or sixth daily doses, along with activities of blood and gut esterases and intestinal Ugts. Caco-2 cells and bile-cannulate mice were used to further investigate intestinal and biliary disposition of irinotecan and its metabolites. KEY RESULTS: Significant differences in IID severity were observed with the susceptible rank of Bcrp1(-/-)>wildtype FVB>Mdr1a(-/-)>Mrp2(-/-). This rank order did not correlate with biliary excretion rates of SN-38/SN-38G. Rather, the severity was best correlated (R=0.805) with the intestinal ratio of Css SN-38/SN-38G, a measure of gut Ugt activity. On the contrary, IID was poorly correlated with plasma AUC ratio of SN-38/SN-38G (R=0.227). Increased intestinal esterase activities due to repeated dosing and gut efflux transporter functionality are the other key factors that determine SN-38 enteric exposures. CONCLUSION AND IMPLICATIONS: Intestinal SN-38 exposure is mainly affected by intestinal Ugt activities and blood esterase activities, and strongly correlated with severity of IID. Modulating intestinal SN-38 concentration and gut Ugt expression should be the focus of future studies to alleviate IID. Title: Novozym 435-Catalyzed Synthesis of Well-Defined Hyperbranched Aliphatic Poly(beta-thioether ester) Wu WX, Liu Z Ref: Molecules, 25:, 2020 : PubMed ESTHER: Wu_2020_Molecules_25_ PubMedSearch: Wu 2020 Molecules 25 PubMedID: 32041136 Abstract A series of new hyperbranched aliphatic poly(beta-thioether ester)s were prepared by the enzymatic ring-opening polycondensation of 1,4-oxathiepan-7-one (OTO) and AB2/ABB' comonomer with acid-labile beta-thiopropionate groups. Two kinds of comonomers, methyl 3-((3-hydroxy-2-(hydroxymethyl)propyl)thio)propanoate (HHTP) and methyl 3-((2,3-dihydroxypropyl)thio)propanoate (DHTP), with different primary alcohols and secondary alcohols, were synthesized by thiol-ene click chemistry and thiol-ene Michael addition, respectively. Immobilized lipase B from Candida antarctica (CALB), Novozym 435, was used as the catalyst. The random copolymers were characterized by (1)H-NMR, (13)C-NMR, GPC, TGA, and DSC. All branched copolyesters had high molecular weights over 15,000 Da with narrow polydispersities in the range of 1.75-2.01 and were amorphous polymers. Their degradation properties under acidic conditions were also studied in vitro. The polymeric nanoparticles of hyperbranched poly(beta-thioether ester)s were successfully obtained and showed good oxidation-responsive properties, indicating their potential for biomedical applications. 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: Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II) Ye Q, Wang H, Xia X, Zhou C, Liu Z, Xia ZE, Zhang Z, Zhao Y, Yehenala J and He Y <5 more author(s)> Ye Q, Wang H, Xia X, Zhou C, Liu Z, Xia ZE, Zhang Z, Zhao Y, Yehenala J, Wang S, Zhou G, Hu K, Wu B, Wu CT, He Y (- 5) Ref: Trials, 21:520, 2020 : PubMed ESTHER: Ye_2020_Trials_21_520 PubMedSearch: Ye 2020 Trials 21 520 PubMedID: 32532356 Abstract OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m(2)) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x10(7) human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h +/- 30min, 24h +/- 30min after the injection) and follow-up period D90 +/- 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h +/- 30min, 24h +/- 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 +/- 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 +/- 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 beta, IL-2, TNF-a, ITN-gamma), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood beta-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 +/- 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h +/- 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16(th) April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Title: Soluble epoxide hydrolase as a therapeutic target for obesity-induced disorders: roles of gut barrier function involved Zhang J, Tu M, Liu Z, Zhang G Ref: Prostaglandins Leukot Essent Fatty Acids, 162:102180, 2020 : PubMed ESTHER: Zhang_2020_Prostaglandins.Leukot.Essent.Fatty.Acids_162_102180 PubMedSearch: Zhang 2020 Prostaglandins.Leukot.Essent.Fatty.Acids 162 102180 PubMedID: 33038829 Abstract Emerging research supports that soluble epoxide hydrolase (sEH), an enzyme involved in eicosanoid metabolism, could be a promising target for obesity-associated disorders. The sEH enzyme is overexpressed in many tissues of obese animals. Genetic ablation or pharmacological inhibition of sEH attenuates the development of a wide range of obesity-induced disorders, including endoplasmic reticulum stress, metabolic syndrome, kidney diseases, insulin resistance, fatty liver, hepatic steatosis, inflammation, and endothelial dysfunction. Furthermore, our recent research showed that genetic ablation or inhibition of sEH attenuated obesity-induced intestinal barrier dysfunction and its resulted bacterial translocation, which is widely regarded to be a central mechanism for the pathogenesis of various obesity-induced disorders. Together, these results support that targeting sEH could be a promising strategy to reduce risks of obesity-induced disorders, at least in part through blocking obesity-induced leaky gut syndrome. 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: Structure of a gut microbial diltiazem-metabolizing enzyme suggests possible substrate binding mode Zhou S, Ko TP, Huang JW, Liu W, Zheng Y, Wu S, Wang Q, Xie Z, Liu Z and Guo RT <1 more author(s)> Zhou S, Ko TP, Huang JW, Liu W, Zheng Y, Wu S, Wang Q, Xie Z, Liu Z, Chen CC, Guo RT (- 1) Ref: Biochemical & Biophysical Research Communications, :, 2020 : PubMed ESTHER: Zhou_2020_Biochem.Biophys.Res.Commun__ PubMedSearch: Zhou 2020 Biochem.Biophys.Res.Commun PubMedID: 32423809 Abstract When administrated orally, the vasodilating drug diltiazem can be metabolized into diacetyl diltiazem in the presence of Bacteroides thetaiotaomicron, a human gut microbe. The removal of acetyl group from the parent drug is carried out by the GDSL/SGNH-family hydrolase BT4096. Here the crystal structure of the enzyme was solved by mercury soaking and single-wavelength anomalous diffraction. The protein folds into two parts. The N-terminal part comprises the catalytic domain which is similar to other GDSL/SGNH hydrolases. The flanking C-terminal part is made up of a beta-barrel subdomain and an alpha-helical subdomain. Structural comparison shows that the catalytic domain is most akin to acetyl-xylooligosaccharide esterase and allows a plausible binding mode of diltiazem to be proposed. The beta-barrel subdomain is similar in topology to the immunoglobulin-like domains, including some carbohydrate-binding modules, of various bacterial glycoside hydrolases. Consequently, BT4096 might originally function as an oligosaccharide deacetylase with additional subdomains that could enhance substrate binding, and it acts on diltiazem just by accident. Title: Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation Gan L, Guo M, Si J, Zhang J, Liu Z, Zhao J, Wang F, Yan J, Li H, Zhang H Ref: Artif Cells Nanomed Biotechnol, 47:4202, 2019 : PubMed ESTHER: Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202 PubMedSearch: Gan 2019 Artif.Cells.Nanomed.Biotechnol 47 4202 PubMedID: 31713449 Abstract Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 muM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and gamma-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis. Title: Ratiometric two-photon fluorescent probe for in situ imaging of carboxylesterase (CE)-mediated mitochondrial acidification during medication Jiang A, Chen G, Xu J, Liu Y, Zhao G, Liu Z, Chen T, Li Y, James TD Ref: Chem Commun (Camb), 55:11358, 2019 : PubMed ESTHER: Jiang_2019_Chem.Commun.(Camb)_55_11358 PubMedSearch: Jiang 2019 Chem.Commun.(Camb) 55 11358 PubMedID: 31482158 Abstract We report on a dual ratiometric two-photon fluorescent probe for in situ sensing of mitochondrial CE activity and pH. Using the probe it is possible to visualize the CE-mediated acidification of hepatoma cells and hepatic tissues during medication with antipyretic anti-inflammatory drugs. Title: Pharmacodynamic and urinary metabolomics studies on the mechanism of Schisandra polysaccharide in the treatment of Alzheimer's disease Liu Y, Liu Z, Wei M, Hu M, Yue K, Bi R, Zhai S, Pi Z, Song F Ref: Food Funct, 10:432, 2019 : PubMed ESTHER: Liu_2019_Food.Funct_10_432 PubMedSearch: Liu 2019 Food.Funct 10 432 PubMedID: 30623955 Abstract Schisandra chinensis (Turcz.) Baill is produced mainly in northeast China, Korea and Japan. Its fruit has been used in food as a nutritional and functional ingredient for centuries. Polysaccharide is an important chemical component in Schisandra. Previous studies have shown that Schisandra polysaccharide (SCP) could be used to improve cognitive function clinically and treat age-related neurodegenerative disorders. In this study, a urinary metabolomics method based on ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was established to investigate the change of endogenous metabolites in an amyloid beta-protein (Abeta) 25-35-induced Alzheimer's disease (AD) rat model. Meanwhile, levels of 9 neurotransmitters were evaluated with ultrahigh-performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-TQ-MS) to explore the therapeutic mechanisms of SCP on the AD rat model. Additionally, the synthesis of phosphorylated tau protein (p-tau), acetylcholinesterase (AchE) activity and oxidative damage in the brain of the AD rats were assessed using glycogen synthase kinase-3beta (GSK3beta), AchE and antioxidant assays, NOS (nitric oxide synthase) and SOD (superoxide dismutase), respectively. The results indicated that the AD model was established successfully and the inducement of Abeta25-35 caused the phosphorylation of tau protein and the deposition of Abeta. In the AD model rats, the levels of AchE, GSK-3beta and NOS were significantly elevated and SOD activity was reduced. In the hippocampus of the model rats, the contents of gamma-aminobutyric acid, acetylcholine, glycine, norepinephrine, taurine, serotonin and dopamine were significantly decreased and the contents of glutamate and aspartic acid were increased significantly. However, SCP could reduce the degree of phosphorylation of tau protein, the deposition of Abeta and oxidative damage and reverse these changes of neurotransmitters in the AD rats. In a metabolomics study, a total of 38 metabolites were finally identified as potential biomarkers of AD and all of them had a significant recovery compared with the AD model after SCP administration. Metabolomics studies have shown that SCP plays a role in protecting the central nervous system, regulating intestinal microbial metabolism, regulating energy metabolism, and promoting antioxidant effects by regulating the levels of endogenous metabolites in related pathways. This is first report of the use of urine metabolomics combined with the evaluation of 9 neurotransmitter levels to investigate the mechanism of SCP on the treatment of AD. Title: The effect on congenital heart diseases of maternal EPHX1 polymorphisms modified by polycyclic aromatic hydrocarbons exposure Tao J, Li N, Liu Z, Deng Y, Li X, Chen M, Yu J, Zhu J, Yu P, Wang Y Ref: Medicine (Baltimore), 98:e16556, 2019 : PubMed ESTHER: Tao_2019_Medicine.(Baltimore)_98_e16556 PubMedSearch: Tao 2019 Medicine.(Baltimore) 98 e16556 PubMedID: 31348278 Abstract Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure. Title: Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters Trotter JH, Hao J, Maxeiner S, Tsetsenis T, Liu Z, Zhuang X, Sudhof TC Ref: Journal of Cell Biology, 218:2677, 2019 : PubMed ESTHER: Trotter_2019_J.Cell.Biol_218_2677 PubMedSearch: Trotter 2019 J.Cell.Biol 218 2677 PubMedID: 31262725 Abstract Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate that neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature of synaptic architecture. Synapses generally contain a single nanocluster that comprises more than four neurexin-1 molecules and that also includes neurexin-2 and/or neurexin-3 isoforms. Moreover, we find that neurexin-1 is physiologically cleaved by ADAM10 similar to its ligand neuroligin-1, with approximately 4-6% of neurexin-1 and approximately 2-3% of neuroligin-1 present in the adult brain as soluble ectodomain proteins. Blocking ADAM10-mediated neurexin-1 cleavage dramatically increased the synaptic neurexin-1 content, thereby elevating the percentage of Homer1(+) excitatory synapses containing neurexin-1 nanoclusters from 40-50% to approximately 80%, and doubling the number of neurexin-1 molecules per nanocluster. Taken together, our results reveal an unexpected nanodomain organization of synapses in which neurexin-1 is assembled into discrete presynaptic nanoclusters that are dynamically regulated via ectodomain cleavage. Title: Candidate detoxification-related genes in brown planthopper, Nilaparvata lugens, in response to beta-asarone based on transcriptomic analysis Xu X, Li X, Wang F, Han K, Liu Z, Fan L, Hua H, Cai W, Yao Y Ref: Ecotoxicology & Environmental Safety, 185:109735, 2019 : PubMed ESTHER: Xu_2019_Ecotoxicol.Environ.Saf_185_109735 PubMedSearch: Xu 2019 Ecotoxicol.Environ.Saf 185 109735 PubMedID: 31586846 Abstract Nilaparvata lugens(Stal) is a serious pest of rice and has evolved different levels of resistance against most chemical pesticides. beta-asarone is the main bioactive insecticidal compound of Acorus calamus L. that shows strong insecticidal activity against pests. In this study, we conducted a bioassay experiment to determine the contact toxicity of beta-asarone to N. lugens nymphs. The LD30 sublethal dose was 0.106mug per nymph, with 95% confidence limits of 0.070-0.140mug. We applied the LD30 concentration of beta-asarone to nymphs for 24h or 72h and then performed a transcriptome sequence analysis by referencing the N. lugens genome to characterize the variation. The transcriptomic analysis showed that several GO terms and KEGG pathways presented significant changes. Individually, 126 differentially expressed genes (DEGs), including 72 upregulated and 54 downregulated genes, were identified at 24h, and 1771 DEGs, including 882 upregulated and 889 downregulated genes, were identified at 72h. From the DEGs, we identified a total of 40 detoxification-related genes, including eighteen Cytochrome P450 monooxygenase genes (P450s), three Glutathione S-transferase genes, one Carboxylesterase gene, twelve UDP-glucosyltransferases and six ATP-binding cassette genes. We selected the eighteen P450s for subsequent verification by quantitative PCR. These findings indicated that beta-asarone presented strong contact toxicity to N. lugens nymphs and induced obvious variation of detoxification-related genes that may be involved in the response to beta-asarone. Title: Catalytic Hydrolysis Mechanism of Cocaine by Human Carboxylesterase 1: An Orthoester Intermediate Slows Down the Reaction Yan M, Zhang Z, Liu Z, Zhang C, Zhang J, Fan S, Yang Z Ref: Molecules, 24:, 2019 : PubMed ESTHER: Yan_2019_Molecules_24_ PubMedSearch: Yan 2019 Molecules 24 PubMedID: 31717501 Gene_locus related to this paper: human-CES1 Abstract Human carboxylesterase 1 (hCES1) is a major carboxylesterase in the human body and plays important roles in the metabolism of a wide variety of substances, including lipids and drugs, and therefore is attracting more and more attention from areas including lipid metabolism, pharmacokinetics, drug-drug interactions, and prodrug activation. In this work, we studied the catalytic hydrolysis mechanism of hCES1 by the quantum mechanics computation method, using cocaine as a model substrate. Our results support the four-step theory of the esterase catalytic hydrolysis mechanism, in which both the acylation stage and the deacylation stage include two transition states and a tetrahedral intermediate. The roles and cooperation of the catalytic triad, S221, H468, and E354, were also analyzed in this study. Moreover, orthoester intermediates were found in hCES1-catalyzed cocaine hydrolysis reaction, which significantly elevate the free energy barrier and slow down the reaction. Based on this finding, we propose that hCES1 substrates with beta-aminocarboxylester structure might form orthoester intermediates in hCES1-catalyzed hydrolysis, and therefore prolong their in vivo half-life. Thus, this study helps to clarify the catalytic mechanism of hCES1 and elucidates important details of its catalytic process, and furthermore, provides important insights into the metabolism of hCES1 substrates and drug designing. Title: Transcript-Level Analysis of Detoxification Gene Mutation-Mediated Chlorpyrifos Resistance in Laodelphax striatellus (Hemiptera: Delphacidae) Zhang Y, Ma X, Han Y, Wang L, Liu Z, Guo H, Fang J Ref: J Econ Entomol, 112:1285, 2019 : PubMed ESTHER: Zhang_2019_J.Econ.Entomol_112_1285 PubMedSearch: Zhang 2019 J.Econ.Entomol 112 1285 PubMedID: 30615131 Abstract Enhanced detoxification and target mutations that weaken insecticide binding ability are major mechanisms of insecticide resistance. Among these, over-expression or site mutations of carboxylesterase (CarE), cytochrome P450s (CYP450), and glutathione-S-transferase (GST) were the main form responsible for insecticide detoxification; however, transcript-level analysis of the relationship of detoxification gene mutations with chlorpyrifos (an organophosphorus insecticide) resistance is scarce thus far. In this study, multiple sites exhibiting polymorphisms within three detoxification genes were firstly examined via sequencing among different chlorpyrifos-resistant and susceptible individuals of Laodelphax striatellus. For example, the mutation frequencies of A374V in LsCarE16 were 83, 33, and 3%, S277A in LsCarE24 were 88, 28, and 3%, E36K in LsCYP426A1 were 100, 65, and 0% for chlorpyrifos-resistant, resistant decay, and susceptible individuals, respectively. Analysis also found expression levels of GSTd1, GSTt1, GSTs2, CYP4DE1U1, and CYP425B1 are coordinated with chlorpyrifos resistance levels; moreover, we found the deficiencies of 43S and 44A as well as two point mutations of E60D and Q61H at N-terminal region of the OP potential target acetylcholinesterase (AChE) in high resistant but not in low-chlorpyrifos resistant individuals. The results above all demonstrated the dynamic evolutionary process of insecticide resistance and revealed some resistance factors that only played roles at certain resistance level; high insecticide resistance in this example is the result of synergistic impact from multiple resistance factors. Title: Bio-/Nanoimmobilization Platform Based on Bioinspired Fibrin-Bone@Polydopamine-Shell Adhesive Composites for Biosensing Zhang L, Liu Z, Zha S, Liu G, Zhu W, Xie Q, Li Y, Ying Y, Fu Y Ref: ACS Appl Mater Interfaces, 11:47311, 2019 : PubMed ESTHER: Zhang_2019_ACS.Appl.Mater.Interfaces_11_47311 PubMedSearch: Zhang 2019 ACS.Appl.Mater.Interfaces 11 47311 PubMedID: 31742992 Abstract Inspired by blood coagulation and mussel adhesion, we report novel adhesive fibrin-bone@polydopamine (PDA)-shell composite matrix as highly efficient immobilization platform for biomacromolecules and nanomaterials. Fibrin, as a bioglue, and PDA, as a chemical adhesive, are integrated in a one-pot simultaneous polymerization consisting of biopolymerization of fibrinogen and chemical polymerization of dopamine. Fibrin fibers act as adhesive bones to construct scaffold, while PDA coat on the scaffold to form adhesive shell, generating 3D porous composite matrix with unique bone@shell structure. Two types of enzymes (glucose oxidase and acetylcholinesterase) and Au nanoparticles were adopted as respective model biomolecules and nanomaterials to investigate the immobilization capability of the matrix. The bionanocomposites showed high efficiency in capturing nanoparticles and enzymes, as well as significant mass-transfer and biocatalysis efficiencies. Therefore, the bionanocomposites exhibited significant potential in biosensing of glucose and paraoxon with limits of detection down to 5.2 muM and 4 ppt, respectively. The biological-chemical-combined polymerization strategy and composite platform with high immobilization capacity and mass-transfer efficiency open up a novel way for the preparation of high-performance bionanocomposites for various applications, in particular, biosensing. Title: Dual effects of insect nAChR chaperone RIC-3 on hybrid receptor: Promoting assembly on endoplasmic reticulum but suppressing transport to plasma membrane on Xenopus oocytes Bao H, Xu X, Liu W, Yu N, Liu Z Ref: Neurochem Int, 115:24, 2018 : PubMed ESTHER: Bao_2018_Neurochem.Int_115_24 PubMedSearch: Bao 2018 Neurochem.Int 115 24 PubMedID: 29032010 Abstract Resistance to inhibitors of cholinesterase (RIC) -3 promotes the maturation (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs) as a molecular chaperone. The modulation effects of RIC-3 on homomeric alpha7 nAChRs are always positive, but its effects on heteromeric subtypes are inconsistent among reports. In this study, five RIC-3 isoforms were identified from Locusta migratoria. Four isoforms showed obvious effects on hybrid receptor Localpha1/rbeta2 expressed in Xenopus oocytes. As a representative, the co-expression of RIC-3v4 exhibited the decreased agonist responses (Imax) on oocytes, lower specific [(3)H]epibatidine binding (Bmax) on plasma membrane protein (PMP), and reduced subunit levels in PMP, which showed that the mature Localpha1/rbeta2 on the plasma membrane was decreased by the co-expression of RIC-3. In contrast, the [(3)H]epibatidine binding and mature Localpha1/rbeta2 levels in the endoplasmic reticulum membrane protein (ERMP) were much increased when co-expressing with RIC-3v4. The [(3)H]epibatidine binding and mature Localpha1/rbeta2 levels in total membrane protein (TMP) gave the similar results as that in ERMP. Taking data together, the results showed that the co-expression of RIC-3 increased the mature Localpha1/rbeta2 receptor levels on ER of Xenopus oocytes, but these mature receptors were mostly kept on ER and suppressed to transport to plasma membrane. Title: Engineering and characterization of a novel low temperature active and thermo stable esterase from marine Enterobacter cloacae Ke M, Ramesh B, Hang Y, Liu Z Ref: Int J Biol Macromol, 118:304, 2018 : PubMed ESTHER: Ke_2018_Int.J.Biol.Macromol_118_304 PubMedSearch: Ke 2018 Int.J.Biol.Macromol 118 304 PubMedID: 29842953 Abstract Esterases are one of the most important industrial enzymes. Here, a novel estA was cloned from Enterobacter sp. and characterized. The sequence alignment results showed that it was a novel esterase. The purified EstA had a molecular weight of 26 KDa with an optimum temperature and pH of 40 degrees C and 9.0. EstA retained >70% activity between 0 degrees C and 20 degrees C, indicating it was a low temperature active enzyme. EstA exhibited low activity after incubation at 45 degrees C for 120min or 50 degrees C for 30min. In the presence of organic solvents, detergents and different concentrations of NaCl, EstA retained high activity. In order to improve thermal stability, a mutant A92D with better thermal stability than EstA was obtained by random mutation. ESTA92D showed high activity at 45 degrees C for 120min and maintained 85% of the original activity at 50 degrees C for 30min, approximately a 3.4-fold increase over EstA. Homology modeling analysis showed that the improved thermostability of ESTA92D was attributed to hydrophilic Asp rather than hydrophobic Ala, leading to an increase of the interaction and solubility as well as the surrounding area. The improved thermostability of low-temperature-active EstA suggests its immense applications in industrial applications. Title: The Cholinergic and Adrenergic Autocrine Signaling Pathway Mediates Immunomodulation in Oyster Crassostrea gigas Liu Z, Wang L, Lv Z, Zhou Z, Wang W, Li M, Yi Q, Qiu L, Song L Ref: Front Immunol, 9:284, 2018 : PubMed ESTHER: Liu_2018_Front.Immunol_9_284 PubMedSearch: Liu 2018 Front.Immunol 9 284 PubMedID: 29535711 Abstract It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine-immune (NEI) system was identified in oyster, which modulated neural immune response via a "nervous-hemocyte"-mediated neuroendocrine immunomodulatory axis (NIA)-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system. After hemocytes were exposed to lipopolysaccharide (LPS) stimulation, acetylcholine (ACh), and norepinephrine (NE) in the cell supernatants, both increased to a significantly higher level (2.71- and 2.40-fold, p < 0.05) comparing with that in the control group. The mRNA expression levels and protein activities of choline O-acetyltransferase and dopamine beta-hydroxylase in hemocytes which were involved in the synthesis of ACh and NE were significantly elevated at 1 h after LPS stimulation, while the activities of acetylcholinesterase and monoamine oxidase, two enzymes essential in the metabolic inactivation of ACh and NE, were inhibited. These results demonstrated the existence of the sophisticated intracellular machinery for the generation, release and inactivation of ACh and NE in oyster hemocytes. Moreover, the hemocyte-derived neurotransmitters could in turn regulate the mRNA expressions of tumor necrosis factor (TNF) genes, the activities of superoxide dismutase, catalase and lysosome, and hemocyte phagocytosis. The phagocytic activities of hemocytes, the mRNA expressions of TNF and the activities of key immune-related enzymes were significantly changed after the block of ACh and NE receptors with different kinds of antagonists, suggesting that autocrine/paracrine self-regulation was mediated by transmembrane receptors on hemocyte. The present study proved that oyster hemocyte could de novo synthesize and release cholinergic and adrenergic neurotransmitters, and the hemocyte-derived