Author Report for: Wang ZNo contact information in database for Wang Z
Chen Z, Yu J, Sun K, Song J, Chen L, Jiang Y, Wang Z Ref: Analyst, :, 2023 : PubMed ESTHER: Chen_2023_Analyst__ PubMedSearch: Chen 2023 Analyst PubMedID: 36661088 Abstract In vivo selective fluorescence imaging of carboxylesterase 2 (CES2) remains a great challenge because existing fluorescence probes can potentially suffer from interference by other hydrolases. In addition, some fluorescent probes that have been separately reported for measuring CES2 activity in vitro are affected by autofluorescence and absorption of the biological matrix due to their limited emission wavelength or short Stokes shift. Herein, based on the substrate preference and catalytic performance of CES2, a novel and NIR fluorescent probe was developed, in which a hemi-cyanine dye ester derivative was used as the basic fluorescent group. In the presence of CES2, the probe was hydrolyzed to expose the fluorophore CZX-OH (lambda(abs) - 675 nm, lambda(em) - 850 nm), which led to a notable red-shift in the fluorescence (-175 nm) spectrum. Confocal imaging of cells and live mice demonstrated that the fluorescent signal of this probe was related to the real activities of CES2 in cancer cells. All these results will powerfully promote the screening of CES2 regulators and the analysis of CES2-related physiological and pathological processes. Title: Strigolactone regulates adventitious root formation via the MdSMXL7-MdWRKY6-MdBRC1 signaling cascade in apple Fan X, Li Y, Deng CH, Wang S, Wang Z, Wang Y, Qiu C, Xu X, Han Z, Li W Ref: Plant J, 113:772, 2023 : PubMed ESTHER: Fan_2023_Plant.J_113_772 PubMedSearch: Fan 2023 Plant.J 113 772 PubMedID: 36575587 Abstract Propagation through stem cuttings is a popular method worldwide for species such as fruit tree rootstocks and forest trees. Adventitious root (AR) formation from stem cuttings is crucial for effective and successful clonal propagation of apple rootstocks. Strigolactones (SLs) are newly identified hormones involved in AR formation. However, the regulatory mechanisms underpinning this process remain elusive. In the present study, weighted gene co-expression network analysis, as well as rooting assays using stable transgenic apple materials, revealed that MdBRC1 served as a key gene in the inhibition of AR formation by SLs. We have demonstrated that MdSMXL7 and MdWRKY6 synergistically regulated MdBRC1 expression, depending on the interactions of MdSMXL7 and MdWRKY6 at the protein level downstream of SLs as well as the direct promoter binding on MdBRC1 by MdWRKY6. Furthermore, biochemical studies and genetic analysis revealed that MdBRC1 inhibited AR formation by triggering the expression of MdGH3.1 in a transcriptional activation pathway. Finally, the present study not only proposes a component, MdWRKY6, that enables MdSMXL7 to regulate MdBRC1 during the process of SL-controlled AR formation in apple, but also provides prospective target genes to enhance AR formation capacity using CRISPR (i.e. clustered regularly interspaced short palindromic repeats) technology, particularly in woody plants. Title: High-efficiency depolymerization/degradation of polyethylene terephthalate plastic by a whole-cell biocatalyst Fang Y, Chao K, He J, Wang Z, Chen Z Ref: 3 Biotech, 13:138, 2023 : PubMed ESTHER: Fang_2023_3.Biotech_13_138 PubMedSearch: Fang 2023 3.Biotech 13 138 PubMedID: 37124986 Abstract Polyethylene terephthalate (PET) is the most abundantly produced plastic due to its excellent performance, but is also the primary source of poorly degradable plastic pollution. The development of environment-friendly PET biodegradation is attracting increasing interest. The leaf-branch compost cutinase mutant ICCG (F243I/D238C/S283C/Y127G) exhibits the best hydrolytic activity and thermostability of all known PET hydrolases. However, its superior PET degradation is highly dependent on its preparation as a purified enzyme, which critically reduces its industrial utility. Herein, we report the use of rational design and combinatorial mutagenesis to develop a novel ICCG mutant RITK (D53R/R143I/D193T/E208K) that demonstrated excellent whole-cell biocatalytic activity. Whole cells expressing RITK showed an 8.33-fold increase in biocatalytic activity compared to those expressing ICCG. Thermostability was also improved. After reacting at 85 degreesC for 3 h, purified RITK exhibited a 12.75-fold increase in depolymerization compared to ICCG. These results will greatly enhance the industrial utility of PET hydrolytic enzymes and further the progress of PET recycling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03557-4. Title: Enzymatic enrichment of acylglycerols rich in n - 3 polyunsaturated fatty acids by selective methanolysis: Optimization and kinetic studies Jiang C, Wang Z, Huang Y, Wang X, Chang M Ref: J Food Sci, :, 2023 : PubMed ESTHER: Jiang_2023_J.Food.Sci__ PubMedSearch: Jiang 2023 J.Food.Sci PubMedID: 37219384 Abstract n - 3 Polyunsaturated fatty acids (n - 3 PUFA) have special physiological effect, but their contents in natural oils may not meet the growing demand. Lipase-catalyzed selective methanolysis could be used to produce acylglycerols rich in n - 3 PUFA. To explore the kinetics of enzymatic methanolysis, factors affecting the reaction, including reaction system, water content, substrate molar ratio, temperature, lipase loading, and reaction time, were first investigated in the view of optimizing the reaction. Then the effects of triacylglycerol concentrations and methanol concentrations on initial reaction rate were studied. Finally, the key kinetic parameters of methanolysis were determined subsequently. The results showed that under optimal conditions, the n - 3 PUFA content in acylglycerols increased from 39.88% to 71.41%, and the n - 3 PUFA yield was 73.67%. The reaction followed a Ping-Pong Bi Bi mechanism with inhibition by methanol. The kinetic analysis indicated the lipase could selectively remove saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in acylglycerols. The inhibition constant of methanol to the n - 3 PUFA (K(iM) , 0.30 mmol/L) was lower than that to the SFA and MUFA (219.64 and 79.71 mmol/L). The combined effects of the fatty acid selectivity of Candida antarctica lipase A and methanol inhibition resulted in an enrichment of n - 3 PUFA in acylglycerols. Overall, the methanolysis reaction catalyzed by the lipase A is a prospective enrichment method. PRACTICAL APPLICATION: This study demonstrated that enzymatic selective methanolysis is a prospective enrichment method to produce acylglycerols rich in n - 3 PUFA. This method is highly efficient, environment-friendly, and simple. n - 3 PUFA concentrates have been widely applied in the food, health-care food, and pharmaceutical industries. Title: Salicylic acid attenuates brassinosteroid signaling via protein de-S-acylation Liu X, Chen Z, Huang L, Ouyang Y, Wang Z, Wu S, Ye W, Yu B, Zhang Y and Lai J <1 more author(s)> Liu X, Chen Z, Huang L, Ouyang Y, Wang Z, Wu S, Ye W, Yu B, Zhang Y, Yang C, Lai J (- 1) Ref: EMBO j, :e112998, 2023 : PubMed ESTHER: Liu_2023_EMBO.J__e112998 PubMedSearch: Liu 2023 EMBO.J e112998 PubMedID: 37211868 Gene_locus related to this paper: arath-AT5G20520 Abstract Brassinosteroids (BRs) are important plant hormones involved in many aspects of development. Here, we show that BRASSINOSTEROID SIGNALING KINASEs (BSKs), key components of the BR pathway, are precisely controlled via de-S-acylation mediated by the defense hormone salicylic acid (SA). Most Arabidopsis BSK members are substrates of S-acylation, a reversible protein lipidation that is essential for their membrane localization and physiological function. We establish that SA interferes with the plasma membrane localization and function of BSKs by decreasing their S-acylation levels, identifying ABAPT11 (ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17-LIKE ACYL PROTEIN THIOESTERASE 11) as an enzyme whose expression is quickly induced by SA. ABAPT11 de-S-acylates most BSK family members, thus integrating BR and SA signaling for the control of plant development. In summary, we show that BSK-mediated BR signaling is regulated by SA-induced protein de-S-acylation, which improves our understanding of the function of protein modifications in plant hormone cross talk. Title: Sensitive detection of butyrylcholinesterase activity based on a stimuli-responsive fluorescence reaction Pang Y, Ma Z, Song Q, Wang Z, Shi YE Ref: Spectrochim Acta A Mol Biomol Spectrosc, 299:122886, 2023 : PubMed ESTHER: Pang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_299_122886 PubMedSearch: Pang 2023 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 299 122886 PubMedID: 37210854 Abstract A fluorogenic reaction between the chelate of Mn(II)-citric acid and terephthalic acid (PTA) was discovered, which was carried out through heating the aqueous mixture of Mn(2+), citric acid and PTA. Detailed investigations indicated the reaction products were 2-hydroxyterephthalic acid (PTA-OH), which was attributed to the reaction between PTA and OH, formed by the triggering of Mn(II)-citric acid in the presence of dissolved O(2). PTA-OH showed a strong blue fluorescence, peaked at 420 nm, and the fluorescence intensity presented a sensitive response to pH of the reaction system. Based on these mechanisms, the fluorogenic reaction was used for the detection of butyrylcholinesterase activity, achieving a detection limit of 0.15 U/L. The detection strategy was successfully applied in human serum samples, and it was also extended for the detection of organophosphorus pesticides and radical scavengers. Such a facile fluorogenic reaction and its stimuli-responsive properties offered an effective tool for designing detection pathways in the fields of clinical diagnosis, environmental monitoring and bioimaging. Title: Hesperidin methylchalcone (HMC) hinders amyloid-beta induced Alzheimer's disease by attenuating cholinesterase activity, macromolecular damages, oxidative stress and apoptosis via regulating NF-B and Nrf2/HO-1 pathways Wang Z, Gao C, Zhang L, Sui R Ref: Int J Biol Macromol, :123169, 2023 : PubMed ESTHER: Wang_2023_Int.J.Biol.Macromol__123169 PubMedSearch: Wang 2023 Int.J.Biol.Macromol 123169 PubMedID: 36623626 Abstract Phytocompounds therapy has recently emerged as an effective strategy to treat Alzheimer's disease. Herein, the protective effect of hesperidin methylchalcone (HMC) was evaluated through Alzheimer's disease models of Neuro-2a cells and Wistar rats. The in vitro results showed that HMC possesses significant ability to inhibit the acetylcholinesterase enzyme and exhibiting anti-aggregation and disaggregation properties. Furthermore, HMC could protect the Neuro-2a cells against Abeta-induced neurotoxicity. Simultaneously, HMC treatment significantly improved the cognitive deficits caused by Abeta-peptide on spatial memory in Wistar rats. HMC significantly enhanced the cholinergic effects by inhibiting AChE, BuChE, beta-secretase activity, caspase-3 activity, and attenuating macromolecular damages and apoptosis. Notably, HMC reduced the Abeta-induced oxidative stress by activating the antioxidative defence enzymes. In addition, the HMC treatment suppressed the expression of immunocytokines such as p-NF-kappaB p65, p-IkappaBalpha, induced by Abeta; whereas upregulating Nrf2, HO-1 in brain homogenate. These results suggest that HMC could attenuate Abeta-induced neuroinflammation in brain via suppressing NF-kappaB signalling pathway and activating the Nrf2/HO-1 pathway, thereby improving memory and cognitive impairments in Wistar rats. Overall, the present study reports that HMC can act as a potent candidate with multi-faceted neuroprotective potential against Abeta-induced memory dysfunction in Wistar rats for the treatment of Alzheimer's disease. Title: Bidirectional selection of the functional properties and environmental friendliness of organophosphorus (OP) pesticide derivatives: Design, screening, and mechanism analysis Wang Z, Pu Q, Li Y Ref: Sci Total Environ, :163043, 2023 : PubMed ESTHER: Wang_2023_Sci.Total.Environ__163043 PubMedSearch: Wang 2023 Sci.Total.Environ 163043 PubMedID: 36963678 Abstract Organophosphorus pesticides (OPs) are widely used in agricultural production, but the resulting pollution and drug resistance have sparked widespread concern. Therefore, this paper built a model to design OP substitute molecules with high functionality and environmental friendliness, as well as conducted various human health and ecological environment evaluations, synthetic accessibility screening, and easy detection screening. The functionality of the two OP substitute molecules, DIM-100 and DIM-164, increased by 22.79 % and 22.18 %, respectively, and the environmental friendliness increased by 18.07 % and 24.02 %, respectively. The human health risk and ecological, environmental risks were significantly reduced. Both molecules are easy to synthesize, and their detection sensitivity is 9.85 % and 11.24 % higher than that of the target molecule, respectively. Furthermore, significant changes in the distribution of electrons and holes near the C8 and S1 atoms of the OP substitute molecule resulted in easier breakage of the C8-S1 bond, enhancing its photodegradation ability. The charge transfer ability between the atoms of the molecule (as increasing the electron-withdrawing group led to an increase in charge of the P atom) and the volume of the cholinesterase active pocket both affect the functionality of the DIM substitute molecule. That is, the volume of the cholinesterase active pocket of the bee is smaller than that of the brown planthopper and is more affected by the volume of the OP molecule. Furthermore, the mutual verification analysis of the bidirectional selectivity effect of OP substitute molecules between the BayesianRidge model and the 3D-QS(A(2) + (3))R model reveals that the overall charge transfer degree of DIM substitute molecules is the main reason for the increase in the bidirectional selectivity effect. Title: Spatial distribution differences of cholinesterase in healthy Chinese under the influence of geographical environmental factors Yang W, Ge M, Wang Z, Li T Ref: Environ Sci Pollut Res Int, :, 2023 : PubMed ESTHER: Yang_2023_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Yang 2023 Environ.Sci.Pollut.Res.Int PubMedID: 36800095 Abstract The main targets of this were to screen the factors that may influence the distribution of cholinesterase (CHE) reference value in healthy people, and further explored the geographical distribution differences of CHE reference value in China. In this study, we collected the CHE data of 17,601 healthy people from 173 cities in China to analyse the correlation between CHE and 22 geography secondary indexes through spearman regression analysis. Six indexes with significant correlation were extracted, and a ridge regression model was built, and the country's urban CHE reference value of healthy Chinese was predicted. By using the disjunctive kriging method, we obtained the geographical distribution of CHE reference values for healthy people in China. The reference value of CHE for healthy Chinese was significantly correlated with the 6 secondary indexes, namely, latitude ( degrees), altitude (m), annual average temperature ( degreesC), annual average relative humidity (%) and annual precipitation (mm), and topsoil sand gravel percentage (% wt). The geographical distribution of CHE values of healthy Chinese showed a trend of being higher in southeast China and lower in northwest. This study lays a foundation for further research on the mechanism of different influencing factors on the reference value of CHE index. A ridge regression model composed of significant influencing factors has been established to provide the basis for formulating reference criteria for the treatment factors of the liver damage diseases and liver cancer using CHE reference values in different regions. Title: Green biosynthesis of rare DHA-phospholipids by lipase-catalyzed transesterification with edible algal oil in solvent-free system and catalytic mechanism study Zhang T, Li B, Wang Z, Hu D, Zhang X, Zhao B, Wang J Ref: Front Bioeng Biotechnol, 11:1158348, 2023 : PubMed ESTHER: Zhang_2023_Front.Bioeng.Biotechnol_11_1158348 PubMedSearch: Zhang 2023 Front.Bioeng.Biotechnol 11 1158348 PubMedID: 37064237 Abstract Docosahexaenoic acid (DHA)-enriched phosphatidylcholine (PC) has received significant scientific attention due to the health benefits in food and pharmaceutical products. In this work, the edible algal oil rich in DHA-triacylglycerol (DHA-TAG) without pretreatment was first used as the DHA donor for the transesterification of phospholipids (PLs) to prepare three kinds of rare PLs, including DHA-PC, DHA-phosphatidylethanolamine (DHA-PE), and DHA-phosphatidylserine (DHA-PS). Here, 153 protein structures of triacylglycerol lipase (EC 3.1.1.3) were virtually screened and evaluated by transesterification. PLA1 was the best candidate due to a higher DHA incorporation. Results showed that the transesterification of PC with DHA-TAG at 45 degreesC and 0.7% water content (without additional water addition) could produce DHA-PC with 39.1% DHA incorporation at 30 min. The different DHA donors, including forms of fatty acid, methyl ester, and triglycerides, were compared. Molecular dynamics (MD) was used to illustrate the catalytic mechanism at the molecular level containing the diffusions of substrates, the structure-activity relationship of PLA1, and the effect of water content. Title: Nanobodies as binding-chaperones stabilize the recombinant Bombyx mori acetylcholinesterase and protect the enzyme activity in pesticide detection Cai J, Romao E, Wu G, Li J, Li L, Wang Z, Li Y, Yang J, Shen Y and Wang H <2 more author(s)> Cai J, Romao E, Wu G, Li J, Li L, Wang Z, Li Y, Yang J, Shen Y, Xu Z, Muyldermans S, Wang H (- 2) Ref: Enzyme Microb Technol, 155:109992, 2022 : PubMed ESTHER: Cai_2022_Enzyme.Microb.Technol_155_109992 PubMedSearch: Cai 2022 Enzyme.Microb.Technol 155 109992 PubMedID: 35114480 Abstract In our previous study, the recombinant type II acetylcholinesterase from Bombyx mori (rBmAChE) presented outstanding sensitivity to pesticides, which exhibited great potential in pesticides detection. However, the poor stability of rBmAChE and also the unclear mechanism of its sensitivity hindered the applications in on-site testing of pesticides residues. In this study, we constructed an immune nanobody library, in which we obtained 48 rBmAChE-specific nanobodies. Among them, Nb4 and Nb9 were verified as the most prominent enhancers of the enzyme activity and stabilizers under thermal stress, which indicated their usage as protective reagents for rBmAChE. The simultaneously addition of the two Nbs enhanced the thermal-stability of rBmAChE against exposure to 50-70 degreesC, and also remained 100% residual activity after 30 days storage at - 20 degreesC or 4 degreesC, whereas 80% and 62% at - 80 degreesC and 25 degreesC. The homologous modeling and docking of Nb4 and Nb9 to rBmAChE indicated the stabilization of Nb4 to the peripheral anion site (PAS) of rBmAChE while Nb9 protected the C-terminal structure. Substrate docking demonstrated the importance of electrostatic attraction during catalytic process, that might be enhanced by Nbs. As a result, Nb4 and Nb9 were proved to have great potential on rBmAChE applications due to their regulation on enzyme activity and protection against thermal-inactivation and long-term storage of rBmAChE. Title: An efficient multi-enzyme cascade platform based on mesoporous metal-organic frameworks for the detection of organophosphorus and glucose Cao X, Guo Y, Zhao M, Li J, Wang C, Xia J, Zou T, Wang Z Ref: Food Chem, 381:132282, 2022 : PubMed ESTHER: Cao_2022_Food.Chem_381_132282 PubMedSearch: Cao 2022 Food.Chem 381 132282 PubMedID: 35176684 Abstract An efficient colorimetric detection platform based on multi-enzyme cascade has been developed for detection of organophosphorus. Firstly, the dual-enzyme platform was prepared and applied for sensitive glucose detection (detection limit 0.32 microM). And then three enzymes, including acetylcholinesterase, horseradish peroxidase and choline oxidase were encapsulated in cruciate flower-like zeolitic imidazolate framework-8 (CF-ZIF-8) through one-step co-precipitation to construct detection platform with acetylcholine chloride as substrate. The acephate inhibited the activity of acetylcholinesterase, obstructed the cascade reaction and reduced the production of H(2)O(2), resulting in the changes of color intensity for the colorimetric detection. With suitable size and porous structure, CF-ZIF-8 provided a good microenvironment for guaranteeing the activity and spatial proximity of enzymes. The multi-enzyme platform displayed great performances with the detection limit of 0.23 nM for acephate. It was applied to the detection of acephate in Chinese cabbage and romaine, verifying the practicability of this platform. Title: A Sensitive and Selective Colorimetric Method Based on the Acetylcholinesterase-like Activity of Zeolitic Imidazolate Framework-8 and Its Applications Chen X, He X, Sun J, Wang Z, Chen GY, Qian ZM, Yin SJ, Zhou X, Yang FQ Ref: Molecules, 27:, 2022 : PubMed ESTHER: Chen_2022_Molecules_27_ PubMedSearch: Chen 2022 Molecules 27 PubMedID: 35458616 36364318 Abstract In this study, a simple colorimetric method was established to detect copper ion (Cu(2+)), sulfathiazole (ST), and glucose based on the acetylcholinesterase (AChE)-like activity of zeolitic imidazolate framework-8 (ZIF-8). The AChE-like activity of ZIF-8 can hydrolyze acetylthiocholine chloride (ATCh) to thiocholine (TCh), which will further react with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) to generate 2-nitro-5-thiobenzoic acid (TNB) that has a maximum absorption peak at 405 nm. The effects of different reaction conditions (buffer pH, the volume of ZIF-8, reaction temperature and time, and ATCh concentration) were investigated. Under the optimized conditions, the value of the Michaelis-Menten constant (K(m)) is measured to be 0.83 mM, which shows a high affinity toward the substrate (ATCh). Meanwhile, the ZIF-8 has good storage stability, which can maintain more than 80.0% of its initial activity after 30 days of storage at room temperature, and the relative standard deviation (RSD) of batch-to-batch (n = 3) is 5.1%. The linear dependences are obtained based on the AChE-like activity of ZIF-8 for the detection of Cu(2+), ST, and glucose in the ranges of 0.021-1.34 and 5.38-689.66 M, 43.10-517.24 M, and 0.0054-1.40 mM, respectively. The limit of detections (LODs) are calculated to be 20.00 nM, 9.25 M, and 5.24 M, respectively. Moreover, the sample spiked recoveries of Cu(2+) in lake water, ST in milk, and glucose in strawberry samples were measured, and the results are in the range of 98.4-115.4% with the RSD (n = 3) lower than 3.3%. In addition, the method shows high selectivity in the real sample analysis. Title: Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin Chen Z, Duan R, Xiao Y, Wei Y, Zhang H, Sun X, Wang S, Cheng Y, Wang X and Wang Z <5 