ACh/NE could then execute a negative regulation on hemocyte phagocytosis and synthesis of immune effectors with similar autocrine/paracrine signaling pathway identified in vertebrate macrophages. Findings in the present study demonstrated that the immune and neuroendocrine system evolved from a common origin and enriched our knowledge on the evolution of NEI system. Title: Insecticidal Mechanism of Wintergreen Oil Against the Health Pest Paederus fuscipes (Coleoptera: Staphylinidae) Liu Z, Zhang Q, Wu X, Yu W, Guo S Ref: Journal of Medical Entomology, 55:155, 2018 : PubMed ESTHER: Liu_2018_J.Med.Entomol_55_155 PubMedSearch: Liu 2018 J.Med.Entomol 55 155 PubMedID: 29029320 Abstract Paederus fuscipes, a health pest, causes dermatitis linearis in humans. Wintergreen oil exhibits optimal insecticidal activity against P. fuscipes. However, the insecticidal mechanism remains unclear not only in P. fuscipes but also in other pests. In this study, we explored the insecticidal mechanism of wintergreen oil in terms of its effect on the activity of acetylcholinesterase (AChE) enzyme and detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and mixed function oxidase); such effect was studied by fumigation both in vivo and in vitro in P. fuscipes male and female adults. In the in vivo and in vitro experiments on male and female adults, wintergreen oil did not significantly affect the activities of the three detoxifying enzymes. Hence, the mode of action of wintergreen oil may be unrelated to the three detoxifying enzymes. Wintergreen oil significantly inhibited AChE activity. When wintergreen oil was tested at different times in vivo, the highest inhibition rates were 41.99% (male) and 40.91% (female). When different doses of wintergreen oil were used for in vivo treatment, the highest inhibition rates were 33.78% (male) and 43.33% (female). When wintergreen oil was tested in vitro, the highest inhibition rates were 31.06% (male) and 35.57% (female). In vitro with chlorpyrifos as a positive control, the AChE activity of 3-mul wintergreen oil treatment was significantly lower than that of 10 mg/liter chlorpyrifos in both P. fuscipes male and female adults. The results demonstrated that AChE is a potential key factor, maybe a target enzyme, in the mechanism of wintergreen oil against P. fuscipes. Title: Possible mechanism of Vitis vinifera L. flavones on neurotransmitters, synaptic transmission and related learning and memory in Alzheimer model rats Ma L, Xiao H, Wen J, Liu Z, He Y, Yuan F Ref: Lipids Health Dis, 17:152, 2018 : PubMed ESTHER: Ma_2018_Lipids.Health.Dis_17_152 PubMedSearch: Ma 2018 Lipids.Health.Dis 17 152 PubMedID: 29973282 Abstract BACKGROUND: This study explored the possible mechanism of flavones from Vitis vinifera L. (VTF) on neurotransmitters, synaptic transmission and related learning and memory in rats with Alzheimer disease (AD). METHODS: The researchers injected amyloid-beta(25-35) into the hippocampus to establish AD model rats. The Sprague-Dawley (SD) rats were divided into a control group, a donepezil group, an AD model group, a VTF low-dose group, a VTF medium-dose group and a VTF high-dose group. The researchers detected the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) according to kit instructions. The protein expression of brain-derived neurotrophic factor (BDNF), synaptotagmin-1 (SYT1) and cyclic adenosine monophosphate response element binding protein (CREB) in the rats' hippocampi was detected by immunohistochemistry and Western blot, and the gene expression of cAMP-regulated enhancer (CRE) was detected by real-time quantitative polymerase chain reaction (PCR). RESULTS: VTF may enhance the protein expression of p-CREB, BDNF and SYT1 in rat hippocampi, depending on dose. The messenger RNA (mRNA) level of CREB was significantly higher in the VTF high-dose group than in the model group, which was consistent with the results of Western blotting. VTF may reduce the activity of AChE and increase that of ChAT in rat hippocampi. Finally, VTF effectively improved the learning and memory abilities of AD rats. CONCLUSIONS: VTF can promote synaptic plasticity and indirectly affect the expression of cholinergic neurotransmitters, which may be one mechanism of VTF protection in AD rats. Title: Comparative genomics of the wheat fungal pathogen Pyrenophora tritici-repentis reveals chromosomal variations and genome plasticity Moolhuijzen P, See PT, Hane JK, Shi G, Liu Z, Oliver RP, Moffat CS Ref: BMC Genomics, 19:279, 2018 : PubMed ESTHER: Moolhuijzen_2018_BMC.Genomics_19_279 PubMedSearch: Moolhuijzen 2018 BMC.Genomics 19 279 PubMedID: 29685100 Gene_locus related to this paper: 9pleo-a0a2w1h6j9, pyrtr-b2vzr5, 9pleo-a0a2w1duy4 Abstract BACKGROUND: Pyrenophora tritici-repentis (Ptr) is a necrotrophic fungal pathogen that causes the major wheat disease, tan spot. We set out to provide essential genomics-based resources in order to better understand the pathogenicity mechanisms of this important pathogen. RESULTS: Here, we present eight new Ptr isolate genomes, assembled and annotated; representing races 1, 2 and 5, and a new race. We report a high quality Ptr reference genome, sequenced by PacBio technology with Illumina paired-end data support and optical mapping. An estimated 98% of the genome coverage was mapped to 10 chromosomal groups, using a two-enzyme hybrid approach. The final reference genome was 40.9 Mb and contained a total of 13,797 annotated genes, supported by transcriptomic and proteogenomics data sets. CONCLUSIONS: Whole genome comparative analysis revealed major chromosomal segmental rearrangements and fusions, highlighting intraspecific genome plasticity in this species. Furthermore, the Ptr race classification was not supported at the whole genome level, as phylogenetic analysis did not cluster the ToxA producing isolates. This expansion of available Ptr genomics resources will directly facilitate research aimed at controlling tan spot disease. Title: The role of ursodeoxycholic acid on cholestatic hepatic fibrosis in infant rats Tang N, Zhang Y, Liang Q, Liu Z, Shi Y Ref: Mol Med Rep, 17:3837, 2018 : PubMed ESTHER: Tang_2018_Mol.Med.Rep_17_3837 PubMedSearch: Tang 2018 Mol.Med.Rep 17 3837 PubMedID: 29257337 Abstract The aim of the present study was to identify the impact of ursodeoxycholic acid (UDCA) on liver function and fibrosis markers in infant rats by establishing a cholestaticinduced hepatic fibrosis model. alphanaphthylisothiocyanate (ANIT) was administrated by gavage to induce cholestatic hepatic fibrosis in infant rats. UCDA treatment was performed to assess its impact on biochemical indicators of liver function, four serum biomarkers of hepatic fibrosis, hepatic fibrosis indices in liver tissues and the pathology of liver tissues. Colorimetric assays and biochemical assays based on the initial rate method were performed to determine the levels of liver function markers in the serum, whereas the serum biomarkers of hepatic fibrosis were measured via radioimmunoassay. Sections of liver tissue were harvested and stained with hematoxylineosin or picric acidSirius red, and subjected to immunohistochemical staining to analyze liver pathology. All indicators of liver function, except for cholinesterase, were significantly higher in the ANIT model than in the control group (P<0.01). gammaglutamyl transpeptidase and total bile acids of the UDCA treatment group were significantly lower than the ANIT model (P<0.05); whereas no significant differences were observed in alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and indirect bilirubin between the two groups. Serum laminin protein (LN) and typeIV collagen (cIV) in the UDCA treatment group were significantly lower than in the ANIT model (P<0.01); whereas no significant differences were observed in hyaluronic acid and typeIII procollagen between the two groups. Liver LN and cIV in the UDCA treatment group were significantly lower than in the ANIT model (P<0.01). The degree of hepatic fibrosis in the UDCA treatment group was significantly lower than in the ANIT model (P<0.01). The results of the present study demonstrated that UDCA is able to reduce LN and cIV in serum and protect liver tissues against hepatic fibrosis. Title: Studies on the interaction of BDE-47 and BDE-209 with acetylcholinesterase (AChE) based on the neurotoxicity through fluorescence, UV-vis spectra, and molecular docking Wang S, Wu C, Liu Z, You H Ref: Toxicol Lett, 287:42, 2018 : PubMed ESTHER: Wang_2018_Toxicol.Lett_287_42 PubMedSearch: Wang 2018 Toxicol.Lett 287 42 PubMedID: 29407791 Abstract The neurotoxicity of polybrominated diphenyl ethers (PBDEs) has been of concern. Acetylcholinesterase (AChE) is a critical enzyme in the central and peripheral nervous system related to neurotoxicity. The interaction between BDE-47, BDE-209, and AChE was investigated through fluorescence and UV-vis spectra combined with molecular docking. Both BDE-47 and BDE-209 bound with AChE and changed the microenvironment of some amino acid residues, resulting in a change of AChE conformation. Hydrophobic interaction is the main binding force between BDE-47, BDE-209, and AChE, and electrostatic interaction exists according to the thermodynamic parameters of the interaction between them. A hydrophobic interaction of BDE-47-AChE and BDE-209-AChE has been confirmed through molecular docking to dominate the binding force. The binding constants of BDE-47-AChE and BDE-209-AChE were 4.2x10(4) and 4.1x10(4)L/mol, respectively, and the lowest binding energies of BDE-47-AChE and BDE-209-AChE were -7.8 and -5.9kJ/mol, respectively. BDE-47 is more likely to bind with AChE than BED-209. Title: Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy Wang Q, Liang Y, Qiao Y, Zhao X, Yang Y, Yang S, Li B, Zhao Q, Dong L and Liu Z <2 more author(s)> Wang Q, Liang Y, Qiao Y, Zhao X, Yang Y, Yang S, Li B, Zhao Q, Dong L, Quan S, Tian R, Liu Z (- 2) Ref: American Journal of Physiology Renal Physiol, 315:F915, 2018 : PubMed ESTHER: Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915 PubMedSearch: Wang 2018 Am.J.Physiol.Renal.Physiol 315 F915 PubMedID: 29717935 Abstract Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in the kidney remains unknown. In this study, we investigated the relationships between the level of sEH and clinical and pathological parameters in IgA nephropathy. The level of sEH expression positively correlated with proteinuria and infiltration of macrophages. sEH-positive tubules were found to be surrounded by macrophages. Furthermore, we found that incubation of immortalized human proximal tubular HK-2 cells with total urinary protein and overexpression of sEH promoted inflammatory factor production, which was associated with M1 polarization. We also exposed RAW264.7 mouse leukemic monocytes/macrophages to different HK-2 cell culture media conditioned by incubation with various substances affecting sEH amount or activity. We found that the upregulation of sEH promoted M1 polarization. However, pharmacological inhibition of sEH and supplementation with EETs reversed the conditioning effects of urinary proteins by inhibiting M1 polarization through the NF-kappaB pathway and stimulating M2 polarization through the phosphatidylinositol 3-kinase pathway. These data suggest that inhibition of sEH could be a new strategy to prevent the progression of inflammation and to attenuate renal tubulointerstitial fibrosis. Title: Impact of dipeptidyl-peptidase 4 inhibitors on cardiovascular diseases Xie W, Song X, Liu Z Ref: Vascul Pharmacol, 109:17, 2018 : PubMed ESTHER: Xie_2018_Vascul.Pharmacol_109_17 PubMedSearch: Xie 2018 Vascul.Pharmacol 109 17 PubMedID: 29879463 Abstract Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications. DPP-4 has the capability to inactivate not only incretins, but also a series of cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. Pre-clinical studies suggested that DPP-4 inhibitors may have potential cardiovascular protective effects in addition to their antidiabetic actions. In recent years, a number of clinical trials have been conducted to evaluate the effect of different DPP-4 inhibitors on the cardiovascular system. We herein review the available clinical studies in cardiovascular effects played by each DPP-4 inhibitor and discuss the prospective application of DPP-4 inhibitors on cardiovascular diseases. Title: Accumulation of polystyrene microplastics in juvenile Eriocheir sinensis and oxidative stress effects in the liver Yu P, Liu Z, Wu D, Chen M, Lv W, Zhao Y Ref: Aquat Toxicol, 200:28, 2018 : PubMed ESTHER: Yu_2018_Aquat.Toxicol_200_28 PubMedSearch: Yu 2018 Aquat.Toxicol 200 28 PubMedID: 29709883 Abstract As a widespread and ubiquitous pollutant of marine ecosystems, microplastic has the potential to become an emerging global threat for aquatic organisms. The present study aims to elucidate the effects of microplastics on the growth, accumulation and oxidative stress response in the liver of Eriocheir sinensis. Fluorescent microplastic particles (diameter=0.5mum) accumulated in the gill, liver and gut tissues of E. sinensis were investigated when crabs were exposed to a concentration of 40000mug/L for 7days. A 21day toxicity test suggested that the rate of weight gain, specific growth rate, and hepatosomatic index of E. sinensis decreased with increasing microplastic concentration (0mug/L, 40mug/L, 400mug/L, 4000mug/L and 40000mug/L). The activities of AChE and GPT in crabs exposed to microplastics were lower than those in control group. GOT activity increased significantly after exposure to a low concentration of microplastics and then decreased continuously with increasing microplastic concentrations. The activities of superoxide dismutase (SOD), aspartate transaminase (GOT), glutathione (GSH), and glutathione peroxidase (GPx) increased in specimens exposed to low concentrations of microplastics (40 and 400mug/L) compared to the control and decreased in organisms exposed to high concentrations (4000 and 40000mug/L). In contrast, the activities of acetylcholinesterase, catalase (CAT), and alanine aminotransferase were significantly lower in the organisms exposed to microplastics compared to control animals. Upon exposure to increasing microplastic concentrations, the expression of genes encoding the antioxidants SOD, CAT, GPx and glutathione S-transferase in the liver decreased after first increasing. Exposure to microplastics increased the expression of the gene encoding p38 in the MAPK signaling pathway and significantly decreased the expressions of genes encoding ERK, AKT, and MEK. The results of this study demonstrate that microplastics can accumulate in the tissues of E. sinensis and negatively affect growth. In addition, exposure to microplastics causes damage and induces oxidative stress in the hepatopancreas of E. sinensis. The findings provide basic biological data for environmental and human risk assessments of microplastics of high concern. Title: Occurrence, distribution and ecological risks of organophosphate esters and synthetic musks in sediments from the Hun River Zeng X, Hu Q, He L, Liu Z, Gao S, Yu Z Ref: Ecotoxicology & Environmental Safety, 160:178, 2018 : PubMed ESTHER: Zeng_2018_Ecotoxicol.Environ.Saf_160_178 PubMedSearch: Zeng 2018 Ecotoxicol.Environ.Saf 160 178 PubMedID: 29804014 Abstract The Hun River is an important main tributary of the Liao River system. It is located in northeast China, and provides water resources for agriculture and industry. A man made reservoir (Dahuofang Reservoir, DHF) has been constructed mid-stream in the Hun River, supplying drinking water to surrounding cities. Pollution from organic contaminants is of great concern. In the present study, 40 sediment samples were collected and analyzed for the occurrence and distribution of two groups of emerging organic pollutants; namely, organophosphate esters (OPs) and synthetic musks (SMs). In all samples taken from upstream of the Hun River (UHR), downstream of the Hun River (DHR), and from DHF, the following concentrations were recorded: 0.141-4.39, 1.21-245, and 0.117-0.726microg/kg galaxolide (HHCB), and 0.098-3.82, 2.79-213, 0.430-0.956microg/kg tonalide (AHTN), respectively. For OPs, seven target analytes were detected in most of the sediment samples, with chlorinated OPs Tris-(2-chloroethyl) phosphate and Tris(2-chloro-isopropyl) phosphate being the dominant components, at levels varied in the range of LOD-0.810, ND-49.6, and 0.532-3.18microg/kg, and LOD-0.786, ND-60.1, and 0.352-1.32microg/kg from UHR, DHR and DHF, respectively. The elevated levels of these target compounds were detected in DHR, including its two main tributaries, Xi River and Pu River, which drain through cities with industrial development and dense populations. Our results indicate that domestic and industrial wastewater contributed to OPs and SMs sediment pollution, posing low to medium ecological risks to sediment dwelling organisms. Title: Neuroprotective Effects and Mechanisms of Action of Multifunctional Agents Targeting Free Radicals, Monoamine Oxidase B and Cholinesterase in Parkinson's Disease Model Liu Z, Cai W, Lang M, Yan R, Li Z, Zhang G, Yu P, Wang Y, Sun Y, Zhang Z Ref: Journal of Molecular Neuroscience, 61:498, 2017 : PubMed ESTHER: Liu_2017_J.Mol.Neurosci_61_498 PubMedSearch: Liu 2017 J.Mol.Neurosci 61 498 PubMedID: 28144826 Abstract Parkinson's disease (PD) is a complex neurodegenerative disorder with multifactorial pathologies, including progressive loss of dopaminergic (DA) neurons, oxidative stress, mitochondrial dysfunction, and increased monoamine oxidase (MAO) enzyme activity. There are currently only a few agents approved to ameliorate the symptoms of PD; however, no agent is able to reverse the progression of the disease. Due to the multifactorial pathologies, it is necessary to develop multifunctional agents that can affect more than one target involved in the disease pathology. We have designed and synthesized a series of new multifunctional anti-Parkinson's compounds which can protect cerebral granular neurons from 1-methyl-4-phenylpyridinium (MPP+) insult, scavenge free radicals, and inhibit monoamine oxidase (MAO)/cholinesterase (ChE) activities. Among them, MT-20R exhibited the most potent MAO-B inhibition both in vitro and in vivo. We further investigated the neuroprotective effects of MT-20R using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. In vivo, MT-20R alleviated MPTP-induced motor deficits, raised the striatal contents of dopamine and its metabolites, and restored the expression of tyrosine hydroxylase (TH) and the number of TH-positive DA neurons in the substantia nigra. Additionally, MT-20R enhanced the expression of Bcl-2, decreased the expression of Bax and Caspase 3, and activated the AKT/Nrf2/HO-1 signaling pathway. These findings suggest that MT-20R may be a novel therapeutic candidate for treatment of PD. Title: Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property Liu Z, Fang L, Zhang H, Gou S, Chen L Ref: Bioorganic & Medicinal Chemistry, 25:2387, 2017 : PubMed ESTHER: Liu_2017_Bioorg.Med.Chem_25_2387 PubMedSearch: Liu 2017 Bioorg.Med.Chem 25 2387 PubMedID: 28302511 Abstract Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H2O2/Abeta42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Abeta aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K3-2, can be considered as potential therapeutic agents for Alzheimer's disease. 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: Functional characterization of two acetylcholinesterase genes in the brown citrus aphid, Aphis (Toxoptera) citricidus (Kirkaldy), using heterologous expression and RNA interference Mou X, Yuan GR, Jiang HB, Liu Z, Wang JJ Ref: Pestic Biochem Physiol, 138:76, 2017 : PubMed ESTHER: Mou_2017_Pestic.Biochem.Physiol_138_76 PubMedSearch: Mou 2017 Pestic.Biochem.Physiol 138 76 PubMedID: 28456308 Gene_locus related to this paper: toxci-a0a0x9e4f6, toxci-a0a0x9fvc0 Abstract Acetylcholinesterase (AChE) is the primary target of organophosphate- and carbamate-based insecticides. We sequenced the full-length cDNAs of two AChE genes from the brown citrus aphid Aphis (Toxoptera) citricidus (Kirkaldy). These two genes, Tcace1 and Tcace2, which encode TcAChE1 and TcAChE2, respectively, had a shared amino acid identity of 29% and were highly similar to other insect ace1 and ace2 genes, respectively, having specific functional motifs. Potential differences in enzymatic function were characterized by the heterologous expression of the two genes using a baculovirus system in Sf9 insect cells. Both of the recombinant AChEs had high specific activities for three typical substrates, acetylthiocholine iodide, butyrylthiocholine iodide, and propinylthiocholine iodide. TcAChE1 had a lower Michaelis-Menten constant value and a higher maximal reaction velocity than recombinant TcAChE2, indicating a higher affinity for substrates and greater catalytic efficiency, respectively. Bioassays showed a greater sensitivity of recombinant TcAChE1 to the 10 tested insecticides. Silencing of Tcace1 and Tcace2 by RNA interference significantly increased the susceptibility of A. citricidus to malathion and carbaryl; however, silencing Tcace1 resulted in a higher mortality rate than silencing Tcace2. Additionally, the specific enzyme activity decreased more after silencing Tcace1 than after silencing Tcace2. Thus, TcAChE1 plays a major role in postsynaptic neurotransmission in A. citricidus. Title: Characterization of a Novel Thermo-Stable Lipasefrom Endophyte Pseudomonas putida in Pistacia chinensis Bunge Song C, Liu Z, Xie Q, Wang H, Huang Y, Ruan Y, Chen D Ref: Applied Biochemistry and Microbiology, 53:524, 2017 : PubMed ESTHER: Song_2017_Appl.Biochem.Microbiol_53_524 PubMedSearch: Song 2017 Appl.Biochem.Microbiol 53 524 Gene_locus related to this paper: psepu-a0a160gpc6 Abstract A novel lipolytic enzyme-producing endophytic strain PC2 was successfully isolated from the seeds of an ideal bioenergy plant Pistacia chinensis Bunge. Based on the analysis of morphology and 16S rRNA sequence, bacterial strain PC2 was identified as a subspecies of Pseudomonas putida, therefore named as P. putida PC2. Whole-genome sequencing showed PC2 contained a 1224-nucleotide lipase gene (named lip-PC2) predicted to encode a 407-amino-acid protein. Purified lipases from both the original PC2 strain and heterologously expressed Escherichia coli were nearly 50 kD with specific activity of 9.48 U/mL. LIP-PC2 displayed the maximal activity at 50C or pH 8.0, and maintained above 80% relative activity in the range of from 40 to 60degC or pH in the range of from 6.0 to 8.0, indicating thermostable and alkaline properties. Enzyme activity was enhanced by Mg2+, Na+ and Mn2+, but strongly inhibited by Cu2+, Zn2+ Co2+, EDTA as well as organic solvents and surfactants. Additionally, the analysis of amino acid sequence and structure indicated that LIP-PC2 was a novel member belonging to family I.3 of bacterial lipolytic enzymes and its catalytic triad was consisted of Ser-200, Asp-342 and His-374 Title: Point mutations in acetylcholinesterase 1 associated with chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens Stal Zhang Y, Yang B, Li J, Liu M, Liu Z Ref: Insect Molecular Biology, 26:453, 2017 : PubMed ESTHER: Zhang_2017_Insect.Mol.Biol_26_453 PubMedSearch: Zhang 2017 Insect.Mol.Biol 26 453 PubMedID: 28407384 Abstract Insecticide resistance frequently results from target-site insensitivity, such as point mutations in acetylcholinesterases (AChEs) for resistance to organophosphates and carbamates. From a field-originated population of Nilaparvata lugens, a major rice pest, a resistant population (R9) was obtained by nine-generation continuous selection with chlorpyrifos. From the same field population, a relatively susceptible population (S9) was also constructed through rearing without any insecticides. Compared to the susceptible strain, Sus [medium lethal dose (LC50 ) = 0.012 mg/l], R9 had a resistance ratio (RR) of 253.08-fold, whereas the RR of S9 was only 2.25-fold. Piperonyl butoxide and triphenyl phosphate synergized chlorpyrifos in R9 less than three-fold, indicating other important mechanisms for high resistance. The target-site insensitivity was supported by the key property differences of crude AChEs between R9 and S9. Compared to S9, three mutations (G119S, F331C and I332L) were detected in NlAChE1 from individuals of the R9 and field populations, but no mutation was detected in NlAChE2. G119S and F331C could decreased insecticide sensitivities in recombinant NlAChE1, whereas I332L took effect through increasing the influence of F331C on target insensitivity. F331C might be deleterious because of its influence on the catalytic efficiency of NlAChE1, whereas I332L would decrease these adverse effects and maintain the normal functions of AChEs. Title: Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents Fang L, Chen M, Liu Z, Fang X, Gou S, Chen L Ref: Bioorganic & Medicinal Chemistry, 24:886, 2016 : PubMed ESTHER: Fang_2016_Bioorg.Med.Chem_24_886 PubMedSearch: Fang 2016 Bioorg.Med.Chem 24 886 PubMedID: 26795115 Abstract In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9muM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture. Title: Drosophila SLC22A Transporter Is a Memory Suppressor Gene that Influences Cholinergic Neurotransmission to the Mushroom Bodies Gai Y, Liu Z, Cervantes-Sandoval I, Davis RL Ref: Neuron, 90:581, 2016 : PubMed ESTHER: Gai_2016_Neuron_90_581 PubMedSearch: Gai 2016 Neuron 90 581 PubMedID: 27146270 Abstract The mechanisms that constrain memory formation are of special interest because they provide insights into the brain's memory management systems and potential avenues for correcting cognitive disorders. RNAi knockdown in the Drosophila mushroom body neurons (MBn) of a newly discovered memory suppressor gene, Solute Carrier DmSLC22A, a member of the organic cation transporter family, enhances olfactory memory expression, while overexpression inhibits it. The protein localizes to the dendrites of the MBn, surrounding the presynaptic terminals of cholinergic afferent fibers from projection neurons (Pn). Cell-based expression assays show that this plasma membrane protein transports cholinergic compounds with the highest affinity among several in vitro substrates. Feeding flies choline or inhibiting acetylcholinesterase in Pn enhances memory, an effect blocked by overexpression of the transporter in the MBn. The data argue that DmSLC22A is a memory suppressor protein that limits memory formation by helping to terminate cholinergic neurotransmission at the Pn:MBn synapse. Title: Comparative genomic and transcriptomic analyses of the Fuzhuan brick tea-fermentation fungus Aspergillus cristatus Ge Y, Wang Y, Liu Y, Tan Y, Ren X, Zhang X, Hyde KD, Liu Z Ref: BMC Genomics, 17:428, 2016 : PubMed ESTHER: Ge_2016_BMC.Genomics_17_428 PubMedSearch: Ge 2016 BMC.Genomics 17 428 PubMedID: 27267057 Gene_locus related to this paper: 9euro-a0a1e3ba25, 9euro-a0a1e3bs39, 9euro-a0a1e3bjz1, 9euro-a0a1e3b9q3, 9euro-a0a1e3bp23 Abstract BACKGROUND: Aspergillus cristatus is the dominant fungus involved in the fermentation of Chinese Fuzhuan brick tea. Aspergillus cristatus is a homothallic fungus that undergoes a sexual stage without asexual conidiation when cultured in hypotonic medium. The asexual stage is induced by a high salt concentration, which completely inhibits sexual development. The taxon is therefore appropriate for investigating the mechanisms of asexual and sexual reproduction in fungi. In this study, de novo genome sequencing and analysis of transcriptomes during culture under high- and low-osmolarity conditions were performed. These analyses facilitated investigation of the evolution of mating-type genes, which determine the mode of sexual reproduction, in A. cristatus, the response of the high-osmolarity glycerol (HOG) pathway to osmotic stimulation, and the detection of mycotoxins and evaluation of the relationship with the location of the encoding genes. Title: Chronic administration of isocarbophos induces vascular cognitive impairment in rats Li P, Yin YL, Zhu ML, Pan GP, Zhao FR, Lu JX, Liu Z, Wang SX, Hu CP Ref: J Cell Mol Med, 20:731, 2016 : PubMed ESTHER: Li_2016_J.Cell.Mol.Med_20_731 PubMedSearch: Li 2016 J.Cell.Mol.Med 20 731 PubMedID: 26818681 Abstract Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. Title: Overexpression of Candida rugosa lipase Lip1 via combined strategies in Pichia pastoris Li X, Liu Z, Wang G, Pan D, Jiao L, Yan Y Ref: Enzyme Microb Technol, 82:115, 2016 : PubMed ESTHER: Li_2016_Enzyme.Microb.Technol_82_115 PubMedSearch: Li 2016 Enzyme.Microb.Technol 82 115 PubMedID: 26672457 Abstract In this study, combined strategies were employed to heterologously overexpress Candida rugosa lipase Lip1 (CRL1) in a Pichia pastoris system. The LIP1 gene was systematically codon-optimized and synthesized in vitro. The Lip1 activity of a recombinant strain harboring three copies of the codon-optimized LIP1 gene reached 1200 U/mL in a shake flask culture. Higher lipase activity, 1450 U/mL, was obtained using a five copy number construct. Co-expressing one copy of the ERO1p and BiP chaperones with Lip1p, the CRL1 lipase yield further reached 1758 U/mL, which was significantly higher than that achieved by expressing Lip1p alone or only co-expressing one molecular chaperone. When cultivated in a 3 L fermenter under optimal conditions, the recombinant strain GS115/87-ZA-ERO1p-BiP #7, expressing the molecular chaperones Ero1p and BiP, produced 13,490 U/mL of lipase activity at 130 h, which was greater than the 11,400 U/mL of activity for the recombinant strain GS115/pAO815-alpha-mCRL1 #87, which did not express a molecular chaperone. This study indicates that a strategy of combining codon optimization with co-expression of molecular chaperones has great potential for the industrial-scale production of pure CRL1. Title: Atrazine and its main metabolites alter the locomotor activity of larval zebrafish (Danio rerio) Liu Z, Wang Y, Zhu Z, Yang E, Feng X, Fu Z, Jin Y Ref: Chemosphere, 148:163, 2016 : PubMed ESTHER: Liu_2016_Chemosphere_148_163 PubMedSearch: Liu 2016 Chemosphere 148 163 PubMedID: 26803580 Abstract Atrazine (ATZ) and its main chlorometabolites, i.e., diaminochlorotriazine (DACT), deisopropylatrazine (DIP), and deethylatrazine (DE), have been widely detected in aquatic systems near agricultural fields. However, their possible effects on aquatic animals are still not fully understood. In this study, it was observed that several developmental endpoints such as the heart beat, hatchability, and morphological abnormalities were influenced by ATZ and its metabolites in different developmental stages. In addition, after 5 days of exposure to 30, 100, 300 mug L-1 ATZ and its main chlorometabolites, the swimming behaviors of larval zebrafish were significantly disturbed, and the acetylcholinesterase (AChE) activities were consistently inhibited. Our results also demonstrate that ATZ and its main chlorometabolites are neuroendocrine disruptors that impact the expression of neurotoxicity-related genes such as Ache, Gap43, Gfap, Syn2a, Shha, Mbp, Elavl3, Nestin and Ngn1 in early developmental stages of zebrafish. According to our results, it is possible that not only ATZ but also its metabolites (DACT, DIP and DE) have the same or even more toxic effects on different endpoints of the early developmental stages of zebrafish. Title: Genome-wide identification, classification and expression analysis in fungal-plant interactions of cutinase gene family and functional analysis of a putative ClCUT7 in Curvularia lunata Liu T, Hou J, Wang Y, Jin Y, Borth W, Zhao F, Liu Z, Hu J, Zuo Y Ref: Mol Genet Genomics, 291:1105, 2016 : PubMed ESTHER: Liu_2016_Mol.Genet.Genomics_291_1105 PubMedSearch: Liu 2016 Mol.Genet.Genomics 291 1105 PubMedID: 26767524 Abstract Cutinase is described as playing various roles in fungal-plant pathogen interactions, such as eliciting host-derived signals, fungal spore attachment and carbon acquisition during saprophytic growth. However, the characteristics of the cutinase genes, their expression in compatible interactions and their roles in pathogenesis have not been reported in Curvularia lunata, an important leaf spot pathogen of maize in China. Therefore, a cutinase gene family analysis could have profound significance. In this study, we identified 13 cutinase genes (ClCUT1 to ClCUT13) in the C. lunata genome. Multiple sequence alignment showed that most fungal cutinase proteins had one highly conserved GYSQG motif and a similar DxVCxG[ST]-[LIVMF](3)-x(3)H motif. Gene structure analyses of the cutinases revealed a complex intron-exon pattern with differences in the position and number of introns and exons. Based on phylogenetic relationship analysis, C. lunata cutinases and 78 known cutinase proteins from other fungi were classified into four groups with subgroups, but the C. lunata cutinases clustered in only three of the four groups. Motif analyses showed that each group of cutinases from C. lunata had a common motif. Real-time PCR indicated that transcript levels of the cutinase genes in a compatible interaction between pathogen and host had varied expression patterns. Interestingly, the transcript levels of ClCUT7 gradually increased during early pathogenesis with the most significant up-regulation at 3 h post-inoculation. When ClCUT7 was deleted, pathogenicity of the mutant decreased on unwounded maize (Zea mays) leaves. On wounded maize leaves, however, the mutant caused symptoms similar to the wild-type strain. Moreover, the ClCUT7 mutant had an approximately 10 % reduction in growth rate when cutin was the sole carbon source. In conclusion, we identified and characterized the cutinase family genes of C. lunata, analyzed their expression patterns in a compatible host-pathogen interaction, and explored the role of ClCUT7 in pathogenicity. This work will increase our understanding of cutinase genes in other fungal-plant pathogens. Title: The cholinergic immune regulation mediated by a novel muscarinic acetylcholine receptor through TNF pathway in oyster Crassostrea gigas Liu Z, Zhou Z, Wang L, Dong W, Qiu L, Song L Ref: Dev Comp Immunol, 65:139, 2016 : PubMed ESTHER: Liu_2016_Dev.Comp.Immunol_65_139 PubMedSearch: Liu 2016 Dev.Comp.Immunol 65 139 PubMedID: 27394930 Abstract Muscarinic receptors, which selectively take muscarine as their ligand, are critical for the immunological and physiological processes in animals. In the present study, the open region frame (ORF) of a homologue of muscarinic acetylcholine (ACh) receptor (mAChR) was amplified from oyster Crassostrea gigas (named as CgmAChR-1), whose full length was 1983 bp and the protein it encoded contained 660 amino acids with a seven transmembrane region. Phylogeny analysis suggested that CgmAChR-1 shared homology with M5 muscarinic receptor found in invertebrates including Habropoda laboriosa, Acromyrmex echinatior and Echinococcus granulosus. After cell transfection of CgmAChR-1 into HEK293T cells and ACh incubation, the level of intracellular Ca(2+) and cAMP increased significantly (p < 0.05). Such trend could be reverted with the addition of M3 and M5 muscarinic receptor antagonists DAMP and DAR. The CgmAChR-1 transcripts were ubiquitously detectable in seven different tissues with the maximal expression level in adductor muscle. When the oysters received LPS stimulation, CgmAChR-1 mRNA expression in haemocyte was increased to the highest level (6.05-fold, p < 0.05) at 24 h, while blocking CgmAChR-1 using receptor antagonists before LPS stimulation promoted the expression of oyster TNF, resulting in the increase of haemocyte apoptosis index. These results suggested that CgmAChR-1 was the key molecule in cholinergic neuroendocrine-immune system contributing to the regulation of TNF expression and apoptosis process. Title: Muscarinic acetylcholine receptors mediate eIF4B phosphorylation in SNU-407 colon cancer cells Liu Z, Cho NJ Ref: Biochemical & Biophysical Research Communications, 480:450, 2016 : PubMed ESTHER: Liu_2016_Biochem.Biophys.Res.Commun_480_450 PubMedSearch: Liu 2016 Biochem.Biophys.Res.Commun 480 450 PubMedID: 27773818 Abstract We have previously shown that muscarinic acetylcholine receptors (mAChRs) promote global protein biosynthesis in SNU-407 colon cancer cells. To gain insight into the molecular mechanisms underlying this event, we examined whether mAChRs regulate the phosphorylation of eIF4B (eukaryotic initiation factor 4B), an essential component of the translation machinery. When SNU-407 cells were treated with the cholinergic agonist carbachol, eIF4B was phosphorylated in a dose- and time-dependent manner. This carbachol effect was almost completely blocked by the muscarinic antagonist atropine, demonstrating that mAChRs specifically mediate the phosphorylation of eIF4B. Carbachol-stimulated eIF4B phosphorylation was significantly reduced by the MEK1/2 inhibitor U0126, indicating that the MEK1/2-ERK1/2 pathway plays an important role in mAChR-mediated eIF4B phosphorylation. However, treating the cells with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 or the mTORC1 (mammalian target of rapamycin complex 1) inhibitor rapamycin had little effect on carbachol-stimulated eIF4B phosphorylation, suggesting that PI3K and mTORC1 are not the key participants in this process. We also observed that the inhibition of protein kinase C (PKC) by GF109203X greatly diminished carbachol-stimulated eIF4B phosphorylation. Together, our data show that mAChRs modulate eIF4B phosphorylation via the ERK1/2 and PKC signaling pathways in SNU-407 colon cancer cells. Title: Clinical Outcomes of Thymectomy in Myasthenia Gravis Patients with a History of Crisis Liu Z, Lai Y, Yao S, Feng H, Zou J, Liu W, Lei Y, Zhu H, Cheng C Ref: World J Surg, 40:2681, 2016 : PubMed ESTHER: Liu_2016_World.J.Surg_40_2681 PubMedSearch: Liu 2016 World.J.Surg 40 2681 PubMedID: 27312319 Abstract BACKGROUND: The use of thymectomy in myasthenia gravis (MG) patients with a history of myasthenic crisis (MC) has not been well established. Here, we determined the efficacy of thymectomy by assessing the long-term clinical outcomes and reviewed thymectomy reports on MC patients. Title: Identification and Biochemical Properties of Two New Acetylcholinesterases in the Pond Wolf Spider (Pardosa pseudoannulata) Meng X, Li C, Xiu C, Zhang J, Li J, Huang L, Zhang Y, Liu Z Ref: PLoS ONE, 11:e0158011, 2016 : PubMed ESTHER: Meng_2016_PLoS.One_11_e0158011 PubMedSearch: Meng 2016 PLoS.One 11 e0158011 PubMedID: 27337188 Gene_locus related to this paper: 9arac-KU501290, 9arac-KU501289, 9arac-KU501288, 9arac-KU501287, 9arac-v5qqc6, 9arac-v5qqr1 Abstract Acetylcholinesterase (AChE), an important neurotransmitter hydrolase in both invertebrates and vertebrates, is targeted by organophosphorus and carbamate insecticides. In this study, two new AChEs were identified in the pond wolf spider Pardosa pseudoannulata, an important predatory natural enemy of several insect pests. In total, four AChEs were found in P. pseudoannulata (including two AChEs previously identified in our laboratory). The new putative AChEs PpAChE3 and PpAChE4 contain most of the common features of the AChE family, including cysteine residues, choline binding sites, the conserved sequence 'FGESAG' and conserved aromatic residues but with a catalytic triad of 'SDH' rather than 'SEH'. Recombinant enzymes expressed in Sf9 cells showed significant differences in biochemical properties compared to other AChEs, such as the optimal pH, substrate specificity, and catalytic efficiency. Among three test substrates, PpAChE1, PpAChE3 and PpAChE4 showed the highest catalytic efficiency (Vmax/KM) for ATC (acetylthiocholine iodide), with PpAChE3 exhibiting a clear preference for ATC based on the VmaxATC/VmaxBTC ratio. In addition, the four PpAChEs were more sensitive to the AChE-specific inhibitor BW284C51, which acts against ATC hydrolysis, than to the BChE-specific inhibitor ISO-OMPA, which acts against BTC hydrolysis, with at least a 8.5-fold difference in IC50 values for each PpAChE. PpAChE3, PpAChE4, and PpAChE1 were more sensitive than PpAChE2 to the tested Carb insecticides, and PpAChE3 was more sensitive than the other three AChEs to the tested OP insecticides. Based on all the results, two new functional AChEs were identified from P. pseudoannulata. The differences in AChE sequence between this spider and insects enrich our knowledge of invertebrate AChE diversity, and our findings will be helpful for understanding the selectivity of insecticides between insects and natural enemy spiders. Title: The ERK1/2 and mTORC1 Signaling Pathways Are Involved in the Muscarinic Acetylcholine Receptor-Mediated Proliferation of SNU-407 Colon Cancer Cells Park YS, Liu Z, Vasamsetti BM, Cho NJ Ref: Journal of Cellular Biochemistry, 117:2854, 2016 : PubMed ESTHER: Park_2016_J.Cell.Biochem_117_2854 PubMedSearch: Park 2016 J.Cell.Biochem 117 2854 PubMedID: 27167250 Abstract Muscarinic acetylcholine receptors (mAChRs) regulate diverse cellular functions, including cell growth and proliferation, via multiple signaling pathways. Previously, we showed that mAChRs stimulate the MEK1/2-ERK1/2-RSK pathway in SNU-407 colon cancer cells and subsequently promote cell proliferation. In this study, we provide evidence that the PI3K-Akt-mTORC1-S6K1 pathway is activated by mAChRs in SNU-407 cells and that this pathway is associated with protein biosynthesis and cell proliferation. When the cells were treated with the cholinergic agonist carbachol, Akt was activated in a dose- and time-dependent fashion. This carbachol effect was almost completely blocked by the PI3K inhibitor LY294002, implying that PI3K is responsible for the Akt activation. S6K1, a major downstream target of mTORC1, was also activated by carbachol in a temporal profile similar to that of the Akt activation. This carbachol-stimulated S6K1 activation was abrogated by LY294002 or the mTORC1 inhibitor rapamycin, supporting the notion that mAChRs mediate S6K1 activation via the PI3K-Akt-mTORC1 pathway. We observed that global protein biosynthesis, monitored by puromycin incorporation, was strongly increased by carbachol in an atropine-sensitive manner. Inhibition experiments indicated that the ERK1/2 and mTORC1 signaling pathways may be involved in carbachol-stimulated global protein biosynthesis. We also found that treating SNU-407 cells with LY294002 or rapamycin significantly suppressed carbachol-stimulated cell proliferation. In the presence of the MEK1/2 inhibitor U0126, cell proliferation was further reduced by rapamycin treatment. Our data thus suggest that both the MEK1/2-ERK1/2 and mTORC1 pathways play important roles in mAChR-mediated cell proliferation in SNU-407 colon cancer cells. J. Cell. Biochem. 117: 2854-2863, 2016. (c) 2016 Wiley Periodicals, Inc. Title: Characterization of a novel cold active and salt tolerant esterase from Zunongwangia profunda Rahman MA, Culsum U, Tang W, Zhang SW, Wu G, Liu Z Ref: Enzyme Microb Technol, 85:1, 2016 : PubMed ESTHER: Rahman_2016_Enzyme.Microb.Technol_85_1 PubMedSearch: Rahman 2016 Enzyme.Microb.Technol 85 1 PubMedID: 26920474 Abstract A novel cold active esterase, EstLiu was cloned from the marine bacterium Zunongwangia profunda, overexpressed in E. coli BL21 (DE3) and purified by glutathione-S transferase (GST) affinity chromatography. The mature esterase EstLiu sequence encodes a protein of 273 amino acids residues, with a predicted molecular weight of 30KDa and containing the classical pentapeptidase motif from position 156 to 160 with the catalytic triad Ser158-Asp211-His243. Although, EstLiu showed 64% similarity with the hypothetical esterase from Chryseobacterium sp. StRB126 (WP_045498424), phylogenetic analysis showed it had no similarity with any of the established family of lipases/esterases, suggesting that it could be considered as a new family. The purified enzyme showed broad substrate specificity with the highest hydrolytic activity against p-nitrophenyl butyrate (C4). EstLiu showed remarkable activity (75%) at 0 degrees Cand the optimal activity at pH 8.0 and 30 degrees C with good thermostability and quickened inactivation above 60 degrees C. EstLiu retained 81, 103, 67 and 78% of its original activity at 50% (v/v) in ethanol, isopropanol, DMSO and ethylene glycol, respectively. In the presence of Tween 20, Tween 80 and Triton X-100, EstLiu showed 88, 100 and 117% of relative activity. It is also co-factor independent. The high activity at low temperature and desirable stability in organic solvents and salts of this novel family esterase represents a good evidence of novel biocatalyst. Overall, this novel enzyme showed better activity than previously reported esterases in extreme reaction conditions and could promote the reaction in both aqueous and non-aqueous conditions, indicating its great potential for industrial applications. Title: Correlation analysis between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis Tang N, Zhang Y, Liu Z, Fu T, Liang Q, Ai X Ref: Biomed Rep, 5:107, 2016 : PubMed ESTHER: Tang_2016_Biomed.Rep_5_107 PubMedSearch: Tang 2016 Biomed.Rep 5 107 PubMedID: 27347413 Abstract The aim of the present study was to investigate the correlation between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis. A total of 30 infants with cholestasis and 20 healthy infants were included in the study. Biochemical assays based on the initial rate method and colorimetric assays were conducted to determine the levels of liver function markers in the serum [such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), gamma-glutamyl transferase (gamma-GT), cholinesterase (CHE) and total bile acids (TBA)] and four serum biomarkers of liver fibrosis were measured using radioimmunoassays [hyaluronic acid (HA), procollagen type III (PCIII), laminin (LN) and collagen type IV (cIV)]. The serum levels of ALT, AST, TBIL, DBIL, IBIL, gamma-GT and TBA in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01); the serum levels of CHE in the infants with cholestasis were significantly lower compared to the healthy infants (P<0.01). The serum levels of HA, PCIII, and cIV in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01). Correlation analyses between liver function and the four biomarkers of liver fibrosis showed that HA was positively correlated with AST and gamma-GT (P<0.05) and negatively correlated with ALT, CHE and TBA (P<0.05). cIV was positively correlated with gamma-GT (P<0.05) and negatively correlated with CHE (P<0.05). In conclusion, statistically significant differences were identified for the liver function markers (ALT, AST, TBIL, DBIL, IBIL, gamma-GT and TBA) and the biomarkers HA, PCIII and cIV of liver fibrosis between infants with cholestasis and healthy infants. Thus, the serum levels of HA, cIV, gamma-GT and CHE are sensitive markers for cholestatic liver fibrosis in infants. Title: Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in vitro Wang X, Wu Q, Wan D, Liu Q, Chen D, Liu Z, Martinez-Larranaga MR, Martinez MA, Anadon A, Yuan Z Ref: Archives of Toxicology, 90:81, 2016 : PubMed ESTHER: Wang_2016_Arch.Toxicol_90_81 PubMedSearch: Wang 2016 Arch.Toxicol 90 81 PubMedID: 26419546 Abstract Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB1 into metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its partial (pHFB1) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage. Title: Biosynthesis of Antibiotic Leucinostatins in Bio-control Fungus Purpureocillium lilacinum and Their Inhibition on Phytophthora Revealed by Genome Mining Wang G, Liu Z, Lin R, Li E, Mao Z, Ling J, Yang Y, Yin WB, Xie B Ref: PLoS Pathog, 12:e1005685, 2016 : PubMed ESTHER: Wang_2016_PLoS.Pathog_12_E1005685 PubMedSearch: Wang 2016 PLoS.Pathog 12 E1005685 PubMedID: 27416025 Gene_locus related to this paper: metcm-a0a179g1m3, metcm-a0a179g2w0, metcm-a0a4q7js68, purli-lcse Abstract Purpureocillium lilacinum of Ophiocordycipitaceae is one of the most promising and commercialized agents for controlling plant parasitic nematodes, as well as other insects and plant pathogens. However, how the fungus functions at the molecular level remains unknown. Here, we sequenced two isolates (PLBJ-1 and PLFJ-1) of P. lilacinum from different places Beijing and Fujian. Genomic analysis showed high synteny of the two isolates, and the phylogenetic analysis indicated they were most related to the insect pathogen Tolypocladium inflatum. A comparison with other species revealed that this fungus was enriched in carbohydrate-active enzymes (CAZymes), proteases and pathogenesis related genes. Whole genome search revealed a rich repertoire of secondary metabolites (SMs) encoding genes. The non-ribosomal peptide synthetase LcsA, which is comprised of ten C-A-PCP modules, was identified as the core biosynthetic gene of lipopeptide leucinostatins, which was specific to P. lilacinum and T. ophioglossoides, as confirmed by phylogenetic analysis. Furthermore, gene expression level was analyzed when PLBJ-1 was grown in leucinostatin-inducing and non-inducing medium, and 20 genes involved in the biosynthesis of leucionostatins were identified. Disruption mutants allowed us to propose a putative biosynthetic pathway of leucinostatin A. Moreover, overexpression of the transcription factor lcsF increased the production (1.5-fold) of leucinostatins A and B compared to wild type. Bioassays explored a new bioactivity of leucinostatins and P. lilacinum: inhibiting the growth of Phytophthora infestans and P. capsici. These results contribute to our understanding of the biosynthetic mechanism of leucinostatins and may allow us to utilize P. lilacinum better as bio-control agent. 