more author(s)> Chen Z, Duan R, Xiao Y, Wei Y, Zhang H, Sun X, Wang S, Cheng Y, Wang X, Tong S, Yao Y, Zhu C, Yang H, Wang Y, Wang Z (- 5) Ref: Nat Commun, 13:7138, 2022 : PubMed ESTHER: Chen_2022_Nat.Commun_13_7138 PubMedSearch: Chen 2022 Nat.Commun 13 7138 PubMedID: 36414665 Gene_locus related to this paper: idesa-peth Abstract The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET. Title: Integrative analysis uncovers response mechanism of Pirata subpiraticus to chronic cadmium stress Dai OL, Lei ZY, Peng YD, Wang Z Ref: Environ Sci Pollut Res Int, :, 2022 : PubMed ESTHER: Dai_2022_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Dai 2022 Environ.Sci.Pollut.Res.Int PubMedID: 35864398 Abstract Soil cadmium (Cd) pollution is global environmental pollution and adversely affects paddy field organisms. Wolf spider grants a new insight to evaluate the toxicity triggered by Cd, yet the impact of chronic Cd exposure on the spider and its molecular mechanism remains unclear. The present study found that the wolf spider Pirata subpiraticus fed with Cd-accumulated flies for 5 weeks presented lower catalase, peroxidase, and acetylcholinesterase activities and higher malonaldehyde content than the control spiders (p < 0.05). An in-depth transcriptomic analysis yielded a total of 5995 differentially expressed genes (DEGs, with 3857 up-regulated and 2138 down-regulated genes) from the comparison, and 19 DEGs encoding three enzymatic indicators were down-regulated. Further enrichment analysis indicated that Cd stress could inhibit the expression of cuticle and chitin-encoding genes via the down-regulation of several key enzymes, such as chitin synthase, glutamine-fructose-6-phosphate transaminase, and chitinase. In addition, our findings suggested that hedgehog and FoxO signaling pathways might play an essential role in regulating survival, cell cycle, and autophagy process in spiders, which were primarily down-regulated under Cd stress. An intensely interactive network displayed that Cd exposure could repress key biological processes in P. subpiraticus, particularly peptide metabolic process and peptide biosynthetic process. To sum up, this integrative investigation confirmed an effective bioindicator for assessing Cd-induced toxicity; provided a mass of genes, proteins, and enzymes for further validation; and granted novel perspectives to uncover the molecular responses of spiders to Cd pollution. Title: Comprehensive Enantioselectivity Evaluation of Insecticidal Activity and Mammalian Toxicity of Fenobucarb He Z, Li C, Xia W, Wang Z, Li R, Zhang Y, Wang M Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: He_2022_J.Agric.Food.Chem__ PubMedSearch: He 2022 J.Agric.Food.Chem PubMedID: 35451821 Abstract To comprehensively evaluate the efficiency and risk of the chiral pesticide fenobucarb, the bioactivity, toxicity, and environmental behavior of fenobucarb (FNC) enantiomers were investigated. The results showed that R-FNC possesses 1.8-2.7 times more bioactivity than S-FNC but 1.3-3.0 times lower toxicity than S-FNC against four nontarget organisms: Chlorella pyrenoidosa, HepG2, and Danio rerio and its embryos. The corresponding enzyme inhibitory activity showed consistent results; the acetylcholinesterase inhibitory activity of target organisms was ordered as R-FNC > rac-FNC > S-FNC, while the reduction in catalase activity after exposure to R-FNC was 2.5 times that after exposure to S-FNC in zebrafish. The enantioselective bioactivity mechanism of FNC enantiomers was further explored in silico. No significant enantioselective degradation was found in soils or rat liver microsomes. In sum, R-FNC possesses higher insecticidal activity and lower toxicity. The development of R-FNC as a commercial agrochemical is beneficial for reducing pesticide inputs. Title: Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck) Li Z, Wu L, Wang C, Wang Y, He L, Wang Z, Ma X, Bai F, Feng G and Song F <2 more author(s)> Li Z, Wu L, Wang C, Wang Y, He L, Wang Z, Ma X, Bai F, Feng G, Liu J, Jiang Y, Song F (- 2) Ref: BMC Genomics, 23:185, 2022 : PubMed ESTHER: Li_2022_BMC.Genomics_23_185 PubMedSearch: Li 2022 BMC.Genomics 23 185 PubMedID: 35249536 Abstract BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus. Title: Highly Selective Detection of Paraoxon in Food Based on the Platform of Cu Nanocluster/MnO(2) Nanosheets Liu S, Zhang P, Miao Y, Li C, Shi YE, Liu J, Lv YK, Wang Z Ref: Nanomaterials (Basel), 12:, 2022 : PubMed ESTHER: Liu_2022_Nanomaterials.(Basel)_12_ PubMedSearch: Liu 2022 Nanomaterials.(Basel) 12 PubMedID: 35564138 Abstract Selective and sensitive identification of paraoxon residue in agricultural products is greatly significant for food safety but remains a challenging task. Herein, a detection platform was developed by integrating Cu nanoclusters (Cu NCs) with MnO(2) nanosheets, where the fluorescence of Cu NCs was effectively quenched. Upon introducing butyrylcholinesterase and butyrylcholine into the system, their hydrolysate, thiocholine, leads to the decomposition of the platform through a reaction between the MnO(2) nanosheets and thiol groups on thiocholine. The electron-rich groups on thiocholine can further promote the fluorescence intensity of Cu NCs through host-guest interactions. Adding paraoxon results in the failure of fluorescence recovery and further promotion, which could be utilized for the quantitative detection of paraoxon, and a limit of detection as low as 0.22 ng/mL can be achieved. The detection platform shows strong tolerance to common interference species, which endows its applications for the detection of paraoxon in vegetables and fruit. These presented results not only open a new door for the functionalization of metal nanoclusters but also offer an inspiring strategy for analytic techniques in nanomedicine and environmental science. Title: Fosthiazate exposure induces oxidative stress, nerve damage, and reproductive disorders in nontarget nematodes Liu BD, Dong HT, Rong HW, Zhang RJ, Liu S, Wu Q, Zhong Y, He Z, Wang Z and Wang M <1 more author(s)> Liu BD, Dong HT, Rong HW, Zhang RJ, Liu S, Wu Q, Zhong Y, He Z, Wang Z, Li R, Wang M (- 1) Ref: Environ Sci Pollut Res Int, :, 2022 : PubMed ESTHER: Liu_2022_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Liu 2022 Environ.Sci.Pollut.Res.Int PubMedID: 35796928 36112285 Abstract As a forceful nematicide, fosthiazate has been largely applied in the management of root-knot nematodes and other herbivorous nematodes. However, the toxicity of fosthiazate to nontarget nematodes is unclear. To explore the toxicity and the mechanisms of fosthiazate in nontarget nematodes, Caenorhabditis elegans was exposed to 0.01-10 mg/L fosthiazate. The results implied that treatment with fosthiazate at doses above 0.01 mg/L could cause injury to the growth, locomotion behavior, and reproduction of the nematodes. Moreover, L1 larvae were more vulnerable to fosthiazate exposure than L4 larvae. Reactive oxygen species (ROS) production and lipofuscin accumulation were fairly increased in 1 mg/L fosthiazate-exposed nematodes. Treatment with 0.1 mg/L fosthiazate significantly inhibited the activity of acetylcholinesterase (p < 0.01). Furthermore, subacute exposure to 10 mg/L fosthiazate strongly influenced the expression of genes related to oxidative stress, reproduction, and nerve function (e.g., gst-1, sod-1, puf-8, wee-1.3, and ace-1 genes). These findings suggested that oxidative stress, reproduction and nerve disorders could serve as key endpoints of toxicity induced by fosthiazate. The cyp-35a family gene was the main metabolic fosthiazate in C. elegans, and the cyp-35a5 subtype was the most sensitive, with a change in expression level of 2.11-fold compared with the control. These results indicate that oxidative stress and neurological and reproductive disorders played fundamental roles in the toxicity of fosthiazate in C. elegans and may affect the abundance and function of soil nematodes. Title: Karrikin Receptor KAI2 Coordinates Salt Tolerance Mechanisms in Arabidopsis thaliana Mostofa MG, Abdelrahman M, Rahman MM, Tran CD, Nguyen KH, Watanabe Y, Itouga M, Li W, Wang Z and Tran LP <1 more author(s)> Mostofa MG, Abdelrahman M, Rahman MM, Tran CD, Nguyen KH, Watanabe Y, Itouga M, Li W, Wang Z, Mochida K, Tran LP (- 1) Ref: Plant Cell Physiol, :, 2022 : PubMed ESTHER: Mostofa_2022_Plant.Cell.Physiol__ PubMedSearch: Mostofa 2022 Plant.Cell.Physiol PubMedID: 35997763 Abstract Plants activate a myriad of signaling cascades to tailor adaptive responses under environmental stresses, such as salinity. While the roles of exogenous karrikins (KARs) in salt stress mitigation are well comprehended, genetic evidence of KAR signaling during salinity responses in plants remains unresolved. Here, we explored the functions of the possible KAR receptor KARRIKIN INSENSITIVE2 (KAI2) in Arabidopsis thaliana resistance to salt stress by investigating comparative responses of wild-type (WT) and kai2 mutant plants under a gradient of NaCl. Defect in KAI2 functions resulted in delayed and inhibited cotyledon opening in kai2 seeds compared with WT seeds, suggesting that KAI2 played an important role in enhancing seed germination under salinity. Salt-stressed kai2 plants displayed more phenotypic aberrations, biomass reduction, water loss and oxidative damage than WT plants. kai2 shoots accumulated significantly more Na+, and thus had a lower K+/Na+ ratio, than WT, indicating a severe ion-toxicity in salt-stressed kai2 plants. Accordingly, kai2 plants displayed lower expression of the genes associated with Na+ homeostasis, such as SALT OVERLY SENSITIVE (SOS) 1, SOS2, HIGH AFFINITY POTASSIUM TRANSPORTER 1;1 (HKT1;1) and CATION-HYDROGEN EXCHANGER 1 (NHX1) than WT plants. WT plants maintained a better status of glutathione level, glutathione-related redox status and antioxidant enzyme activities relative to kai2 plants, implying KAI2's function in oxidative stress mitigation in response to salinity. kai2 shoots had lower expression levels of the genes involved in the biosynthesis of strigolactones, salicylic acid and jasmonic acid, and the signaling of abscisic acid and strigolactones than those of WT plants, indicating interactive functions of KAI2 signaling with other hormone signaling in modulating plant responses to salinity. Collectively, these results underpin the likely roles of KAI2 in alleviation of salinity effects in plants by regulating several physiological and biochemical mechanisms involved in ionic and osmotic balance, oxidative stress tolerance and hormonal crosstalk. Title: Tanshinone IIA regulates glycogen synthase kinase-3beta-related signaling pathway and ameliorates memory impairment in APP/PS1 transgenic mice Peng X, Chen L, Wang Z, He Y, Ruganzu JB, Guo H, Zhang X, Ji S, Zheng L, Yang W Ref: European Journal of Pharmacology, :174772, 2022 : PubMed ESTHER: Peng_2022_Eur.J.Pharmacol__174772 PubMedSearch: Peng 2022 Eur.J.Pharmacol 174772 PubMedID: 35090935 Inhibitor(s) related to this paper: Tanshinone-IIA Abstract Our previous findings indicated that tanshinone IIA (tan IIA), a natural component extracted from the root and rhizome of danshen, significantly attenuated beta-amyloid accumulation, neuroinflammation, and endoplasmic reticulum stress, as well as improved learning and memory deficits in APP/PS1 transgenic mouse model of Alzheimer's disease (AD). However, whether tan IIA can ameliorate tau pathology and the underlying mechanism in APP/PS1 mice remains unclear. In the current study, tan IIA (15 mg/kg and 30 mg/kg) or saline was intraperitoneally administered to the 5-month-old APP/PS1 mice once daily for 4 weeks. The open-field test, novel object recognition test, Y-maze test, and Morris water maze test were performed to assess the cognitive function. Nissl staining, immunohistochemistry, TUNEL, and western blotting were conducted to explore tau hyperphosphorylation, neuronal injury, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt)/glycogen synthase kinase-3beta (GSK-3beta) signaling pathway. The activity of GSK-3beta, acetylcholinesterase (AChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) were measured using commercial kits. Our results revealed that tan IIA treatment significantly ameliorated behavioral deficits and improved spatial learning and memory ability of APP/PS1 mice. Additionally, tan IIA markedly attenuated tau hyperphosphorylation and prevented neuronal loss and apoptosis in the parietal cortex and hippocampus. Simultaneously, tan IIA reversed cholinergic dysfunction and reduced oxidative stress. Furthermore, tan IIA activated the PI3K/Akt signaling pathway and suppressed GSK-3beta. Taken together, the above findings suggested that tan IIA improves cognitive decline and tau pathology may through modulation of PI3K/Akt/GSK-3beta signaling pathway. Title: Fluorescence-activated droplet sorting of PET degrading microorganisms Qiao Y, Hu R, Chen D, Wang L, Wang Z, Yu H, Fu Y, Li C, Dong Z and Du W <1 more author(s)> Qiao Y, Hu R, Chen D, Wang L, Wang Z, Yu H, Fu Y, Li C, Dong Z, Weng YX, Du W (- 1) Ref: J Hazard Mater, 424:127417, 2022 : PubMed ESTHER: Qiao_2022_J.Hazard.Mater_424_127417 PubMedSearch: Qiao 2022 J.Hazard.Mater 424 127417 PubMedID: 34673397 Abstract Enzymes that can decompose synthetic plastics such as polyethylene terephthalate (PET) are urgently needed. Still, a bottleneck remains due to a lack of techniques for detecting and sorting environmental microorganisms with vast diversity and abundance. Here, we developed a fluorescence-activated droplet sorting (FADS) pipeline for high-throughput screening of PET-degrading microorganisms or enzymes (PETases). The pipeline comprises three steps: generation and incubation of droplets encapsulating single cells, picoinjection of fluorescein dibenzoate (FDBz) as the fluorogenic probe, and screening of droplets to obtain PET-degrading cells. We characterized critical factors associated with this method, including specificity and sensitivity for discriminating PETase from other enzymes. We then optimized its performance and compatibility with environmental samples. The system was used to screen a wastewater sample from a PET textile mill. We successfully obtained PET-degrading species from nine different genera. Moreover, two putative PETases from isolates Kineococcus endophyticus Un-5 and Staphylococcus epidermidis Un-C2-8 were genetically derived, heterologously expressed, and preliminarily validated for PET-degrading activities. We speculate that the FADS pipeline can be widely adopted to discover new plastic-degrading microorganisms and enzymes in various environments and may be utilized in the directed evolution of degrading enzymes using synthetic biology. Title: Novel pathogenic variant combination in LPL causing familial chylomicronemia syndrome in an Asian family and experimental validation in vitro: a case report Shi H, Wang Z Ref: Transl Pediatr, 11:1717, 2022 : PubMed ESTHER: Shi_2022_Transl.Pediatr_11_1717 PubMedSearch: Shi 2022 Transl.Pediatr 11 1717 PubMedID: 36345447 Gene_locus related to this paper: human-LPL Abstract BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder, typically caused by biallelic pathogenic variants in the lipoprotein lipase (LPL) gene. Lipoprotein lipase, encoded by the LPL gene, catalyzes the hydrolysis of triglycerides, and its deficiency or dysfunction can lead to chylomicronemia and potentially fatal recurrent acute pancreatitis. CASE DESCRIPTION: Here, we report an Asian child with FCS due to compound heterozygous LPL variants. The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. Based on the clinical features and family history, the diagnosis of FCS was suspected, and confirmed by the identification of compound heterozygous variants in the LPL gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient, inheriting one from each parent. According to the clinical and genetic findings, the patient was diagnosed with FCS. In vitro experimental validation found that the LPL p.H154R variant reduced the expression of lipoprotein lipase and decreased its lipolytic activity, while the LPL p.L263Q variant mainly impaired its lipolytic activity. CONCLUSIONS: FCS was molecularly diagnosed using whole exome sequencing in the case presented. When interpreting abnormal coagulation profiles measured by turbidity-based assay, the possibility of lipemic blood (or chylomicronemia) should be considered and the presence of this phenomenon might indicate the diagnosis of FCS. In vitro experiments showed that the two LPL variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic. Title: Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor Sun S, Shi T, Peng Y, Zhang H, Zhuo L, Peng X, Li Q, Wang M, Wang S, Wang Z Ref: Front Pharmacol, 13:1043397, 2022 : PubMed ESTHER: Sun_2022_Front.Pharmacol_13_1043397 PubMedSearch: Sun 2022 Front.Pharmacol 13 1043397 PubMedID: 36561337 Abstract Inspired by the crucial roles of (hetero)aryl rings in cholinesterase inhibitors and the pyrrole ring in new drug discovery, we synthesized 19 pyrrole derivatives and investigated their cholinesterase inhibitory activity. As a result, compounds 3o, 3p, and 3s with a 1,3-diaryl-pyrrole skeleton showed high selectivity toward BChE over AChE with a best IC(50) value of 1.71 +/- 0.087smicroM, which were comparable to donepezil. The pharmaceutical potential of these structures was further predicted and compounds 3o and 3p were proved to meet well with the Lipinsky's five rules. In combination of the inhibition kinetic studies with the results of molecular docking, we concluded that compound 3p inhibited BChE in a mixed competitive mode. This research has proved the potential of the 1,3-diaryl-pyrrole skeleton as a kind of selective BChE inhibitor. Title: Improvement of methanol tolerance and catalytic activity of Rhizomucor miehei lipase for one-step synthesis of biodiesel by semi-rational design Tian M, Yang L, Lv P, Wang Z, Fu J, Miao C, Li Z, Li L, Liu T and Luo W <1 more author(s)> Tian M, Yang L, Lv P, Wang Z, Fu J, Miao C, Li Z, Li L, Liu T, Du W, Luo W (- 1) Ref: Bioresour Technol, :126769, 2022 : PubMed ESTHER: Tian_2022_Bioresour.Technol__126769 PubMedSearch: Tian 2022 Bioresour.Technol 126769 PubMedID: 35092821 Abstract Exploiting highly active and methanol-resistant lipase is of great significance for biodiesel production. A semi-rational directed evolution method combined with N-glycosylation is reported, and all mutants exhibiting higher catalytic activity and methanol tolerance than the wild type (WT). Mutant N267 retained 64% activity after incubation in 50% methanol for 8 h, which was 48% greater than that of WT. The catalytic activity of mutants N267 and N167 was 30- and 71- fold higher than that of WT. Molecular dynamics simulations of N267 showed that the formation of new strong hydrogen bonds between glycan and the protein stabilized the structure of lipase and improved its methanol tolerance. N267 achieved biodiesel yields of 99.33% (colza oil) and 81.70% (waste soybean oil) for 24 h, which was much higher than WT (51.6% for rapeseed oil and 44.73% for wasted soybean oil). The engineered ProRML mutant has high potential for commercial biodiesel production. Title: N-glycosylation as an effective strategy to enhance characteristics of Rhizomucor miehei lipase for biodiesel production Tian M, Wang Z, Fu J, Lv P, Liang C, Li Z, Yang L, Liu T, Li M, Luo W Ref: Enzyme Microb Technol, 160:110072, 2022 : PubMed ESTHER: Tian_2022_Enzyme.Microb.Technol_160_110072 PubMedSearch: Tian 2022 Enzyme.Microb.Technol 160 110072 PubMedID: 35689964 Abstract The construction of methanol-resistant lipases with high catalytic activity is world-shattering for biodiesel production. A semi-rational method has been constructed to enhance the properties of Rhizomucor miehei lipase with propeptide (ProRML) by introducing N-glycosylation sites in the Loop structure. The enzyme activities of the mutants N288 (1448.89 +/- 68.64 U/mg) and N142 (1073.68 +/- 33.87 U/mg) increased to 56.09 and 41.56 times relative to that of wild type ProRML (WT, 25.83 +/- 0.73 U/mg), respectively. After incubation in 50 % methanol for 2.5 h, the residual activities of N314 and N174-1 were 95 % and 85%, which were higher than the WT (27 %). Additionally, the biodiesel yield of all mutants was increased after a one-time addition of methanol for 24 h. Among them, N288 increased the quantity of biodiesel from colza oil from 9.49 % to 88 %, and N314 increased the amount of biodiesel from waste soybean oil from 8.44% to 70%. This study provides an effective method to enhance the properties of lipase and improve its application potential in biodiesel production. Title: Novel Bisamide Alkaloids Enantiomers from Pepper Roots (Piper nigrum L.) with Acetylcholinesterase Inhibitory and Anti-Neuroinflammatory Effects Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M and Song SJ <7 more author(s)> Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M, Wang YX, Xu ZY, Qin SY, Du NN, Yao GD, Lin B, Huang XX, Song SJ (- 7) Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_J.Agric.Food.Chem__ PubMedSearch: Wang 2022 J.Agric.Food.Chem PubMedID: 35184556 36450093 Abstract The roots of Piper nigrum L., a seasoning for cooking various types of broths, are renowned for their high nutritional content and potential medicinal benefits. In this study, nine pairs of novel cyclohexene-type bisamide alkaloids (1a/1b-9a/9b) were isolated from the pepper roots using molecular network analysis strategies. Their structures were determined by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and X-ray diffraction analyses. Using an intermolecular Diels-Alder reaction, a strategy for the synthesis of bisamide alkaloids from different monomeric amide alkaloids was developed. Furthermore, these compounds were chirally separated for the first time, and compounds 3a and 5a/5b showed significant anti-neuroinflammation effects in the models of lipopolysaccharide(LPS)-induced BV2 microglial cells. Meanwhile, compounds 6b and 7a displayed concentration-dependent inhibitory activities against acetylcholinesterase with IC(50) values of 6.05 +/- 1.10 and 3.81 +/- 0.10 microM, respectively. These findings confirmed that these bisamide alkaloids could be applied in functional food formulations and pharmaceutical products as well as facilitate the further development and usage of pepper roots. Title: Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K and Qian Z <1 more author(s)> Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K, Zhu E, Qian Z (- 1) Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem__ PubMedSearch: Wang 2022 Anal.Chem PubMedID: 35315662 Abstract Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca(2+) by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells. Title: Evaluation of Antioxidative and Neuroprotective Activities of Total Flavonoids From Sea Buckthorn (Hippophae rhamnoides L.) Wang Z, Wang W, Zhu C, Gao X, Chu W Ref: Front Nutr, 9:861097, 2022 : PubMed ESTHER: Wang_2022_Front.Nutr_9_861097 PubMedSearch: Wang 2022 Front.Nutr 9 861097 PubMedID: 35799585 Abstract The aim of this study was to investigate the antioxidative and neuroprotective activities of total flavonoids from sea buckthorn (Hippophae rhamnoides L.) (TFH). Results indicated that TFH possessed DPPH radicals, hydroxyl radicals and superoxide anions scavenging activities. The neuroprotective potential was assessed with acetylcholinesterase (AChE) and monoamine oxidase A (MAO-A). The inhibition rates of AChE and MAO-A by 50 microg/ml TFH were 75.85 and 51.22%, respectively. The in vivo antioxidative and neuroprotective potential of TFH were explored in Caenorhabditis elegans. In the longevity assay, TFH (50 microg/ml) significantly increased the lifespan of wild-type C. elegans (29.40%). In the hydrogen peroxide-induced oxidative stress challenge, the antioxidant capacity of TFH-treated wild-type C. elegans was significantly enhanced. The C. elegans mutant strain CL4176 was used to study the neuroprotective effect of TFH in vivo. Results showed that TFH significantly delayed paralysis in C. elegans CL4176. Our study suggested total flavonoids from sea buckthorn (Hippophae rhamnoides L.) had the potential as an antioxidative and neuroprotective agent to extend aging and treat neurodegenerative diseases. Title: Discovery of carbamate-based N-salicyloyl tryptamine derivatives as novel pleiotropic agents for the treatment of Alzheimer's disease Wang Y, Zhang H, Liu D, Li X, Long L, Peng Y, Qi F, Jiang W, Wang Z Ref: Bioorg Chem, 127:105993, 2022 : PubMed ESTHER: Wang_2022_Bioorg.Chem_127_105993 PubMedSearch: Wang 2022 Bioorg.Chem 127 105993 PubMedID: 35834980 Abstract In this work, based on the potential anti-AD molecule previously studied by our group, we continue to introduce different substituents at different positions to improve both drug-like properties and on target activities. 