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: Discovering New Acetylcholinesterase Inhibitors by Mining the Buzhongyiqi Decoction Recipe Data Cui L, Wang Y, Liu Z, Chen H, Wang H, Zhou X, Xu J Ref: J Chem Inf Model, 55:2455, 2015 : PubMed ESTHER: Cui_2015_J.Chem.Inf.Model_55_2455 PubMedSearch: Cui 2015 J.Chem.Inf.Model 55 2455 PubMedID: 26509353 Abstract Myasthenia gravis (MG) is a neuromuscular disease that is conventionally treated with acetylcholinesterase (AChE) inhibitors, which may not fully remove the symptom for many reasons. When AChE inhibitors do not work, Chinese patients turn to Chinese medicine, such as the Buzhongyiqi decoction (BD), to treat MG. By elucidating the relations between the herbs of the Buzhongyiqi decoction recipe and AChE inhibitors with structure-based and ligand-based drug design methods and chemoinformatics approaches, we have found the key active components of BD. Using these key active components as templates, we have discovered five new AChE inhibitors through virtual screening of a commercial compound library. The new AChE inhibitors have been confirmed with Ellman assays. This study demonstrates that lead identification can be inspired by elucidating Chinese medicine. Since BD is a mixture, further studies against other drug targets are needed. Title: Development of ESI-MS-based continuous enzymatic assay for real-time monitoring of enzymatic reactions of acetylcholinesterase Fu Q, Tang J, Cui M, Zheng Z, Liu Z, Liu S Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 990:169, 2015 : PubMed ESTHER: Fu_2015_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_990_169 PubMedSearch: Fu 2015 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 990 169 PubMedID: 25875590 Abstract The continuous enzymatic assay based on ESI-MS was developed to real-time monitoring of enzymatic reactions of acetylcholinesterase (AChE). The changes of product concentrations were continuously measured. Calibration curves were established for quantitative calculation. By this method, the Michaelis constant (Km) of acetylcholinesterase was determined to be 70.60+/-0.93muM and Huperzine A as an effective inhibitor of acetylcholinesterase displayed a mixed inhibition with competitive and noncompetitive inhibition behaviors. The half maximal inhibitory concentration (IC50) and inhibition constant (Ki) value of Huperzine A were also calculated as 48.51+/-1.16nM and 26.73+/-0.27nM, respectively. This method provides the rapid and accurate ways to monitor enzyme reactions. Title: The toxicity of chlorpyrifos on the early life stage of zebrafish: A survey on the endpoints at development, locomotor behavior, oxidative stress and immunotoxicity Jin Y, Liu Z, Peng T, Fu Z Ref: Fish Shellfish Immunol, 43:405, 2015 : PubMed ESTHER: Jin_2015_Fish.Shellfish.Immunol_43_405 PubMedSearch: Jin 2015 Fish.Shellfish.Immunol 43 405 PubMedID: 25634256 Abstract Chlorpyrifos (CPF) is one of the most toxic pesticides in aquatic ecosystem, but its toxicity mechanisms to fish are still not fully understood. This study examined the toxicity targets of CPF in early life stage of zebrafish on the endpoints at developmental toxicity, neurotoxicity, oxidative stress and immunotoxicity. Firstly, CPF exposure decreased the body length, inhibited the hatchability and heart rate, and resulted in a number of morphological abnormalities, primarily spinal deformities (SD) and pericardial edema (PE), in larval zebrafish. Secondly, the free swimming activities and the swimming behaviors of the larvae in response to the stimulation of light-to-dark photoperiod transition were significantly influenced by the exposure to 100 and 300 mug/L CPF. In addition, the activity of acetylcholinesterase (AChE) and the transcription of some genes related to neurotoxicity were also influenced by CPF exposure. Thirdly, CPF exposure induced oxidative stress in the larval zebrafish. The malondialdehyde (MDA) levels increased and the glutathione (GSH) contents decreased significantly in a concentration-dependent manner after the exposure to CPF for 96 hours post fertilization (hpf). CPF affected not only the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST), but also the transcriptional levels of their respective genes. Finally, the mRNA levels of the main cytokines including tumor necrosis factor alpha (Tnfalpha), interferon (Ifn), interleukin-1 beta (Il-1beta), interleukin 6 (Il6), complement factor 4 (C4) in the larvae increased significantly after the exposure to 100 or 300 mug/L CPF for 96 hpf, suggesting that the innate immune system disturbed by CPF in larvae. Taken together, our results suggested that CPF had the potential to cause developmental toxicity, behavior alterations, oxidative stress and immunotoxicity in the larval zebrafish. Title: Deciphering the venomic transcriptome of killer-wasp Vespa velutina Liu Z, Chen S, Zhou Y, Xie C, Zhu B, Zhu H, Liu S, Wang W, Chen H, Ji Y Ref: Sci Rep, 5:9454, 2015 : PubMed ESTHER: Liu_2015_Sci.Rep_5_9454 PubMedSearch: Liu 2015 Sci.Rep 5 9454 PubMedID: 25896434 Gene_locus related to this paper: vesve-pa1 Abstract Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world. Title: Metabolism elucidation of BJ-B11 (a heat shock protein 90 inhibitor) by human liver microsomes: identification of main contributing enzymes Lu D, Dong D, Liu Z, Wang Y, Wu B Ref: Expert Opin Drug Metab Toxicol, 11:1029, 2015 : PubMed ESTHER: Lu_2015_Expert.Opin.Drug.Metab.Toxicol_11_1029 PubMedSearch: Lu 2015 Expert.Opin.Drug.Metab.Toxicol 11 1029 PubMedID: 26073578 Abstract OBJECTIVE: The aim of this article is to elucidate the metabolic pathways of BJ-B11, a heat shock protein 90 inhibitor, in human liver microsomes (HLM) and determine the main enzymes responsible for formation of each metabolite. Title: Validating the importance of two acetylcholinesterases in insecticide sensitivities by RNAi in Pardosa pseudoannulata, an important predatory enemy against several insect pests Meng X, Li C, Bao H, Fang J, Liu Z, Zhang Y Ref: Pestic Biochem Physiol, 125:26, 2015 : PubMed ESTHER: Meng_2015_Pestic.Biochem.Physiol_125_26 PubMedSearch: Meng 2015 Pestic.Biochem.Physiol 125 26 PubMedID: 26615147 Abstract The pond wolf spider (Pardosa pseudoannulata) is an important predatory enemy against several insect pests and showed relative different sensitivities to organophosphate and carbamate insecticides compared to insect pests. In our previous studies, two acetylcholinesterases were identified in P. pseudoannulata and played important roles in insecticide sensitivities. In order to understand the contributions of the two acetylcholinesterases to insecticide sensitivities, we firstly employed the RNAi technology in the spider. For a suitable microinjection RNAi method, the injection site, injection volume and interference time were optimized, which then demonstrated that the injection RNAi method was applicable in this spider. With the new RNAi method, it was revealed that both Pp-AChE1 and Pp-AChE2, encoded by genes Ppace1 and Ppace2, were the targets of organophosphate insecticides, but Pp-AChE1 would be more important. In contrast, the carbamate acted selectively on Pp-AChE1. The results showed that Pp-AChE1 was the major catalytic enzyme in P. pseudoannulata and the major target of organophosphate and carbamate insecticides. In a word, an RNAi method was established in the pond wolf spider, which further validated the importance of two acetylcholinesterases in insecticide sensitivities in this spider. Title: Preventive effect of Lee on activated carbon-induced constipation in mice Qian Y, Suo H, Du M, Zhao X, Li J, Li GJ, Song JL, Liu Z Ref: Exp Ther Med, 9:272, 2015 : PubMed ESTHER: Qian_2015_Exp.Ther.Med_9_272 PubMedSearch: Qian 2015 Exp.Ther.Med 9 272 PubMedID: 25452815 Abstract The aim of this study was to investigate the effects of Lactobacillus fermentum Lee (LF-Lee) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered lactic acid bacteria for nine days. Body weight, dietary and water intake, defecation status, gastrointestinal (GI) transit and defecation time, as well as levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were measured to evaluate the preventive effects of LF-Lee on constipation. Bisacodyl, a laxative drug, was administered as a positive control. The time taken until the first defecation of a black stool for normal, control, bisacodyl- (100 mg/kg, oral administration), Lactobacillus bulgaricus (LB)-, LF-Lee low dose (L)- and LF-Lee high dose (H)-treated mice was 90, 218, 117, 180, 161 and 151 min, respectively. Following the consumption of LB, LF-Lee (L) or LF-Lee (H), or the oral administration of bisacodyl, the GI transit was reduced to 55.2, 65.8, 73.1 and 94.6%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and those of SS were reduced in the mice treated with LF-Lee compared with those in the untreated control mice (P<0.05). These results demonstrate that lactic acid bacteria have preventive effects on constipation in mice and that LF-Lee has superior functional activity. Title: Probing role of key residues in the divergent evolution of Yarrowia lipolytica lipase 2 and Aspergillus niger eruloyl esterase A Wang G, Liu Z, Xu L, Zhang H, Yan Y Ref: Microbiol Res, 178:27, 2015 : PubMed ESTHER: Wang_2015_Microbiol.Res_178_27 PubMedSearch: Wang 2015 Microbiol.Res 178 27 PubMedID: 26302844 Abstract Yarrowia lipolytica lipase 2 (YLLip2) and Aspergillus niger feruloyl esterase A (AnFaeA) are enzymes of similar structures but with different functions. They are both classified into the same homologous family in Lipase Engineering Database (LED). The major difference between the two enzymes is that YLLip2 exhibits interfacial activity while AnFaeA does not. In order to better understand the interfacial activation mechanisms of YLLip2, structure guided site-directed mutagenesis were performed, mutants were constructed, kinetics parameters and lipase properties were detected. Mutant enzymes showed enhanced catalytic efficiency towards p-nitrophenyl butyrin (pNPB) but their catalytic efficiency decreased towards p-nitrophenyl palmitate (pNPP), their catalysis behavior was more close to feruloyl esterase. Moreover, the mutant enzymes exhibited enhanced thermostability compared with their wild type. These results indicate that I100 and F129 are probably cut-off point of divergent functions between the two enzymes during evolution. Title: A cold-adapted, solvent and salt tolerant esterase from marine bacterium Psychrobacter pacificensis Wu G, Zhang X, Wei L, Kumar A, Mao T, Liu Z Ref: Int J Biol Macromol, 81:180, 2015 : PubMed ESTHER: Wu_2015_Int.J.Biol.Macromol_81_180 PubMedSearch: Wu 2015 Int.J.Biol.Macromol 81 180 PubMedID: 26231332 Abstract Lipolytic enzymes with unique physico-chemical characteristics are gaining more attention for their immense industrial importance. In this study, a novel lipolytic enzyme (Est11) was cloned from the genomic library of a marine bacterium Psychrobacter pacificensis. The enzyme was expressed in Escherichia coli and purified to homogeneity with molecular mass of 32.9kDa. The recombinant Est11 was able to hydrolyze short chain esters (C2-C8) and displayed an optimum activity against butyrate ester (C4). The optimal temperature and pH were 25 degrees C and 7.5, respectively. Est11 retained more than 70% of its original activity at 10 degrees C, suggesting that it was a cold-active esterase. The enzyme was highly active and stable at high concentration of NaCl (5M). Further, incubation with ethanol, isopropanol, propanediol, DMSO, acetonitrile, and glycerol rendered remarkable positive effects on Est11 activity. Typically, even at the concentration of 30% (v/v), ethanol, DMSO, and propanediol increased Est11 activity by 1.3, 2.0, and 2.4-folds, respectively. This new robust enzyme with remarkable properties like cold-adaptability, exceptional tolerance to salt and organic solvents provides us a promising candidate to meet the needs of some harsh industrial processes. Title: Reduction in mRNA and protein expression of a nicotinic acetylcholine receptor alpha8 subunit is associated with resistance to imidacloprid in the brown planthopper, Nilaparvata lugens Zhang Y, Wang X, Yang B, Hu Y, Huang L, Bass C, Liu Z Ref: Journal of Neurochemistry, 135:686, 2015 : PubMed ESTHER: Zhang_2015_J.Neurochem_135_686 PubMedSearch: Zhang 2015 J.Neurochem 135 686 PubMedID: 26259922 Abstract Target-site resistance is commonly caused by qualitative changes in insecticide target-receptors and few studies have implicated quantitative changes in insecticide targets in resistance. Here we show that resistance to imidacloprid in a selected strain of Nilaparvata lugens is associated with a reduction in expression levels of the nicotinic acetylcholine receptor (nAChR) subunit Nlalpha8. Synergism bioassays of the selected strain suggested resistance was conferred, in part, by a target-site mechanism. Sequencing of N. lugens nAChR subunit genes identified no mutations associated with resistance, however, a decrease in mRNA and protein levels of Nlalpha8 was observed during selection. RNA interference knockdown of Nlalpha8 decreased the sensitivity of N. lugens to imidacloprid, demonstrating that a decrease in Nlalpha8 expression is sufficient to confer resistance in vivo. Radioligand binding assays revealed that the affinity of the high-affinity imidacloprid-binding site of native nAChRs was reduced by selection, and reducing the amount of Nlalpha8 cRNA injected into Xenopus oocytes significantly decreased imidacloprid potency on recombinant receptors. Taken together, these results provide strong evidence that a decrease in Nlalpha8 levels confers resistance to imidacloprid in N. lugens, and thus provides a rare example of target-site resistance associated with a quantitative rather than qualitative change. In insects, target-site mutations often cause high resistance to insecticides, such as neonicotinoids acting on nicotinic acetylcholine receptors (nAChRs). Here we found that a quantitative change in target-protein level, decrease in mRNA and protein levels of Nlalpha8, contributed importantly to imidacloprid resistance in Nilaparvata lugens. This finding provides a new target-site mechanism of insecticide resistance. Title: Preventive Effect of Lactobacillus fermentum Zhao on Activated Carbon-Induced Constipation in Mice Zhao X, Qian Y, Suo H, Du M, Li G, Liu Z, Li J Ref: J Nutr Sci Vitaminol (Tokyo), 61:131, 2015 : PubMed ESTHER: Zhao_2015_J.Nutr.Sci.Vitaminol.(Tokyo)_61_131 PubMedSearch: Zhao 2015 J.Nutr.Sci.Vitaminol.(Tokyo) 61 131 PubMedID: 26052143 Abstract The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1x10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1x10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB. Title: Plant genetics. Early allopolyploid evolution in the post-Neolithic Brassica napus oilseed genome Chalhoub B, Denoeud F, Liu S, Parkin IA, Tang H, Wang X, Chiquet J, Belcram H, Tong C and Wincker P <70 more author(s)> Chalhoub B, Denoeud F, Liu S, Parkin IA, Tang H, Wang X, Chiquet J, Belcram H, Tong C, Samans B, Correa M, Da Silva C, Just J, Falentin C, Koh CS, Le Clainche I, Bernard M, Bento P, Noel B, Labadie K, Alberti A, Charles M, Arnaud D, Guo H, Daviaud C, Alamery S, Jabbari K, Zhao M, Edger PP, Chelaifa H, Tack D, Lassalle G, Mestiri I, Schnel N, Le Paslier MC, Fan G, Renault V, Bayer PE, Golicz AA, Manoli S, Lee TH, Thi VH, Chalabi S, Hu Q, Fan C, Tollenaere R, Lu Y, Battail C, Shen J, Sidebottom CH, Canaguier A, Chauveau A, Berard A, Deniot G, Guan M, Liu Z, Sun F, Lim YP, Lyons E, Town CD, Bancroft I, Meng J, Ma J, Pires JC, King GJ, Brunel D, Delourme R, Renard M, Aury JM, Adams KL, Batley J, Snowdon RJ, Tost J, Edwards D, Zhou Y, Hua W, Sharpe AG, Paterson AH, Guan C, Wincker P (- 70) Ref: Science, 345:950, 2014 : PubMed ESTHER: Chalhoub_2014_Science_345_950 PubMedSearch: Chalhoub 2014 Science 345 950 PubMedID: 25146293 Gene_locus related to this paper: braol-Q8GTM3, braol-Q8GTM4, brana-a0a078j4a9, brana-a0a078e1m0, brana-a0a078cd75, brana-a0a078evd3, brana-a0a078j4f0, brana-a0a078cta5, brana-a0a078cus4, brana-a0a078f8c2, brana-a0a078jql1, brana-a0a078dgj3, brana-a0a078hw50, brana-a0a078cuu0, brana-a0a078iyl8, brana-a0a078dfa9, brana-a0a078ic91, brana-a0a078cnf7, brana-a0a078fh41, brana-a0a078ca65, brana-a0a078ctc8, brana-a0a078h021, brana-a0a078h0h8, brana-a0a078jx23, brana-a0a078ci96, brana-a0a078cqd7, brana-a0a078dh94, brana-a0a078h612, brana-a0a078ild2, brana-a0a078j2t3, braol-a0a0d3dpb2, braol-a0a0d3dx76, brana-a0a078jxa8, brana-a0a078i2k3, braol-a0a0d3ef55, brarp-m4dcj8, brana-a0a078fw53, brana-a0a078itf3, brana-a0a078jsn1, brana-a0a078jrt9, brana-a0a078i6d2, brana-a0a078jku0, brana-a0a078fss7, brana-a0a078i1l0, brana-a0a078i402 Abstract Oilseed rape (Brassica napus L.) was formed ~7500 years ago by hybridization between B. rapa and B. oleracea, followed by chromosome doubling, a process known as allopolyploidy. Together with more ancient polyploidizations, this conferred an aggregate 72x genome multiplication since the origin of angiosperms and high gene content. We examined the B. napus genome and the consequences of its recent duplication. The constituent An and Cn subgenomes are engaged in subtle structural, functional, and epigenetic cross-talk, with abundant homeologous exchanges. Incipient gene loss and expression divergence have begun. Selection in B. napus oilseed types has accelerated the loss of glucosinolate genes, while preserving expansion of oil biosynthesis genes. These processes provide insights into allopolyploid evolution and its relationship with crop domestication and improvement. Title: Escherichia coli isolate for studying colonization of the mouse intestine and its application to two-component signaling knockouts Lasaro M, Liu Z, Bishar R, Kelly K, Chattopadhyay S, Paul S, Sokurenko E, Zhu J, Goulian M Ref: Journal of Bacteriology, 196:1723, 2014 : PubMed ESTHER: Lasaro_2014_J.Bacteriol_196_1723 PubMedSearch: Lasaro 2014 J.Bacteriol 196 1723 PubMedID: 24563035 Gene_locus related to this paper: ecoli-yaim, ecoli-ybff, ecoli-ycfp, ecoli-yqia, ecoli-YfhR Abstract The biology of Escherichia coli in its primary niche, the animal intestinal tract, is remarkably unexplored. Studies with the streptomycin-treated mouse model have produced important insights into the metabolic requirements for Escherichia coli to colonize mice. However, we still know relatively little about the physiology of this bacterium growing in the complex environment of an intestine that is permissive for the growth of competing flora. We have developed a system for studying colonization using an E. coli strain, MP1, isolated from a mouse. MP1 is genetically tractable and does not require continuous antibiotic treatment for stable colonization. As an application of this system, we separately knocked out each two-component system response regulator in MP1 and performed competitions against the wild-type strain. We found that only three response regulators, ArcA, CpxR, and RcsB, produce strong colonization defects, suggesting that in addition to anaerobiosis, adaptation to cell envelope stress is a critical requirement for E. coli colonization of the mouse intestine. We also show that the response regulator OmpR, which had previously been hypothesized to be important for adaptation between in vivo and ex vivo environments, is not required for MP1 colonization due to the presence of a third major porin. Title: Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Abeta Liu Z, Zhao X, Liu B, Liu AJ, Li H, Mao X, Wu B, Bi KS, Jia Y Ref: European Journal of Pharmacology, 738C:206, 2014 : PubMed ESTHER: Liu_2014_Eur.J.Pharmacol_738C_206 PubMedSearch: Liu 2014 Eur.J.Pharmacol 738C 206 PubMedID: 24886882 Abstract Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for thousands of years. Recently, SZS has also shown notable neuroprotective activities via anti-oxidative and anti-inflammatory effects in dementia animals. Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic-sedative component of SZS. In the present study, we firstly evaluated the effects of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five consecutive days on cognitive impairment induced by ICV injection of Abeta1-42. The results showed that ICV treatment with JuA significantly mitigated learning and memory impairment in mice induced by Abeta1-42 as measured by the Y-maze, active avoidance and Morris water maze. Furthermore, ICV treatment with JuA reduced the level of Abeta1-42 in hippocampus, significantly inhibited the activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice treated with ICV injection of Abeta1-42. Shrinkage of nuclei, swollen and eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice induced by Abeta1-42, however, JuA noticeably improved the histopathological damage. Cumulatively, the present study indicates that JuA may serve as a potential therapeutic agent for the treatment of Alzheimers disease. Title: Genome Sequence of the Thermophilic Cyanobacterium Thermosynechococcus sp. Strain NK55a Stolyar S, Liu Z, Thiel V, Tomsho LP, Pinel N, Nelson WC, Lindemann SR, Romine MF, Haruta S and Fredrickson JK <2 more author(s)> Stolyar S, Liu Z, Thiel V, Tomsho LP, Pinel N, Nelson WC, Lindemann SR, Romine MF, Haruta S, Schuster SC, Bryant DA, Fredrickson JK (- 2) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Stolyar_2014_Genome.Announc_2_e01060 PubMedSearch: Stolyar 2014 Genome.Announc 2 e01060 PubMedID: 24482507 Gene_locus related to this paper: 9chro-v5v7l5 Abstract The genome of the unicellular cyanobacterium Thermosynechococcus sp. strain NK55a, isolated from the Nakabusa hot spring, Nagano Prefecture, Japan, comprises a single, circular, 2.5-Mb chromosome. The genome is predicted to contain 2,358 protein-encoding genes, including genes for all typical cyanobacterial photosynthetic and metabolic functions. No genes encoding hydrogenases or nitrogenase were identified. Title: Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment Suo H, Zhao X, Qian Y, Li G, Liu Z, Xie J, Li J Ref: Int J Mol Sci, 15:21875, 2014 : PubMed ESTHER: Suo_2014_Int.J.Mol.Sci_15_21875 PubMedSearch: Suo 2014 Int.J.Mol.Sci 15 21875 PubMedID: 25464378 Abstract The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription-polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity. Title: Aromatic Amino Acid Mutagenesis at the Substrate Binding Pocket of Yarrowia lipolytica Lipase Lip2 Affects Its Activity and Thermostability Wang G, Liu Z, Xu L, Yan Y Ref: ScientificWorldJournal, 2014:382581, 2014 : PubMed ESTHER: Wang_2014_ScientificWorldJournal_2014_382581 PubMedSearch: Wang 2014 ScientificWorldJournal 2014 382581 PubMedID: 25197700 Abstract The lipase2 from Yarrowia lipolytica (YLLip2) is a yeast lipase exhibiting high homologous to filamentous fungal lipase family. Though its crystal structure has been resolved, its structure-function relationship has rarely been reported. By contrast, there are two amino acid residues (V94 and I100) with significant difference in the substrate binding pocket of YLLip2; they were subjected to site-directed mutagenesis (SDM) to introduce aromatic amino acid mutations. Two mutants (V94W and I100F) were created. The enzymatic properties of the mutant lipases were detected and compared with the wild-type. The activities of mutant enzymes dropped to some extent towards p-nitrophenyl palmitate (pNPC16) and their optimum temperature was 35 degrees C, which was 5 degrees C lower than that of the wild-type. However, the thermostability of I100F increased 22.44% after incubation for 1 h at 40 degrees C and its optimum substrate shifted from p-nitrophenyl laurate (pNPC12) to p-nitrophenyl caprate (pNPC10). The above results demonstrated that the two substituted amino acid residuals have close relationship with such enzymatic properties as thermostability and substrate selectivity. Title: Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W and Shi Q <31 more author(s)> You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W, Zhang X, Sun Y, Chen S, Hong W, Li Y, Cheng S, Fan G, Shi C, Liang J, Tom Tang Y, Yang C, Ruan Z, Bai J, Peng C, Mu Q, Lu J, Fan M, Yang S, Huang Z, Jiang X, Fang X, Zhang G, Zhang Y, Polgar G, Yu H, Li J, Liu Z, Ravi V, Coon SL, Yang H, Venkatesh B, Shi Q (- 31) Ref: Nat Commun, 5:5594, 2014 : PubMed ESTHER: You_2014_Nat.Commun_5_5594 PubMedSearch: You 2014 Nat.Commun 5 5594 PubMedID: 25463417 Gene_locus related to this paper: 9gobi-a0a3b4bh68, 9gobi-a0a3b4bmj6, 9gobi-a0a3b4alj9, 9gobi-a0a3b4biy6, 9gobi-a0a3b4ah01, 9gobi-a0a3b3z8m7, 9gobi-a0a3b4aaj5, 9gobi-a0a3b4b6y7 Abstract Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. Title: Identification of two acetylcholinesterases in Pardosa pseudoannulata and the sensitivity to insecticides Zhang Y, Shao Y, Jiang F, Li J, Liu Z Ref: Insect Biochemistry & Molecular Biology, 46C:25, 2014 : PubMed ESTHER: Zhang_2014_Insect.Biochem.Mol.Biol_46C_25 PubMedSearch: Zhang 2014 Insect.Biochem.Mol.Biol 46C 25 PubMedID: 24463359 Gene_locus related to this paper: 9arac-v5qqc6, 9arac-v5qqr1 Inhibitor(s) related to this paper: Isoprocarb, Fenobucarb Abstract Pardosa pseudoannulata is an important predatory enemy against insect pests, such as rice planthoppers and leafhoppers. In order to understand the insecticide selectivity between P. pseudoannulata and insect pests, two acetylcholinesterase genes, Pp-ace1 and Pp-ace2, were cloned from this natural enemy. The putative proteins encoded by Pp-ace1 and Pp-ace2 showed high similarities to insect AChE1 (63% to Liposcelis entomophila AChE1) and AChE2 (36% to Culex quinquefasciatus AChE2) with specific functional motifs, which indicated that two genes might encode AChE1 and AChE2 proteins respectively. The recombinant proteins by expressing Pp-ace1 and Pp-ace2 genes in insect sf9 cells showed high AChE activities. The kinetic parameters, Vmax and Km, of two recombinant AChE proteins were significantly different. The sensitivities to six insecticides were determined in two recombinant AChEs. Pp-AChE1 was more sensitive to all tested insecticides than Pp-AChE2, such as fenobucarb (54 times in Ki ratios), isoprocarb (31 times), carbaryl (13 times) and omethoate (6 times). These results indicated that Pp-AChE1 might be the major synaptic enzyme in the spider. By sequence comparison of P. pseudoannulata and insect AChEs, the key amino acid differences at or close to the functional sites were found. The locations of some key amino acid differences were consistent with the point mutation sites in insect AChEs that were associated with insecticide resistance, such as Phe331 in Pp-AChE2 corresponding to Ser331Phe mutation in Myzus persicae and Aphis gossypii AChE2, which might play important roles in insecticide selectivity between P. pseudoannulata and insect pests. Of course, the direct evidences are needed through further studies. Title: Improved thermostability of esterase from Aspergillus fumigatus by site-directed mutagenesis Zhang S, Wu G, Feng S, Liu Z Ref: Enzyme Microb Technol, 64-65:11, 2014 : PubMed ESTHER: Zhang_2014_Enzyme.Microb.Technol_64-65_11 PubMedSearch: Zhang 2014 Enzyme.Microb.Technol 64-65 11 PubMedID: 25152411 Abstract A 1.020-bp esterase gene, estQ, encoding for a protein of 339 amino acids, was cloned from Aspergillus fumigatus and expressed in E. coli. EstQ exhibited the optimal activity around 40 degrees C and pH 9.0. In order to obtain more thermostable esterases, three mutants (A134T, V160T, A134T-V160T) were constructed by site-directed mutagenesis and also characterized for further research. Compared to A134T and V160T displaying their optimum activity at 40 degrees C, A134T-V160T exhibited a 5 degrees C higher optimal temperature and a longer half-life more than 24 times than that of WT at 50 degrees C. All the mutants displayed favorable effects on thermostability and retained 53-76% activity after pre-incubation for 30min at 45 degrees C, about 20-40% higher than that of the WT. With an increase in Km of the three mutants, a decrease in catalytic efficiency in kcat/Km was observed in mutant V160T and A134T-V160T against p-nitrophenyl butyrate. Homology models of WT and A134T-V160T were built to understand the structure-function relationship. The analysis results showed that the improved thermostability may be due to the favorable interaction and additional hydrogen bonds formed in the mutants by substitution of hydrophobic residues with hydrophilic residues. This study provide useful theoretical reference for enzyme evolution in vitro. Title: Characterization of EstB, a novel cold-active and organic solvent-tolerant esterase from marine microorganism Alcanivorax dieselolei B-5(T) Zhang S, Wu G, Liu Z, Shao Z Ref: Extremophiles, 18:251, 2014 : PubMed ESTHER: Zhang_2014_Extremophiles_18_251 PubMedSearch: Zhang 2014 Extremophiles 18 251 PubMedID: 24318107 Abstract A novel esterase gene, estB, was cloned from the marine microorganism Alcanivorax dieselolei B-5(T) and overexpressed in E. coli DE3 (BL21). The expressed protein EstB with a predicted molecular weight of 45.1 kDa had a distinct catalytic triad (Ser(211)-Trp(353)-Gln(385)) and the classical consensus motif conserved in most lipases and esterases Gly(209)-X-Ser(211)-X-Gly(213). EstB showed very low similarity to any known proteins and displayed the highest similarity to the hypothetical protein (46%) from Rhodococcus jostii RHA1. EstB showed the optimal activity around pH 8.5 and 20 degrees C and was identified to be extremely cold-adaptative retaining more than 95% activity between 0 and 10 degrees C. The values of kinetic parameters on p-NP caproate (K m, K cat and K cat/K m) were 0.15 mM, 0.54 x 10(3) s(-1) and 3.6 x 10(3) s(-1) mM(-1), respectively. In addition, EstB showed remarkable stability in several studied organic solvents and detergents of high concentrations with the retention of more than 70% activity after treatment for 30 min. The cold activity and its tolerance towards organic solvents made it a promising biocatalyst for industrial applications under extreme conditions. Title: Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history Zhou X, Wang B, Pan Q, Zhang J, Kumar S, Sun X, Liu Z, Pan H, Lin Y and Li R <24 more author(s)> Zhou X, Wang B, Pan Q, Zhang J, Kumar S, Sun X, Liu Z, Pan H, Lin Y, Liu G, Zhan W, Li M, Ren B, Ma X, Ruan H, Cheng C, Wang D, Shi F, Hui Y, Tao Y, Zhang C, Zhu P, Xiang Z, Jiang W, Chang J, Wang H, Cao Z, Jiang Z, Li B, Yang G, Roos C, Garber PA, Bruford MW, Li R (- 24) Ref: Nat Genet, 46:1303, 2014 : PubMed ESTHER: Zhou_2014_Nat.Genet_46_1303 PubMedSearch: Zhou 2014 Nat.Genet 46 1303 PubMedID: 25362486 Gene_locus related to this paper: rhibe-a0a2k6jtl7, rhibe-ACHE, rhibe-a0a2k6k3y7, rhibe-a0a2k6k493, rhibe-a0a2k6lev4, rhibe-a0a2k6lfa5, rhibe-a0a2k6m6k8, rhiro-a0a2k6p1u8, rhiro-a0a2k6q1t8, rhiro-a0a2k6q1w3, rhibe-a0a2k6n5t9, rhibe-a0a2k6ju46, rhibe-a0a2k6kt48, rhibe-a0a2k6llm5, rhibe-a0a2k6lnt5, rhiro-a0a2k6qzp6, rhiro-a0a2k6q4a6, rhibe-a0a2k6kn93, rhibe-a0a2k6lm22, rhibe-a0a2k6jwp8, rhiro-a0a2k6qun2, rhiro-a0a2k6nj56, rhiro-a0a2k6n885, rhiro-a0a2k6nnj4, rhiro-a0a2k6n7n5, rhibe-a0a2k6jvz4, rhiro-a0a2k6nfk9, rhiro-a0a2k6qjv0, rhibe-a0a2k6jn19, rhibe-a0a2k6k333, rhibe-a0a2k6mff5 Abstract Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates. Title: Draft genome sequences of two super-extensively drug-resistant isolates of Mycobacterium tuberculosis from China Lin N, Liu Z, Zhou J, Wang S, Fleming J Ref: FEMS Microbiology Letters, 347:93, 2013 : PubMed ESTHER: Lin_2013_FEMS.Microbiol.Lett_347_93 PubMedSearch: Lin 2013 FEMS.Microbiol.Lett 347 93 PubMedID: 23965132 Gene_locus related to this paper: mycmm-b2ht49, myctu-cut3, myctu-Rv1069c, myctu-RV1215C, myctu-Rv2045c Abstract The prevalence of drug-resistance in Mycobacterium tuberculosis is already having a negative impact on the control of tuberculosis. We report the draft genome sequences of two super-extensively drug-resistant M. tuberculosis isolates from China, FJ05194 (lineage 2) and GuangZ0019 (lineage 4), and compare them with the H37Rv reference strain to identify possible sources of genetic variation associated with their extensive drug resistance. Our results suggest that their extensive drug resistance probably results from the stepwise accumulation of resistances to individual drugs. Title: Whole-Genome Sequencing of Lactobacillus shenzhenensis Strain LY-73T Lin Z, Liu Z, Yang R, Zou Y, Wan D, Chen J, Guo M, Zhao J, Fang C, Liu F Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Lin_2013_Genome.Announc_1_e00972 PubMedSearch: Lin 2013 Genome.Announc 1 e00972 PubMedID: 24265500 Gene_locus related to this paper: 9laco-u4tvs6, 9laco-u4ti93 Abstract Lactobacillus shenzhenensis strain LY-73(T) is a novel species which was first isolated from fermented goods. Here, we report the draft genome sequence of Lactobacillus shenzhenensis LY-73(T). Title: Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration Liu Z, Jiang M, Kang T, Miao D, Gu G, Song Q, Yao L, Hu Q, Tu Y and Chen J <4 more author(s)> Liu Z, Jiang M, Kang T, Miao D, Gu G, Song Q, Yao L, Hu Q, Tu Y, Pang Z, Chen H, Jiang X, Gao X, Chen J (- 4) Ref: Biomaterials, 34:3870, 2013 : PubMed ESTHER: Liu_2013_Biomaterials_34_3870 PubMedSearch: Liu 2013 Biomaterials 34 3870 PubMedID: 23453061 Abstract Development of effective non-invasive drug delivery systems is of great importance to the treatment of Alzheimer's diseases and has made great progress in recent years. In this work, lactoferrin (Lf), a natural iron binding protein, whose receptor is highly expressed in both respiratory epithelial cells and neurons is here utilized to facilitate the nose-to-brain drug delivery of neuroprotection peptides. The Lf-conjugated PEG-PCL nanoparticle (Lf-NP) was constructed via a maleimide-thiol reaction with the Lf conjugation confirmed by CBQCA Protein Quantitation and XPS analysis. Other important parameters such as particle size distribution, zeta potential and in vitro release of fluorescent probes were also characterized. Compared with unmodified nanoparticles (NP), Lf-NP exhibited a significantly enhanced cellular accumulation in 16HBE14o-cells through both caveolae-/clathrin-mediated endocytosis and direct translocation. Following intranasal administration, Lf-NP facilitated the brain distribution of the coumarin-6 incorporated with the AUC0-8h in rat cerebrum (with hippocampus removed), cerebellum, olfactory tract, olfactory bulb and hippocampus 1.36, 1.53, 1.70, 1.57 and 1.23 times higher than that of coumarin-6 carried by NP, respectively. Using a neuroprotective peptide - NAPVSIPQ (NAP) as the model drug, the neuroprotective and memory improvement effect of Lf-NP was observed even at lower dose than that of NP in a Morris water maze experiment, which was also confirmed by the evaluation of acetylcholinesterase, choline acetyltransferase activity and neuronal degeneration in the mice hippocampus. In conclusion, Lf-NP may serve as a promising nose-to-brain drug delivery carrier especially for peptides and proteins. Title: Comparative analyses of lipoprotein lipase, hepatic lipase, and endothelial lipase, and their binding properties with known inhibitors Wang Z, Li S, Sun L, Fan J, Liu Z Ref: PLoS ONE, 8:e72146, 2013 : PubMed ESTHER: Wang_2013_PLoS.One_8_e72146 PubMedSearch: Wang 2013 PLoS.One 8 e72146 PubMedID: 23991054 Abstract The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investigated the kinetic characteristics for the catalytic residues using a molecular dynamics simulation strategy. To elucidate the molecular interactions and determine potential key residues involved in the binding to lipase inhibitors, we analyzed the binding pockets and binding poses of known inhibitors of the three lipases. We identified the spatial consensus catalytic triad "Ser-Asp-His", a characteristic motif in all three lipases. Furthermore, we found that the spatial characteristics of the binding pockets of the lipase molecules play a key role in ligand recognition, binding poses, and affinities. To the best of our knowledge, this is the first report that systematically builds homology models of all the triglyceride lipase gene subfamily members. Our data provide novel insights into the molecular structures of lipases and their structure-function relationship, and thus provides groundwork for functional probe design towards lipase-based therapeutic inhibitors for the treatment of hyperlipidemia and atherosclerosis. Title: A novel esterase from a psychrotrophic bacterium Psychrobacter celer 3Pb1 showed cold-adaptation and salt-tolerance Wu G, Zhang S, Zhang H, Zhang SS, Liu Z Ref: J Mol Catal B Enzym, 98:119, 2013 : PubMed ESTHER: Wu_2013_J.Mol.Catal.B.Enzym_98_119 PubMedSearch: Wu 2013 J.Mol.Catal.B.Enzym 98 119 Gene_locus related to this paper: 9gamm-s5dq61 Abstract A genomic library of a psychrotrophic Psychrobacter celer 3Pb1 was constructed and screened for lipolytic proteins, and a novel esterase Est12 was cloned and characterized. The esterase gene, est12, contained an open reading frame of 990 bp that encoded a protein of 329 amino acids with an estimated molecular mass of 35,150 Da. Est12 displayed the highest amino acid identity (77%) with a hypothetical esterase from Psychrobacter sp. PAMC 21119 (WP_010200623.1). Phylogenetic analysis suggested that the protein belonged to a new lipase/esterase family. Substrate specifity study showed that Est12 preferred short-chain p-nitrophenyl esters and was most active toward p-nitrophenyl butyrate. Est12 displayed the optimal activity at pH 7.5 and 35C, and remained 41% activity at 0C while being unstable at temperatures above 40C, indicating its cold-adaptation. Besides, Est12 was a salt-tolerant esterase as 4.5 M NaCl significantly declined Km from 0.069 to 0.033 mM and increased kcat from 4.20 to 9.21 s-1, resulting in the increased catalytic efficiency kcat/Km from 60.72 to 276.31 s-1 mM-11. The enzyme activity was also quite stable after 24 h incubation in 0-4.5 M NaCl solutions. In addition, Est12 was very active and stable in the presence of several detergents and organic solvents. This new cold-active and halotolerant esterase would be a potential candidate in industrial applications under extreme conditions (low temperatures, high salinity), and was valuable for studying other unknown esterases/lipases in this new family. Title: Biocatalysts for cascade reaction: porcine pancreas lipase (PPL)-catalyzed synthesis of bis(indolyl)alkanes Xiang Z, Liu Z, Chen X, Wu Q, Lin X Ref: Amino Acids, 45:937, 2013 : PubMed ESTHER: Xiang_2013_Amino.Acids_45_937 PubMedSearch: Xiang 2013 Amino.Acids 45 937 PubMedID: 23860845 Abstract A cascade reaction between aldehydes and indole catalyzed by lipase from porcine pancreas Type II (PPL) in solvent mixture at 50 degrees C was reported for the first time. Some control experiments had been designed to demonstrate that the PPL was responsible for the cascade reaction. After the optimization of the stepwise process, a series of bis(indolyl)alkanes were prepared in moderate to excellent yields under the catalysis of PPL. Title: Identification and comparison of cutinases for synthetic polyester degradation Baker PJ, Poultney C, Liu Z, Gross R, Montclare JK Ref: Applied Microbiology & Biotechnology, 93:229, 2012 : PubMed ESTHER: Baker_2012_Appl.Microbiol.Biotechnol_93_229 PubMedSearch: Baker 2012 Appl.Microbiol.Biotechnol 93 229 PubMedID: 21713515 Gene_locus related to this paper: humin-cut Abstract Cutinases have been exploited for a broad range of reactions, from hydrolysis of soluble and insoluble esters to polymer synthesis. To further expand the biotechnological applications of cutinases for synthetic polyester degradation, we perform a comparative activity and stability analysis of five cutinases from Alternaria brassicicola (AbC), Aspergillus fumigatus (AfC), Aspergillus oryzae (AoC), Humicola insolens (HiC), and the well-characterized Fusarium solani (FsC). Of the cutinases, HiC demonstrated enhanced poly(epsilon-caprolactone) hydrolysis at high temperatures and under all pH values, followed by AoC and AfC. Both AbC and FsC are least stable and function poorly at high temperatures as well as at acidic pH conditions. Surface charge calculations and phylogenetic analysis reveal two important modes of cutinase stabilization: (1) an overall neutral surface charge within the "crowning area" by the active site and (2) additional disulfide bond formation. These studies provide insights useful for reengineering such enzymes with improved function and stability for a wide range of biotransformations. Title: Complete genome of Candidatus Chloracidobacterium thermophilum, a chlorophyll-based photoheterotroph belonging to the phylum Acidobacteria Garcia Costas AM, Liu Z, Tomsho LP, Schuster SC, Ward DM, Bryant DA Ref: Environ Microbiol, 14:177, 2012 : PubMed ESTHER: Garcia_2012_Environ.Microbiol_14_177 PubMedSearch: Garcia 2012 Environ.Microbiol 14 177 PubMedID: 21951563 Gene_locus related to this paper: chltf-g2led8 Abstract Candidatus Chloracidobacterium thermophilum, which naturally inhabits microbial mats of alkaline siliceous hot springs in Yellowstone National Park, is the only known chlorophototroph in the phylum Acidobacteria. The Ca. C. thermophilum genome was composed of two chromosomes (2,683,362 bp and 1,012,010 bp), and both encoded essential genes. The genome included genes to produce chlorosomes, the Fenna-Matthews-Olson protein, bacteriochlorophylls a and c as principal pigments, and type-1, homodimeric reaction centres. Ca. C. thermophilum is an aerobic photoheterotroph that lacks the ability to synthesize several essential nutrients. Key genes of all known carbon fixation pathways were absent, as were genes for assimilatory nitrate and sulfate reduction and vitamin B(12) synthesis. Genes for the synthesis of branched-chain amino acids (valine, isoleucine and leucine) were also absent, but genes for catabolism of these compounds were present. This observation suggested that Ca. C. thermophilum may synthesize branched-chain amino acids from an intermediate(s) of the catabolic pathway by reversing these reactions. The genome encoded an aerobic respiratory electron transport chain that included NADH dehydrogenase, alternative complex III and cytochrome oxidase. The chromosomes of the laboratory isolate were compared with assembled, metagenomic scaffolds from the major Ca. C. thermophilum population in hot-spring mats. The larger chromosomes of the two populations were highly syntenous but significantly divergent (~13%) in sequence. In contrast, the smaller chromosomes have undergone numerous rearrangements, contained many transposases, and might be less constrained by purifying selection than the large chromosomes. Some transposases were homologous to those of mat community members from other phyla. Title: Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH and Bierut LJ <142 more author(s)> Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikainen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hallfors J, Han S, Hartmann AM, Hayward C, Heikkila K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkarsdottir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeboller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kahonen M, Kendler KS, Lehtimaki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nothen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Volzke H, Wei Q, Wichmann HE, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ (- 142) Ref: Arch Gen Psychiatry, 69:854, 2012 : PubMed ESTHER: Hartz_2012_Arch.Gen.Psychiatry_69_854 PubMedSearch: Hartz 2012 Arch.Gen.Psychiatry 69 854 PubMedID: 22868939 Abstract CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD </=10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset </=16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. Title: Complete Genome of Ignavibacterium album, a Metabolically Versatile, Flagellated, Facultative Anaerobe from the Phylum Chlorobi Liu Z, Frigaard NU, Vogl K, Iino T, Ohkuma M, Overmann J, Bryant DA Ref: Front Microbiol, 3:185, 2012 : PubMed ESTHER: Liu_2012_Front.Microbiol_3_185 PubMedSearch: Liu 2012 Front.Microbiol 3 185 PubMedID: 22661972 Gene_locus related to this paper: ignaj-i0aj72, ignaj-i0an88 Abstract Prior to the recent discovery of Ignavibacterium album (I. album), anaerobic photoautotrophic green sulfur bacteria (GSB) were the only members of the bacterial phylum Chlorobi that had been grown axenically. In contrast to GSB, sequence analysis of the 3.7-Mbp genome of I. album shows that this recently described member of the phylum Chlorobi is a chemoheterotroph with a versatile metabolism. I. album lacks genes for photosynthesis and sulfur oxidation but has a full set of genes for flagella and chemotaxis. The occurrence of genes for multiple electron transfer complexes suggests that I. album is capable of organoheterotrophy under both oxic and anoxic conditions. The occurrence of genes encoding enzymes for CO(2) fixation as well as other enzymes of the reductive TCA cycle suggests that mixotrophy may be possible under certain growth conditions. However, known biosynthetic pathways for several amino acids are incomplete; this suggests that I. album is dependent upon on exogenous sources of these metabolites or employs novel biosynthetic pathways. Comparisons of I. album and other members of the phylum Chlorobi suggest that the physiology of the ancestors of this phylum might have been quite different from that of modern GSB. Title: Efficient assembly and annotation of the transcriptome of catfish by RNA-Seq analysis of a doubled haploid homozygote Liu S, Zhang Y, Zhou Z, Waldbieser G, Sun F, Lu J, Zhang J, Jiang Y, Zhang H and Liu Z <5 more author(s)> Liu S, Zhang Y, Zhou Z, Waldbieser G, Sun F, Lu J, Zhang J, Jiang Y, Zhang H, Wang X, Rajendran KV, Khoo L, Kucuktas H, Peatman E, Liu Z (- 5) Ref: BMC Genomics, 13:595, 2012 : PubMed ESTHER: Liu_2012_BMC.Genomics_13_595 PubMedSearch: Liu 2012 BMC.Genomics 13 595 PubMedID: 23127152 Gene_locus related to this paper: ictpu-w5u6j2, ictpu-w5ub99, ictpu-w5uc03, ictpu-w5utq3, ictpu-w5u610, ictpu-w5ui62, ictpu-w5uj33, ictpu-w5u9s1, ictpu-a0a2d0rtv8, ictpu-w5uf93, ictpu-w5u6h4, ictpu-a0a2d0qam4, ictpu-w5u7r0, ictpu-w5ugq3 Abstract BACKGROUND: Upon the completion of whole genome sequencing, thorough genome annotation that associates genome sequences with biological meanings is essential. Genome annotation depends on the availability of transcript information as well as orthology information. In teleost fish, genome annotation is seriously hindered by genome duplication. Because of gene duplications, one cannot establish orthologies simply by homology comparisons. Rather intense phylogenetic analysis or structural analysis of orthologies is required for the identification of genes. To conduct phylogenetic analysis and orthology analysis, full-length transcripts are essential. Generation of large numbers of full-length transcripts using traditional transcript sequencing is very difficult and extremely costly. Title: Glutamatergic synapse formation is promoted by alpha7-containing nicotinic acetylcholine receptors Lozada AF, Wang X, Gounko NV, Massey KA, Duan J, Liu Z, Berg DK Ref: Journal of Neuroscience, 32:7651, 2012 : PubMed ESTHER: Lozada_2012_J.Neurosci_32_7651 PubMedSearch: Lozada 2012 J.Neurosci 32 7651 PubMedID: 22649244 Abstract Glutamate is the primary excitatory transmitter in adult brain, acting through synapses on dendritic spines and shafts. Early in development, however, when glutamatergic synapses are only beginning to form, nicotinic cholinergic excitation is already widespread; it is mediated by acetylcholine activating nicotinic acetylcholine receptors (nAChRs) that generate waves of activity across brain regions. A major class of nAChRs contributing at this time is a species containing alpha7 subunits (alpha7-nAChRs). These receptors are highly permeable to calcium, influence a variety of calcium-dependent events, and are diversely distributed throughout the developing CNS. Here we show that alpha7-nAChRs unexpectedly promote formation of glutamatergic synapses during development. The dependence on alpha7-nAChRs becomes clear when comparing wild-type (WT) mice with mice constitutively lacking the alpha7-nAChR gene. Ultrastructural analysis, immunostaining, and patch-clamp recording all reveal synaptic deficits when alpha7-nAChR input is absent. Similarly, nicotinic activation of alpha7-nAChRs in WT organotypic culture, as well as cell culture, increases the number of glutamatergic synapses. RNA interference demonstrates that the alpha7-nAChRs must be expressed in the neuron being innervated for normal innervation to occur. Moreover, the deficits persist throughout the developmental period of major de novo synapse formation and are still fully apparent in the adult. GABAergic synapses, in contrast, are undiminished in number under such conditions. As a result, mice lacking alpha7-nAChRs have an altered balance in the excitatory/inhibitory input they receive. This ratio represents a fundamental feature of neural networks and shows for the first time that endogenous nicotinic cholinergic signaling plays a key role in network construction. Title: Induction of dendritic spines by beta2-containing nicotinic receptors Lozada AF, Wang X, Gounko NV, Massey KA, Duan J, Liu Z, Berg DK Ref: Journal of Neuroscience, 32:8391, 2012 : PubMed ESTHER: Lozada_2012_J.Neurosci_32_8391 PubMedSearch: Lozada 2012 J.Neurosci 32 8391 PubMedID: 22699919 Abstract Glutamatergic synapses are located mostly on dendritic spines in the adult nervous system. The spines serve as postsynaptic compartments, containing components that mediate and control the synaptic signal. Early in development, when glutamatergic synapses are initially forming, waves of excitatory activity pass through many parts of the nervous system and are driven in part by a class of heteropentameric beta2-containing nicotinic acetylcholine receptors (beta2*-nAChRs). These beta2*-nAChRs are widely distributed and, when activated, can depolarize the membrane and elevate intracellular calcium levels in neurons. We show here that beta2*-nAChRs are essential for acquisition of normal numbers of dendritic spines during development. Mice constitutively lacking the beta2-nAChR gene have fewer dendritic spines than do age-matched wild-type mice at all times examined. Activation of beta2*-nAChRs by nicotine either in vivo or in organotypic slice culture quickly elevates the number of spines. RNA interference studies both in vivo and in organotypic culture demonstrate that the beta2*-nAChRs act in a cell-autonomous manner to increase the number of spines. The increase depends on intracellular calcium and activation of calcium, calmodulin-dependent protein kinase II. Absence of beta2*-nAChRs in vivo causes a disproportionate number of glutamatergic synapses to be localized on dendritic shafts, rather than on spines as occurs in wild type. This shift in synapse location is found both in the hippocampus and cortex, indicating the breadth of the effect. Because spine synapses differ from shaft synapses in their signaling capabilities, the shift observed is likely to have significant consequences for network function. Title: Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L and Wang FS <5 more author(s)> Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, Zhang A, Shi J, Chen L, Lv S, He W, Geng H, Jin L, Liu Z, Wang FS (- 5) Ref: Stem Cells Transl Med, 1:725, 2012 : PubMed ESTHER: Shi_2012_Stem.Cells.Transl.Med_1_725 PubMedSearch: Shi 2012 Stem.Cells.Transl.Med 1 725 PubMedID: 23197664 Abstract Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. Title: Study on improvement of extracellular production of recombinant Thermobifida fusca cutinase by Escherichia coli Chen S, Liu Z, Chen J, Wu J Ref: Appl Biochem Biotechnol, 165:666, 2011 : PubMed ESTHER: Chen_2011_Appl.Biochem.Biotechnol_165_666 PubMedSearch: Chen 2011 Appl.Biochem.Biotechnol 165 666 PubMedID: 21594592 Abstract Escherichia coli is one of the most commonly used host strains for recombinant protein production. More and more research works on the production of recombinant protein indicate that extracellular production throughout a culture medium is more convenient and attractive compared to intracellular production. In present work, inducing temperature and isopropyl beta-D: -1-thiogalactopyranoside (IPTG) concentration were investigated to decrease the formation of inclusion body and increase the amount of soluble recombinant cutinase initially. Enzyme activity in the culture medium reached to 118.9 U/ml at 64 h of culture, and no inclusion body was detected in cytoplasm under the inducement condition of 0.2 mM IPTG and 30 degrees C. In addition, it was found that a large amount of cutinase had been accumulated in periplasm since 16-h cultivation under the same inducement condition. Therefore, glycine and surfactant sodium taurodeoxycholate (TDOC) were further used to promote the leakage of recombinant cutinase from periplasm. Supplied with 100 mM glycine and 1 mM TDOC, the amount of cutinase in periplasm decreased remarkably, and the activity in the culture medium reached to 146.2 and 149.2 U/ml after 54 h of culturing, respectively. Title: A lipase-responsive vehicle using amphipathic polymer synthesized with the lipase as catalyst Ge J, Lu D, Yang C, Liu Z Ref: Macromol Rapid Commun, 32:546, 2011 : PubMed ESTHER: Ge_2011_Macromol.Rapid.Commun_32_546 PubMedSearch: Ge 2011 Macromol.Rapid.Commun 32 546 PubMedID: 21433214 Abstract We describe an enzyme-responsive polymeric vehicle, which is of great interest in controlled drug delivery, biosensing, and other related areas. The polymer synthesized using lipase