33 N-salicyloyl tryptamine-carbamate hybrids were designed, synthesized and evaluated as cholinesterase inhibitors. H327 was the most potent BChE inhibitor (eqBChE IC(50) = 0.057 +/- 0.005 microM), and showed threefold improved inhibitory potency than the positive drug rivastigmine (eqBChE IC(50) = 0.19 +/- 0.001 microM). In addition, H327 as a pseudo-irreversible BChE inhibitor was endowed with neuroprotective, antioxidative and anti-neuroinflammatory properties. Cytotoxicity and acute toxicity tests confirmed the safety of compound H327. The pharmacokinetics study showed that compound H327 had a longer T(1/2) time and higher bioavailability than the lead compound 1 g. Compound H327 was able to cross the blood-brain barrier (BBB) in vivo. Moreover, the behavioral tests showed that compound H327 could significantly improve scopolamine-induced cognitive impairment in vivo. Overall, these results demonstrated that compound H327 is a promising multi-target agent for the treatment of AD. Title: From Function to Metabolome: Metabolomic Analysis Reveals the Effect of Probiotic Fermentation on the Chemical Compositions and Biological Activities of Perilla frutescens Leaves Wang Z, Jin X, Zhang X, Xie X, Tu Z, He X Ref: Front Nutr, 9:933193, 2022 : PubMed ESTHER: Wang_2022_Front.Nutr_9_933193 PubMedSearch: Wang 2022 Front.Nutr 9 933193 PubMedID: 35898707 Abstract This study aimed to investigate the impact of probiotic fermentation on the active components and functions of Perilla frutescens leaves (PFL). PFL was fermented for 7 days using six probiotics (Lactobacillus Plantarum SWFU D16, Lactobacillus Plantarum ATCC 8014, Lactobacillus Rhamnosus ATCC 53013, Streptococcus Thermophilus CICC 6038, Lactobacillus Casei ATCC 334, and Lactobacillus Bulgaricus CICC 6045). The total phenol and flavonoid contents, antioxidant abilities, as well as alpha-glucosidase and acetylcholinesterase inhibition abilities of PFL during the fermentation process were evaluated, and its bioactive compounds were further quantified by high-performance liquid chromatography (HPLC). Finally, non-targeted ultra-HPLC-tandem mass spectroscopy was used to identify the metabolites affected by fermentation and explore the possible mechanisms of the action of fermentation. The results showed that most of the active component contents and functional activities of PFL exhibited that it first increased and then decreased, and different probiotics had clearly distinguishable effects from each other, of which fermentation with ATCC 53013 for 1 day showed the highest enhancement effect. The same trend was also confirmed by the result of the changes in the contents of 12 phenolic acids and flavonoids by HPLC analysis. Further metabolomic analysis revealed significant metabolite changes under the best fermentation condition, which involved primarily the generation of fatty acids and their conjugates, flavonoids. A total of 574 and 387 metabolites were identified in positive ion and negative ion modes, respectively. Results of Spearman's analysis indicated that some primary metabolites and secondary metabolites such as flavonoids, phenols, and fatty acids might play an important role in the functional activity of PFL. Differential metabolites were subjected to the KEGG database and 97 metabolites pathways were obtained, of which biosyntheses of unsaturated fatty acids, flavonoid, and isoflavonoid were the most enriched pathways. The above results revealed the potential reason for the differences in metabolic and functional levels of PFL after fermentation. This study could provide a scientific basis for the further study of PFL, as well as novel insights into the action mechanism of probiotic fermentation on the chemical composition and biological activity of food/drug. Title: Tannic acid reduced apparent protein digestibility and induced oxidative stress and inflammatory response without altering growth performance and ruminal microbiota diversity of Xiangdong black goats Wang Z, Yin L, Liu L, Lan X, He J, Wan F, Shen W, Tang S, Tan Z, Yang Y Ref: Front Vet Sci, 9:1004841, 2022 : PubMed ESTHER: Wang_2022_Front.Vet.Sci_9_1004841 PubMedSearch: Wang 2022 Front.Vet.Sci 9 1004841 PubMedID: 36187804 Abstract The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH(3)-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1beta, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats. Title: Construction of a Novel Lipase Catalytic System Based on Hybrid Membranes with Interwoven Electrospun Polyacrylic Acid and Polyvinyl Pyrrolidone Gel Fibers Wang Z, Lin S, Zhang Q, Li J, Yin S Ref: Gels, 8:, 2022 : PubMed ESTHER: Wang_2022_Gels_8_ PubMedSearch: Wang 2022 Gels 8 PubMedID: 36547336 Abstract Efficient lipase catalysis requires sufficient oil-water interface engineered through structural design. Inspired by the architectural features of fabrics, a novel lipase-membrane catalytic system with interwoven polyacrylic acid (PAA) gel fibers and polyvinyl pyrrolidone (PVP) gel fibers was developed in this study by using double-needle electrospinning and gelation. It has been demonstrated that PAA/PVP hybrid gel fiber membranes (HGFMs) have a high swelling capacity for both water and oil phases, which created numerous discontinuous oil-water contact surface units in limited space of HGFMs, consequently forming effective interfacial catalytic systems. Volume competition between the water and oil phases suggests that balancing the proportions of these phases is very important for effective construction of oil-water interfaces and conditioning catalysis. Regulation of multiple factors of PAA/PVP HGFMs resulted in a catalytic efficiency of up to 2.1 times that of a macroscopic 'oil-up/water-down' system (room temperature, pH = 7), and 2.9 times when three membranes are superimposed, as well as excellent pH and temperature stability. HGFMs were stacked to build a high-performing catalytic performance reactor. We expect that this study will be a beneficial exploration for expanding the lipase catalytic system. Title: Hydrolysis Mechanism of Carbamate Methomyl by a Novel Esterase PestE: A QM/MM Approach Wang Z, Zhang Q, Wang G, Wang W, Wang Q Ref: Int J Mol Sci, 24:, 2022 : PubMed ESTHER: Wang_2022_Int.J.Mol.Sci_24_ PubMedSearch: Wang 2022 Int.J.Mol.Sci 24 PubMedID: 36613879 Abstract Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: () serine-initiated nucleophilic attack and () C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps and , respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based k(cat) prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases. Title: Biodegradation of polybutylene adipate-co-terephthalate by Priestia megaterium, Pseudomonas mendocina, and Pseudomonas pseudoalcaligenes following incubation in the soil Wei S, Zhao Y, Zhou R, Lin J, Su T, Tong H, Wang Z Ref: Chemosphere, :135700, 2022 : PubMed ESTHER: Wei_2022_Chemosphere__135700 PubMedSearch: Wei 2022 Chemosphere 135700 PubMedID: 35850225 Abstract Soil that contained polybutylene adipate-co-terephthalate (PBAT) was incubated with Priestia megaterium, Pseudomonas mendocina, and Pseudomonas pseudoalcaligenes to improve the biodegradative process of this polymer. The mixture of Pr. megaterium and Ps. mendocina was highly effective at biodegrading the PBAT, and after eight weeks of soil incubation, approximately 84% of the PBAT film weight was lost. Mixtures of the other two species also positively affected the synergistic degradation of PBAT film in the soil, but the mixture of three species had a negative effect. The residual PBAT film microstructure clearly demonstrated the degradation of PBAT, and the degree of degradation was related to the different species. Cleavage of the PBAT film ester bond after soil microbial action affected its properties. The incubation of PBAT in soil that contained these species affected soil dehydrogenase and soil lipase in particular. The secretion of lipase by these species could play an important role in the degradation of PBAT in the soil. Title: From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders Wu J, Zhang H, Wang Y, Yin G, Li Q, Zhuo L, Chen H, Wang Z Ref: Front Pharmacol, 13:1036030, 2022 : PubMed ESTHER: Wu_2022_Front.Pharmacol_13_1036030 PubMedSearch: Wu 2022 Front.Pharmacol 13 1036030 PubMedID: 36518670 Abstract A novel class of benzyl-free and benzyl-substituted carbamylated tryptamine derivatives (CDTs) was designed and synthesized to serve as effective building blocks for the development of novel multi-target directed ligands (MTDLs) for the treatment of neurological disorders linked to cholinesterase (ChE) activity. The majority of them endowed butyrylcholinesterase (BuChE) with more substantial inhibition potency than acetylcholinesterase (AChE), according to the full study of ChE inhibition. Particularly, hybrids with dibenzyl groups (2b-2f, 2j, 2o, and 2q) showed weak or no neuronal toxicity and hepatotoxicity and single-digit nanomolar inhibitory effects against BuChE. Through molecular docking and kinetic analyses, the potential mechanism of action on BuChE was first investigated. In vitro H(2)O(2)-induced HT-22 cells assay demonstrated the favorable neuroprotective potency of 2g, 2h, 2j, 2m, 2o, and 2p. Besides, 2g, 2h, 2j, 2m, 2o, and 2p endowed good antioxidant activities and COX-2 inhibitory effects. This study suggested that this series of hybrids can be applied to treat various ChE-associated neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as promising building blocks for further structure modification to develop efficient MTDLs. Title: Insights into acylation mechanisms: co-expression of serine carboxypeptidase-like acyltransferases and their non-catalytic companion paralogs Yao S, Liu Y, Zhuang J, Zhao Y, Dai X, Jiang C, Wang Z, Jiang X, Zhang S and Xia T <6 more author(s)> Yao S, Liu Y, Zhuang J, Zhao Y, Dai X, Jiang C, Wang Z, Jiang X, Zhang S, Qian Y, Tai Y, Wang Y, Wang H, Xie DY, Gao L, Xia T (- 6) Ref: Plant J, 111:117, 2022 : PubMed ESTHER: Yao_2022_Plant.J_111_117 PubMedSearch: Yao 2022 Plant.J 111 117 PubMedID: 35437852 Gene_locus related to this paper: dioka-dkSCPL1, camsi-SCPL5, camsi-SCPL4 Abstract Serine carboxypeptidase-like acyltransferases (SCPL-ATs) play a vital role in the diversification of plant metabolites. Galloylated flavan-3-ols highly accumulate in tea (Camellia sinensis), grape (Vitis vinifera), and persimmon (Diospyros kaki). To date, the biosynthetic mechanism of these compounds remains unknown. Herein, we report that two SCPL-AT paralogs are involved in galloylation of flavan-3-ols: CsSCPL4, which contains the conserved catalytic triad S-D-H, and CsSCPL5, which has the alternative triad T-D-Y. Integrated data from transgenic plants, recombinant enzymes, and gene mutations showed that CsSCPL4 is a catalytic acyltransferase, while CsSCPL5 is a non-catalytic companion paralog (NCCP). Co-expression of CsSCPL4 and CsSCPL5 is likely responsible for the galloylation. Furthermore, pull-down and co-immunoprecipitation assays showed that CsSCPL4 and CsSCPL5 interact, increasing protein stability and promoting post-translational processing. Moreover, phylogenetic analyses revealed that their homologs co-exist in galloylated flavan-3-ol- or hydrolyzable tannin-rich plant species. Enzymatic assays further revealed the necessity of co-expression of those homologs for acyltransferase activity. Evolution analysis revealed that the mutations of the CsSCPL5 catalytic residues may have taken place about 10 million years ago. These findings show that the co-expression of SCPL-ATs and their NCCPs contributes to the acylation of flavan-3-ols in the plant kingdom. Title: A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis Yin K, Yang J, Wang F, Wang Z, Xiang P, Xie X, Sun J, He X, Zhang X Ref: Front Nutr, 9:1018733, 2022 : PubMed ESTHER: Yin_2022_Front.Nutr_9_1018733 PubMedSearch: Yin 2022 Front.Nutr 9 1018733 PubMedID: 36313078 Abstract This study aimed to preliminary investigate the phytochemistry, bioactivity, hypoglycemic potential, and mechanism of action of Bombax ceiba L. flower (BCF), a wild edible and food plant in China. By using methanol extraction and liquid-liquid extraction, the crude extract (CE) of BCF and its petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and aqueous (AQ) fractions were obtained, and their chemical components and biological activities were evaluated. Further high-performance liquid chromatography (HPLC) analysis was carried out to identify and quantify the active constituents of BFC and its five fractions, and the phytochemical composition of the best-performing fraction was then analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC/Q-TOF-MS). Finally, a network pharmacology strategy based on the chemical profile of this fraction was applied to speculate its main hypoglycemic mechanism. Results revealed the excellent biological activities of BCF, especially the EtOAc fraction. In addition to the highest total flavonoid content (TFC) (367.72 microg RE/mg E) and total phenolics content (TPC) (47.97 microg GAE/mg E), EtOAc showed the strongest DPPH scavenging ability (IC(50) value = 29.56 microg/mL), ABTS (+) scavenging ability (IC(50) value = 84.60 microg/mL), and ferric reducing antioxidant power (FRAP) (889.62 microg FeSO(4)/mg E), which were stronger than the positive control BHT. EtOAc also exhibited the second-best alpha-glucosidase inhibitory capacity and second-best acetylcholinesterase (AChE) inhibitory capacity with the IC(50) values of 2.85 and 3.27 mg/mL, respectively. Also, EtOAc inhibited HepG2, MCF-7, Raw264.7, and A549 cell with IC(50) values of 1.08, 1.62, 0.77, and 0.87 mg/mL, which were the second or third strongest in all fractions. Additionally, HPLC analysis revealed significant differences in the compounds' abundance between different fractions. Among them, EtOAc had the most detected compounds and the highest content. According to the results of UPLC/Q-TOF-MS, 38 compounds were identified in EtOAc, including 24 phenolic acids and 6 flavonoids. Network pharmacological analysis further confirmed 41 potential targets of EtOAc in the treatment of type 2 diabetes, and intracellular receptor signaling pathways, unsaturated fatty acid, and DNA transcription pathways were the most possible mechanisms. These findings suggested that BCF was worthwhile to be developed as an antioxidant and anti-diabetic food/drug. Title: Activated autophagy-lysosomal pathway in dairy cows with hyperketonemia is associated with lipolysis of adipose tissues Yu H, Fan M, Chen X, Jiang X, Loor JJ, Aboragah A, Zhang C, Bai H, Fang Z and Du X <5 more author(s)> Yu H, Fan M, Chen X, Jiang X, Loor JJ, Aboragah A, Zhang C, Bai H, Fang Z, Shen T, Wang Z, Song Y, Li X, Liu G, Du X (- 5) Ref: J Dairy Sci, :, 2022 : PubMed ESTHER: Yu_2022_J.Dairy.Sci__ PubMedSearch: Yu 2022 J.Dairy.Sci PubMedID: 35688731 Abstract Activated autophagy-lysosomal pathway (ALP) can degrade virtually all kinds of cellular components, including intracellular lipid droplets, especially during catabolic conditions. Sustained lipolysis and increased plasma fatty acids concentrations are characteristic of dairy cows with hyperketonemia. However, the status of ALP in adipose tissue during this physiological condition is not well known. The present study aimed to ascertain whether lipolysis is associated with activation of ALP in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes. In vivo, blood and subcutaneous adipose tissue (SAT) biopsies were collected from nonhyperketonemic (nonHYK) cows [blood beta-hydroxybutyrate (BHB) concentration <1.2 mM, n = 10] and hyperketonemic (HYK) cows (blood BHB concentration 1.2-3.0 mM, n = 10) with similar days in milk (range: 3-9) and parity (range: 2-4). In vitro, calf adipocytes isolated from 5 healthy Holstein calves (1 d old, female, 30-40 kg) were differentiated and used for (1) treatment with lipolysis inducer isoproterenol (ISO, 10 microM, 3 h) or mammalian target of rapamycin inhibitor Torin1 (250 nM, 3 h), and (2) pretreatment with or without the ALP inhibitor leupeptin (10 microg/mL, 4 h) followed by ISO (10 microM, 3 h) treatment. Compared with nonHYK cows, serum concentration of free fatty acids was greater and serum glucose concentration, DMI, and milk yield were lower in HYK cows. In SAT of HYK cows, ratio of phosphorylated hormone-sensitive lipase to hormone-sensitive lipase, and protein abundance of adipose triacylglycerol lipase were greater, but protein abundance of perilipin 1 (PLIN1) and cell death-inducing DNA fragmentation factor-alpha-like effector c (CIDEC) was lower. In addition, mRNA abundance of autophagy-related 5 (ATG5), autophagy-related 7 (ATG7), and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), protein abundance of lysosome-associated membrane protein 1, and cathepsin D, and activity of beta-N-acetylglucosaminidase were greater, whereas protein abundance of sequestosome-1 (p62) was lower in SAT of HYK cows. In calf adipocytes, treatment with ISO or Torin1 decreased protein abundance of PLIN1, and CIDEC, and triacylglycerol content in calf adipocytes, but increased glycerol content in the supernatant of calf adipocytes. Moreover, the mRNA abundance of ATG5, ATG7, and MAP1LC3B was upregulated, the protein abundance of lysosome-associated membrane protein 1, cathepsin D, and activity of beta-N-acetylglucosaminidase were increased, whereas the protein abundance of p62 was decreased in calf adipocytes treated with ISO or Torin1 compared with control group. Compared with treatment with ISO alone, the protein abundance of p62, PLIN1, and CIDEC, and triacylglycerol content in calf adipocytes were higher, but the glycerol content in the supernatant of calf adipocytes was lower in ISO and leupeptin co-treated group. Overall, these data indicated that activated ALP is associated with increased lipolysis in adipose tissues of dairy cows with hyperketonemia and in calf adipocytes. Title: Ferulic acid regulates miR-17/PTEN axis to inhibit LPS-induced pulmonary microvascular endothelial cells apoptosis through activation of PI3K/Akt pathway Zhang Q, Wang Z, Zhu J, Peng Z, Tang C Ref: Journal of Toxicological Sciences, 47:61, 2022 : PubMed ESTHER: Zhang_2022_J.Toxicol.Sci_47_61 PubMedSearch: Zhang 2022 J.Toxicol.Sci 47 61 PubMedID: 35110471 Abstract Acute lung injury (ALI) is mainly mediated by the damage of pulmonary microvascular endothelial cells (PMVECs). LPS is one of the pathogenic factors leading to microcirculatory abnormalities of ALI. Ferulic acid (FA) exhibits therapeutic eects against various diseases. During lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress. However, the concrete role and underlying mechanism of FA in ALI have not been well characterized. Ten microg/mL Lipopolysaccharide (LPS) was used to treat rat PMVECs for 24 hr. qRT-PCR was used to detect the level of miR-17 and phosphatase and tensin homolog deleted on chromosome ten (PTEN). Western blot was used to analyze the associated proteins in the PI3K/Akt pathway, and the apoptosis-related proteins. Flow cytometric analysis was performed to detect the apoptosis of PMVECs. MTT assay was constructed to detect the cell viability. Luciferase assay was conducted to detect the target gene of miR-17 and PTEN. A cell model for in vitro studying the role of FA in ALI was established using PMVECs. Our data demonstrate that FA up-regulates miR-17 and declines apoptosis induced by LPS. FA inhibits apoptosis mediated by up-regulating miR-17. Furthermore, we found miR-17 targeted PTEN negatively. FA inhibits cleaved caspase-3 and Bax expression through the PI3K/Akt pathway mediated by up-regulating miR-17. Over-expression of PTEN could contribute to the similar expression trend of the PI3K/Akt signal pathway protein compared to miR-17 inhibitor transfected cells. FA inhibits PMVECs apoptosis induced by LPS via miR-17/PTEN to further regulate the activation of the PI3K/Akt pathway in ALI. We anticipate that our data will provoke additional studies for ALI clinical therapy. Title: Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues Zhang X, Xu W, Xu R, Wang Z, Wang P, Peng K, Li M, Li J, Tan Y and Pei H <1 more author(s)> Zhang X, Xu W, Xu R, Wang Z, Wang P, Peng K, Li M, Li J, Tan Y, Wang X, Pei H (- 1) Ref: Oxid Med Cell Longev, 2022:4594956, 2022 : PubMed ESTHER: Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956 PubMedSearch: Zhang 2022 Oxid.Med.Cell.Longev 2022 4594956 PubMedID: 35401929 Abstract Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection. Title: Carbamate-based N-Substituted tryptamine derivatives as novel pleiotropic molecules for Alzheimer's disease Zhang H, Wang Y, Liu D, Li J, Feng Y, Lu Y, Yin G, Li Z, Shi T, Wang Z Ref: Bioorg Chem, 125:105844, 2022 : PubMed ESTHER: Zhang_2022_Bioorg.Chem_125_105844 PubMedSearch: Zhang 2022 Bioorg.Chem 125 105844 PubMedID: 35594720 Inhibitor(s) related to this paper: 6H6-Heptyl-Carbamate Abstract A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC(50) > 100 microM; eqBChE IC(50) = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease. Title: Biodegradation of polyester polyurethane by the marine fungus Cladosporium halotolerans 6UPA1 Zhang K, Hu J, Yang S, Xu W, Wang Z, Zhuang P, Grossart HP, Luo Z Ref: J Hazard Mater, 437:129406, 2022 : PubMed ESTHER: Zhang_2022_J.Hazard.Mater_437_129406 PubMedSearch: Zhang 2022 J.Hazard.Mater 437 129406 PubMedID: 35753302 Abstract Lack of degradability and the accumulation of polymeric wastes increase the risk for the health of the