as catalyst in DMSO has a favorable molecular structure that is quickly hydrolyzed by lipase in aqueous phase, and allows a fast release of encapsulated molecules. Title: Preparation and characterization of single-enzyme nanogels Ge J, Yan M, Lu D, Liu Z Ref: Methods Mol Biol, 743:119, 2011 : PubMed ESTHER: Ge_2011_Methods.Mol.Biol_743_119 PubMedSearch: Ge 2011 Methods.Mol.Biol 743 119 PubMedID: 21553187 Abstract Enzymes have been incorporated in nanostructures in order to provide robust catalysts for valuable reactions, particularly those performed under harsh and denaturing conditions. This chapter describes the encapsulation of enzymes in polyacrylamide nanogels by a two-step in situ polymerization process for preparing robust biocatalysts. The first step in this process is the generation of vinyl groups on the enzyme surface, while the second step involves in situ polymerization using acrylamide as the monomer. Encapsulation of the enzyme in the hydrophilic, porous, and flexible polyacrylamide gel of several nanometers thick would help to both give a significantly enhanced thermostability and prevent the removal of essential water by polar solvents. The hydrophilic flexible polymer shell also allows the protein structure to undergo necessary conformational transitions during the catalytic reaction and, at the same time, impose marginal mass transfer restrictions for the substrates entering across the polymer shell. The effectiveness of this method is demonstrated with horseradish peroxidase (HRP), carbonic anhydrase, and lipase. The impacts of such an encapsulation on the activity and stability of enzymes are also discussed. Title: Draft genome sequence of the marine bacterium Streptomyces griseoaurantiacus M045, which produces novel manumycin-type antibiotics with a pABA core component Li F, Jiang P, Zheng H, Wang S, Zhao G, Qin S, Liu Z Ref: Journal of Bacteriology, 193:3417, 2011 : PubMed ESTHER: Li_2011_J.Bacteriol_193_3417 PubMedSearch: Li 2011 J.Bacteriol 193 3417 PubMedID: 21551298 Gene_locus related to this paper: 9acto-f3ngb7, 9acto-f3nim7, 9acto-f3ntg3, 9acto-f3nmw3, 9actn-f3nh76, 9actn-f3nh94 Abstract Streptomyces griseoaurantiacus M045, isolated from marine sediment, produces manumycin and chinikomycin antibiotics. Here we present a high-quality draft genome sequence of S. griseoaurantiacus M045, the first marine Streptomyces species to be sequenced and annotated. The genome encodes several gene clusters for biosynthesis of secondary metabolites and has provided insight into genomic islands linking secondary metabolism to functional adaptation in marine S. griseoaurantiacus M045. Title: [Correlation research of isolated liver tissue pathology and clinical diagnosis in patients with chronic severe hepatitis B] Sun J, Yu HW, Liu Z, Liu H, Zhang Q, Yao QW, Feng YM, Li J, Meng QH Ref: Zhonghua Gan Zang Bing Za Zhi, 19:603, 2011 : PubMed ESTHER: Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603 PubMedSearch: Sun 2011 Zhonghua.Gan.Zang.Bing.Za.Zhi 19 603 PubMedID: 22152318 Abstract To study the coincidence rate of clinical diagonisis with pathological diagnosis for chronic severe hepatitis, and to screen out clinical indicators consistent with pathological diagnosis. Fifty-one patients diagnosed as chronic severe hepatitis and underwent liver transplantation in Beijing You'an hospital from November 2004 to June 2009 participated in this study. The clinical data were selected as following: ALT, AST, urea nitrogen, creatinine, glucose, cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase, serum potassium, serum sodium, prothrombin activity and blood ammonia level. The width of the portal vein and splenic vein thickness were measured by color Doppler ultrasound and were compared in different groups. Data were ananlyzed with independent sample t test and F test. The coincidence rate between clinical and pathological diagnoses in this study was 64.7%. ALT and AST levels for Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L, 67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0 U/L (P is less than to 0.01) respectively, with statistically significant difference existed. The mean level of ALT in Chronic severe hepatitis group was significantly different in the situations of onset less than 30 days or more than 30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to 0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The coincidence rate of clinical with pathological diagnoses for Chronic Severe Hepatitis was low, increased ALT and AST levels would help improve the diagnostic accuracy. Title: Ultra-sensitive biosensor based on mesocellular silica foam for organophosphorous pesticide detection Wu S, Zhang L, Qi L, Tao S, Lan X, Liu Z, Meng C Ref: Biosensors & Bioelectronics, 26:2864, 2011 : PubMed ESTHER: Wu_2011_Biosens.Bioelectron_26_2864 PubMedSearch: Wu 2011 Biosens.Bioelectron 26 2864 PubMedID: 21185711 Abstract A sensitive amperometric acetylcholinesterase (AChE) biosensor was fabricated based on mesocellular silica foam (MSF), which functioned as both an enzyme immobilization matrix and a solid phase extraction (SPE) material for the preconcentration of target molecules. The hydrophilic interface, the good mechanical/chemical stability, and the suitable pore dimension of MSF provided the entrapped AChE a good environment to well maintain its bioactivity at basic condition. The AChE immobilized in MSF showed improved catalytic ability for the hydrolysis of acetylthiocholine, as evidenced by the increasing of the oxidation current of thiocholine, the enzymatic catalytic hydrolysis production of acetylthiocholine. In addition, the MSF with large surface area showed a modest adsorption capacity for monocrotophos, a model organophosphate used in this study, via the hydrogen bond or physical adsorption interaction. The combination of the SPE and the good enzyme immobilization ability in MSF significantly promoted the sensitivity of the biosensor, and the limit of detection has lowered to 0.05 ng/mL. The biosensor exhibited accuracy, good reproducibility, and acceptable stability when used for garlic samples analysis. The strategy may provide a new method to fabricate highly sensitive biosensors for the detection of ultra-trace organophosphorous pesticide infield. Title: A comparison of hepatic in vitro metabolism of T-2 toxin in rats, pigs, chickens, and carp Wu Q, Huang L, Liu Z, Yao M, Wang Y, Dai M, Yuan Z Ref: Xenobiotica, 41:863, 2011 : PubMed ESTHER: Wu_2011_Xenobiotica_41_863 PubMedSearch: Wu 2011 Xenobiotica 41 863 PubMedID: 21745144 Abstract T-2 toxin, a highly toxic member of the type-A trichothecenes, is produced by various Fusarium moulds that can potentially affect human health. It is strongly cytotoxic for human hematopoietic progenitors. Alimentary toxic aleukia (ATA), a disease typically associated with human, is primarily induced by T-2 toxin. A comparison of the metabolism of T-2 toxin incubated with hepatocytes of rats, piglets, chickens, and the hepatic subcellular fractions (microsomes and cytosol) of piglets, chickens, rats, and carp (common carp and grass carp) was carried out. The activities of the recombinant pig CYP3A29 on the transformation of T-2 and HT-2 toxins were preliminary studied. Metabolites were identified by novel LC/MS-IT-TOF. Qualitative similarities and differences across the species were observed. In liver microsomes, HT-2 toxin, neosolaniol (NEO), 3'-OH-T-2, and 3'-OH-HT-2 were detected in rats, chickens, and pigs. 3'-OH-HT-2 and HT-2 toxin was not detectable in common carp and grass crap, respectively. Moreover, in liver microsomes, the hydroxyl metabolites accounted for the largest percentage in carp, whereas the hydrolysis product, HT-2 toxin, was the major one for the land animals. Only hydrolysis products such as NEO and HT-2 toxin were detected in hepatocytes. Recombinant pig CYP3A29 was able to convert T-2 and HT-2 toxins to high rates of 3'-OH-T-2 and 3'-OH-HT-2, respectively. Both CYP450 and carboxylesterase enzymes have been found to play a role in the metabolism of T-2 toxin. Metabolism of T-2 toxin across species produces a similar spectrum of metabolites. Preliminary metabolic studies of carp reveal that ester hydrolysis of T-2 toxin in carp may not play as important a role as is the case with land animals. Title: Identification and characterization of full-length cDNAs in channel catfish (Ictalurus punctatus) and blue catfish (Ictalurus furcatus) Chen F, Lee Y, Jiang Y, Wang S, Peatman E, Abernathy J, Liu H, Liu S, Kucuktas H and Liu Z <1 more author(s)> Chen F, Lee Y, Jiang Y, Wang S, Peatman E, Abernathy J, Liu H, Liu S, Kucuktas H, Ke C, Liu Z (- 1) Ref: PLoS ONE, 5:e11546, 2010 : PubMed ESTHER: Chen_2010_PLoS.ONE_5_E11546 PubMedSearch: Chen 2010 PLoS.ONE 5 E11546 PubMedID: 20634964 Gene_locus related to this paper: ictpu-e3teh0, ictpu-e3tfr7, ictpu-a0a2d0pnc6 Abstract BACKGROUND: Genome annotation projects, gene functional studies, and phylogenetic analyses for a given organism all greatly benefit from access to a validated full-length cDNA resource. While increasingly common in model species, full-length cDNA resources in aquaculture species are scarce. METHODOLOGY AND PRINCIPAL FINDINGS: Through in silico analysis of catfish (Ictalurus spp.) ESTs, a total of 10,037 channel catfish and 7,382 blue catfish cDNA clones were identified as potentially encoding full-length cDNAs. Of this set, a total of 1,169 channel catfish and 933 blue catfish full-length cDNA clones were selected for re-sequencing to provide additional coverage and ensure sequence accuracy. A total of 1,745 unique gene transcripts were identified from the full-length cDNA set, including 1,064 gene transcripts from channel catfish and 681 gene transcripts from blue catfish, with 416 transcripts shared between the two closely related species. Full-length sequence characteristics (ortholog conservation, UTR length, Kozak sequence, and conserved motifs) of the channel and blue catfish were examined in detail. Comparison of gene ontology composition between full-length cDNAs and all catfish ESTs revealed that the full-length cDNA set is representative of the gene diversity encoded in the catfish transcriptome. Title: A first genome assembly of the barley fungal pathogen Pyrenophora teres f. teres Ellwood SR, Liu Z, Syme RA, Lai Z, Hane JK, Keiper F, Moffat CS, Oliver RP, Friesen TL Ref: Genome Biol, 11:R109, 2010 : PubMed ESTHER: Ellwood_2010_Genome.Biol_11_R109 PubMedSearch: Ellwood 2010 Genome.Biol 11 R109 PubMedID: 21067574 Gene_locus related to this paper: pyrtr-b2vv71, pyrtr-b2w1y6, pyrtr-b2w948, pyrtr-b2wbz8, pyrtr-b2wcq8, pyrtr-b2wgg5, pyrtr-dapb, pyrtt-e3rcw4, pyrtt-e3rfb1, pyrtt-e3rfu0, pyrtt-e3rgg7, pyrtt-e3rh98, pyrtt-e3ril1, pyrtt-e3rjq5, pyrtt-e3rkg6, pyrtt-e3rkr9, pyrtt-e3rl87, pyrtt-e3rp29, pyrtt-e3rpe8, pyrtt-e3rqg8, pyrtt-e3rrt3, pyrtt-e3rs40, pyrtt-e3rth6, pyrtt-e3rtt7, pyrtt-e3ruq0, pyrtt-e3ruw6, pyrtt-e3rvm2, pyrtt-e3rwp7, pyrtt-e3rxf7, pyrtt-e3s2m6, pyrtt-e3s5q8, pyrtt-e3s8r6, pyrtt-e3s292, pyrtt-e3s479, pyrtt-e3s701, pyrtt-e3s716, pyrtt-e3s922, pyrtt-e3sa06, pyrtt-e3ru14, pyrtt-e3rg15, pyrtt-e3rxy1, pyrtr-b2vyg1, pyrtt-e3rnt0, pyrtt-e3rwh1, pyrtt-e3rtw2, pyrtt-e3s3k4, pyrtt-e3rs45, pyrtr-b2w571, pyrtt-e3s9z0, pyrtt-e3rxj8, pyrtt-e3s3p6, pyrtt-e3rqx0, pyrtt-e3rpq8, pyrtt-e3rx11, pyrtr-b2vzr5, pyrtt-e3s4g0, pyrtt-e3rqw7, pyrtt-e3rgu8 Abstract BACKGROUND: Pyrenophora teres f. teres is a necrotrophic fungal pathogen and the cause of one of barley's most important diseases, net form of net blotch. Here we report the first genome assembly for this species based solely on short Solexa sequencing reads of isolate 0-1. The assembly was validated by comparison to BAC sequences, ESTs, orthologous genes and by PCR, and complemented by cytogenetic karyotyping and the first genome-wide genetic map for P. teres f. teres. Title: Characterization of a novel esterase Rv0045c from Mycobacterium tuberculosis Guo J, Zheng X, Xu L, Liu Z, Xu K, Li S, Wen T, Liu S, Pang H Ref: PLoS ONE, 5:, 2010 : PubMed ESTHER: Guo_2010_PLoS.One_5_ PubMedSearch: Guo 2010 PLoS.One 5 PubMedID: 20957207 Gene_locus related to this paper: myctu-RV0045C Abstract BACKGROUND: It was proposed that there are at least 250 enzymes in M. tuberculosis involved in lipid metabolism. Rv0045c was predicted to be a hydrolase by amino acid sequence similarity, although its precise biochemical characterization and function remained to be defined. METHODOLOGY/PRINCIPAL FINDINGS: We expressed the Rv0045c protein to high levels in E. coli and purified the protein to high purity. We confirmed that the prepared protein was the Rv0045c protein by mass spectrometry analysis. Circular dichroism spectroscopy analysis showed that the protein possessed abundant beta-sheet secondary structure, and confirmed that its conformation was stable in the range pH 6.0-10.0 and at temperatures <= 40 degrees C. Enzyme activity analysis indicated that the Rv0045c protein could efficiently hydrolyze short chain p-nitrophenyl esters (C(2)-C(8)), and its suitable substrate was p-nitrophenyl caproate (C(6)) with optimal catalytic conditions of 39 degrees C and pH 8.0. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that the Rv0045c protein is a novel esterase. These experiments will be helpful in understanding ester/lipid metabolism related to M. tuberculosis. Title: Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M and Yu Z <1 more author(s)> He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M, Wang S, Yu Z (- 1) Ref: Journal of Bacteriology, 192:4074, 2010 : PubMed ESTHER: He_2010_J.Bacteriol_192_4074 PubMedSearch: He 2010 J.Bacteriol 192 4074 PubMedID: 20525827 Gene_locus related to this paper: bacan-BA3703, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1677, bacce-BC1788, bacce-BC2141, bacce-BC2171, bacce-BC2456, bacce-BC2458, bacce-BC3133, bacce-BC4102, bacce-BC4854, bacce-BC4862, bacce-BC5130, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory. Title: Native subunit composition of two insect nicotinic receptor subtypes with differing affinities for the insecticide imidacloprid Li J, Shao Y, Ding Z, Bao H, Liu Z, Han Z, Millar NS Ref: Insect Biochemistry & Molecular Biology, 40:17, 2010 : PubMed ESTHER: Li_2010_Insect.Biochem.Mol.Biol_40_17 PubMedSearch: Li 2010 Insect.Biochem.Mol.Biol 40 17 PubMedID: 20005950 Abstract Neonicotinoid insecticides, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) and are used extensively to control a variety of insect pest species. The brown planthopper (Nilaparvata lugens), an insect pest of rice crops throughout Asia, is an important target species for control with neonicotinoid insecticides such as imidacloprid. Studies with nAChRs purified from N. lugens have identified two [(3)H]imidacloprid binding sites with different affinities (K(d) = 3.5 +/- 0.6 pM and 1.5 +/- 0.2 nM). Co-immunoprecipitation studies with native preparations of N. lugens nAChRs, using subunit-selective antisera, have demonstrated the co-assembly of Nlalpha1, Nlalpha2 and Nlbeta1 subunits into one receptor complex and of Nlalpha3, Nlalpha8 and Nlbeta1 into another. Immunodepletion of Nlalpha1 or Nlalpha2 subunits resulted in the selective loss of the lower affinity imidacloprid binding site, whereas immunodepletion of Nlalpha3 or Nlalpha8 caused the selective loss of the high-affinity site. Immunodepletion of Nlbeta1 resulted in a complete absence of specific imidacloprid binding. In contrast, immunodepletion with antibodies selective for other N. lugens nAChR subunits (Nlalpha4, Nlalpha6, Nlalpha7 and Nlbeta2) had no significant effect on imidacloprid binding. Taken together, these data suggest that nAChRs containing Nlalpha1, Nlalpha2 and Nlbeta1 constitute the lower affinity binding site, whereas nAChRs containing Nlalpha3, Nlalpha8 and Nlbeta1 constitute the higher affinity binding site for imidacloprid in N. lugens. Title: Crystal structure of a secreted lipase from Gibberella zeae reveals a novel double-lock mechanism Lou Z, Li M, Sun Y, Liu Y, Liu Z, Wu W, Rao Z Ref: Protein Cell, 1:760, 2010 : PubMed ESTHER: Lou_2010_Protein.Cell_1_760 PubMedSearch: Lou 2010 Protein.Cell 1 760 PubMedID: 21203917 Gene_locus related to this paper: gibze-q6wer3 Inhibitor(s) related to this paper: Ebelactone-B Abstract Fusarium graminearum (sexual stage: Gibberella zeae) is the causative agent of Fusarium Head Blight (FHB), which is one of the most destructive plant disease of cereals, accounting for high grain yield losses, especially for wheat and maize. Like other fungal pathogens, several extracellular enzymes secreted by G. zeae are known to be involved in host infection. Among these secreted lipases, G. zeae lipase (GZEL), which is encoded by the FGL1 gene, was demonstrated to be crucial to G. zeae pathogenicity. However, the precise mechanism of GZEL remains unclear due to a lack of detailed structural information. In this study, we report the crystal structure of GZEL at the atomic level. The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique "double lock" enzymatic mechanism. To gain insight into substrate/inhibitor recognition, we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B (based on the reported structures of GZEL homologues), which defines possible substrate binding sites within the catalytic cleft and suggests an "anti sn-l" binding mode. These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors. Title: Purification and characterization of functional human paraoxonase-1 expressed in Trichoplusia ni larvae Otto TC, Kasten SA, Kovaleva E, Liu Z, Buchman G, Tolosa M, Davis D, Smith JR, Balcerzak R and Cerasoli DM <1 more author(s)> Otto TC, Kasten SA, Kovaleva E, Liu Z, Buchman G, Tolosa M, Davis D, Smith JR, Balcerzak R, Lenz DE, Cerasoli DM (- 1) Ref: Chemico-Biological Interactions, 187:388, 2010 : PubMed ESTHER: Otto_2010_Chem.Biol.Interact_187_388 PubMedSearch: Otto 2010 Chem.Biol.Interact 187 388 PubMedID: 20176005 Abstract Human serum paraoxonase-1 (HuPON1) is difficult to either purify from plasma or functionally express in high yield from recombinant sources. Here, we describe the characterization of functional HuPON1 expressed and purified from Trichoplusia ni (T. ni) larvae infected with an orally active form of baculovirus. SDS-PAGE and anti-HuPON1 Western blot analyses yielded only three bands of approximately 41, 42, and 44 kDa. MALDI-TOF confirmed the identity of each of these bands as HuPON1 with greater than 95% confidence. These isoforms result from differential glycosylation of the enzyme as indicated by peptide mapping, mass analysis, and PNGase F deglycosylation experiments. Recombinant insect-produced HuPON1 hydrolyzed phenyl acetate, paraoxon, and the nerve agents GF, VX, and VR. The enzyme had dramatic stereoselectivity for the P+ isomers of VX and VR. T. ni larvae expressing HuPON1 were remarkably resistant to the pesticide chlorpyrifos. Together, these results demonstrate that the caterpillar of the T. ni moth can be used as an expression system to produce large quantities of functional recombinant HuPON1. Insect production of HuPON1 may provide a source for both in vitro enzymatic and crystallographic studies and in vivo stability and anti-nerve agent efficacy testing. Title: Genome sequencing and analysis of the model grass Brachypodium distachyon. Vogel JP, Garvin DF, Mockler TC, Schmutz J, Rokhsar D, Bevan MW, Barry K, Lucas S, Harmon-Smith M and Baxter I <127 more author(s)> Vogel JP, Garvin DF, Mockler TC, Schmutz J, Rokhsar D, Bevan MW, Barry K, Lucas S, Harmon-Smith M, Lail K, Tice H, Grimwood J, McKenzie N, Huo N, Gu YQ, Lazo GR, Anderson OD, You FM, Luo MC, Dvorak J, Wright J, Febrer M, Idziak D, Hasterok R, Lindquist E, Wang M, Fox SE, Priest HD, Filichkin SA, Givan SA, Bryant DW, Chang JH, Wu H, Wu W, Hsia AP, Schnable PS, Kalyanaraman A, Barbazuk B, Michael TP, Hazen SP, Bragg JN, Laudencia-Chingcuanco D, Weng Y, Haberer G, Spannagl M, Mayer K, Rattei T, Mitros T, Lee SJ, Rose JK, Mueller LA, York TL, Wicker T, Buchmann JP, Tanskanen J, Schulman AH, Gundlach H, Bevan M, de Oliveira AC, Maia Lda C, Belknap W, Jiang N, Lai J, Zhu L, Ma J, Sun C, Pritham E, Salse J, Murat F, Abrouk M, Bruggmann R, Messing J, Fahlgren N, Sullivan CM, Carrington JC, Chapman EJ, May GD, Zhai J, Ganssmann M, Gurazada SG, German M, Meyers BC, Green PJ, Tyler L, Wu J, Thomson J, Chen S, Scheller HV, Harholt J, Ulvskov P, Kimbrel JA, Bartley LE, Cao P, Jung KH, Sharma MK, Vega-Sanchez M, Ronald P, Dardick CD, De Bodt S, Verelst W, Inz D, Heese M, Schnittger A, Yang X, Kalluri UC, Tuskan GA, Hua Z, Vierstra RD, Cui Y, Ouyang S, Sun Q, Liu Z, Yilmaz A, Grotewold E, Sibout R, Hematy K, Mouille G, Hofte H, Michael T, Pelloux J, O'Connor D, Schnable J, Rowe S, Harmon F, Cass CL, Sedbrook JC, Byrne ME, Walsh S, Higgins J, Li P, Brutnell T, Unver T, Budak H, Belcram H, Charles M, Chalhoub B, Baxter I (- 127) Ref: Nature, 463:763, 2010 : PubMed ESTHER: Vogel_2010_Nature_463_763 PubMedSearch: Vogel 2010 Nature 463 763 PubMedID: 20148030 Gene_locus related to this paper: bradi-i1grm0, bradi-i1gx82, bradi-i1hb80, bradi-i1hkv6, bradi-i1hpu6, bradi-i1i3e4, bradi-i1i9i0, bradi-i1i435, bradi-i1ix93, bradi-i1gsk6, bradi-i1hk44, bradi-i1hk45, bradi-i1hnk7, bradi-i1hsd5, bradi-i1huy4, bradi-i1huy9, bradi-i1huz0, bradi-i1gxx9, bradi-i1hl25, bradi-i1hcw7, bradi-i1hyv6, bradi-i1hyb5, bradi-i1hvr8, bradi-i1hmu2, bradi-i1hf05, bradi-i1gry7, bradi-i1hf06, bradi-i1i5z8, bradi-i1icy3, bradi-i1j1h3, bradi-i1h1e3, bradi-i1hvr9, bradi-a0a0q3r7i7, bradi-i1i377, bradi-i1hjg5, bradi-i1h3i9, bradi-i1gsg5, bradi-a0a0q3mph9, bradi-i1h682, bradi-a0a0q3lc91, bradi-i1gx49, bradi-i1i839, bradi-a0a2k2dsp5, bradi-i1gsb5 Title: Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica Wang T, Choi RC, Li J, Bi CWC, Zang L, Liu Z, Dong TTX, Bi K, Tsim KWK Ref: Planta Med, 76:1642, 2010 : PubMed ESTHER: Wang_2010_Planta.Med_76_1642 PubMedSearch: Wang 2010 Planta.Med 76 1642 PubMedID: 20509104 Abstract Developing drugs against metabolic-related disorders, including obesity and hyperlipidemia, is of importance for human health. Here, a bioactive phytochemical, protodioscin, isolated from the rhizomes of Dioscorea nipponica (Rhizoma Dioscoreae Nipponicae), was identified for its anti-hyperlipidemic effect. In hyperlipidemic rats, the post-administration of protodioscin significantly reduced the time of blood coagulation. In addition, the blood levels of triglyceride, cholesterol, low-density and high-density lipoproteins were also changed accordingly. Taken together, this was the first report of an antihyperlipidemic effect of protodioscin. Its great availability in various vegetables and medicinal plants will be useful in developing health food supplement(s) and/or drug(s) against hyperlipidemia. Title: Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans Haas BJ, Kamoun S, Zody MC, Jiang RH, Handsaker RE, Cano LM, Grabherr M, Kodira CD, Raffaele S and Nusbaum C <86 more author(s)> Haas BJ, Kamoun S, Zody MC, Jiang RH, Handsaker RE, Cano LM, Grabherr M, Kodira CD, Raffaele S, Torto-Alalibo T, Bozkurt TO, Ah-Fong AM, Alvarado L, Anderson VL, Armstrong MR, Avrova A, Baxter L, Beynon J, Boevink PC, Bollmann SR, Bos JI, Bulone V, Cai G, Cakir C, Carrington JC, Chawner M, Conti L, Costanzo S, Ewan R, Fahlgren N, Fischbach MA, Fugelstad J, Gilroy EM, Gnerre S, Green PJ, Grenville-Briggs LJ, Griffith J, Grunwald NJ, Horn K, Horner NR, Hu CH, Huitema E, Jeong DH, Jones AM, Jones JD, Jones RW, Karlsson EK, Kunjeti SG, Lamour K, Liu Z, Ma L, Maclean D, Chibucos MC, McDonald H, McWalters J, Meijer HJ, Morgan W, Morris PF, Munro CA, O'Neill K, Ospina-Giraldo M, Pinzon A, Pritchard L, Ramsahoye B, Ren Q, Restrepo S, Roy S, Sadanandom A, Savidor A, Schornack S, Schwartz DC, Schumann UD, Schwessinger B, Seyer L, Sharpe T, Silvar C, Song J, Studholme DJ, Sykes S, Thines M, van de Vondervoort PJ, Phuntumart V, Wawra S, Weide R, Win J, Young C, Zhou S, Fry W, Meyers BC, van West P, Ristaino J, Govers F, Birch PR, Whisson SC, Judelson HS, Nusbaum C (- 86) Ref: Nature, 461:393, 2009 : PubMed ESTHER: Haas_2009_Nature_461_393 PubMedSearch: Haas 2009 Nature 461 393 PubMedID: 19741609 Gene_locus related to this paper: phyin-ENDO2, phyin-q2m440, phyin-q58g92, phyit-d0mqp1, phyit-d0mqp2, phyit-d0mt75, phyit-d0muv1, phyit-d0mv34, phyit-d0mv35, phyit-d0mwf9, phyit-d0mxu5, phyit-d0n935, phyit-d0nax9, phyit-d0nfs3, phyit-d0nhj2, phyit-d0nhj4, phyit-d0nhj8, phyit-d0ni28, phyit-d0nj14, phyit-d0nj53, phyit-d0nj54, phyit-d0njf2, phyit-d0nkm4, phyit-d0nr53, phyit-d0nrb1, phyit-d0nrk9, phyit-d0nrl4, phyit-d0ns26, phyit-d0ns42, phyit-d0ns43, phyit-d0nsr8, phyit-d0nu41, phyit-d0nvt3, phyit-d0nwb6, phyit-d0nwm8, phyit-d0nzc0, phyit-d0nzc1, phyit-d0p0z1, phyit-d0p3z2, phyit-kex1, phyit-d0n6q6, phyit-d0n4i8, phyit-d0mqf7, phyit-d0n5g6 Abstract Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $$6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential. Title: Heteromeric co-assembly of two insect nicotinic acetylcholine receptor alpha subunits: influence on sensitivity to neonicotinoid insecticides Liu Z, Han Z, Zhang Y, Song F, Yao X, Liu S, Gu J, Millar NS Ref: Journal of Neurochemistry, 108:498, 2009 : PubMed ESTHER: Liu_2009_J.Neurochem_108_498 PubMedSearch: Liu 2009 J.Neurochem 108 498 PubMedID: 19046356 Abstract Neonicotinoid insecticides, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) and are used extensively in areas of crop protection and animal health to control a variety of insect pest species. Here, we describe studies performed with nAChR subunits Nlalpha1 and Nlalpha2 cloned from the brown planthopper Nilaparvata lugens, a major insect pest of rice crops in many parts of Asia. The influence of Nlalpha1 and Nlalpha2 subunits upon the functional properties of recombinant nAChRs has been examined by expression in Xenopus oocytes. In addition, the influence of a Nlalpha1 mutation (Y151S), which has been linked to neonicotinoid lab generated resistance in N. lugens, has been examined. As in previous studies of insect alpha subunits, functional expression has been achieved by co-expression with the mammalian beta2 subunit. This approach has revealed a significantly higher apparent affinity of imidacloprid for Nlalpha1/beta2 than for Nlalpha2/beta2 nAChRs. In addition, evidence has been obtained for the co-assembly of Nlalpha1 and Nlalpha2 subunits into 'triplet' nAChRs of subunit composition Nlalpha1/Nlalpha2/beta2. Evidence has also been obtained which demonstrates that the resistance-associated Y151S mutation has a significantly reduced effect on neonicotinoid agonist activity when Nlalpha1 is co-assembled with Nlalpha2 than when expressed as the sole alpha subunit in a heteromeric nAChR. These findings may be of importance in assessing the likely impact of the target-site mutations such as Y151S upon neonicotinoid insecticide resistance in insect field populations. Title: A CD26-controlled cell surface cascade for regulation of T cell motility and chemokine signals Liu Z, Christensson M, Forslow A, De Meester I, Sundqvist KG Ref: J Immunol, 183:3616, 2009 : PubMed ESTHER: Liu_2009_J.Immunol_183_3616 PubMedSearch: Liu 2009 J.Immunol 183 3616 PubMedID: 19687096 Abstract Chemokines are key regulators of cell trafficking, and dipeptidyl peptidase IV/CD26 (CD26) inactivates chemokines. Here we show that the CD26-processed chemokines SDF1alpha/CXCL12 and RANTES/CCL5, in contrast to a control chemokine not processed by CD26, are potent inducers of cell surface expression of thrombospondin-1 (TSP-1) in T lymphocytes through a CD26-controlled mechanism and that TSP-1 stimulates expression of lipoprotein receptor related protein/CD91. Accordingly, intact TSP-1 and a peptide mimetic of a sequence in TSP-1 were sufficient to stimulate CD91 expression. The chemokine-induced expression of TSP-1 and CD91 was mimicked by inhibitors of CD26 and CXCL12 and CCL5 as well as inhibitors of CD26 stimulated polarized cytoplasmic spreading and migration through TSP-1. Silencing of CD26 using small interfering RNA or Ab-induced modulation of CD26 also increased TSP-1 expression and enhanced cytoplasmic spreading and T cell migration markedly. These results indicate that CD26 is an endogenous inhibitor of T cell motility through inhibition of TSP-1 expression and that chemokines stimulate cell polarity and migration through abrogation of the CD26-dependent inhibition. This suggests that T cell motility is regulated by a cascade of interacting cell surface molecules. Title: Structural and functional studies of Aspergillus oryzae cutinase: enhanced thermostability and hydrolytic activity of synthetic ester and polyester degradation Liu Z, Gosser Y, Baker PJ, Ravee Y, Lu Z, Alemu G, Li H, Butterfoss GL, Kong XP and Montclare JK <1 more author(s)> Liu Z, Gosser Y, Baker PJ, Ravee Y, Lu Z, Alemu G, Li H, Butterfoss GL, Kong XP, Gross R, Montclare JK (- 1) Ref: Journal of the American Chemical Society, 131:15711, 2009 : PubMed ESTHER: Liu_2009_J.Am.Chem.Soc_131_15711 PubMedSearch: Liu 2009 J.Am.Chem.Soc 131 15711 PubMedID: 19810726 Gene_locus related to this paper: aspor-cutas Abstract Cutinases are responsible for hydrolysis of the protective cutin lipid polyester matrix in plants and thus have been exploited for hydrolysis of small molecule esters and polyesters. Here we explore the reactivity, stability, and structure of Aspergillus oryzae cutinase and compare it to the well-studied enzyme from Fusarium solani. Two critical differences are highlighted in the crystallographic analysis of the A. oryzae structure: (i) an additional disulfide bond and (ii) a topologically favored catalytic triad with a continuous and deep groove. These structural features of A. oryzae cutinase are proposed to result in an improved hydrolytic activity and altered substrate specificity profile, enhanced thermostability, and remarkable reactivity toward the degradation of the synthetic polyester polycaprolactone. The results presented here provide insight into engineering new cutinase-inspired biocatalysts with tailor-made properties. Title: The B73 maize genome: complexity, diversity, and dynamics Schnable PS, Ware D, Fulton RS, Stein JC, Wei F, Pasternak S, Liang C, Zhang J, Fulton L and Wilson RK <147 more author(s)> Schnable PS, Ware D, Fulton RS, Stein JC, Wei F, Pasternak S, Liang C, Zhang J, Fulton L, Graves TA, Minx P, Reily AD, Courtney L, Kruchowski SS, Tomlinson C, Strong C, Delehaunty K, Fronick C, Courtney B, Rock SM, Belter E, Du F, Kim K, Abbott RM, Cotton M, Levy A, Marchetto P, Ochoa K, Jackson SM, Gillam B, Chen W, Yan L, Higginbotham J, Cardenas M, Waligorski J, Applebaum E, Phelps L, Falcone J, Kanchi K, Thane T, Scimone A, Thane N, Henke J, Wang T, Ruppert J, Shah N, Rotter K, Hodges J, Ingenthron E, Cordes M, Kohlberg S, Sgro J, Delgado B, Mead K, Chinwalla A, Leonard S, Crouse K, Collura K, Kudrna D, Currie J, He R, Angelova A, Rajasekar S, Mueller T, Lomeli R, Scara G, Ko A, Delaney K, Wissotski M, Lopez G, Campos D, Braidotti M, Ashley E, Golser W, Kim H, Lee S, Lin J, Dujmic Z, Kim W, Talag J, Zuccolo A, Fan C, Sebastian A, Kramer M, Spiegel L, Nascimento L, Zutavern T, Miller B, Ambroise C, Muller S, Spooner W, Narechania A, Ren L, Wei S, Kumari S, Faga B, Levy MJ, McMahan L, Van Buren P, Vaughn MW, Ying K, Yeh CT, Emrich SJ, Jia Y, Kalyanaraman A, Hsia AP, Barbazuk WB, Baucom RS, Brutnell TP, Carpita NC, Chaparro C, Chia JM, Deragon JM, Estill JC, Fu Y, Jeddeloh JA, Han Y, Lee H, Li P, Lisch DR, Liu S, Liu Z, Nagel DH, McCann MC, SanMiguel P, Myers AM, Nettleton D, Nguyen J, Penning BW, Ponnala L, Schneider KL, Schwartz DC, Sharma A, Soderlund C, Springer NM, Sun Q, Wang H, Waterman M, Westerman R, Wolfgruber TK, Yang L, Yu Y, Zhang L, Zhou S, Zhu Q, Bennetzen JL, Dawe RK, Jiang J, Jiang N, Presting GG, Wessler SR, Aluru S, Martienssen RA, Clifton SW, McCombie WR, Wing RA, Wilson RK (- 147) Ref: Science, 326:1112, 2009 : PubMed ESTHER: Schnable_2009_Science_326_1112 PubMedSearch: Schnable 2009 Science 326 1112 PubMedID: 19965430 Gene_locus related to this paper: maize-b4ffc7, maize-b6u7e1, maize-c0pcy5, maize-c0pgf7, maize-c0pgw1, maize-c0pfl3, maize-b4fpr7, maize-k7vy73, maize-a0a096swr3, maize-k7v3i9, maize-b6u9v9, maize-a0a3l6e780, maize-b4fv80, maize-a0a1d6nse2, maize-c4j9a1, maize-k7uba1 Abstract We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize. Title: The angiopoietin-like proteins ANGPTL3 and ANGPTL4 inhibit lipoprotein lipase activity through distinct mechanisms Shan L, Yu XC, Liu Z, Hu Y, Sturgis LT, Miranda ML, Liu Q Ref: Journal of Biological Chemistry, 284:1419, 2009 : PubMed ESTHER: Shan_2009_J.Biol.Chem_284_1419 PubMedSearch: Shan 2009 J.Biol.Chem 284 1419 PubMedID: 19028676 Gene_locus related to this paper: human-LPL Abstract Two members of the angiopoietin-like family of proteins, ANGPTL3 and ANGPTL4, have been shown to play important roles in modulating lipoprotein metabolism in the body. Both proteins were found to suppress lipoprotein lipase (LPL) activity in vitro as well as in vivo. However, their mechanisms of inhibition remained poorly understood. Using enzyme kinetic analysis with purified recombinant proteins, we have found key mechanistic differences between ANGPTL3 and ANGPTL4. ANGPTL3 reduced LPL catalytic activity but did not significantly alter its self-inactivation rate. In contrast, ANGPTL4 suppressed LPL by accelerating the irreversible inactivation of LPL. Furthermore, heparin was able to overcome the inhibitory effect of ANGPTL3 on LPL but not that of ANGPTL4. Site-directed mutagenesis demonstrated the critical function of Glu(40) in ANGPTL4. In contrast, when cysteine residues involved in disulfide bond formation were mutated to serines, ANGPTL4 retained its activity. Taken together, our data provide a more detailed view of the structure and mechanisms of these proteins. The finding that ANGPTL3 and ANGPTL4 inhibit LPL activity through distinct mechanisms indicates that the two proteins play unique roles in modulation of lipid metabolism in vivo. Title: Functional co-expression of two insect nicotinic receptor subunits (Nlalpha3 and Nlalpha8) reveals the effects of a resistance-associated mutation (Nlalpha3) on neonicotinoid insecticides Yixi Z, Liu Z, Han Z, Song F, Yao X, Shao Y, Li J, Millar NS Ref: Journal of Neurochemistry, 110:1855, 2009 : PubMed ESTHER: Yixi_2009_J.Neurochem_110_1855 PubMedSearch: Yixi 2009 J.Neurochem 110 1855 PubMedID: 19627438 Abstract Neonicotinoid insecticides, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) and are used extensively to control a variety of insect pest species. Previously, we have identified a nAChR point mutation (Y151S) associated with insecticide resistance in the brown planthopper Nilaparvata lugens. Although this mutation has been identified in two different N. lugens nAChR subunits (Nlalpha1 and Nlalpha3) because of difficulties in heterologous expression of Nlalpha3; its influence on agonist potency has been examined only in Nlalpha1-containing nAChRs. Here we describe the cloning of a novel nAChR subunit from N. lugens (Nlalpha8), together with evidence for its co-assembly with Nlalpha3 in native and recombinant nAChRs. This has, for the first time, enabled the functional effects of the Nlalpha3(Y151S) mutation to be examined. The Nlalpha3(Y151S) mutation has little effect on agonist potency of acetylcholine but has a dramatic effect on neonicotinoid insecticides (reducing I(max) values and increasing EC(50) values). The apparent affinity of neonicotinoids was higher and the effect of the Y151S mutation on neonicotinoid agonist potency was more profound in Nlalpha3-containing, rather than Nlalpha1-containing nAChR. We conclude that Nlalpha3- and Nlalpha1-containing nAChRs may be representative of two distinct insect nAChR populations. Title: Molecular fundamentals of enzyme nanogels Ge J, Lu D, Wang J, Yan M, Lu Y, Liu Z Ref: J Phys Chem B, 112:14319, 2008 : PubMed ESTHER: Ge_2008_J.Phys.Chem.B_112_14319 PubMedSearch: Ge 2008 J.Phys.Chem.B 112 14319 PubMedID: 18939792 Abstract The assembly of a monomer around an enzyme as the essential step in the fabrication of enzyme nanogel by in situ polymerization was illustrated by molecular dynamics simulation and evidenced by a fluorescence resonance energy transfer spectrum, using lipase/acrylamide as a model system. The subsequent polymerization generated a hydrophilic gel network which not only strengthened the protein structural integrity via multipoint linkage but also increased the number of intramolecular H-bonds of the encapsulated protein, as suggested by the blue shift of the fluorescence spectrum of the encapsulated lipase. This greatly enhanced the stability of lipase at high temperature, as experimentally demonstrated. The exclusion of polar solvent molecules from the encapsulated enzyme, in contrast to the enrichment of water molecules, due to the presence of a hydrophilic gel network was displayed. This established a hydrophilic microenvironment for the encapsulated protein and thus gave the encapsulated protein an enhanced tolerance to the organic solvent, as experimentally observed in the present study and reported elsewhere. These results have given a molecular insight into the enzyme nanogel as well as its high potential as a robust enzyme model for an expended application spectrum of enzymatic catalysis. Title: EphB receptors co-distribute with a nicotinic receptor subtype and regulate nicotinic downstream signaling in neurons Liu Z, Conroy WG, Stawicki TM, Nai Q, Neff RA, Berg DK Ref: Molecular & Cellular Neurosciences, 38:236, 2008 : PubMed ESTHER: Liu_2008_Mol.Cell.Neurosci_38_236 PubMedSearch: Liu 2008 Mol.Cell.Neurosci 38 236 PubMedID: 18403216 Abstract Activation of nicotinic acetylcholine receptors (nAChRs) on neurons engages calcium-dependent signaling pathways regulating numerous events. Receptors containing alpha7 subunits (alpha7-nAChRs) are prominent in this because of their abundance and high relative calcium permeability. We show here that EphB2 receptors are co-localized with postsynaptic alpha7-nAChRs on chick ciliary ganglion neurons and that treatment of the cells with an ephrinB1 construct to activate the EphB receptors exerts physical restraints on both classes of receptors, diminishing their dispersal after spine retraction or lipid raft disruption. Moreover, the ephrinB1/EphB receptor complex specifically enhances the ability of alpha7-nAChRs to activate the transcription factor CREB, acting through a pathway including a receptor tyrosine kinase, a Src family member, PI3 kinase, and protein kinase A most distally. The enhancement does not appear to result from a change in the alpha7-nAChR current amplitude, suggesting a downstream target. The results demonstrate a role for ephrin/EphB action in nicotinic signaling. Title: Cloning, characterization and expression of the extracellular lipase gene from Aureobasidium pullulans HN2-3 isolated from sea saltern Liu Z, Li X, Chi Z, Wang L, Li J, Wang X Ref: Antonie Van Leeuwenhoek, 94:245, 2008 : PubMed ESTHER: Liu_2008_Antonie.Van.Leeuwenhoek_94_245 PubMedSearch: Liu 2008 Antonie.Van.Leeuwenhoek 94 245 PubMedID: 18340544 Abstract The extracellular lipase structural gene was isolated from cDNA of Aureobasidium pullulans HN2-3 by using SMART(TM) RACE cDNA amplification kit. The gene had an open reading frame of 1245 bp long encoding a lipase. The coding region of the gene was interrupted by only one intron (55 bp). It encodes 414 amino acid residues of a protein with a putative signal peptide of 26 amino acids. The protein sequence deduced from the extracellular lipase structural gene contained the lipase consensus sequence (G-X-S-X-G) and three conserved putative N-glycosylation sites. According to the phylogenetic tree of the lipases, the lipase from A. pullulans was closely related to that from Aspergillus fumigatus (XP_750543) and Neosartorya fischeri (XP_001257768) and the identities were 50% and 52%, respectively. The mature peptide encoding cDNA was subcloned into pET-24a (+) expression vector. The recombinant plasmid was expressed in Escherichia coli BL21(DE3). The expressed fusion protein was analyzed by SDS-PAGE and western blotting and a specific band with molecular mass of about 47 kDa was found. Enzyme activity assay verified the recombinant protein as a lipase. A maximum activity of 0.96 U/mg was obtained from cellular extract of E. coli BL21(DE3) harboring pET-24a(+)LIP1. Optimal pH and temperature of the crude recombinant lipase were 8.0 and 35 degrees C, respectively and the crude recombinant lipase had the highest hydrolytic activity towards peanut oil. Title: Molecular cloning and characterization of a juvenile hormone esterase gene from brown planthopper, Nilaparvata lugens Liu S, Yang B, Gu J, Yao X, Zhang Y, Song F, Liu Z Ref: J Insect Physiol, 54:1495, 2008 : PubMed ESTHER: Liu_2008_J.Insect.Physiol_54_1495 PubMedSearch: Liu 2008 J.Insect.Physiol 54 1495 PubMedID: 18804476 Gene_locus related to this paper: nillu-b8q962 Abstract Juvenile hormone (JH) plays key roles in the regulation of growth, development, diapause and reproduction in insects, and juvenile hormone esterase (JHE) plays an important role in regulating JH titers. We obtained a full-length cDNA encoding JHE in Nilaparvata lugens (NlJHE), the first JHE gene cloned from the hemipteran insects. The deduced protein sequence of Nljhe contains the five conserved motifs identified in JHEs of other insect species, including a consensus GQSAG motif that is required for the enzymatic activity of JHE proteins. Nljhe showed high amino acid similarities with Athalia rosae JHE (40%) and Apis mellifera JHE (39%). Recombinant NlJHE protein expressed in the baculovirus expression system hydrolyzed [3H] JH III at high activity and yielded the specificity constants (kcat/KM=4.28x10(6) M(-1) s(-1)) close to those of the validated JHEs from other insect species, indicating that Nljhe cDNA encodes a functional JH esterase. The Nljhe transcript was expressed mainly in the fat body and the expression level reached a peak at 48 h after ecdysis of the 5th instar nymphs. In the 5th instar, macropterous insects showed significantly higher Nljhe mRNA levels and JHE activities, but much lower JH III levels, than those detected in the brachypterous insects soon after ecdysis and at 48 h after ecdysis. These data suggest that NlJHE might play important roles in regulation of JH levels and wing form differentiation. Title: Overexpression of Drosophila juvenile hormone esterase binding protein results in anti-JH effects and reduced pheromone abundance Liu Z, Li X, Prasifka JR, Jurenka R, Bonning BC Ref: General & Comparative Endocrinology, 156:164, 2008 : PubMed ESTHER: Liu_2008_Gen.Comp.Endocrinol_156_164 PubMedSearch: Liu 2008 Gen.Comp.Endocrinol 156 164 PubMedID: 18275960 Abstract The titer of juvenile hormone (JH), which has wide ranging physiological effects in insects, is regulated in part by JH esterase (JHE). We show that overexpression in Drosophila melanogaster of the JHE binding protein, DmP29 results in a series of apparent anti-JH effects. We hypothesize that DmP29 functions in transport of JHE such that over- or under-expression of DmP29 results in increased or decreased JH degradation at specific sites respectively. Overexpression of DmP29 during the first or second instar was lethal, while overexpression during the third instar resulted in eclosion of small adults. Overexpression of DmP29 in newly eclosed flies reduced ovarian development and fecundity in addition to reducing the abundance of aggregation pheromone (cis-vaccenyl acetate) in males and courtship pheromone (cis,cis-7,11-heptacosadiene) in females. Both sexes also had lower levels of 23 and 25 carbon monoenes. Females exhibited reduced receptivity to mating, and males exhibited male-male courtship behavior, with both sexes being hyperactive: Male flies covered 2.7 times the distance of control flies at 2.9 times the maximum velocity. Application of the JH analog methoprene reversed impaired ovarian development, supporting a role for reduced JH in production of this phenotype. Rather than increasing lifespan as expected from a JH deficiency, overexpression of DmP29 reduced the life span of adult flies which may result from the hyperactivity of these flies. Underexpression of DmP29 resulted in reduced longevity, increased fecundity and reduced titers of pupal JHE. An alternative hypothesis, that mitochondrial dysfunction rather than JHE results in the JH-mediated phenotypes, is discussed. Title: Complete genome of Phenylobacterium zucineum--a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562 Luo Y, Xu X, Ding Z, Liu Z, Zhang B, Yan Z, Sun J, Hu S, Hu X Ref: BMC Genomics, 9:386, 2008 : PubMed ESTHER: Luo_2008_BMC.Genomics_9_386 PubMedSearch: Luo 2008 BMC.Genomics 9 386 PubMedID: 18700039 Gene_locus related to this paper: phezh-b4r8z3, phezh-b4r801, phezh-b4r876, phezh-b4ras1, phezh-b4ras4, phezh-b4ray3, phezh-b4rb44, phezh-b4rd51, phezh-b4re02, phezh-b4rfb7, phezh-b4rfk3, phezh-b4rfq9, phezh-b4rfw5, phezh-b4rgf2, phezh-b4rh78, phezh-b4rh88, phezh-b4rhb1, phezh-b4rhb2, phezh-dhma, phezh-b4r875, phezh-b4rfb8, phezh-b4rbt7 Abstract BACKGROUND: Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter. RESULTS: Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former. CONCLUSION: This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum. Title: The genome of the model beetle and pest Tribolium castaneum Richards S, Gibbs RA, Weinstock GM, Brown SJ, Denell R, Beeman RW, Gibbs R, Bucher G, Friedrich M and Grossmann D <181 more author(s)> Richards S, Gibbs RA, Weinstock GM, Brown SJ, Denell R, Beeman RW, Gibbs R, Bucher G, Friedrich M, Grimmelikhuijzen CJ, Klingler M, Lorenzen M, Roth S, Schroder R, Tautz D, Zdobnov EM, Muzny D, Attaway T, Bell S, Buhay CJ, Chandrabose MN, Chavez D, Clerk-Blankenburg KP, Cree A, Dao M, Davis C, Chacko J, Dinh H, Dugan-Rocha S, Fowler G, Garner TT, Garnes J, Gnirke A, Hawes A, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Jackson L, Kovar C, Kowis A, Lee S, Lewis LR, Margolis J, Morgan M, Nazareth LV, Nguyen N, Okwuonu G, Parker D, Ruiz SJ, Santibanez J, Savard J, Scherer SE, Schneider B, Sodergren E, Vattahil S, Villasana D, White CS, Wright R, Park Y, Lord J, Oppert B, Brown S, Wang L, Weinstock G, Liu Y, Worley K, Elsik CG, Reese JT, Elhaik E, Landan G, Graur D, Arensburger P, Atkinson P, Beidler J, Demuth JP, Drury DW, Du YZ, Fujiwara H, Maselli V, Osanai M, Robertson HM, Tu Z, Wang JJ, Wang S, Song H, Zhang L, Werner D, Stanke M, Morgenstern B, Solovyev V, Kosarev P, Brown G, Chen HC, Ermolaeva O, Hlavina W, Kapustin Y, Kiryutin B, Kitts P, Maglott D, Pruitt K, Sapojnikov V, Souvorov A, Mackey AJ, Waterhouse RM, Wyder S, Kriventseva EV, Kadowaki T, Bork P, Aranda M, Bao R, Beermann A, Berns N, Bolognesi R, Bonneton F, Bopp D, Butts T, Chaumot A, Denell RE, Ferrier DE, Gordon CM, Jindra M, Lan Q, Lattorff HM, Laudet V, von Levetsow C, Liu Z, Lutz R, Lynch JA, da Fonseca RN, Posnien N, Reuter R, Schinko JB, Schmitt C, Schoppmeier M, Shippy TD, Simonnet F, Marques-Souza H, Tomoyasu Y, Trauner J, Van der Zee M, Vervoort M, Wittkopp N, Wimmer EA, Yang X, Jones AK, Sattelle DB, Ebert PR, Nelson D, Scott JG, Muthukrishnan S, Kramer KJ, Arakane Y, Zhu Q, Hogenkamp D, Dixit R, Jiang H, Zou Z, Marshall J, Elpidina E, Vinokurov K, Oppert C, Evans J, Lu Z, Zhao P, Sumathipala N, Altincicek B, Vilcinskas A, Williams M, Hultmark D, Hetru C, Hauser F, Cazzamali G, Williamson M, Li B, Tanaka Y, Predel R, Neupert S, Schachtner J, Verleyen P, Raible F, Walden KK, Angeli S, Foret S, Schuetz S, Maleszka R, Miller SC, Grossmann D (- 181) Ref: Nature, 452:949, 2008 : PubMed ESTHER: Richards_2008_Nature_452_949 PubMedSearch: Richards 2008 Nature 452 949 PubMedID: 18362917 Gene_locus related to this paper: trica-ACHE1, trica-ACHE2, trica-d2a0g9, trica-d2a0h0, trica-d2a0w9, trica-d2a0x0, trica-d2a0x1, trica-d2a0x3, trica-d2a0x4.1, trica-d2a0x4.2, trica-d2a0x6, trica-d2a2b8, trica-d2a2h1, trica-d2a3c3, trica-d2a3g9, trica-d2a5y5, trica-d2a309, trica-d2a514, trica-d2a515, trica-d2a516, trica-d2a577, trica-d2a578, trica-d6w6x8, trica-d6w7f9, trica-d6w7h2, trica-d6w8e7, trica-d6w9c0, trica-d6w855, trica-d6wac8, trica-d6wan4, trica-d6wd50, trica-d6wd73, trica-d6wd74, trica-A0A139WM97, trica-d6wfu3, trica-d6wgl2, trica-d6wj57, trica-d6wj59, trica-d6wjs3, trica-d6wl31, trica-d6wnv1, trica-d6wpl0, trica-d6wqd6, trica-d6wqr4, trica-d6ws52, trica-d6wsm0, trica-d6wu38, trica-d6wu39, trica-d6wu40, trica-d6wu41, trica-d6wu44, trica-d6wvk5, trica-d6wvz7, trica-d6wwu9, trica-d6wwv0, trica-d6wxz0, trica-d6wyy1, trica-d6wyy2, trica-d6x0z2, trica-d6x0z5, trica-d6x0z6, trica-d6x4b2, trica-d6x4e8, trica-d6x4e9, trica-d6x197, trica-d7eip7, trica-d7eld3, trica-d7us45, trica-q5wm43, trica-q5zex9, trica-d6wie5, trica-d6w7t0, trica-d6x4h0, trica-d6x4h1, trica-a0a139wae8, trica-a0a139wc96, trica-d6x325, trica-d2a4s2, trica-d6wvw8 Abstract Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control. Title: Crystallization and preliminary crystallographic analysis of Gibberella zeae extracellular lipase Sun Y, Li M, Zhang Y, Liu L, Liu Y, Liu Z, Li X, Lou Z Ref: Acta Crystallographica Sect F Struct Biol Cryst Commun, 64:813, 2008 : PubMed ESTHER: Sun_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_813 PubMedSearch: Sun 2008 Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun 64 813 PubMedID: 18765911 Gene_locus related to this paper: gibze-q6wer3 Abstract Fusarium head blight, one of the most destructive crop diseases, is mainly caused by Fusarium graminearum (known in its sexual stage as Gibberella zeae). F. graminearum secretes various extracellular enzymes that have been hypothesized to be involved in host infection. One of the extracellular enzymes secreted by this organism is the G. zeae extracellular lipase (GZEL), which is encoded by the FGL1 gene. In order to solve the crystal structure of GZEL and to gain a better understanding of the biological functions of the protein and of possible inhibitory mechanisms of lipase inhibitors, recombinant GZEL was crystallized at 291 K using PEG 3350 as a precipitant. A data set was collected to 2.8 A resolution from a single flash-cooled crystal (100 K). The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 78.4, b = 91.0, c = 195.8 A, alpha = beta = gamma = 90 degrees . The presence of four molecules was assumed per asymmetric unit, which gave a Matthews coefficient of 2.6 A(3) Da(-1). Title: Multiple cell adhesion molecules shaping a complex nicotinic synapse on neurons Triana-Baltzer GB, Liu Z, Gounko NV, Berg DK Ref: Molecular & Cellular Neurosciences, 39:74, 2008 : PubMed ESTHER: Triana-Baltzer_2008_Mol.Cell.Neurosci_39_74 PubMedSearch: Triana-Baltzer 2008 Mol.Cell.Neurosci 39 74 PubMedID: 18585463 Abstract Neuroligin, SynCAM, and L1-CAM are cell adhesion molecules with synaptogenic roles in glutamatergic pathways. We show here that SynCAM is expressed in the chick ciliary ganglion, embedded in a nicotinic pathway, and, as shown previously for neuroligin and L1-CAM, acts transcellularly to promote synaptic maturation on the neurons in culture. Moreover, we show that electroporation of chick embryos with dominant negative constructs disrupting any of the three molecules in vivo reduces the total amount of presynaptic SV2 overlaying the neurons expressing the constructs. Only disruption of L1-CAM and neuroligin, however, reduces the number of SV2 puncta specifically overlaying nicotinic receptor clusters. Disrupting L1-CAM and neuroligin together produces no additional decrement, indicating that they act on the same subset of synapses. SynCAM may affect synaptic maturation rather than synapse formation. The results indicate that individual neurons can express multiple synaptogenic molecules with different effects