environment. Recently, recycling of polymeric waste materials becomes increasingly important as raw materials for polymer synthesis are in short supply due to the rise in price and supply chain disruptions. As an important polymer, polyurethane (PU) is widely used in modern life, therefore, PU biodegradation is desirable to avoid its accumulation in the environment. In this study, we isolated a fungal strain Cladosporium halotolerans from the deep sea which can grow in mineral medium with a polyester PU (Impranil DLN) as a sole carbon source. Further, we demonstrate that it can degrade up to 80% of Impranil PU after 3 days of incubation at 28 degC by breaking the carbonyl groups (1732 cm(-1)) and C-N-H bonds (1532 cm(-1) and 1247 cm(-1)) as confirmed by Fourier-transform infrared (FTIR) spectroscopy analysis. Gas chromatography-mass spectrometry (GC-MS) analysis revealed polyols and alkanes as PU degradation intermediates, indicating the hydrolysis of ester and urethane bonds. Esterase and urease activities were detected in 7 days-old cultures with PU as a carbon source. Transcriptome analysis showed a number of extracellular protein genes coding for enzymes such as cutinase, lipase, peroxidase and hydrophobic surface binding proteins A (HsbA) were expressed when cultivated on Impranil PU. The yeast two-hybrid assay revealed that the hydrophobic surface binding protein ChHsbA1 directly interacts with inducible esterases, ChLip1 (lipase) and ChCut1 (cutinase). Further, the KEGG pathway for "fatty acid degradation" was significantly enriched in Impranil PU inducible genes, indicating that the fungus may use the degradation intermediates to generate energy via this pathway. Taken together, our data indicates secretion of both esterase and hydrophobic surface binding proteins by C. halotolerans plays an important role in Impranil PU absorption and subsequent degradation. Our study provides a mechanistic insight into Impranil PU biodegradation by deep sea fungi and provides the basis for future development of biotechnological PU recycling. Title: Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease Zhang H, Wang Y, Li X, Wang S, Wang Z Ref: Eur Journal of Medicinal Chemistry, 240:114606, 2022 : PubMed ESTHER: Zhang_2022_Eur.J.Med.Chem_240_114606 PubMedSearch: Zhang 2022 Eur.J.Med.Chem 240 114606 PubMedID: 35858523 Abstract Alzheimer's disease (AD), as the fourth leading cause of death among the elderly worldwide, has brought enormous challenge to the society. Due to its extremely complex pathogeneses, the development of multi-target directed ligands (MTDLs) becomes the major strategy for combating AD. Carbamate moiety, as an essential building block in the development of MTDLs, exhibits structural similarity to neurotransmitter acetylcholine (ACh) and has piqued extensive attention in discovering multifunctional cholinesterase inhibitors. To date, numerous preclinical studies demonstrate that carbamate-based cholinesterase inhibitors can prominently increase the level of ACh and improve cognition impairments and behavioral deficits, providing a privileged strategy for the treatment of AD. Based on the recent research focus on the novel cholinesterase inhibitors with multiple biofunctions, this review aims at summarizing and discussing the most recent studies excavating the potential carbamate-based MTDLs with cholinesterase inhibition efficacy, to accelerate the pace of pleiotropic cholinesterase inhibitors for coping AD. Title: Recent advance on pleiotropic cholinesterase inhibitors bearing amyloid modulation efficacy Zhang H, Peng Y, Zhuo L, Wang Y, Zeng G, Wang S, Long L, Li X, Wang Z Ref: Eur Journal of Medicinal Chemistry, 242:114695, 2022 : PubMed ESTHER: Zhang_2022_Eur.J.Med.Chem_242_114695 PubMedSearch: Zhang 2022 Eur.J.Med.Chem 242 114695 PubMedID: 36044812 Abstract Due to the hugely important roles of neurotransmitter acetylcholine (ACh) and amyloid-beta (Abeta) in the pathogenesis of Alzheimer's disease (AD), the development of multi-target directed ligands (MTDLs) focused on cholinesterase (ChE) and Abeta becomes one of the most attractive strategies for combating AD. To date, numerous preclinical studies toward multifunctional conjugates bearing ChE inhibition and anti-Abeta aggregation have been reported. Noteworthily, most of the reported multifunctional cholinesterase inhibitors are carbamate-based compounds due to the initial properties of carbamate moiety. However, because their easy hydrolysis in vivo and the instability of the compound-enzyme conjugate, the mechanism of action of these compounds is rare. Thus, non-carbamate compounds are of great need for developing novel cholinesterase inhibitors. Besides, given that Abeta accumulation begins to occur 10-15 years before AD onset, modulating Abeta is ineffective only in inhibiting its aggregation but not eliminate the already accumulated Abeta if treatment is started when the patient has been diagnosed as AD. Considering the limitation of current Abeta accumulation modulators in ameliorating cognitive deficits and ineffectiveness of ChE inhibitors in blocking disease progression, the development of a practically valuable strategy with multiple pharmaceutical properties including ChE inhibition and Abeta modulation for treating AD is indispensable. In this review, we focus on summarizing the scaffold characteristics of reported non-carbamate cholinesterase inhibitors with Abeta modulation since 2020, and understanding the ingenious multifunctional drug design ideas to accelerate the pace of obtaining more efficient anti-AD drugs in the future. Title: Effects of Fatty-Type and Lean-Type on Growth Performance and Lipid Droplet Metabolism in Pekin Ducks Zhuang Z, Yang T, Jia W, Bai M, Bai H, Wang Z, Chen G, Jiang Y, Chang G Ref: Animals (Basel), 12:, 2022 : PubMed ESTHER: Zhuang_2022_Animals.(Basel)_12_ PubMedSearch: Zhuang 2022 Animals.(Basel) 12 PubMedID: 36077988 Abstract The reasons for differences in lipid depositions between fatty-type (F-T) and lean-type (L-T) ducks remain unknown. The present study aimed to compare the growth performance, lipid deposition, and gene expression related to lipid droplet formation in F-T and L-T Pekin ducks. One-day-old, 140 each L-T and F-T male ducks were selected and distributed separately into 20 replicate cages. All ducks were fed commercial diets up to 35 d of age. F-T ducks had a higher average daily gain from 21 to 28 d of age. On 35-day-old, F-T ducks had higher serum levels of high- and low-density lipoprotein cholesterol, cholesterol, albumin, and hydroxybutyrate dehydrogenase activity than L-T ducks. F-T ducks had higher abdominal fat and subcutaneous fat percentages than those in L-T ducks. Liver histological examination showed that L-T ducks contained more lipid droplets in the liver, which gradually decreased with increasing age. The average adipocyte area and diameter of abdominal fat and subcutaneous fat in the F-T and L-T ducks increased with age and were higher in F-T ducks than those in L-T ducks. Furthermore, the gene expression of perilipin 1, perilipin 2, angiopoietin-like protein 4, adipose triglyceride lipase, alpha/beta-hydrolase domain-containing protein 5 (ABHD5), and serine/threonine kinase 17a in the liver, abdominal fat, and subcutaneous fat of F-T ducks was higher than that in L-T ducks, and it increased with age. Compared to L-T ducks, F-T ducks had higher expression of ABHD5 in the abdominal fat and subcutaneous fat and lower expression in the liver. Thus, F-T ducks displayed lower hepatic lipid deposition and a higher percentage of abdominal fat and subcutaneous fat, suggesting that F-T ducks had higher lipid storage capacity due to increased gene expression related to lipid droplets. Title: Yeast cell surface display of bacterial PET hydrolase as a sustainable biocatalyst for the degradation of polyethylene terephthalate Chen Z, Xiao Y, Weber G, Wei R, Wang Z Ref: Methods Enzymol, 648:457, 2021 : PubMed ESTHER: Chen_2021_Methods.Enzymol_648_457 PubMedSearch: Chen 2021 Methods.Enzymol 648 457 PubMedID: 33579416 Gene_locus related to this paper: idesa-peth Abstract Enzymatic hydrolysis of polyethylene terephthalate (PET) is considered to be an environmentally friendly method for the recycling of plastic waste. Recently, a bacterial enzyme named IsPETase was found in Ideonella sakaiensis with the ability to degrade amorphous PET at ambient temperature suggesting its possible use in recycling of PET. However, applying the purified IsPETase in large-scale PET recycling has limitations, i.e., a complicated production process, high cost of single-use, and instability of the enzyme. Yeast cell surface display has proven to be an effectual alternative for improving enzyme degradation efficiency and realizing industrial applications. This chapter deals with the construction and application of a whole-cell biocatalyst by displaying IsPETase on the surface of yeast (Pichia pastoris) cells. Title: Tralopyril affects locomotor activity of zebrafish (Danio rerio) by impairing tail muscle tissue, the nervous system, and energy metabolism Chen X, Zheng J, Teng M, Zhang J, Qian L, Duan M, Cheng Y, Zhao W, Wang Z, Wang C Ref: Chemosphere, 286:131866, 2021 : PubMed ESTHER: Chen_2021_Chemosphere_286_131866 PubMedSearch: Chen 2021 Chemosphere 286 131866 PubMedID: 34391112 Abstract Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism. Title: Ultrasensitive detection of butyrylcholinesterase activity based on self-polymerization modulated fluorescence of sulfur quantum dots Chen M, Zhang J, Chang J, Li H, Zhai Y, Wang Z Ref: Spectrochim Acta A Mol Biomol Spectrosc, 269:120756, 2021 : PubMed ESTHER: Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756 PubMedSearch: Chen 2021 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 269 120756 PubMedID: 34952437 Abstract Butyrylcholinesterase (BChE) is an important clinical diagnosing index for liver dysfunction and organophosphate toxicity. However, the current assays for BChE activity are suffering from the relative poor detection sensitivity. In this work, an ultrasensitive fluorescence assay for BChE activity was developed based on the self-polymerization modulated fluorescence of sulfur quantum dots (S-dots). The luminescence of S-dots can be quenched by the self-polymerized dopamine. The hydrolysate of substrates, thiocholine, under the catalysis of BChE can reduce dopamine, which results in the inhibition of self-polymerization and the fluorescence recovery of S-dots. BChE can be quantitatively detected by recording the recovered fluorescence of S-dots, and a linear relationship is observed between the ratio of fluorescence and the concentration of BChE in the range from 0.01 to 10 U/L. A limit of detection as low as 0.0069 U/L calculated, which is the lowest number so far. The assay also shows excellent selectivity towards various interference species and acetylcholinesterase. These features allowed the direct detection of BChE activity in human serum, demonstrating the great practical applications of our assay. Title: Behaviors and biochemical responses of macroinvertebrate Corbicula fluminea to polystyrene microplastics Fu L, Xi M, Nicholaus R, Wang Z, Wang X, Kong F, Yu Z Ref: Sci Total Environ, 813:152617, 2021 : PubMed ESTHER: Fu_2021_Sci.Total.Environ_813_152617 PubMedSearch: Fu 2021 Sci.Total.Environ 813 152617 PubMedID: 34963588 Abstract Microplastic, a well-documented emerging contaminant, is widespread in aquatic environments resulting from the production and fragmentation of large plastics items. The knowledge about the chronic toxic effects and behavioral toxicity of microplastics, particularly on freshwater benthic macroinvertebrates, is limited. In this study, adult Asian clams (Corbicula fluminea) were exposed to gradient microplastic solutions for 42 days to evaluate behavioral toxicity and chronic biotoxicity. The results showed that microplastics caused behavior toxicity, oxidative stress, and tissue damage in high-concentration treatments. Siphoning, breathing, and excretion was significantly inhibited (p < 0.05) at high-concentration treatments, suggesting that high-concentration microplastics induced behavioral toxicity in C. fluminea. Malondialdehyde content, superoxide dismutase, catalase, and glutathione reductase activities were significantly enhanced (p < 0.05) and the acetylcholinesterase was significantly inhibited (p < 0.05) throughout the exposure period in high-concentration treatments. Enzymes associated with energy supply were significantly higher at high-concentration microplastics treatments on D7 and D21. However, they recovered to a normal level on D42. The instability of the enzymes indicated that high-concentration microplastics induced oxidative stress and disorder in neurotransmission and energy supply. The gills of C. fluminea in treatments underwent cilia degeneration, which indicated that microplastics caused tissue damage in the gills. The analysis of integrated biomarker response values revealed that high-concentration microplastics led to long-term effects on the health of C. fluminea. In conclusion, continuous exposure to microplastics (10 mg L(-1)) would damage physical behavior and the antioxidant system of C. fluminea. Title: Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-alpha synthetsis and antagonizing tumour necrosis factor-alpha-related effects Issotina Zibrila A, Wang Z, Ali MA, Osei JA, Sun Y, Zafar S, Liu K, Li C, Kang Y, Liu J Ref: J Hypertens, :, 2021 : PubMed ESTHER: Issotina_2021_J.Hypertens__ PubMedSearch: Issotina 2021 J.Hypertens PubMedID: 34232157 Abstract OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-alpha was evaluated in normal and preeclampsia pregnant women. PYR (20mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-alpha (150ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-alpha-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-alpha expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-alpha-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-alpha decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-alpha but also by acting against TNF-alpha-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management. Title: Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia Issotina Zibrila A, Li Y, Wang Z, Zhao G, Liu H, Leng J, Ahasan Ali M, Ampofo Osei J, Kang YM, Liu J Ref: Int Immunopharmacol, :108365, 2021 : PubMed ESTHER: Issotina_2021_Int.Immunopharmacol__108365 PubMedSearch: Issotina 2021 Int.Immunopharmacol 108365 PubMedID: 34815190 Abstract Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator's signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-alpha (TNF-alpha, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-alpha, interleukin-1beta (IL-1beta), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-alpha mediated central effect was evaluated in TNF-alpha-infused pregnant rats. TNF-alpha infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-alpha-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE. Title: The impact of ABCB1 and CES1 polymorphisms on dabigatran pharmacokinetics and pharmacodynamics in patients with atrial fibrillation Ji Q, Zhang C, Xu Q, Wang Z, Li X, Lv Q Ref: British Journal of Clinical Pharmacology, 87:2247, 2021 : PubMed ESTHER: Ji_2021_Br.J.Clin.Pharmacol_87_2247 PubMedSearch: Ji 2021 Br.J.Clin.Pharmacol 87 2247 PubMedID: 33179295 Abstract AIMS: Our study aimed to determine the impact of genetic polymorphisms of ABCB1 and CES1 on the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We conducted a prospective study and enrolled NVAF patients treated with dabigatran. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration (PDC) and coagulation parameters including activated partial thromboplastin time (APTT) and thrombin time. Patients' demographics and clinical outcomes from scheduled follow-up visits were all recorded. Statistical analysis was performed to identify the impact of genetic polymorphisms on the PK/PD and bleeding risk of dabigatran. RESULTS: A total of 198 patients were included in analysis. For the ABCB1 polymorphisms rs4148738 and rs1045642, no significant association was found with dabigatran PK/PD. For the CES1 polymorphism rs8192935, the minor allele(C) was associated with increased trough PDCs (ANOVA: P < .001; CC vs. TT genotype, P < .001; CT vs. TT genotype, P = .014) and with APTT values at trough level (P = .015). For the CES1 polymorphism rs2244613, the minor allele(A) carriers had higher levels of trough PDC than noncarriers (ANOVA: P < .001; AA vs. CC genotype, P < .001; CA vs. CC genotype, P = .004) and increased risk for minor bleeding (P = .034; odds ratio = 2.71, 95% confidence interval 1.05-7.00). CONCLUSION: Our study indicated that the minor allele(C) on the CES1 SNP rs8192935 was associated with PDCs and APTT values at trough level. The minor allele(A) on the CES1 SNP rs2244613 was associated with increased trough PDCs and higher risk for minor bleeding in NVAF patients treated with dabigatran. Title: Phytochemical Composition, Antioxidant Activity, and Enzyme Inhibitory Activities (alpha-Glucosidase, Xanthine Oxidase, and Acetylcholinesterase) of Musella lasiocarpa Li R, Ru Y, Wang Z, He X, Kong KW, Zheng T, Zhang X Ref: Molecules, 26:, 2021 : PubMed ESTHER: Li_2021_Molecules_26_ PubMedSearch: Li 2021 Molecules 26 PubMedID: 34361630 Abstract In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their alpha-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH. scavenging ability, ABTS.(+) scavenging ability, and alpha-glucosidase inhibitory activity with the IC(50) values of 22.17, 12.10, and 125.66 microg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO(4)/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC(50) = 10.11 microg/mL), and the best xanthine oxidase inhibitory ability (IC(50) = 5.23 microg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 microg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications. Title: A novel lipase from Aspergillus oryzae WZ007 catalyzed synthesis of brivaracetam intermediate and its enzymatic characterization Li Q, Zhang M, Li X, Zhang Y, Wang Z, Zheng J Ref: Chirality, 33:62, 2021 : PubMed ESTHER: Li_2021_Chirality_33_62 PubMedSearch: Li 2021 Chirality 33 62 PubMedID: 33274501 Abstract Brivaracetam is a structural derivative of the chiral drug levetiracetam and has been approved for the adjuvant treatment of partial epilepsy. As a new antiepileptic drug, it is widely used in a variety of epilepsy models. In this study, a novel lipase M16 derived from Aspergillus oryzae WZ007 was cloned, expressed, and used for chiral resolution. Lipase M16 has a high enantioselectivity to the racemic substrate (R,S)-methyl 2-propylsuccinate 4-tert-butyl ester, and the intermediate (R)-2-propylsuccinic acid 4-tert-butyl ester of brivaracetam was obtained efficiently. Under optimal conditions, the enantiomeric excess of substrate was up to 99.26%, and the e.e.(p) was 96.23%. The conversion and apparent E value were 50.63% and 342.48, respectively. This study suggests a new biocatalytic resolution via lipase M16 for preparing the brivaracetam chiral intermediate and its potential application in the pharmaceutical industry. Title: Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer's Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit Li L, Li J, Dai Y, Yang M, Liang S, Wang Z, Liu W, Chen L, Tao J Ref: Front Aging Neurosci, 13:770948, 2021 : PubMed ESTHER: Li_2021_Front.Aging.Neurosci_13_770948 PubMedSearch: Li 2021 Front.Aging.Neurosci 13 770948 PubMedID: 35185516 Abstract OBJECTIVES: To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 x FAD) mice. METHODS: Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions. (1)H-MRS, Nissl staining, immunohistochemistry, and immunofluorescence were performed to examine the cholinergic system alteration. Thioflavin S staining and 6E10 immunofluorescence were performed to detect the amyloid-beta (Abeta). Furthermore, hM4Di designer receptors exclusively activated by designer drugs (DREADDs) virus and long-term clozapine-N-oxide injection were used to inhibit the medial septal and vertical limb of the diagonal band and dentate gyrus (MS/VDB-DG) cholinergic neural circuit. Cognitive-behavioral tests and immunofluorescence were performed to investigate the cholinergic neural circuit mechanism of EA treatment improving cognition in 5 x FAD mice. RESULTS: Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 x FAD mice. Abeta deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG). CONCLUSION: Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 x FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment. Title: Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease Liu D, Zhang H, Wang Y, Liu W, Yin G, Wang D, Li J, Shi T, Wang Z Ref: Eur Journal of Medicinal Chemistry, 229:114044, 2021 : PubMed ESTHER: Liu_2021_Eur.J.Med.Chem_229_114044 PubMedSearch: Liu 2021 Eur.J.Med.Chem 229 114044 PubMedID: 34923430 Abstract In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-alpha, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Abeta(1-42). Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD. Title: Molecular response uncovers neurotoxicity of Pardosa pseudoannulata exposed to cadmium pressure Lv B, Wang J, He Y, Zeng Z, Tang YE, Li N, Chen LJ, Wang Z, Song QS Ref: Environ Pollut, 280:117000, 2021 : PubMed ESTHER: Lv_2021_Environ.Pollut_280_117000 PubMedSearch: Lv 2021 Environ.Pollut 280 117000 PubMedID: 33784568 Abstract Cadmium (Cd) is a widely distributed heavy metal in south of China. Growing evidence indicates that systemic exposure to Cd, particularly the long-term exposure, may cause neurotoxic effects. Nevertheless, mechanisms underlying Cd neurotoxicity remain not completely understood. In this report, we investigated the neural alterations in the spider Pardosa pseudoannulata (Bosenberg and Strand, 1906) exposed to long-term Cd (LCd) and short-term Cd (SCd) pressure. Cd stress lowered foraging ability and prey consuming time in the spiders. In addition, enzymatic analysis results indicated that Cd exposure reduced the level of acetylcholinesterase at subcellular level. We then identified differentially expressed genes (DEGs) in the Cd exposed spiders using pairwise comparisons and found that a large number of DEGs were related to neurotransmitter receptors and ion transport and binding proteins. Notably, LCd exposure harbored more altered genes in ion transporter activity comparing with SCd exposure. From six K-means clusters, 53 putative transcriptional factors (TFs) belonging to 21 families were characterized, and ZBTB subfamily displayed the most distinctive alterations in the characterized genes, which is assumed to play a key role in the regulation of ion transmembrane process under Cd stress. A protein-to-protein interaction network constructed by the yielded DEGs also showed that ion and receptor binding activities were affected under long-term Cd exposure. Four key modules from the network indicated that Cd may further down-regulate energy metabolism pathway in spiders. Collectively, this comprehensive analysis provides multi-dimensional insights to understand the molecular response of spiders to Cd exposure. Title: Ratiometric sensing of butyrylcholinesterase activity based on the MnO(2) nanosheet-modulated fluorescence of sulfur quantum dots and o-phenylenediamine Ma Z, Li P, Jiao M, Shi YE, Zhai Y, Wang Z Ref: Mikrochim Acta, 188:294, 2021 : PubMed ESTHER: Ma_2021_Mikrochim.Acta_188_294 PubMedSearch: Ma 2021 Mikrochim.Acta 188 294 PubMedID: 34363549 Abstract Butyrylcholinesterase (BChE) can modulate the expression level of cholinesterase, which emerges as an important clinical diagnose index. However, the currently reported assays for BChE are suffering from the problem of interferences. A ratiometric fluorescence assay was developed based on the MnO(2) nanosheet (NS)-modulated fluorescence of sulfur quantum dots (S-dots) and o-phenylenediamine (OPD). MnO(2) NS can not only quench the fluorescence of blue emissive S-dots, but also enhance the yellow emissive OPD by catalyzing its oxidation reactions. Upon introducing BChE and substrate into the system, their hydrolysate can reduce MnO(2) into Mn(2+), leading to the fluorescence recovery of S-dots and failure of OPD oxidation. BChE activity can be quantitatively detected by recording the change of fluorescence signals in the blue and yellow regions. A linear relationship is observed between the ratio of F(435)/F(560) and the concentration of BChE in the range 30 to 500 U/L, and a limit of detection of 17.8 U/L has been calculated. The ratiometric fluorescence assay shows an excellent selectivity to acetylcholinesterase and tolerance to various other species. The method developed provides good detection performances in human serum medium and for screening of inhibitors. Title: Point-of-care testing of butyrylcholinesterase activity through modulating the photothermal effect of cuprous oxide nanoparticles Ma J, Ma L, Cao L, Miao Y, Dong J, Shi YE, Wang Z Ref: Mikrochim Acta, 188:392, 2021 : PubMed ESTHER: Ma_2021_Mikrochim.Acta_188_392 PubMedSearch: Ma 2021 Mikrochim.Acta 188 392 PubMedID: 34697648 Abstract Butyrylcholinesterase (BChE) is an important indicator for clinical diagnosis of liver dysfunction, organophosphate toxicity, and poststroke dementia. Point-of-care testing (POCT) of BChE activity is still a challenge, which is a critical requirement for the modern clinical diagnose. A portable photothermal BChE assay is proposed through modulating the photothermal effects of Cu(2)O nanoparticles. BChE can catalyze the decomposition of butyrylcholine, producing thiocholine, which further reduce and coordinate with CuO on surface of Cu(2)O nanoparticle. This leads to higher efficiency of formation of Cu(9)S(8) nanoparticles, through the reaction between Cu(2)O nanoparticle and NaHS, together with the promotion of photothermal conversion efficiency from 3.1 to 59.0%, under the excitation of 1064 nm laser radiation. An excellent linear relationship between the temperature change and the logarithm of BChE concentration is obtained in the range 1.0 to 7.5 U/mL, with a limit of detection of 0.076 U/mL. In addition, the portable photothermal assay shows strong detection robustness, which endows the accurate detection of BChE in human serum, together with the screening and quantification of organophosphorus pesticides. Such a simple, sensitive, and robust assay shows great potential for the applications to clinical BChE detection and brings a new horizon for the development of temperature based POCT. Title: Biodegradation of erythromycin by Delftia lacustris RJJ-61 and characterization of its erythromycin esterase Ren J, Wang Z, Deng L, Niu D, Fan B, Huhe T, Li Z, Zhang J, Li C Ref: J Basic Microbiol, 61:55, 2021 : PubMed ESTHER: Ren_2021_J.Basic.Microbiol_61_55 PubMedSearch: Ren 2021 J.Basic.Microbiol 61 55 PubMedID: 33332633 Abstract The residual erythromycin in fermentation waste can pollute the environment and threaten human health. However, there are no effective approaches to remedy this issue. In this study, an erythromycin-degrading bacterium named RJJ-61 was isolated and identified as a strain of Delftia lacustris based on morphological and phylogenetic analyses. The degradation ability of this strain was also evaluated; it could degrade 45.18% of erythromycin at 35 degreesC in 120h. Furthermore, the key degradation gene ereA was cloned from strain RJJ-61 and expressed in Escherichia coli BL21; the molecular weight of the expressed protein was ~45kDa. The enzyme activity of EreA was 108.0mUml(-1) at 35 degreesC and pH 7.0. Finally, the EreA protein was used to degrade erythromycin from mycelial dregs and 50% diluted solution, and the removal rates in them were 41.42% and 69.78%, respectively. In summary, D. lacustris RJJ-61 is a novel erythromycin-degrading strain that has great potential to remove erythromycin pollutants from the environment. Title: [Propeptide-mediated protein folding: mechanism and its impact on lipase] Tian M, Zhang J, Luo W, Wang Z, Fu J, Huang S, Lu P Ref: Sheng Wu Gong Cheng Xue Bao, 37:88, 2021 : PubMed ESTHER: Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88 PubMedSearch: Tian 2021 Sheng.Wu.Gong.Cheng.Xue.Bao 37 88 PubMedID: 33501792 Abstract The formation of most proteins consists of two steps: the synthesis of precursor proteins and the synthesis of functional proteins. In these processes, propeptides play important roles in assisting protein folding or inhibiting its activity. As an important polypeptide chain coded by a gene sequence in lipase gene, propeptide usually functions as an intramolecular chaperone, assisting enzyme molecule folding. Meanwhile, some specific sites on propeptide such as glycosylated sites, have important effect on the activity, stability in extreme environment, methanol resistance and the substrate specificity of the lipase. Studying the mechanism of propeptide-mediated protein folding, as well as the influence of propeptide on lipases, will allow to regulate lipase by alternating the propeptide folding behavior and in turn pave new ways for protein engineering research. Title: Enhanced activity of Rhizomucor miehei lipase by directed saturation mutation of the propeptide Tian M, Huang S, Wang Z, Fu J, Lv P, Miao C, Liu T, Yang L, Luo W Ref: Enzyme Microb Technol, 150:109870, 2021 : PubMed ESTHER: Tian_2021_Enzyme.Microb.Technol_150_109870 PubMedSearch: Tian 2021 Enzyme.Microb.Technol 150 109870 PubMedID: 34489029 Abstract The propeptide is a short sequence that facilitates protein folding. In this study, four highly active Rhizomucor miehei lipase (RML) mutants were obtained through saturation mutagenesis at three propeptide positions: Ser8, Pro35, and Pro47. The enzyme activities of mutants P35 N, P47 G, P47 N, and S8E/P35S/P47A observed at 40 degreesC, and pH 8.0 were 10.19, 7.53, 6.15, and 8.24 times of that wild-type RML, respectively. The S8E/P35S/P47A mutant showed good thermostability. After incubation at 40 degreesC for 1 h, 98.98 % of its initial activity remained, whereas wild-type RML retained only 78.76 %. This result indicated that the enhancement of hydrophilicity of 35- and 47- amino-acid residues could promote the interaction between the propeptide and the mature peptide and the enzyme activity and expression level. Highly conserved sites had a more significant impact on enzyme performance than did other sites, similar to the Pro35 and Pro47 mutants showed in this study. This study provides a new idea for protein modification: enzyme performance can be improved through propeptide regulation. Title: Improved methanol tolerance of Rhizomucor miehei lipase based on Nglycosylation within the alpha-helix region and its application in biodiesel production Tian M, Yang L, Wang Z, Lv P, Fu J, Miao C, Li M, Liu T, Luo W Ref: Biotechnol Biofuels, 14:237, 2021 : PubMed ESTHER: Tian_2021_Biotechnol.Biofuels_14_237 PubMedSearch: Tian 2021 Biotechnol.Biofuels 14 237 PubMedID: 34911574 Abstract BACKGROUND: Liquid lipases are widely used to convert oil into biodiesel. Methanol-resistant lipases with high catalytic activity are the first choice for practical production. Rhizomucor miehei lipase (RML) is a single-chain alpha/beta-type protein that is widely used in biodiesel preparation. Improving the catalytic activity and methanol tolerance of RML is necessary to realise the industrial production of biodiesel. RESULTS: In this study, a semi-rational design method was used to optimise the catalytic activity and methanol tolerance of ProRML. After N-glycosylation modification of the alpha-helix of the mature peptide in ProRML, the resulting mutants N218, N93, N115, N260, and N183 increased enzyme activity by 66.81, 13.54, 10.33, 3.69, and 2.39 times than that of WT, respectively. The residual activities of N218 and N260 were 88.78% and 86.08% after incubation in 50% methanol for 2.5 h, respectively. In addition, the biodiesel yield of all mutants was improved when methanol was added once and reacted for 24 h with colza oil as the raw material. N260 and N218 increased the biodiesel yield from 9.49% to 88.75% and 90.46%, respectively. CONCLUSIONS: These results indicate that optimising N-glycosylation modification in the alpha-helix structure is an effective strategy for improving the performance of ProRML. This study provides an effective approach to improve the design of the enzyme and the properties of lipase mutants, thereby rendering them suitable for industrial biomass conversion. Title: Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (alpha-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities Wang Z, Tu Z, Xie X, Cui H, Kong KW, Zhang L Ref: Foods, 10:, 2021 : PubMed ESTHER: Wang_2021_Foods_10_ PubMedSearch: Wang 2021 Foods 10 PubMedID: 33546380 Abstract This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid-liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 microg GAE/mg DE) and flavonoid content (455.22 microg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful alpha-glucosidase inhibitory ability with the IC(50) value of 190.03 microg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC(50) values of 37.92 and 13.43 microg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent. Title: The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model Wang Z, Chen Y, Xiao H, Li S, Zhang T, Hu J, Lu H, Xie H Ref: Am J Sports Med, :363546520988680, 2021 : PubMed ESTHER: Wang_2021_Am.J.Sports.Med__363546520988680 PubMedSearch: Wang 2021 Am.J.Sports.Med 363546520988680 PubMedID: 33592162 Abstract BACKGROUND: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. HYPOTHESIS: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10(-5) M ACh group (received FG containing 10(-5) M ACh), 10(-6) M ACh group (received FG containing 10(-6) M ACh), and PYR group (received FG containing 25 microg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. RESULTS: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10(-5) M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks (P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. CONCLUSION: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. CLINICAL RELEVANCE: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing. Title: Responses of Asian clams (Corbicula fluminea) to low concentration cadmium stress: Whether the depuration phase restores physiological characteristics Wang Z, Kong F, Fu L, Li Y, Li M, Yu Z Ref: Environ Pollut, 284:117182, 2021 : PubMed ESTHER: Wang_2021_Environ.Pollut_284_117182 PubMedSearch: Wang 2021 Environ.Pollut 284 117182 PubMedID: 33901982 Abstract The effect of low concentration Cd stress on bivalves is unclear. In this study, Asian clams (Corbicula fluminea) were continuously exposed to 0, 0.05, 0.10, and 0.20 mg/L Cd for 14 d (exposure phase) and to artificial freshwater for 7 d (depuration phase). A total of 16 variables were measured to explore the toxic effects on C. fluminea. All physiological characteristics were significantly inhibited in the treatments (p < 0.05), and the negative effects of Cd did not return to normal levels in the short term. Tissue damage was found in the feet and gills of C. fluminea in all the treatments. On the 7th day (D7), enzyme activity in all the treatments was significantly higher (p < 0.05) than in the control group. Acetylcholinesterase, superoxide dismutase, and catalase activities were enhanced on D14 in all the treatments. However, only glutathione S-transferase activity was significantly higher in all the treatments (p < 0.05) than in the control group on D21. The instability of the enzymes indicated that the adaptability of C. fluminea became stronger throughout the experiment. In each group, the maximum bioaccumulation of Cd followed the order: 0.20 mg/L > 0.05 mg/L > 0.10 mg/L, which might be caused by the filtration capacity of C. fluminea in the 0.05-mg/L group, which was higher than that of the 0.10-mg/L group. Thus, low Cd concentrations effect the physiological characteristics, tissue health, and antioxidant system of C. fluminea and may require a long recovery time to be restored to normal levels. Title: An Evolving Technology That Integrates Classical Methods with Continuous Technological Developments: Thin-Layer Chromatography Bioautography Wang M, Zhang Y, Wang R, Wang Z, Yang B, Kuang H Ref: Molecules, 26:, 2021 : PubMed ESTHER: Wang_2021_Molecules_26_ PubMedSearch: Wang 2021 Molecules 26 PubMedID: 34361800 Abstract Thin-layer chromatography (TLC) bioautography is an evolving technology that integrates the separation and analysis technology of TLC with biological activity detection technology, which has shown a steep rise in popularity over the past few decades. It connects TLC with convenient, economic and intuitive features and bioautography with high levels of sensitivity and specificity. In this study, we discuss the research progress of TLC bioautography and then establish a definite timeline to introduce it. This review summarizes known TLC bioautography types and practical applications for determining antibacterial, antifungal, antitumor and antioxidant compounds and for inhibiting glucosidase, pancreatic lipase, tyrosinase and cholinesterase activity constitutes. Nowadays, especially during the COVID-19 pandemic, it is important to identify original, natural products with anti-COVID potential compounds from Chinese traditional medicine and natural medicinal plants. We also give an account of detection techniques, including in situ and ex situ techniques; even in situ ion sources represent a major reform. Considering the current technical innovations, we propose that the technology will make more progress in TLC plates with higher separation and detection technology with a more portable and extensive scope of application. We believe this technology will be diffusely applied in medicine, biology, agriculture, animal husbandry, garden forestry, environmental management and other fields in the future. Title: Transesterification of Indazole-3-Carboxamide Synthetic Cannabinoids: Identification of Metabolite Biomarker for Diagnosing Co-Abuse of 5F-MDMB-PINACA and Alcohol Wang Z, Fong CY, Goh EML, Moy HY, Chan ECY Ref: J Anal Toxicol, :, 2021 : PubMed ESTHER: Wang_2021_J.Anal.Toxicol__ PubMedSearch: Wang 2021 J.Anal.Toxicol PubMedID: 34918103 Abstract Concurrent use of alcohol with synthetic cannabinoids (SCs) has been widely recorded among drug abusers. The susceptibilities of three indazole-3-carboxamide type SCs with methyl ester moiety, 5F-MDMB-PINACA, 5F-MMB-PINACA and MMB-FUBINACA, to transesterification in the presence of ethanol warranted further investigation in view of probable augmented toxicity. In vitro metabolite identification experiments were firstly performed using human liver microsomes (HLM) to characterize the novel metabolites of the three parent SCs in the presence of ethanol. Formation of transesterified metabolite, hydrolyzed metabolite and several oxidative metabolites in HLM in the presence of alcohol were further determined for each parent SC and the respective ethyl ester analogue, 5F-EDMB-PINACA, 5F-EMB-PINACA and EMB-FUBINACA, to quantitatively elucidate transesterification and hydrolysis activities. Our results suggested that all three SCs undergo carboxylesterase-mediated transesterification to their respective ethyl ester analogue in the presence of ethanol, which was incubation time- and ethanol concentration-dependent. Each ethyl ester metabolite was sequentially and readily metabolized to novel oxidative metabolites with the intact ethyl ester moiety and the same hydrolyzed metabolite as derived from its parent SC. A smaller extent of transesterification was non-enzymatically driven. Notably, we proposed 5F-EDMB-PINACA oxidative defluorination metabolite as the biomarker for diagnosing the potential co-abuse of 5F-MDMB-PINACA and alcohol. Due to the comparable pharmacological activities between each SC and its ethyl ester metabolite, augmented toxicity associated with co-abuse of SCs and alcohol is probable and deserves further investigation. Title: Rapid screening for natural lipase inhibitors from Alisma orientale combining high-performance thin-layer chromatography-bioautography with mass spectrometry Yang F, Gu L, Han Z, Wang Z Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 1170:122599, 2021 : PubMed ESTHER: Yang_2021_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1170_122599 PubMedSearch: Yang 2021 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 1170 122599 PubMedID: 33713950 Abstract Lipase inhibitors are an attractive class of hypolipidemic compounds, which inhibit the activity of human pancreatic lipase, thereby preventing the absorption of triglycerides in vivo. As a library of promising lead compounds for drug development, traditional Chinese medicine (TCM) has gained growing attention in quick discovery and identification of enzyme inhibitors of natural-origin. The purpose of this work was to discover unknown lipase inhibitors from Alisma orientale by the activity oriented analysis method thin-layer chromatography-bioautography, then use electrospray ionization mass spectrometry technology via the elution based TLC-MS interface to identify their structures. As a result, eleven natural lipase inhibitors from Alisma orientale extracts were identified based on molecular mass and fragment ions obtained by HPTLC-MS, and further confirmed by a series of complementary means including UV spectra, (1)H NMR characteristic proton signals and polarity of compounds, eleven lipase inhibitors were tentatively assigned as triterpenoids: alisol B (m/z 495.50 [M + Na](+)), alisol B 23-acetate (m/z 537.58 [M + Na](+)), 11-deoxy-alisol B (m/z 479.50 [M + Na](+)), 11-deoxy-alisol B 23-acetate (m/z 521.50 [M + Na](+)), alisol A/epialisol A (m/z 513.50 [M + Na](+)), 16-oxo-11-deoxy-alisol A (m/z 511.50 [M + Na](+)), 16-oxo-alisol A (527.50 [M + Na] (+)), alisol C (m/z 509.58 [M + Na](+)), alisol C 23-acetate (m/z 551.50 [M + Na](+)), alisol M 23-acetate (m/z 567.50 [M + Na](+)), and alismanol Q/neoalisol (m/z 493.42 [M + Na](+)). The integrated approach is an efficient method for rapid screening lipase inhibitors from complex plant extracts and provides a reasonable and favorable basis for the identification and separation of other enzymatic system and other important compounds with therapeutic values. Title: Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL-6/STAT3 pathway Yang X, Zhu Y, Shi Q, Zhao X, Huang Y, Yao F, Zhang Y, Wang Z Ref: J Obstet Gynaecol Res, :, 2021 : PubMed ESTHER: Yang_2021_J.Obstet.Gynaecol.Res__ PubMedSearch: Yang 2021 J.Obstet.Gynaecol.Res PubMedID: 33969570 Abstract AIM: To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC). METHODS: DPPIV expression in EC cells was detected by flow cytometry, reverse transcription-polymerase chain reaction analysis and Western blot. Interleukin-6 (IL-6) expression in the supernatant was measured by enzyme-linked immunosorbent assay. The protein levels of signal transducers and activators of transcription-3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit-8 assay was used to determine the half-maximal inhibitory concentration of sitagliptin. RESULTS: Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL-6/STAT3 signaling pathway, and that IL-6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001). CONCLUSION: DPPIV enhances the properties that allow tumorigenesis in EC via IL-6 and STAT3 signaling. Title: Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis Yi J, Wang S, Wang Z, Wang X, Li G, Zhang X, Pan Y, Zhao S, Zhang J and Xi J <2 more author(s)> Yi J, Wang S, Wang Z, Wang X, Li G, Zhang X, Pan Y, Zhao S, Zhang J, Zhou JJ, Wang J, Xi J (- 2) Ref: Front Physiol, 12:674023, 2021 : PubMed ESTHER: Yi_2021_Front.Physiol_12_674023 PubMedSearch: Yi 2021 Front.Physiol 12 674023 PubMedID: 34566671 Abstract Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela. Title: 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: Congenital myasthenic syndrome in China: genetic and myopathological characterization Zhao Y, Li Y, Bian Y, Yao S, Liu P, Yu M, Zhang W, Wang Z, Yuan Y Ref: Ann Clin Transl Neurol, :, 2021 : PubMed ESTHER: Zhao_2021_Ann.Clin.Transl.Neurol__ PubMedSearch: Zhao 2021 Ann.Clin.Transl.Neurol PubMedID: 33756069 Abstract OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. RESULTS: Thirty-five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb-girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha-dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long-term use in patients with COLQ or AGRN mutations. INTERPRETATION: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb-girdle myasthenic syndrome, tubular aggregates, and decreased alpha-dystroglycan were indicative of the specific subtypes. Based on the follow-up findings, we suggest cautious evaluation of the long-term efficacy of therapeutic agents in congenital myasthenic syndrome. Title: Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure Zhou W, Li X, Wang Y, Wang J, Zhang J, Wei H, Peng C, Wang Z, Li G, Li D Ref: J Hazard Mater, 416:126142, 2021 : PubMed ESTHER: Zhou_2021_J.Hazard.Mater_416_126142 PubMedSearch: Zhou 2021 J.Hazard.Mater 416 126142 PubMedID: 34492931 Abstract 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure. Title: Efficient biodegradation of highly crystallized polyethylene terephthalate through cell surface display of bacterial PETase Chen Z, Wang Y, Cheng Y, Wang X, Tong S, Yang H, Wang Z Ref: Sci Total Environ, 709:136138, 2020 : PubMed ESTHER: Chen_2020_Sci.Total.Environ_709_136138 PubMedSearch: Chen 2020 Sci.Total.Environ 709 136138 PubMedID: 31887523 Abstract Polyethylene terephthalate (PET) is one of the most widely used plastics in the world. Accumulation of the discarded PET in the environment is creating a global environmental problem. Recently, a bacterial enzyme named PETase was found to have the novel ability to degrade the highly crystallized PET. However, the enzymatic activity of native PETase is still low limiting its possible use in recycling of PET. In this study, we developed a whole-cell biocatalyst by displaying PETase on the surface of yeast (Pichia pastoris) cell to improve its degradation efficiency. Our data shows that PETase could be functionally displayed on the yeast cell with enhanced pH and thermal stability. The turnover rate of the PETase-displaying yeast whole-cell biocatalyst towards highly crystallized PET dramatically increased about 36-fold compared with that of purified PETase. Furthermore, the whole-cell biocatalyst showed stable turnover rate after seven repeated use and under some chemical/solvent conditions, and its ability to degrade different commercial highly crystallized PET bottles. Our results reveal that PETase-displaying whole-cell biocatalyst affords a promising route for efficient biological recycling of PET. Title: Rv3091, An Extracellular Patatin-Like Phospholipase in Mycobacterium tuberculosis, Prolongs Intracellular Survival of Recombinant Mycolicibacterium smegmatis by Mediating Phagosomal Escape Cui Z, Dang G, Song N, Cui Y, Li Z, Zang X, Liu H, Wang Z, Liu S Ref: Front Microbiol, 11:2204, 2020 : PubMed ESTHER: Cui_2020_Front.Microbiol_11_2204 PubMedSearch: Cui 2020 Front.Microbiol 11 2204 PubMedID: 33042041 Abstract Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A(1), phospholipase A(2), and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival. Title: Toxicological effects of nano- and micro-polystyrene plastics on red tilapia: Are larger plastic particles more harmless? Ding J, Huang Y, Liu S, Zhang S, Zou H, Wang Z, Zhu W, Geng J Ref: J Hazard Mater, 396:122693, 2020 : PubMed ESTHER: Ding_2020_J.Hazard.Mater_396_122693 PubMedSearch: Ding 2020 J.Hazard.Mater 396 122693 PubMedID: 32353735 Abstract Nanoplastics (NPs) and microplastics (MPs) are a heterogeneous class of pollutants with diverse sizes in aquatic environments. To evaluate the hazardous effects of N/MPs with different sizes, the accumulation, oxidative stress, cytochrome P450 (CYP) enzymes, neurotoxicity, and metabolomics changes were investigated in the red tilapia exposed to three sizes of polystyrene (PS) N/MPs (0.3, 5, and 70-90mum). After 14-d exposures, the largest particles (70-90mum) showed the highest accumulation levels in most cases. Exposures to PS-MPs (5 and 70-90mum) caused a more severe oxidative stress in red tilapia than PS-NPs. The activity of CYP3A-related enzyme was obviously inhibited by PS-NPs, whereas the CYP enzymes in the liver may not be sensitive to MP exposures. In the brain, only 5mumPS-MPs significantly inhibited the acetylcholinesterase activity. After exposures, the treatments with 0.3, 5, and 70-90mum N/MPs resulted in 31, 40, and 23 significantly differentially expressed metabolites, respectively, in which the pathway of tyrosine metabolism was significantly affected by all the three PS-N/MP exposures. Overall, the PS particles within the mum size posed more severe stress to red tilapia. Our results suggest that the toxicity of N/MPs may not show a simply monotonic negative correlation with their sizes. Title: Development of a practical prediction scoring system for severe acute organophosphate poisoning Dong N, Liu J, Wang Z, Gao N, Pang L, Xing J Ref: J Appl Toxicol, :, 2020 : PubMed ESTHER: Dong_2020_J.Appl.Toxicol__ PubMedSearch: Dong 2020 J.Appl.Toxicol PubMedID: 32030807 Abstract Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 x 10(9) /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital. Title: Early Use of Blood Purification in Severe Epstein-Barr Virus-Associated Hemophagocytic Syndrome Huang P, Huang C, Xu H, Lu J, Tian R, Wang Z, Chen Y Ref: Pediatrics, :, 2020 : PubMed ESTHER: Huang_2020_Pediatrics__ PubMedSearch: Huang 2020 Pediatrics PubMedID: 32430444 Abstract Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common type of hemophagocytic lymphohistiocytosis (HLH) that exhibits high rates of morbidity and fatalities. Multiorgan failure caused by Epstein-Barr virus (EBV)-induced hypercytokinemia is one of the main reasons for early deaths. Blood purification techniques have been successfully applied in previously treated hypercytokinemia. However, there were insufficient studies to support the combination of plasma exchange (PE) and continuous renal replacement therapy (CRRT) in treating patients with severe EBV-HLH. In this article, we have summarized the effects of early incorporation of PE and CRRT, together with HLH-2004 chemoimmunotherapy, in 8 pediatric patients with severe EBV-HLH. Early use of PE and CRRT appeared to be well tolerated, and no serious side effects and early deaths were observed. After PE and CRRT procedures, cytokine levels were reduced to normal values, except for soluble interleukin 2 receptor, and significant reductions in EBV DNA, serum ferritin, aspartate transaminase, total bilirubin, total bile acid, lactate dehydrogenase, and body temperature values and increases in the neutrophil count in addition to hemoglobin, albumin, and cholinesterase values were observed. Furthermore, through continuous HLH-2004 treatment regimens, lower limits of detection were exhibited for EBV DNA levels, and all other observational indicator levels were restored to normal. Finally, 7 patients achieved and maintained complete remission for 15 to 24 months, culminating in August 2019. Therefore, it is our suggestion that early incorporation of PE and CRRT with chemoimmunotherapy might be a safe and effective treatment for patients with severe EBV-HLH. Title: Lipase catalysis of alpha-linolenic acid-rich medium- and long-chain triacylglycerols from perilla oil and medium-chain triacylglycerols with reduced by-products Huang Z, Cao Z, Guo Z, Chen L, Wang Z, Sui X, Jiang L Ref: J Sci Food Agric, 100:4565, 2020 : PubMed ESTHER: Huang_2020_J.Sci.Food.Agric_100_4565 PubMedSearch: Huang 2020 J.Sci.Food.Agric 100 4565 PubMedID: 32419135 Abstract BACKGROUND: Medium- and long- chain triacylglycerols (MLCTs) are functional structural lipids that can provide the human body with essential fatty acids and a faster energy supply. This study aimed to prepare MLCTs rich in alpha-linolenic by enzymatic interesterification of perilla oil and medium-chain triacylglycerols (MCTs), catalyzed by Lipozyme RM IM, Lipozyme TL IM, Lipozyme 435, and Novozyme 435 respectively. RESULTS: The effects of lipase loading, concentration of MCTs, reaction temperature, and reaction time on the yield of MLCTs were investigated. It was found that the reaction achieved more than a 70% yield of MLCTs in triacylglycerols under the conditions of 400 g kg(-1) MCTs and 60 g kg(-1) lipase loading after equilibrium. A novel two-stage deodorization was also applied to purify the interesterification products. The triacylglycerols reach over 97% purity in the products with significant removal (P < 0.05) of the free fatty acids, and the trans fatty acids were strictly controlled at below 1%. There was more than 40% alpha-linolenic in the purified products, with long-chain fatty acids mostly occupying the desired sn-2 position in acylglycerols, which are more active in hydrolysis. CONCLUSION: A series of novel alpha-linolenic acid-rich medium- and long-chain triacylglycerols was prepared. Under appropriate reaction conditions, the yield of MLCTs in triacylglycerols was above 70%. A novel two-stage deodorization can be used to promote the elimination of free fatty acids and limit the generation of trans fatty acids. Title: Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways Ji X, Li N, Ma M, Rao K, Yang R, Wang Z Ref: Environ Pollut, 264:114747, 2020 : PubMed ESTHER: Ji_2020_Environ.Pollut_264_114747 PubMedSearch: Ji 2020 Environ.Pollut 264 114747 PubMedID: 32559878 Inhibitor(s) related to this paper: Tri-M-cresyl-phosphate, Tri-o-cresylphosphate Abstract Tricresyl phosphates (TCPs), as representative aromatic organophosphate flame retardants (OPFRs), have received much attention due to their potential neurotoxicity and endocrine-disrupting effects. However, the role of estrogen receptor alpha (ERalpha) and G protein-coupled estrogen receptor (GPER) in their estrogen disrupting effects remains poorly understood. Therefore, in this study, three TCP isomers, tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) and tri-p-cresyl phosphate (TpCP), were examined for their activities on ERalpha by using two-hybrid yeast assay, and action on GPER by using Boyden chamber assay, cAMP production assay, calcium mobilization assay and molecular docking analysis. The results showed that three TCP isomers were found to act as ERalpha antagonists. Conversely, they had agonistic activity on GPER to promote GPER-mediated cell migration of MCF7 cells and SKBR3 cells. Both ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP had different mode of action, it only triggered GPER-mediated calcium mobilization, as evidenced by using the specific GPER inhibitor (G15) and GPER overexpressing experiments. Molecular docking further revealed that the way of interaction of TmCP and TpCP with GPER was different from that of ToCP with GPER, and higher activity of ToCP in activating GPER-mediated pathways might be associated with the alkyl substitution at the ortho position of the aromatic ring. Our results, for the first time, found a new target, GPER, for TCPs exerting their estrogen-disrupting effects, and demonstrated complex estrogen-disrupting effects of three TCP isomers involved their opposite activities toward ERalpha and GPER. Title: A Dual-Protein Cascade Reaction for the Regioselective Synthesis of Quinoxalines Li F, Tang X, Xu Y, Wang C, Wang Z, Li Z, Wang L Ref: Org Lett, :, 2020 : PubMed ESTHER: Li_2020_Org.Lett__ PubMedSearch: Li 2020 Org.Lett PubMedID: 32337998 Abstract In this work, an efficient dual-protein (lipase and hemoglobin) system was successfully constructed for the regioselective synthesis of quinoxalines in water. A set of quinoxalines were obtained in high yields under optimal reaction conditions. This dual-protein method exhibited a regioselectivity higher than those of previously reported methods. This study not only provides a green and mild strategy for the synthesis of quinoxalines but also expands the application of lipase and hemoglobin in organic synthesis. Title: MnO(2) switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides Li W, Rong Y, Wang J, Li T, Wang Z Ref: Biosensors & Bioelectronics, 169:112605, 2020 : PubMed ESTHER: Li_2020_Biosens.Bioelectron_169_112605 PubMedSearch: Li 2020 Biosens.Bioelectron 169 112605 PubMedID: 32947079 Abstract Cholinesterases (ChEs) are important indicators of neurological disease, hepatocellular carcinoma, and organophosphate poisoning. In this work, a MnO(2) switch-bridged DNA walker was developed for ultrasensitive sensing of ChEs activity. The fuel strands loaded MnO(2) switch was designed to bridge the hydrolysis activity of ChEs and the running of the DNA walker. Under the action of ChE, the substrate butyrylcholine is first catalytically hydrolyzed to thiocholine, which then mediates MnO(2) nanosheet reduction to Mn(2+), releasing the fuel strands into solution. The fuel strands as substitute targets then trigger the continuous operation of DNA walker with the aid of Mn(2+), generating detectable fluorescence responses. The detection of ChE activity is converted to DNA detection in this method. Benefited from the robust operation and amplification effect of DNA walker, a wide linear range between the BChE activity and fluorescence intensity of nearly six orders of magnitude (1000-0.005 U/mL) and a limit of detection as low as 0.0008 U/mL are achieved. This allows the direct determination of BChE activity in clinical serum samples without any pretreatments. Moreover, the proposed method has remarkable capabilities for inhibitor (organophosphorus pesticide) screening and quantification, and organophosphorus pesticide detection in real samples is also achieved. Therefore, the MnO(2) switch-bridged DNA walker represents a powerful tool for ultrasensitive sensing of ChEs and organophosphorus pesticides, and has great application potential in clinical diagnosis, therapeutics, and drug screening. Title: Ultrasensitive detection of butyrylcholinesterase activity based on the inner filter effect of MnO(2) nanosheets on sulfur nanodots Li T, Gao Y, Li H, Zhang C, Xing Y, Jiao M, Shi YE, Li W, Zhai Y, Wang Z Ref: Analyst, 145:5206, 2020 : PubMed ESTHER: Li_2020_Analyst_145_5206 PubMedSearch: Li 2020 Analyst 145 5206 PubMedID: 32578586 Abstract Butyrylcholinesterase (BChE) activity is an important index for a variety of diseases. In this work, a "turn-on" assay is proposed based on controlling the inner filter effect (IFE) of MnO(2) nanosheets (NSs) on sulfur nanodots (S-dots). The fluorescence of S-dots is effectively quenched by the MnO(2) NSs, due to the wide overlap of the emission spectrum of S-dots and absorption spectrum of MnO(2) NSs, together with the superior light absorption capability of MnO(2) NSs. BChE can catalyze acetylthiocholine and produce thiocholine, which effectively decomposes the MnO(2) NSs into Mn(2+), resulting in the disappearance of the IFE and recovery of fluorescence of S-dots. Two-stage linear relationships between the ratio of fluorescence intensity and concentration of BChE are observed from 0.05 to 10 and from 10 to 500 U L(-1). A limit of detection of 0.035 U L(-1) is achieved, which is the best performance so far. The as-proposed assay is robust enough for practical detection in human serum, and it can avoid interference from its sister enzyme (acetylcholinesterase) and glutathione at the micromolar level. The presented results provide a clue for the functionalization of S-dots, and offer a powerful tool as an analytic technique for nanomedicine and environmental science. Title: Predicting the Effects of CYP2C19 and Carboxylesterases on Vicagrel, a Novel P2Y12 Antagonist, by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Approach Liu S, Wang Z, Tian X, Cai W Ref: Front Pharmacol, 11:591854, 2020 : PubMed ESTHER: Liu_2020_Front.Pharmacol_11_591854 PubMedSearch: Liu 2020 Front.Pharmacol 11 591854 PubMedID: 33424602 Abstract Vicagrel, a novel acetate derivative of clopidogrel, exhibits a favorable safety profile and excellent antiplatelet activity. Studies aim at identifying genetic and non-genetic factors affecting vicagrel metabolic enzymes Cytochrome P450 2C19 (CYP2C19), Carboxylesterase (CES) 1 and 2 (CES1 and CES2), which may potentially lead to altered pharmacokinetics and pharmacodynamics, are warranted. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating vicagrel and its metabolites was constructed, verified and validated in our study, which could simultaneously characterize its sequential two step metabolism and clinical response. Simulations were then performed to evaluate the effects of CYP2C19, CES1 and CES2 genetic polymorphisms as well as inhibitors of these enzymes on vicagrel pharmacokinetics and antiplatelet effects. Results suggested vicagrel was less influenced by CYP2C19 metabolic phenotypes and CES1 428 G > A variation, in comparison to clopidogrel. No pharmacokinetic difference in the active metabolite was also noted for volunteers carrying different CES2 genotypes. Omeprazole, a CYP2C19 inhibitor, and simvastatin, a CES1 and CES2 inhibitor, showed weak impact on the pharmacokinetics and pharmacodynamics of vicagrel. This is the first study proposing a dynamic PBPK/PD model of vicagrel able to capture its pharmacokinetic and pharmacodynamic profiles simultaneously. Simulations indicated that genetic polymorphisms and drug-drug interactions showed no clinical relevance for vicagrel, suggesting its potential advantages over clopidogrel for treatment of cardiovascular diseases. Our model can be utilized to support further clinical trial design aiming at exploring the effects of genetic polymorphisms and drug-drug interactions on PK and PD of this novel antiplatelet agent. Title: Cadmium exposure alters expression of protective enzymes and protein processing genes in venom glands of the wolf spider Pardosa pseudoannulata Lv B, Yang HL, Peng YD, Wang J, Zeng Z, Li N, Tang YE, Wang Z, Song QS Ref: Environ Pollut, 268:115847, 2020 : PubMed ESTHER: Lv_2020_Environ.Pollut_268_115847 PubMedSearch: Lv 2020 Environ.Pollut 268 115847 PubMedID: 33130443 Abstract Cadmium (Cd) pollution is currently the most serious type of heavy metal pollution throughout the world. Previous studies have shown that Cd elevates the mortality of paddy field spiders, but the lethal mechanism remains to be explored profoundly. In the present study, we measured the activities of protective enzymes (acetylcholinesterase, glutathione peroxidase, phenol oxidase) and a heavy metal chelating protein (metallothionein) in the pond wolf spider Pardosa pseudoannulata after Cd exposure. The results indicated that Cd initially increased the enzyme activities and protein concentration of the spider after 10- and 20-day exposure before inhibiting them at 30-day exposure. Further analysis showed that the enzyme activities in the cephalothorax were inhibited to some extent. Since the cephalothorax region contains important venom glands, we performed transcriptome sequencing (RNA-seq) analysis of the venom glands collected from the spiders after long-term Cd exposure. RNA-seq yielded a total of 2826 differentially expressed genes (DEGs), and most of the DEGs were annotated into the process of protein synthesis, processing and degradation. Furthermore, a mass of genes involved in protein recognition and endoplasmic reticulum (ER) -associated protein degradation were down-regulated. The reduction of protease activities supports the view that protein synthesis and degradation in organelles and cytoplasm were dramatically inhibited. Collectively, our outcomes illustrate that Cd poses adverse effects on the expression of protective enzymes and protein, which potentially down-regulates the immune function in the venom glands of the spiders via the alteration of protein processing and degradation in the ER. Title: Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z and Du G <3 more author(s)> Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z, Wang Y, Li L, Liu A, Du G (- 3) Ref: Front Pharmacol, 11:595254, 2020 : PubMed ESTHER: Shen_2020_Front.Pharmacol_11_595254 PubMedSearch: Shen 2020 Front.Pharmacol 11 595254 PubMedID: 33390981 Abstract Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD. Title: Enzymatic hydrolysis of polyester: Degradation of poly(epsilon-caprolactone) by Candida antarctica lipase and Fusarium solani cutinase Shi K, Jing J, Song L, Su T, Wang Z Ref: Int J Biol Macromol, 144:183, 2019 : PubMed ESTHER: Shi_2020_Int.J.Biol.Macromol_144_183 PubMedSearch: Shi 2020 Int.J.Biol.Macromol 144 183 PubMedID: 31843602 Abstract Poly(epsilon-caprolactone) (PCL) particles were melt-pressed into films using a hot press and then subjected to degradation by lipase from Candida antarctica and cutinase from Fusarium solani, respectively. The differences in weight loss, degradation modes, thermal stability, and crystallization were investigated after degradation by two kinds of enzymes. The result showed that mass loss of PCL films degraded by lipase was higher than that degraded by cutinase at the same enzyme concentrations. The degradation mode of PCL films is layered for cutinase degradation and penetrated for lipase degradation. Crystallinity of PCL had no obvious decrease after degradation by cutinase, but it markedly decreased after lipase-degradation. PCL films occurred one-step decomposition during heating and the cutinase-degraded products had similar thermal stability. Whereas the thermal stability of lipase-degraded PCL decreased significantly and the weight loss of the PCL occurred in several steps with increasing lipase hydrolysis time. Title: Preparation of porous materials by selective enzymatic degradation: effect of in vitro degradation and in vivo compatibility Shi K, Ma Q, Su T, Wang Z Ref: Sci Rep, 10:7031, 2020 : PubMed ESTHER: Shi_2020_Sci.Rep_10_7031 PubMedSearch: Shi 2020 Sci.Rep 10 7031 PubMedID: 32341461 Gene_locus related to this paper: fusso-cutas Abstract Poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) were melt-blended and formed into a film by hot press forming. The film was selectively degraded by cutinase and proteinase K to form a porous material. The porous materials were characterized with respect to their pore morphology, pore size, porosity and hydrophilicity. The porous materials were investigated in vitro degradation and in vivo compatibility. The results show that the pore size of the prepared porous materials could be controlled by the proportion of PBS and the degradation time. When the PBS composition of PBS/PLA blends was changed from 40 wt% to 50 wt%, the mean pore diameter of the porous materials significantly increased from 6.91 microm to 120 microm, the porosity improved from 81.52% to 96.90%, and the contact angle decreased from 81.08 degrees to 46.56 degrees . In vitro degradation suggests that the PBS-based porous materials have a good corrosion resistance but the PLA-based porous materials have degradability in simulated body fluid. Subcutaneous implantation of the porous materials did not cause intense inflammatory response, which revealed good compatibility. The results of hematoxylin and eosin and Masson's trichrome staining assays demonstrated that the porous materials promote chondrocyte production. Porous materials have great potential in preparing implants for tissue engineering applications. Title: Kinetics and Mechanism of Solvent Influence on the Lipase-Catalyzed 1,3-Diolein Synthesis Wang Z, Dai L, Liu D, Liu H, Du W Ref: ACS Omega, 5:24708, 2020 : PubMed ESTHER: Wang_2020_ACS.Omega_5_24708 PubMedSearch: Wang 2020 ACS.Omega 5 24708 PubMedID: 33015488 Abstract 1,3-Diacylglycerol preparation has roused increasing attention in recent years as the 1,3-diacylglycerol-rich oils can suppress the deposition of visceral fat and prevent the body weight increasing. Lipozyme TL IM-mediated esterification of oleic acid with monoolein was effective for 1,3-diacylglycerol production. During the esterification process, the solvent shows obvious influence on the diolein synthesis as well as the 1,3-diolein production. This work investigated the related kinetics and mechanism of the solvent effect on the esterification and Lipozyme TL IM performance. The results indicated that both the esterification rate constant and the acyl migration rate constant positively correlated with the logP of the solvent, while the site specificity of lipase has negative correlation with solvent logP. The acylation toward the 2-position of 1-monoolein was more sensitive to the solvent logP compared to the 1-position of glycerides. Molecular dynamics simulation revealed that solvents with different logP influenced the structure of Lipozyme TL IM including RMSD, hydrogen bond, and radial distribution function to a large extent, which subsequently led to the catalytic activity and selectivity variation of the lipase. Title: Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review Wang Z, Yang Y, Liu M, Wei Y, Liu J, Pei H, Li H Ref: Curr Vasc Pharmacol, 18:358, 2020 : PubMed ESTHER: Wang_2020_Curr.Vasc.Pharmacol_18_358 PubMedSearch: Wang 2020 Curr.Vasc.Pharmacol 18 358 PubMedID: 31291876 Abstract BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Abeta generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit gamma-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Abeta deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD. Title: Hybrid Aspen Expressing a Carbohydrate Esterase Family 5 Acetyl Xylan Esterase Under Control of a Wood-Specific Promoter Shows Improved Saccharification Wang Z, Pawar PM, Derba-Maceluch M, Hedenstrom M, Chong SL, Tenkanen M, Jonsson LJ, Mellerowicz EJ Ref: Front Plant Sci, 11:380, 2020 : PubMed ESTHER: Wang_2020_Front.Plant.Sci_11_380 PubMedSearch: Wang 2020 Front.Plant.Sci 11 380 PubMedID: 32322259 Abstract Fast-growing broad-leaf tree species can serve as feedstocks for production of bio-based chemicals and fuels through biochemical conversion of wood to monosaccharides. This conversion is hampered by the xylan acetylation pattern. To reduce xylan acetylation in the wood, the Hypocrea jecorina acetyl xylan esterase (HjAXE) from carbohydrate esterase (CE) family 5 was expressed in hybrid aspen under the control of the wood-specific PtGT43B promoter and targeted to the secretory pathway. The enzyme was predicted to deacetylate polymeric xylan in the vicinity of cellulose due to the presence of a cellulose-binding module. Cell-wall-bound protein fractions from developing wood of transgenic plants were capable of releasing acetyl from finely ground wood powder, indicative of active AXE present in cell walls of these plants, whereas no such activity was detected in wild-type plants. The transgenic lines grew in height and diameter as well as wild-type trees, whereas their internodes were slightly shorter, indicating higher leaf production. The average acetyl content in the wood of these lines was reduced by 13%, mainly due to reductions in di-acetylated xylose units, and in C-2 and C-3 mono-acetylated xylose units. Analysis of soluble cell wall polysaccharides revealed a 4% reduction in the fraction of xylose units and an 18% increase in the fraction of glucose units, whereas the contents of cellulose and lignin were not affected. Enzymatic saccharification of wood from transgenic plants resulted in 27% higher glucose yield than for wild-type plants. Brunauer-Emmett-Teller (BET) analysis and Simons' staining pointed toward larger surface area and improved cellulose accessibility for wood from transgenic plants compared to wood from wild-type plants, which could be achieved by HjAXE deacetylating xylan bound to cellulose. The results show that CE5 family can serve as a source of enzymes for in planta reduction of recalcitrance to saccharification. Title: Patatin primary structural properties and effects on lipid metabolism Wu J, Wu Q, Yang D, Zhou M, Xu J, Wen Q, Cui Y, Bai Y, Xu S and Wang S <1 more author(s)> Wu J, Wu Q, Yang D, Zhou M, Xu J, Wen Q, Cui Y, Bai Y, Xu S, Wang Z, Wang S (- 1) Ref: Food Chem, :128661, 2020 : PubMed ESTHER: Wu_2020_Food.Chem__128661 PubMedSearch: Wu 2020 Food.Chem 128661 PubMedID: 33272761 Abstract Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 g/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects. Title: A novel lipase from Aspergillus oryzae catalyzed resolution of (R,S)-ethyl 2-bromoisovalerate Wu P, Zhang M, Zhang Y, Wang Z, Zheng J Ref: Chirality, 32:231, 2020 : PubMed ESTHER: Wu_2020_Chirality_32_231 PubMedSearch: Wu 2020 Chirality 32 231 PubMedID: 31856428 Gene_locus related to this paper: aspor-q2ue03 Abstract In this study, a novel lipase M5 derived from Aspergillus oryzae WZ007 was prone to exhibit high hydrolytic activity and stereoselectivity towards racemic substrate (R,S)-ethyl 2-bromoisovalerate. (R)-ethyl 2-bromoisovalerate was obtained by enzymatic resolution, which is the key chiral intermediate for highly efficient enantiomerically fluvalinate. The results showed that the enzymatic reaction was carried out in 120mM racemic substrate for 3 hours, the enantiomeric excess reached 98.6%, the conversion was 51.7%, and E value above 120. Therefore, the novel lipase M5 has the ability to efficiently produce (R)-ethyl 2-bromoisovalerate, which greatly reduces the industrial production cost of the highly efficient counterpart of fluvalinate. Title: Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health Yin S, Bai X, Xin D, Li T, Chu X, Ke H, Han M, Chen W, Li X, Wang Z Ref: Neural Plast, 2020:8815195, 2020 : PubMed ESTHER: Yin_2020_Neural.Plast_2020_8815195 PubMedSearch: Yin 2020 Neural.Plast 2020 8815195 PubMedID: 32802036 Abstract Cerebral ischemia is a common cerebrovascular condition which often induces neuronal apoptosis, leading to brain damage. The sonic hedgehog (Shh) signaling pathway has been reported to be involved in ischemic stroke, but the underlying mechanisms have not been fully elucidated. In the present study, we demonstrated that expressions of Shh, Ptch, and Gli-1 were significantly downregulated at 24 h following oxygen-glucose deprivation (OGD) injury in neurons in vitro, effects which were associated with increasing numbers of apoptotic cells and reactive oxygen species generation. In addition, expressions of synaptic proteins (neuroligin and neurexin) were significantly downregulated at 8 h following OGD, also associated with concomitant neuronal apoptosis. Treatment with purmorphamine, a Shh agonist, increased Gli-1 in the nucleus of neurons and protected against OGD injury, whereas the Shh inhibitor, cyclopamine, produced the opposite effects. Activation of Shh signals promoted CREB and Akt phosphorylation; upregulated the expressions of BDNF, neuroligin, and neurexin; and decreased NF-kappaB phosphorylation following OGD. Notably, this activation of Shh signals was accompanied by improved neurobehavioral responses along with attenuations in edema and apoptosis at 48 h postischemic insult in rats. Taken together, these results demonstrate that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health. Title: DL0410 attenuates oxidative stress and neuroinflammation via BDNF/TrkB/ERK/CREB and Nrf2/HO-1 activation Zhang B, Zhao J, Wang Z, Xu L, Liu A, Du G Ref: Int Immunopharmacol, 86:106729, 2020 : PubMed ESTHER: Zhang_2020_Int.Immunopharmacol_86_106729 PubMedSearch: Zhang 2020 Int.Immunopharmacol 86 106729 PubMedID: 32645628 Abstract Oxidative stress and neuroinflammation have been deeply associated with Alzheimer's disease. DL0410 is a novel acetylcholinesterase inhibitor with potential anti-oxidative effects in AD-related animal models, while the specific mechanism has not been fully clarified. In this study, DL0410 was predicted to be related to the modification of cell apoptosis, oxidation-reduction process, inflammatory response and ERK1/ERK2 cascade by in silico target fishing and GO enrichment analysis. Then the possible protective effects of DL0410 were evaluated by hydrogen peroxide (H2O2)-induced oxidative stress model and lipopolysaccharides (LPS)-induced neuroinflammation model H2O2 decreased the viability of SH-SY5Y cells, induced malondialdehyde (MDA) accumulation, mitochondrial membrane potential (Deltapsim) loss and cell apoptosis, which could be reversed by DL0410 dose-dependently, indicating that DL0410 protected SH-SY5Y cells against H2O2-mediated oxidative stress. Western blot analysis showed that DL0410 increased the H2O2-triggered down-regulated TrkB, ERK and CREB phosphorylation and the expression of BDNF. In addition, TrkB inhibitor ANA-12, ERK inhibitor SCH772984 and CREB inhibitor 666-15 eliminated the inhibition of DL0410 on MDA accumulation and Deltapsim loss. Furthermore, DL0410 attenuates inflammatory responses and ROS production in LPS-treated BV2 cells, which is responsible for Nrf2 and HO-1 up-regulation. The present study demonstrates that DL0410 is a potential activator of the BDNF/TrkB/ERK/CREB and Nrf2/HO-1 pathway and may be a potential candidate for regulating oxidative stress and neuroinflammatory response in the brain. Together, the results showed that DL0410 is a promising drug candidate for treating AD and possibly other nervous system diseases associated with oxidative stress and neuroinflammation. Title: High-efficiency expression of the thermophilic lipase from Geobacillus thermocatenulatus in Escherichia coli and its application in the enzymatic hydrolysis of rapeseed oil Zhang J, Tian M, Lv P, Luo W, Wang Z, Xu J Ref: 3 Biotech, 10:523, 2020 : PubMed ESTHER: Zhang_2020_3.Biotech_10_523 PubMedSearch: Zhang 2020 3.Biotech 10 523 PubMedID: 33194527 Abstract Long-chain fatty acids are widely used in food and chemical industries, and the enzymatic preparation of fatty acids is considered an environmentally friendly process. In the present study, long-chain fatty acids were prepared by the enzymatic hydrolysis of rapeseed oil with a genetically engineered lipase. Because thermophilic lipase has strong stability at higher temperatures, it was more suitable for the industrial production of long-chain fatty acids. Therefore, the thermophilic lipase BTL2 from Geobacillus thermocatenulatus was efficiently expressed in E. coli BL21(DE3) cells with an enzyme activity of 39.50 U/mg followed by gene codon optimisation. Experimental results showed that the recombinant lipase BTL2 exhibited excellent resistance to certain organic solvents (n-hexane, benzene, ethanol, and butanol). The metal cation Ca(2+) and the non-ionic surfactant Triton-100X enhanced enzyme activity by 7.36% and 56.21% respectively. Moreover, the acid value of the liberated long-chain fatty acids by hydrolysing rapeseed oil was approximately 161.64 mg KOH/g at 50 degreeC in 24 h, the hydrolytic conversion rate was 91.45%, and the productivity was approximately 6.735 mg KOH/g h. These results suggested that the recombinant lipase BTL2 has excellent hydrolytic performance for rapeseed oil and showed great potential for the enzymatic preparation of long-chain fatty acids. Title: Directed evolution of Aspergillus oryzae lipase for the efficient resolution of (R,S)-ethyl-2-(4-hydroxyphenoxy) propanoate Zhang M, Li Q, Lan X, Li X, Zhang Y, Wang Z, Zheng J Ref: Bioprocess Biosyst Eng, 43:2131, 2020 : PubMed ESTHER: Zhang_2020_Bioprocess.Biosyst.Eng_43_2131 PubMedSearch: Zhang 2020 Bioprocess.Biosyst.Eng 43 2131 PubMedID: 32959146 Gene_locus related to this paper: aspor-TGLA Abstract Aspergillus oryzae lipase (AOL) is a potential biocatalyst for industrial application. In this study, a mutant lipase AOL-3(F38N/V230R) was screened through two rounds of directed evolution, resulting in a fourfold increase in lipase activity, and threefold in catalytic efficiency (k(cat)/K(m)), while maintaining its excellent stereoselectivity. AOL-3(F38N/V230R) enzyme activity was maximum at pH 7.5 and also at 40 degreesC. And compared with wild-type AOL-3, AOL-3(F38N/V230R) preferentially hydrolyzed the fatty acid ethyl ester carbon chain length from C4 to C6-C10. In the same catalytic reaction conditions, the conversion of (R,S)-ethyl-2-(4-hydroxyphenoxy) propanoate ((R,S)-EHPP) by AOL-3(F38N/V230R) can be increased 169.7% compared to the original enzyme. The e.e.(s) of (R,S)-EHPP achieved 99.4% and conversion about 50.2% with E value being 829.0. Therefore, AOL-3(F38N/V230R) was a potential biocatalyst for obtaining key chiral compounds for aryloxyphenoxy propionate (APP) herbicides. Title: Immobilization of Lipozyme TL 100L for methyl esterification of soybean oil deodorizer distillate Zheng J, Wei W, Wang S, Li X, Zhang Y, Wang Z Ref: 3 Biotech, 10:51, 2020 : PubMed ESTHER: Zheng_2020_3.Biotech_10_51 PubMedSearch: Zheng 2020 3.Biotech 10 51 PubMedID: 32002342 Gene_locus related to this paper: humla-1lipa Abstract An immobilization method for binding cross-linked enzyme aggregates of Lipozyme TL 100L on macroporous resin NKA (CLEA-TLL@NKA) was developed in this study. The esterification activity of CLEA-TLL@NKA reached 6.4 U/mg. The surface structure of immobilized lipase was characterized by scanning electron microscopy. Methyl esterification reaction of soybean oil deodorizer distillate (SODD) was catalyzed by CLEA-TLL@NKA, which the conversion rate reached 98% and its activity retained over 90% after 20 batches of reaction. Compared with the commercial enzyme Lipozyme TLIM, half-life (t 1/2) of CLEA-TLL@NKA increased by 25 times and the catalytic activity increased by approximate 10 times. Thus, CLEA-TLL@NKA had high catalytic activity, good operational stability, and potential industrial application in the field of oil processing. Title: Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus Chen H, Li J, Yan L, Cao J, Li D, Huang GY, Shi WJ, Dong W, Zha J and Xie L <5 more author(s)> Chen H, Li J, Yan L, Cao J, Li D, Huang GY, Shi WJ, Dong W, Zha J, Ying GG, Zhong H, Wang Z, Huang Y, Luo Y, Xie L (- 5) Ref: Fish Shellfish Immunol, 97:283, 2019 : PubMed ESTHER: Chen_2019_Fish.Shellfish.Immunol_97_283 PubMedSearch: Chen 2019 Fish.Shellfish.Immunol 97 283 PubMedID: 31863904 Abstract Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 mug/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 mug/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1beta, IFN-gamma and TNF-alpha) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 mug/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme alpha-glucosidase (alpha-Glu) in the intestine at 12 mug/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus. Title: Visual detection of mixed organophosphorous pesticide using QD-AChE aerogel based microfluidic arrays sensor Hu T, Xu J, Ye Y, Han Y, Li X, Wang Z, Sun D, Zhou Y, Ni Z Ref: Biosensors & Bioelectronics, 136:112, 2019 : PubMed ESTHER: Hu_2019_Biosens.Bioelectron_136_112 PubMedSearch: Hu 2019 Biosens.Bioelectron 136 112 PubMedID: 31054518 Abstract In this paper, we present a simple strategy to fabricate a sensitive fluorescence microfluidic sensor based on quantum dots (QDs) aerogel and acetylcholinesterase enzyme (AChE) for organophosphate pesticides (OPs) detection The detection is based on the change of fluorescence intensity of QDs aerogel, which will be partly quenched as a consequence of the hydrolytic reaction of acetylthiocholine (ATCh) catalyzed by the AChE, and then the fluorescence of QDs aerogel is recovered due to decreasing of the enzymatic activity in the presence of OPs. The QDs-AChE aerogel based microfluidic arrays sensor provided good sensitivity for rapid detection of OPs with a detection limit of 0.38 pM, while the detection range is from 10(-5) to 10(-12)M. Due to the result of random orientations of AChE in the 3D porous aerogel nano-structure, the sensor presents similar calibration curves to difference pesticides, which promises the ability of the sensor to monitor total OPs of mixture. This determination sensor shows a low detection limit, wide linear range, and highly accurate determination of total OPs and carbamate content. Finally, we show the proposed sensor can be used to monitor of simple OPs and mixture in spiked fruit samples. This novel QDs-AChE aerogel sensor has an extremely high sensitivity and large detection range, it is a promising tool for accurate, rapid and cost-effective detection of various OP residues on agricultural products. Title: Mechanism-based pharmacokinetics-pharmacodynamics studies of harmine and harmaline on neurotransmitters regulatory effects in healthy rats: Challenge on monoamine oxidase and acetylcholinesterase inhibition Jiang B, Meng L, Zou N, Wang H, Li S, Huang L, Cheng X, Wang Z, Chen W, Wang C Ref: Phytomedicine, 62:152967, 2019 : PubMed ESTHER: Jiang_2019_Phytomedicine_62_152967 PubMedSearch: Jiang 2019 Phytomedicine 62 152967 PubMedID: 31154274 Inhibitor(s) related to this paper: Harmine Abstract BACKGROUND: beta-Carboline alkaloid harmine (HAR) and harmaline (HAL) are monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors. However, whether HAR and HAL inhibit MAO or AChE selectively and competitively is unclear. PURPOSE: The purpose of this study was to investigate the potential competition inhibition of HAR and HAL on MAO and AChE in brain endothelial cells (RBE4) and in healthy rats to provide a basis for the application of the inhibitors in the treatment of patients with depression and with Parkinson's disease or Alzheimer's disease. STUDY DESIGN/METHODS: The transport properties of HAR and HAL by using blood-brain barrier models constructed with RBE4 were systematically investigated. Then, the modulation effects of HAR and HAL on CNS neurotransmitters (NTs) in healthy rat brains were determined by a microdialysis method coupled with LC-MS/MS. The competition inhibition of HAR and HAL on MAO and AChE was evaluated through real time-PCR, Western blot analysis, and molecular docking experiments. RESULTS: Results showed that HAL and HAR can be detected in the blood and striatum 300min after intravenous injection (1mg/kg). Choline (Ch), gamma-aminobutyric acid (GABA), glutamate (Glu), and phenylalanine (Phe) levels in the striatum decreased in a time-dependent manner after the HAL treatment, with average velocities of 1.41, 0.73, 3.86, and 1.10 (ng/ml)/min, respectively. The Ch and GABA levels in the striatum decreased after the HAR treatment, with average velocities of 1.16 and 0.22ng/ml/min, respectively. The results of the cocktail experiment using the human liver enzyme indicated that the IC50 value of HAL on MAO-A was 0.10 +/- 0.08microm and that of HAR was 0.38 +/- 0.21microm. Their IC50 values on AChE were not obtained. These findings indicated that HAL and HAR selectively acted on MAO in vitro. However, RT-PCR and Western blot analysis results showed that the AChE mRNA and protein expression decreased in a time-dependent manner in RBE4 cells after the HAR and HAL treatments. CONCLUSION: NT analysis results showed that HAL and HAR selectively affect AChE in vivo. HAL and HAR may be highly and suitably developed for the treatment of Alzheimer's disease. Title: Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways Li W, Yu X, Zhu C, Wang Z, Zhao Z, Li Y, Zhang Y Ref: Biol Res, 52:10, 2019 : PubMed ESTHER: Li_2019_Biol.Res_52_10 PubMedSearch: Li 2019 Biol.Res 52 10 PubMedID: 30871618 Gene_locus related to this paper: human-NOTUM Abstract BACKGROUND: Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. METHODS: 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, alpha-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. RESULTS: Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. CONCLUSIONS: Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment. Title: Single and joint oxidative stress-related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa Liu X, Chen Q, Ali N, Zhang J, Wang M, Wang Z Ref: Environ Sci Pollut Res Int, 26:24695, 2019 : PubMed ESTHER: Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695 PubMedSearch: Liu 2019 Environ.Sci.Pollut.Res.Int 26 24695 PubMedID: 31240645 Abstract The biotoxicity of heavy metals in sediments toward benthic organisms has evoked great concern for the health of freshwater ecosystems. This study applied a sediment toxicity testing protocol to investigate the single and joint toxicity of cadmium (Cd) and lead (Pb) on Bellamya aeruginosa. B. aeruginosa were exposed to different concentrations of Cd (5, 25, and 100 mg/kg), Pb (20, 100, and 400 mg/kg), and their different concentration combinations. A suite of biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), metallothionein (MT), malondialdehyde (MDA), and acetylcholinesterase (AChE), were measured after 7, 14, 21, and 28 days of exposure to evaluate their oxidative stress status. Cell apoptosis of soft tissue was also determined after exposure. Results revealed that these endpoints represented sensitive biomarkers for the characterization of the oxidative stress response induced by these metals. Specifically, a decrease of SOD and GPx and an increase of MDA were indicative of the potential failure of the antioxidant defense system in neutralizing the reactive oxygen species (ROS) generated in the exposure of the Pb-treated group. The integrated biomarker response (IBR) index revealed the most significant sub-lethal toxicity for Pb-spiked sediments, leading to the highest rate of cell apoptosis (70.8%). Exposure to Cd resulted in a time- and dose-dependent effect on MT levels, which suggested active detoxification of this metal. Exposure to the mixture resulted in amelioration of Pb toxicity, likely due to the competitive binding of Cd to active enzyme, with the result of an observed antagonistic interaction. This study indicated that B. aeruginosa represents a good biomonitor for assessing Cd and Pb contamination of sediments, and laid the foundation for their potential risk assessments in freshwater ecosystems. Title: Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese population Lv Y, Zheng X, Shi M, Wang Z, Cui L Ref: BMC Neurol, 19:114, 2019 : PubMed ESTHER: Lv_2019_BMC.Neurol_19_114 PubMedSearch: Lv 2019 BMC.Neurol 19 114 PubMedID: 31164100 Abstract BACKGROUND: Epigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. Herein, we investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy. METHODS: Seventy-five northern Han Chinese patients participated in this research. 25 cases were CBZ-resistant epilepsy, 25 cases were CBZ-sensitive epilepsy and the remaining 25 cases were controls. Using a CpG searcher was to make a prediction of CpG islands; bisulfite sequencing PCR (BSP) was applied to test the methylation of EPHX1. We then did statistical analysis between clinical parameters and EPHX1 methylation. RESULTS: There was no difference between CBZ-resistant patients, CBZ-sensitive patients and healthy controls in matched age and gender. However, a significant difference of methylation levels located in NC_000001.11 (225,806,929.....225807108) of the EPHX1 promoter was found in CBZ-resistant patients, which was much higher than CBZ-sensitive and controls. Additionally, there was a significant positive correlation between seizure frequency, disease course and EPHX1 methylation in CBZ-resistant group. CONCLUSION: Methylation levels in EPHX1 promoter associated with CBZ-resistant epilepsy significantly. EPHX1 methylation may be the potential marker for CBZ resistance prior to the CBZ therapy and potential target for treatments. Title: Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors Park YJ, Walls AC, Wang Z, Sauer MM, Li W, Tortorici MA, Bosch BJ, DiMaio F, Veesler D Ref: Nat Struct Mol Biol, 26:1151, 2019 : PubMed ESTHER: Park_2019_Nat.Struct.Mol.Biol_26_1151 PubMedSearch: Park 2019 Nat.Struct.Mol.Biol 26 1151 PubMedID: 31792450 Abstract The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-Lewis(X), alpha2,3-sialyl-N-acetyl-lactosamine and alpha2,6-sialyl-N-acetyl-lactosamine at 2.7-3.0 A resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for alpha2,3-linked over alpha2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry. Title: Liver function and energy metabolism in hepatocellular carcinoma developed in patients with hepatitis B-related cirrhosis Ren M, Li J, Xue R, Wang Z, Coll SL, Meng Q Ref: Medicine (Baltimore), 98:e15528, 2019 : PubMed ESTHER: Ren_2019_Medicine.(Baltimore)_98_e15528 PubMedSearch: Ren 2019 Medicine.