on the same class of nicotinic synapses. Title: A new acetylcholinesterase inhibitor with anti-PAF activity modulates oxidative stress and pro-inflammatory mediators release in stimulated RAW 264.7 macrophage cells. Comparison with tacrine Ezoulin MJ, Liu Z, Dutertre-Catella H, Wu G, Dong CZ, Heymans F, Ombetta JE, Rat P, Massicot F Ref: Int Immunopharmacol, 7:1685, 2007 : PubMed ESTHER: Ezoulin_2007_Int.Immunopharmacol_7_1685 PubMedSearch: Ezoulin 2007 Int.Immunopharmacol 7 1685 PubMedID: 17996678 Abstract Inflammatory injury and induction of oxidative stress have been implicated as causative factors in neurodegenerative diseases such as Alzheimer's disease (AD). Using LPS-stimulated RAW 264.7 macrophages as a model of inflammatory injury, LPS was found to stimulate ROS production (159%), GSH depletion (15%) and loss of mitochondrial activity (32%) as well as TNFalpha release (40%), and NO production (13.7 times), all parameters involved in AD. PMS777, a tetrahydrofuran derivative, designed as a dual PAF and acetylcholinesterase inhibitor, was found to decrease ROS (up to 32%) and NO production (up to 5 times), TNFalpha release (33%). PMS777 also prevents loss of mitochondrial activity, and GSH depletion. In contrast, tacrine was found to decrease ROS production (57% up to 102%) and TNFalpha level (up to 30%). It decreases NO release only at the highest concentrations without preventing loss of mitochondrial activity and GSH depletion. In this study, we show that PMS777 is strongly anti-inflammatory against LPS-induced responses in RAW 264.7. Differential effects between PMS777 and tacrine could be attributed to the anti-PAF activity of PMS777 which was able to fight inflammatory events and oxidative injury whereas tacrine only minimizes them. PMS777 could open a new approach in the treatment of AD. Title: Role of endogenous nicotinic signaling in guiding neuronal development Liu Z, Zhang J, Berg DK Ref: Biochemical Pharmacology, 74:1112, 2007 : PubMed ESTHER: Liu_2007_Biochem.Pharmacol_74(8)_1112 PubMedSearch: Liu 2007 Biochem.Pharmacol 74(8) 1112 PubMedID: 17603025 Abstract Spontaneous nicotinic cholinergic activity is widespread in the developing nervous system. One of the major components mediating this activity is the nicotinic acetylcholine receptor with alpha7 subunits (alpha7-nAChR) and high relative calcium permeability. We recently reported that alpha7-nAChRs co-localize in part with GABA(A) receptors during development, and the sites become co-innervated by cholinergic and GABAergic terminals. Patch-clamp recording either from embryonic chick ciliary ganglion neurons or from early postnatal mouse hippocampal interneurons reveals that alpha7-nAChR activation can impose a rapid and reversible decrease in GABA(A) receptor responses. The effect extends to GABAergic synaptic currents, and depends on intracellular calcium, calcium/calmodulin-dependent protein kinase II, and MAP kinase in the postsynaptic cell. Over the longer term, nicotinic activity has a more profound effect: it determines the time during development when GABAergic signaling converts from excitation to inhibition. It does this by changing the pattern of chloride transporters to establish the mature chloride gradient required for inhibitory GABAergic responses. The excitatory phase of GABAergic signaling is critical for proper development and integration of neurons into circuits. By driving the conversion of GABAergic signaling, nicotinic activity not only terminates one set of developmental instructions, but also initiates another by collaborating with GABAergic inhibition to impose new instructions. The results reveal a multi-layered pattern of activity-dependent controls in development and indicate the significance of nicotinic signaling in shaping these events. Title: Localization of a Drosophila melanogaster homolog of the putative juvenile hormone esterase binding protein of Manduca sexta Liu Z, Ho L, Bonning B Ref: Insect Biochemistry & Molecular Biology, 37:155, 2007 : PubMed ESTHER: Liu_2007_Insect.Biochem.Mol.Biol_37_155 PubMedSearch: Liu 2007 Insect.Biochem.Mol.Biol 37 155 PubMedID: 17244544 Abstract A putative juvenile hormone esterase (JHE) binding protein, P29, was isolated from the tobacco hornworm Manduca sexta [J. Biol. Chem. 275(3), 1802-1806]. A homolog of P29 was identified in Drosophila melanogaster by sequence alignment. This gene, CG3776 was cloned, recombinant DmP29 expressed in Escheriscia coli and two anti-DmP29 antisera raised. In vitro binding of the P29 homolog to Drosophila JHE was confirmed. P29 mRNA and an immunoreactive protein of 25 kDa were detected in Drosophila larvae, pupae and adults. The predicted size of the protein is 30 kDa. Drosophila P29 is predicted to localize to mitochondria (MitoProt; 93% probability) and has a 6 kDa N-terminal targeting sequence. Subcellular organelle fractionation and confocal microscopy of Drosophila S2 cells confirmed that the immunoreactive 25 kDa protein is present in mitochondria but not in the cytosol. Expression of P29 without the predicted N-terminal targeting sequence in High Five cells showed that the N-terminal targeting sequence is shorter than predicted, and that a second, internal mitochondrial targeting signal is also present. An immunoreactive protein of 50 kDa in the hemolymph does not result from alternative splicing of CG3776 but may result from dimerization of P29. The function of P29 in mitochondria and the possible interaction with JHE are discussed. Title: Nicotinic signal transduction machinery Berg DK, Conroy WG, Liu Z, Zago WM Ref: Journal of Molecular Neuroscience, 30:149, 2006 : PubMed ESTHER: Berg_2006_J.Mol.Neurosci_30_149 PubMedSearch: Berg 2006 J.Mol.Neurosci 30 149 PubMedID: 17192663 Abstract Nicotinic synapses employ acetylcholine to activate ligand-gated ion channels that are cation-selective in vertebrates. Although the resulting nicotinic cholinergic transmission is famously excitatory at the neuromuscular junction, it plays many additional roles in the CNS. Most prevalent is that of modulation, usually involving calcium and signal transduction. Because of this, it is becoming increasingly important not only to understand the mechanisms that guide nicotinic receptors to appropriate locations but also to identify the postsynaptic machinery making possible the requisite signal transduction. Clearly, the kinds of components tethered in the vicinity of the receptor will assume a major role in determining the consequences of receptor activation. One of the most abundant and interesting nicotinic receptors in this respect is the species comprised of the alpha7 gene product (Broide and Leslie, 1999). These alpha7 homopentameric nicotinic acetylcholine receptors (alpha7 nAChRs) have a high relative permeability to calcium, rivaling that of NMDA receptors. But unlike NMDA receptors, alpha7 nAChRs promote calcium influx without requiring a coincident event such as membrane depolarization. As a result, the receptors are well equipped to regulate calcium-dependent events in neurons, particularly when depolarization might be occluded. Title: Study of PMS777, a new type of acetylcholinesterase inhibitor, in human HepG2 cells. Comparison with tacrine and galanthamine on oxidative stress and mitochondrial impairment Ezoulin MJ, Dong CZ, Liu Z, Li J, Chen HZ, Heymans F, Lelievre L, Ombetta JE, Massicot F Ref: Toxicol In Vitro, 20:824, 2006 : PubMed ESTHER: Ezoulin_2006_Toxicol.In.Vitro_20_824 PubMedSearch: Ezoulin 2006 Toxicol.In.Vitro 20 824 PubMedID: 16472967 Abstract Acetylcholinesterase inhibitors are commonly used as cognitive enhancers for dementia in aged people. Among them, tacrine (THA) but not galanthamine, was shown to exhibit hepatotoxicity which reduces its clinical use. PMS777, both a PAF antagonist and a new potent acetylcholinesterase inhibitor was recently demonstrated to reverse scopolamine-induced amnesia in mice without toxicity. In the present study, the effects of THA, galanthamine and PMS777 were compared in HepG2 cells on the oxidative parameters involved in the reported hepatotoxicity of THA. THA (> or = 10 microM) induced an oxidative stress as shown by elevated ROS and MDA production and by a decrease in GSH level. Moreover, mitochondrial membrane potential and redox status were decreased. At low concentrations (< or =10 microM), there was no significant disturbance. None of the oxidative stress markers was affected by PMS777 up to the maximum concentration tested and it is suggested that PMS777 is not cytotoxic for HepG2 cells. Galanthamine was also without cytotoxicity. Our results suggest that the toxic effect of THA above 10 microM may be caused by drug-induced mitochondrial energization impairment and destabilisation of membrane phospholipids associated with an oxidative stress. In contrast by preventing these dysfunctions, PMS777 could be safer than THA. Title: Urinary dysfunction and autonomic control in amyloid neuropathy Ito T, Sakakibara R, Yamamoto T, Uchiyama T, Liu Z, Asahina M, Higashi M, Arai K, Ito S and Hattori T <4 more author(s)> Ito T, Sakakibara R, Yamamoto T, Uchiyama T, Liu Z, Asahina M, Higashi M, Arai K, Ito S, Awa Y, Yamamoto K, Kinou M, Yamanishi T, Hattori T (- 4) Ref: Clin Auton Res, 16:66, 2006 : PubMed ESTHER: Ito_2006_Clin.Auton.Res_16_66 PubMedSearch: Ito 2006 Clin.Auton.Res 16 66 PubMedID: 16477499 Abstract Uro-neurological assessment was performed in four patients with small-fiber neuropathy due to amyloidosis (2 transthyretin-type/2 immunoglobulin light-chain-type). Voiding difficulties were due to detrusor weakness and impaired bladder sensation. In two patients cholinesterase inhibition treatment caused urge incontinence, indicating detrusor denervation supersensitivity. The underlying mechanisms of urinary dysfunction seem to involve postganglionic cholinergic and afferent somatic nerves. Title: A nicotinic acetylcholine receptor mutation (Y151S) causes reduced agonist potency to a range of neonicotinoid insecticides Liu Z, Williamson MS, Lansdell SJ, Han Z, Denholm I, Millar NS Ref: Journal of Neurochemistry, 99:1273, 2006 : PubMed ESTHER: Liu_2006_J.Neurochem_99_1273 PubMedSearch: Liu 2006 J.Neurochem 99 1273 PubMedID: 16981889 Abstract Neonicotinoid insecticides are potent selective agonists of insect nicotinic acetylcholine receptors (nAChRs). Since their introduction in 1991, resistance to neonicotinoids has been slow to develop, but it is now established in some insect field populations such as the planthopper, Nilaparvata lugens, a major rice pest in many parts of Asia. We have reported recently the identification of a target-site mutation (Y151S) within two nAChR subunits (Nlalpha1 and Nlalpha3) from a laboratory-selected field population of N. lugens. In the present study, we have examined the influence of this mutation upon the functional properties of recombinant nAChRs expressed in Xenopus oocytes (as hybrid nAChRs, co-expressed with a rat beta2 subunit). The agonist potency of several nicotinic agonists has been examined, including all of the neonicotinoid insecticides that are currently licensed for either crop protection or animal health applications (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam). The Y151S mutation was found to have no significant effect on the maximal current (I(max)) observed with the endogenous agonist, acetylcholine. In contrast, a significant reduction in I(max) was observed for all neonicotinoids (the I(max) for mutant nAChRs ranged from 13 to 81% of that observed on wild-type receptors). In addition, nAChRs containing the Y151S mutation caused a significant rightward shift in agonist dose-response curves for all neonicotinoids, but of varying magnitude (shifts in EC(50) values ranged from 1.3 to 3.6-fold). The relationship between neonicotinoid structure and their potency on nAChRs containing the Y151S target-site mutation is discussed. Title: Sequential interplay of nicotinic and GABAergic signaling guides neuronal development Liu Z, Neff RA, Berg DK Ref: Science, 314:1610, 2006 : PubMed ESTHER: Liu_2006_Science_314_1610 PubMedSearch: Liu 2006 Science 314 1610 PubMedID: 17158331 Abstract GABA (gamma-aminobutyric acid), the major inhibitory transmitter in the brain, goes through a transitory phase of excitation during development. The excitatory phase promotes neuronal growth and integration into circuits. We show here that spontaneous nicotinic cholinergic activity is responsible for terminating GABAergic excitation and initiating inhibition. It does so by changing chloride transporter levels, shifting the driving force on GABA-induced currents. The timing of the transition is critical, because the two phases of GABAergic signaling provide contrasting developmental instructions. Synergistic with nicotinic excitation, GABAergic inhibition constrains neuronal morphology and innervation. The results reveal a multitiered activity-dependent strategy controlling neuronal development. Title: Pre- and postsynaptic actions of L1-CAM in nicotinic pathways Triana-Baltzer GB, Liu Z, Berg DK Ref: Molecular & Cellular Neurosciences, 33:214, 2006 : PubMed ESTHER: Triana-Baltzer_2006_Mol.Cell.Neurosci_33_214 PubMedSearch: Triana-Baltzer 2006 Mol.Cell.Neurosci 33 214 PubMedID: 16952465 Abstract Cell adhesion molecules (CAMs) have long been known to guide axon outgrowth and pathfinding. More recent evidence indicates they contribute to synapse formation as well. The L1 family of IgCAMs has been implicated in long-term potentiation, learning, and some features of synaptic structure. We show here that L1 is localized in nicotinic pathways at both pre- and postsynaptic sites. In the chick ciliary ganglion, postsynaptic L1 is associated with nicotinic receptors and potentiates their downstream signaling. Postsynaptic L1 is also important for aligning presynaptic structures over the postsynaptic cell. Dominant negative experiments suggest this latter effect depends on homophilic interactions with presynaptic L1. At the neuromuscular junction L1 is also found presynaptically where dominant negative experiments again indicate a role in aligning presynaptic structures over postsynaptic receptors, both in culture and in vivo. These findings identify new roles for L1 at nicotinic synapses and underscore the multipotency of L1-CAMs. Title: Pyridostigmine in autonomic failure: can we treat postural hypotension and bladder dysfunction with one drug? Yamamoto T, Sakakibara R, Yamanaka Y, Uchiyama T, Asahina M, Liu Z, Ito T, Koyama Y, Awa Y and Hattori T <2 more author(s)> Yamamoto T, Sakakibara R, Yamanaka Y, Uchiyama T, Asahina M, Liu Z, Ito T, Koyama Y, Awa Y, Yamamoto K, Kinou M, Hattori T (- 2) Ref: Clin Auton Res, 16:296, 2006 : PubMed ESTHER: Yamamoto_2006_Clin.Auton.Res_16_296 PubMedSearch: Yamamoto 2006 Clin.Auton.Res 16 296 PubMedID: 16862395 Inhibitor(s) related to this paper: Pyridostigmine Abstract In a 66-year-old man with autonomic failure, pyridostigmine (180 mg/day orally) improved both postural hypotension and underactive detrusor bladder dysfunction. Acetylcholinesterase inhibition may be useful in the management of orthostatic hypotension and bladder dysfunction in autonomic failure patients. Title: A nicotinic acetylcholine receptor mutation conferring target-site resistance to imidacloprid in Nilaparvata lugens (brown planthopper) Liu Z, Williamson MS, Lansdell SJ, Denholm I, Han Z, Millar NS Ref: Proc Natl Acad Sci U S A, 102:8420, 2005 : PubMed ESTHER: Liu_2005_Proc.Natl.Acad.Sci.U.S.A_102_8420 PubMedSearch: Liu 2005 Proc.Natl.Acad.Sci.U.S.A 102 8420 PubMedID: 15937112 Abstract Neonicotinoids, such as imidacloprid, are nicotinic acetylcholine receptor (nAChR) agonists with potent insecticidal activity. Since its introduction in the early 1990s, imidacloprid has become one of the most extensively used insecticides for both crop protection and animal health applications. As with other classes of insecticides, resistance to neonicotinoids is a significant threat and has been identified in several pest species, including the brown planthopper, Nilaparvata lugens, a major rice pest in many parts of Asia. In this study, radioligand binding experiments have been conducted with whole-body membranes prepared from imidacloprid-susceptible and imidacloprid-resistant strains of N. lugens. The results reveal a much higher level of [3H]imidacloprid-specific binding to the susceptible strain than to the resistant strain (16.7 +/- 1.0 and 0.34 +/- 0.21 fmol/mg of protein, respectively). With the aim of understanding the molecular basis of imidacloprid resistance, five nAChR subunits (Nlalpha1-Nlalpha4 and Nlbeta1) have been cloned from N. lugens.A comparison of nAChR subunit genes from imidacloprid-sensitive and imidacloprid-resistant populations has identified a single point mutation at a conserved position (Y151S) in two nAChR subunits, Nlalpha1 and Nlalpha3. A strong correlation between the frequency of the Y151S point mutation and the level of resistance to imidacloprid has been demonstrated by allele-specific PCR. By expression of hybrid nAChRs containing N. lugens alpha and rat beta2 subunits, evidence was obtained that demonstrates that mutation Y151S is responsible for a substantial reduction in specific [3H]imidacloprid binding. This study provides direct evidence for the occurrence of target-site resistance to a neonicotinoid insecticide. Title: Rapid activity-driven SNARE-dependent trafficking of nicotinic receptors on somatic spines Liu Z, Tearle AW, Nai Q, Berg DK Ref: Journal of Neuroscience, 25:1159, 2005 : PubMed ESTHER: Liu_2005_J.Neurosci_25_1159 PubMedSearch: Liu 2005 J.Neurosci 25 1159 PubMedID: 15689552 Abstract Rapid trafficking of glutamate receptors contributes importantly to synaptic plasticity, but whether similar trafficking extends to other ionotropic receptors is unknown. Nicotinic acetylcholine receptors containing alpha7 subunits are widely expressed in the nervous system and allow calcium influx. Because of this, alpha7-containing receptors regulate diverse events, depending on the signaling pathways available. We find that the receptors codistribute with target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) postsynaptically and that nicotinic stimulation rapidly induces SNARE-dependent vesicular endocytosis accompanied by receptor internalization. At the same time, a SNARE-dependent process recruits receptors to the cell surface from internal pools. Overall, the trafficking does not markedly change the number of surface receptors or their combined whole-cell response to nicotine. SNARE-dependent trafficking is needed, however, for the receptors to remain capable of activating the transcription factor cAMP response element-binding protein and attendant gene expression when repeatedly challenged. Thus, trafficking appears to be essential for maintaining functional coupling between alpha7-receptor responses and downstream signaling. Title: PDZ-containing proteins provide a functional postsynaptic scaffold for nicotinic receptors in neurons Conroy WG, Liu Z, Nai Q, Coggan JS, Berg DK Ref: Neuron, 38:759, 2003 : PubMed ESTHER: Conroy_2003_Neuron_38_759 PubMedSearch: Conroy 2003 Neuron 38 759 PubMedID: 12797960 Abstract Protein scaffolds are essential for specific and efficient downstream signaling at synapses. Though nicotinic receptors are widely expressed in the nervous system and influence numerous cellular events due in part to their calcium permeability, no scaffolds have yet been identified for the receptors in neurons. Here we show that specific members of the PSD-95 family of PDZ-containing proteins are associated with specific nicotinic receptor subtypes. At postsynaptic sites, the PDZ scaffolds are essential for maturation of functional nicotinic synapses on neurons. They also help mediate downstream signaling as exemplified by activation of transcription factors. By tethering components to postsynaptic nicotinic receptors, PDZ scaffolds can organize synaptic structure and determine which calcium-dependent processes will be subject to nicotinic modulation. Title: Olfactory bulb core is a rich source of neural progenitor and stem cells in adult rodent and human Liu Z, Martin LJ Ref: Journal of Comparative Neurology, 459:368, 2003 : PubMed ESTHER: Liu_2003_J.Comp.Neurol_459_368 PubMedSearch: Liu 2003 J.Comp.Neurol 459 368 PubMedID: 12687705 Abstract The olfactory bulb (OB) core is an extension of the rostral migratory stream and thus is a potential source of neural progenitor and neural stem cells. We characterized in vivo and in vitro neuronal progenitor and neural stem cells in the adult OB core. In mouse and rat, bromodeoxyuridine (BrdU) labeling showed that the OB core accumulates newly replicated cells. Nestin, a neuroepithelial stem cell marker, was enriched in the OB core. BrdU-positive cells were immunolabeled for nestin and TUC4, a marker for early postmitotic neurons. The distributions of cells labeled for BrdU, TUC4, and nestin were similarly concentrated in the OB core. Nestin- and TUC4-positive cells were also found in the OB of young and aged humans. Isolated and cultured OB core cells from adult rat and mouse had the capacity to generate numerous neurospheres. Adult OB core neurospheres were cryopreserved and subsequently cultured. Single cell clonal analysis of neurospheres revealed the capacity for self-renewal and multipotency. Cultured adult OB core cells differentiated into neurons, astrocytes, and oligodendrocytes. Some neurons expressed choline acetlytransferase, substance P, and glutamic acid decarboxylase. Basic fibroblast growth factor potentiated the self-renewal of cells and beta-nerve growth factor stimulated differentiation. OB-derived neural stem cells in coculture with skeletal muscle cells were induced to become neurons expressing choline acetyltransferase and substance P and formed neuromuscular synaptic junctions on myocytes displaying acetylcholinesterase-positive motor end plates. Cocultured OB-derived neural stem cells with myoblast cells also generated nonneural cell progeny. We conclude that the adult mammalian OB core is a reservoir of neural progenitor cells and pluripotent neural stem cells. Title: Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-deficient mice Kalla R, Liu Z, Xu S, Koppius A, Imai Y, Kloss CU, Kohsaka S, Gschwendtner A, Moller JC and Raivich G <1 more author(s)> Kalla R, Liu Z, Xu S, Koppius A, Imai Y, Kloss CU, Kohsaka S, Gschwendtner A, Moller JC, Werner A, Raivich G (- 1) Ref: Journal of Comparative Neurology, 436:182, 2001 : PubMed ESTHER: Kalla_2001_J.Comp.Neurol_436_182 PubMedSearch: Kalla 2001 J.Comp.Neurol 436 182 PubMedID: 11438923 Abstract Activation of microglia is among the first cellular changes in the injured CNS. However, little is known about their specific contribution to secondary damage or repair processes in neighboring neurons and nonneuronal cells or to the immune surveillance of the damaged tissue. Animal models with defective microglial response such as osteopetrosis provide an approach to explore these effects. Osteopetrosis (op) is an autosomal recessive mutation with a complete deficiency of the macrophage-colony stimulating factor (MCSF; CSF-1), an important mitogen for brain microglia. In the current study we examined the effects of this MCSF deficiency on the microglial reaction and the overall cellular response to nerve injury in the mouse axotomized facial motor nucleus. In the brain, MCSF receptor immunoreactivity was found only on microglia and was strongly up-regulated following injury. MCSF deficiency led to a failure of microglia to show a normal increase in early activation markers (thrombospondin, MCSF receptor, alpha M beta 2- and alpha 5 beta 1-integrins), to spread on the surface of axotomized motoneurons, and to proliferate after injury. Early recruitment of CD3(+) T-lymphocytes to the facial nucleus 24 hours after injury was reduced by 60%. In contrast, the neuronal and astrocyte response was not affected. There was a normal increase in the neuropeptides calcitonin gene-related peptide and galanin, neuronal c-JUN, and NADPH-diaphorase and a decrease in choline acetyltransferase and acetylcholinesterase. Astrocyte glial fibrillary acidic protein immunoreactivity also showed a normal increase. There was a normal influx of macrophages and granulocytes into the injured facial nerve. Synaptic stripping, neuronal survival, and speed of axonal regeneration were also not affected. The current results show a strong, selective effect of MCSF on the early activation of microglia and, indirectly, on lymphocyte recruitment. This early phase of microglial activation appears not to be involved in the process of repair following peripheral nerve injury. However, it is important in the initiation of inflammatory changes in the brain and in the interaction with the immune system. Title: Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.1-->q13.2 Levitt RC, Liu Z, Nouri N, Meyers DA, Brandriff B, Mohrenweiser HM Ref: Cytogenet Cell Genet, 69:211, 1995 : PubMed ESTHER: Levitt_1995_Cytogenet.Cell.Genet_69_211 PubMedSearch: Levitt 1995 Cytogenet.Cell.Genet 69 211 PubMedID: 7698015 Abstract Free fatty acids are the major source of fuel for mammals, and hormone sensitive lipase (LIPE) plays a critical role in lipid metabolism by mobilizing free fatty acids from stored triglycerides. We have identified and sequenced a partial cDNA for LIPE. Cosmids were identified by hybridization and mapped to 19q13.1-->q13.2 by FISH. Direct sequence analysis of a 1 kb segment of cosmid 26710 identifies a dinucleotide repeat in an intron upstream of exon 8 of human LIPE. This marker was heterozygous 82% of the time with 12 alleles (166-190 bp) detected in 122 chromosomes. The most likely order for this gene is: qter-[D19S178/LIPE]-(3 cM)-D19S47-(1 cM)-D19S190-RYR1-cen. | |||||||
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