(Baltimore) 98 e15528 PubMedID: 31083199 Abstract Energy metabolism in patients with Hepatocellular carcinoma (HCC) accompanying by hepatitis B cirrhosis is unknown.To compare the differences in liver functions and energy metabolism between patients with hepatitis B-related cirrhosis and patients with HCC.This was a retrospective study of patients with hepatitis B-related cirrhosis (LC group, n = 75) and patients with HCC accompanying by hepatitis B cirrhosis (HCC group, n = 80) treated in Beijing You'an Hospital between January 2013 and June 2017. The resting energy expenditure (REE), respiratory quotient (RQ), carbohydrate oxidation rate (CHO%), fat oxidation rate (FAT%), and protein oxidation rate (PRO%) were measured using a metabolic cart. Liver function, renal function, blood coagulation, etc. were collected.Compared to the LC group, patients with HCC had normal metabolism, but RQ (0.83 +/- 0.07 vs 0.85 +/- 0.08, P = .073) and CHO% (35.5% vs 49%, P = .013) were lower and FAT% was higher (41% vs 33%, P = .030). Compared with patients with LC group, albumin (ALB), gamma-glutamyltranspeptadase (GGT), alkaline phosphatase (AKP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and prothrombin time activity (PTA) were elevated in the HCC group, while total bilirubin (TB), total bile acid (TBA), and international normalized ratio (INR) were reduced (P < .05). Cholinesterase (CHE) was positively correlated with RQ, CHO, and CHO% (P < .05), while negatively correlated with FAT and FAT% (P < .05). AKP was negatively correlated with RQ, CHO, and CHO% (P < .05), while positively correlated with FAT and FAT% (P < .05). TBA was negatively correlated with RQ and CHO (P < .05), while positively correlated with FAT (P < .05).HCC leads to increased liver synthetic function and improve the liver functions of patients with LC, at least to some extent, but the nutritional metabolism was poor. Title: Toxicity and possible mechanisms of action of honokiol from Magnolia denudata seeds against four mosquito species Wang Z, Perumalsamy H, Wang X, Ahn YJ Ref: Sci Rep, 9:411, 2019 : PubMed ESTHER: Wang_2019_Sci.Rep_9_411 PubMedSearch: Wang 2019 Sci.Rep 9 411 PubMedID: 30674912 Abstract This study was performed to determine the toxicity and possible mechanism of the larvicidal action of honokiol, extracted from Magnolia denudata seeds, and its 10 related compounds against third-instar larvae of insecticide-susceptible Culex pipiens pallens, Aedes aegypti, and Aedes albopictus and Anopheles sinensis resistant to deltamethrin and temephos. Honokiol (LC50, 6.13-7.37 mg/L) was highly effective against larvae of all of the four mosquito species, although the toxicity of the compound was lower than that of the synthetic larvicide temephos. Structure-activity relationship analyses indicated that electron donor and/or bulky groups at the ortho or para positions of the phenol were required for toxicity. Honokiol moderately inhibited acetylcholinesterase and caused a considerable increase in cyclic AMP levels, indicating that it might act on both acetylcholinesterase and octopaminergic receptors. Microscopy analysis clearly indicated that honokiol was mainly targeted to the midgut epithelium and anal gills, resulting in variably dramatic degenerative responses of the midgut through sequential epithelial disorganization. Honokiol did not affect the AeCS1 mRNA expression level in Ae. aegypti larvae, but did enhance expression of the genes encoding vacuolar-type H(+)-ATPase and aquaporin 4, indicating that it may disturb the Na(+), Cl(-) and K(+) co-transport systems. These results demonstrate that honokiol merits further study as a potential larvicide, with a specific target site, and as a lead molecule for the control of mosquito populations. Title: Direct, selective and ultrasensitive electrochemical biosensing of methyl parathion in vegetables using Burkholderia cepacia lipase@MOF nanofibers-based biosensor Wang Z, Ma B, Shen C, Cheong LZ Ref: Talanta, 197:356, 2019 : PubMed ESTHER: Wang_2019_Talanta_197_356 PubMedSearch: Wang 2019 Talanta 197 356 PubMedID: 30771947 Abstract Methyl parathion is one of the most widely used pesticides in agricultural practices. It caused accumulation of acetylcholine and over-stimulation of receptors in synapses which eventually led to damage of the nervous system. Present study developed a direct, sensitive, rapid and reliable method for methyl parathion residues detection in vegetable samples. MOF nanofibers which demonstrated stable framework structure, good thermal/chemical stability, good electrochemical behavior, high porosity, surface area and pore volume was synthesized and used for fabrication of Burkholderia cepacia lipase (BCL)@MOF nanofibers biosensors. BCL@MOF nanofibers/chitosan/GCE biosensor demonstrated high sensitivity for methyl detection with a wide linear range (0.1-38microM) and low limit of detection 0.067microM. During the 3 weeks storage stability test at 4 degrees C, the fabricated biosensor demonstrated good reusability and excellent stability for methyl parathion detection with retainment of more than 80% of its initial response. When applied for detection of methyl parathion residues in vegetable samples, the BCL@MOF nanofibers/chitosan/GCE biosensors demonstrated good recovery rates. Title: Fabrication and Properties of a Bio-Based Biodegradable Thermoplastic Polyurethane Elastomer Wang Z, Yan J, Wang T, Zai Y, Qiu L, Wang Q Ref: Polymers (Basel), 11:, 2019 : PubMed ESTHER: Wang_2019_Polymers.(Basel)_11_ PubMedSearch: Wang 2019 Polymers.(Basel) 11 PubMedID: 31269638 Abstract Using the melt polycondensation of five bio-based aliphatic monomers (succinic acid, sebacic acid, fumaric acid, 1,3-propanediol, and 1,4-butanediol), we first synthesized the more flexible and biodegradable polyester diols (BPD) with an average molecular weight of 3825. Then, the BPD was polymerized with excessive 4,4'-diphenylmethane diisocyanate (MDI). Finally, the molecular chain extender of 1,4-butanediol (BDO) was used to fabricate the biodegradable thermoplastic polyurethane elastomer (BTPU), comprising the soft segment of BPD and the hard segment polymerized by MDI and BDO. Atomic force microscope (AFM) images showed the two-phase structure of the BTPU. The tensile strength of the BTPU containing 60% BPD was about 30 MPa and elongation at break of the BTPU was over 800%. Notably, the BTPU had superior biodegradability in lipase solution and the biodegradation weight loss ratio of the BTPU containing 80% BPD reached 36.7% within 14 days in the lipase solution. Title: Musa balbisiana genome reveals subgenome evolution and functional divergence Wang Z, Miao H, Liu J, Xu B, Yao X, Xu C, Zhao S, Fang X, Jia C and Jin Z <30 more author(s)> Wang Z, Miao H, Liu J, Xu B, Yao X, Xu C, Zhao S, Fang X, Jia C, Wang J, Zhang J, Li J, Xu Y, Ma W, Wu Z, Yu L, Yang Y, Liu C, Guo Y, Sun S, Baurens FC, Martin G, Salmon F, Garsmeur O, Yahiaoui N, Hervouet C, Rouard M, Laboureau N, Habas R, Ricci S, Peng M, Guo A, Xie J, Li Y, Ding Z, Yan Y, Tie W, D'Hont A, Hu W, Jin Z (- 30) Ref: Nat Plants, 5:810, 2019 : PubMed ESTHER: Wang_2019_Nat.Plants_5_810 PubMedSearch: Wang 2019 Nat.Plants 5 810 PubMedID: 31308504 Gene_locus related to this paper: musam-m0tuu7, musam-a0a804kav5 Abstract Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars. Title: Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats Wu Q, Cao Y, Liu M, Liu F, Brantner AH, Yang Y, Wei Y, Zhou Y, Wang Z and Li H <3 more author(s)> Wu Q, Cao Y, Liu M, Liu F, Brantner AH, Yang Y, Wei Y, Zhou Y, Wang Z, Ma L, Wang F, Pei H, Li H (- 3) Ref: Neuropsychiatr Dis Treat, 15:3167, 2019 : PubMed ESTHER: Wu_2019_Neuropsychiatr.Dis.Treat_15_3167 PubMedSearch: Wu 2019 Neuropsychiatr.Dis.Treat 15 3167 PubMedID: 31814724 Abstract Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction. Title: Discovery of delta-sultone-fused pyrazoles for treating Alzheimer's disease: Design, synthesis, biological evaluation and SAR studies Xu Y, Zhang Z, Jiang X, Chen X, Wang Z, Alsulami H, Qin HL, Tang W Ref: Eur Journal of Medicinal Chemistry, 181:111598, 2019 : PubMed ESTHER: Xu_2019_Eur.J.Med.Chem_181_111598 PubMedSearch: Xu 2019 Eur.J.Med.Chem 181 111598 PubMedID: 31415981 Abstract A class of novel delta-sulfonolactone-fused pyrazole scaffold was prepared via sulfur (VI) fluoride exchange (SuFEx) chemistry using aryl sulfonyl fluorides and pyrazolones. Enzyme screening revealed their cholinesterase inhibitory activity, among them, compounds 4a, 5a and 5d were identified as highly selective submicromolar BuChE inhibitors (IC50=0.20, 0.46 and 0.42muM, respectively), which exhibited nontoxicity, lipophilicity and remarkable neuroprotective activity. Kinetic studies showed that BuChE inhibition of compounds 5a and 5d was reversible, mixed-type and non-competitive inhibition against BuChE (Ki=145nM and 60nM, respectively). Compound 5d can be accommodated into hBuChE via pi-S interaction and hydrophobic interactions. The title compounds are potentially symptomatic treatment in progressive Alzheimer's disease. Title: Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling Xu J, Du YL, Xu JW, Hu XG, Gu LF, Li XM, Hu PH, Liao TL, Xia QQ and Wang Z <4 more author(s)> Xu J, Du YL, Xu JW, Hu XG, Gu LF, Li XM, Hu PH, Liao TL, Xia QQ, Sun Q, Shi L, Luo JH, Xia J, Wang Z (- 4) Ref: Front Cell Neurosci, 13:518, 2019 : PubMed ESTHER: Xu_2019_Front.Cell.Neurosci_13_518 PubMedSearch: Xu 2019 Front.Cell.Neurosci 13 518 PubMedID: 31849609 Abstract Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules that function in synaptogenesis and synaptic transmission. Genetic defects in neuroligin 3 (NL3), a member of the NL protein family, are associated with autism. Studies in rodents have revealed that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system. However, the detailed mechanism is still unclear. In our study, we found that deficiency of NL3 led to morphological changes of the pyramidal neurons in layer II/III somatosensory cortex in mice, including enlarged somata, elongated dendritic length, and increased dendritic complexity. Knockdown of NL3 in cultured rat neurons upregulated Akt/mTOR signaling, resulting in both increased protein synthesis and dendritic growth. Treating neurons with either rapamycin to inhibit the mTOR or LY294002 to inhibit the PI3K/Akt activity rescued the morphological abnormalities resulting from either NL3 knockdown or knockout (KO). In addition, we found that the hyperactivated Akt/mTOR signaling associated with NL3 defects was mediated by a reduction in phosphatase and tensin (PTEN) expression, and that MAGI-2, a scaffold protein, interacted with both NL3 and PTEN and could be a linker between NL3 and Akt/mTOR signaling pathway. In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology. Title: Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells Yuan S, Han Y, Ma M, Rao K, Wang Z, Yang R, Liu Y, Zhou X Ref: Environ Pollut, 250:58, 2019 : PubMed ESTHER: Yuan_2019_Environ.Pollut_250_58 PubMedSearch: Yuan 2019 Environ.Pollut 250 58 PubMedID: 30981936 Inhibitor(s) related to this paper: Diphenyl-phosphate, Diphenyl-methyl-phosphate, EHDPP Abstract Aryl phosphorus-containing flame retardants (aryl-PFRs) have been frequently detected with increasingly used worldwide as one of alternatives for brominated flame retardants. However, information on their adverse effects on human health and ecosystem is insufficient, with limited study on their molecular mode of action insvitro. In this study, the cytotoxicity, DNA damage, mitochondrial impairment and the involved molecular mechanisms of certain frequently detectable aryl-PFRs, including 2-ethylhexyldiphenyl phosphate (EHDPP), methyl diphenyl phosphate (MDPP), bisphenol-A bis (diphenyl phosphate) (BDP), isodecyl diphenyl phosphate (IDPP), cresyl diphenyl phosphate (CDP) and the structurally similar and widely used organophosphorus pesticide chlorpyrifos (CPF), were evaluated in A549 cells using high-content screening (HCS) system. Aryl-PFRs showed different lethal concentration 50 (LC50) values ranging from 97.94 to 546.85 microM in A549 cells using CCK-8 assay. EHDPP, IDPP, CDP, MDPP and CPF demonstrated an ability to induce DNA damage, evidenced by increased DNA content and S phase-reducing cell cycle arrest effect using fluorophore dye cocktail assay. Additionally, the selected aryl-PFRs induced mitochondrial impairment by the increasing mitochondrial mass and decreasing mitochondrial membrane potential. Moreover, BDP, MDPP, and CDP, which contain short alkyl chains showed their potential oxidative stress with intracellular ROS and mitochondrial superoxide overproduction from an initially relatively low concentration. Additionally, based on the promotion of firefly luminescence in p53-transfected A549 cells, p53 activation was found to be involved in aryl-PFRs-induced DNA damage. Further real-time PCR results showed that all selected aryl-PFRs triggered p53/p21/gadd45beta-, and p53/p21/mdm2-mediated cell cycle pathways, and the p53/bax mediated apoptosis pathway to induce DNA damage and cytotoxic effects. These results suggest that aryl-PFRs (e.g., BDP, MDPP, CDP) cause oxidative stress-mediated DNA damage and mitochondrial impairment, and p53-dependent pathway was involved in the aryl-PFRs-induced DNA damage and cell cycle arrest. In conclusion, this study improves the understanding of PFRs-induced adverse outcomes and the involved molecular mechanism. Title: Bioaccumulation, behavior changes and physiological disruptions with gender-dependent in lizards (Eremias argus) after exposure to glufosinate-ammonium and l-glufosinate-ammonium Zhang L, Chen L, Meng Z, Zhang W, Xu X, Wang Z, Qin Y, Deng Y, Liu R and Diao J <1 more author(s)> Zhang L, Chen L, Meng Z, Zhang W, Xu X, Wang Z, Qin Y, Deng Y, Liu R, Zhou Z, Diao J (- 1) Ref: Chemosphere, 226:817, 2019 : PubMed ESTHER: Zhang_2019_Chemosphere_226_817 PubMedSearch: Zhang 2019 Chemosphere 226 817 PubMedID: 30965253 Abstract Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na(+)/K(+)-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance. Title: Purification and characterization of a thermoalkaliphilic esterase from Bacillus cereus WZZ006 for enantioselective resolution of indoxacarb intermediate Zhang H, Xia Y, Zhou M, Zheng J, Wang Z, Zhang Y Ref: Int J Biol Macromol, 140:358, 2019 : PubMed ESTHER: Zhang_2019_Int.J.Biol.Macromol_140_358 PubMedSearch: Zhang 2019 Int.J.Biol.Macromol 140 358 PubMedID: 31430490 Abstract An intracellular esterase (BCE) from Bacillus cereus WZZ006 was purified to homogeneity with an 89.5-fold purification, specific activity of 1.79U/mg, and 26.7% recovery. The estimated molecular weight of BCE was 96kDa which was analyzed by SDS-PAGE and MALDI-TOF-MS. Activity staining denotes that BCE has an unexplored new carboxyl esterase characteristic. BCE enzyme activity was maximum at pH8.5 and also at 50 degrees C with pNP-caproate as a substrate. This indicates that the studied BCE as a thermoalkaliphilic esterase. The kinetic properties like Km, Vmax, kcat and kcat/Km value for BCE was found to be 0.98mM, 0.03mM/min, 69.47min(-1) and 70.89mM(-1)min(-1), respectively. Synthesis of (S)-5-chloro-1-oxo-2,3-dihydro-2-hydroxy-1H-indole-2-carboxylic acid methyl ester ((S)-CODHCM) by BCE can be shortened to 3h compared to 36h with whole-cell catalysis. The e.e.s achieved was 93.83%, and conversion around 52.78% with E being 39.95. These features render BCE as a promising biocatalyst for the synthesis of a key chiral intermediate for indoxacarb. Title: High-level expression and characterization of a stereoselective lipase from Aspergillus oryzae in Pichia pastoris Zheng JY, Lan X, Li XJ, Huang LJ, Zhang YJ, Wang Z Ref: Protein Expr Purif, 155:1, 2019 : PubMed ESTHER: Zheng_2019_Protein.Expr.Purif_155_1 PubMedSearch: Zheng 2019 Protein.Expr.Purif 155 1 PubMedID: 30389593 Gene_locus related to this paper: aspor-TGLA Abstract Pichia pastoris expression is a mature and efficient eukaryotic expression system. In this work, Aspergillus oryzae lipase (AOL, with the molecular mass of 28 kDa), which can perform highly stereoselective hydrolysis of (R, S)-methyl 2-(4-hydroxyphenoxy) propanoate, was expressed in P. pastoris X-33. The specific activity of AOL was 432 U/mg, which was obtained by fed-batch cultivation in a 5 L bioreactor using a methanol feeding strategy. After fermentation, the supernatant was concentrated by ultrafiltration with a 10 kDa cut-off membrane and purified with DEAE-Sepharose FF ion-exchange chromatography and phenyl Seflnose 6 FF hydrophobic interaction chromatography. The purified lipase activity reached 5509 U/mg. AOL showed high activity toward short-chain triacylglyceride (C(4)), and the optimum temperature and pH were 40 degreesC and 8.0, respectively. The purified enzyme activity was inhibited by Zn(2+) and Cu(2+). Moreover, the K(m) and V(max) values were 1 mM and 32.89 mmol/min, respectively. Title: Surface functionalization of graphene oxide by amino acids for Thermomyces lanuginosus lipase adsorption Zhou W, Zhuang W, Ge L, Wang Z, Wu J, Niu H, Liu D, Zhu C, Chen Y, Ying H Ref: J Colloid Interface Sci, 546:211, 2019 : PubMed ESTHER: Zhou_2019_J.Colloid.Interface.Sci_546_211 PubMedSearch: Zhou 2019 J.Colloid.Interface.Sci 546 211 PubMedID: 30921675 Abstract Graphene oxide (GO) with oxygen containing functional groups can be selectively modified by small biomolecules to achieve heterogeneous surface properties. To achieve a hyper-enzymatic activity, the surface functionality of GO should be tailored to the orientation adsorption of the Thermomyces lanuginosus (TL) lipase, and the active center can be covered by a relatively hydrophobic helical lid for protection. In this work, amino acids were used to interact with GO through reduction reaction, hydrophobic forces, electrostatic forces, or hydrogen bonding to alter the surface hydrophobicity and charge density. Characterization of the structure and surface properties confirmed that the GO samples decorated with phenylalanine (Phe) and glutamic acid (Glu) exhibited superior hydrophobicity than other modifications, whereas tryptophan (Trp) and cysteine (Cys) provided weaker reduction effects on GO. Moreover, the zeta potential of the samples modified by amino acids of lysine (Lys) and arginine (Arg) is higher than other modified samples. The adsorption amount of lipase on Glu-GO reached 172mg/g and the relative enzymatic activity reached up to 200%. The thermodynamic data and the Freundlich isotherm model fitting showed that the lipase adsorption process on modified samples was spontaneous, endothermic and entropy increase. Title: Structure-guided Discovery of Dual-recognition Chemibodies Cheng AC, Doherty EM, Johnstone S, DiMauro EF, Dao J, Luthra A, Ye J, Tang J, Nixey T and Wang Z <3 more author(s)> Cheng AC, Doherty EM, Johnstone S, DiMauro EF, Dao J, Luthra A, Ye J, Tang J, Nixey T, Min X, Tagari P, Miranda LP, Wang Z (- 3) Ref: Sci Rep, 8:7570, 2018 : PubMed ESTHER: Cheng_2018_Sci.Rep_8_7570 PubMedSearch: Cheng 2018 Sci.Rep 8 7570 PubMedID: 29765112 Gene_locus related to this paper: ratno-dpp4 Abstract Small molecules and antibodies each have advantages and limitations as therapeutics. Here, we present for the first time to our knowledge, the structure-guided design of "chemibodies" as small molecule-antibody hybrids that offer dual recognition of a single target by both a small molecule and an antibody, using DPP-IV enzyme as a proof of concept study. Biochemical characterization demonstrates that the chemibodies present superior DPP-IV inhibition compared to either small molecule or antibody component alone. We validated our design by successfully solving a co-crystal structure of a chemibody in complex with DPP-IV, confirming specific binding of the small molecule portion at the interior catalytic site and the Fab portion at the protein surface. The discovery of chemibodies presents considerable potential for novel therapeutics that harness the power of both small molecule and antibody modalities to achieve superior specificity, potency, and pharmacokinetic properties. Title: A Novel esterase from Pseudochrobactrum asaccharolyticum WZZ003: Enzymatic properties toward model substrate and catalytic performance in chiral fungicide intermediate synthesis Cheng F, Zheng J, Wu G, Zhang Y, Wang Z Ref: Process Biochemistry, 69:92, 2018 : PubMed ESTHER: Cheng_2018_Process.Biochem_69_92 PubMedSearch: Cheng 2018 Process.Biochem 69 92 Gene_locus related to this paper: 9hyph-a0a2r3sty9 Abstract Only a few esterases have been used for the synthesis of optically pure fungicide. For example, (R)-metalaxyl synthesized using esterase-involved bioreaction displays fungicide activity, whereas (S)-enantiomer is redundant. However, the biosynthesis of (R)-metalaxyl is currently hampered by the lower activity, selectivity and thermostability of esterase. Therefore, to obtain a better biocatalyst, several esterase genes were cloned from Pseudochrobactrum asaccharolyticum WZZ003. The esterase PAE07, among eight enzymes, was selected because it exhibited the highest hydrolysis activity toward (R,S)-DMPM. The DNA and amino acid sequence analysis suggested that PAE07 is a new member of lipolytic enzyme family V. The enzymatic properties of PAE07 toward (R,S)-DMPM and model substrate (p-nitrophenyl acetate) were investigated. PAE07 was found to be a highly active esterase with excellent enantioselectivity. The reaction conditions including temperatureand pH were optimized, and the effects of metal ions, organic solvents and detergents were also investigated. Results indicated that PAE07 is a competitive candidate for (R)-metalaxyl manufacturing. Title: Enzymatic degradation of poly(butylene succinate) with different molecular weights by cutinase Pan W, Bai Z, Su T, Wang Z Ref: Int J Biol Macromol, 111:1040, 2018 : PubMed ESTHER: Pan_2018_Int.J.Biol.Macromol_111_1040 PubMedSearch: Pan 2018 Int.J.Biol.Macromol 111 1040 PubMedID: 29366885 Abstract Poly(butylene succinate) (PBS) films with different molecular weights were enzymatically degraded by cutinase. Changes in the properties of the films before and after enzymatic degradation were studied through scanning electron microscopy, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, proton nuclear magnetic resonance, and gel-permeation chromatography analysis. The weight loss of the films initially decreased and then increased with increasing molecular weight. Crystallinity was inversely proportional to weight loss and tended to decrease with prolonged degradation time. Crystalline and amorphous regions were simultaneously degraded. The thermal stability of PBS films decreased after enzymatic degradation. PBS was the main component of the enzymatically degraded polymers. The molecular weights of the films did not considerably change before and after degradation by cutinase. Title: Molluscicidal activity of Solidago canadensis L. extracts on the snail Pomacea canaliculata Lam Shen X, Wang Z, Liu L, Zou Z Ref: Pestic Biochem Physiol, 149:104, 2018 : PubMed ESTHER: Shen_2018_Pestic.Biochem.Physiol_149_104 PubMedSearch: Shen 2018 Pestic.Biochem.Physiol 149 104 PubMedID: 30033006 Abstract Extracts from the aerial parts of Solidago canadensis L. were evaluated for molluscicidal activity against Pomacea canaliculata Lam. using an immersion bioassay method. The petroleum ether fraction of the ethanolic extract (PEEE) from S. canadensis exhibited strong molluscicidal activity. The PEEE mode of action in the hepatopancreas tissue of P. canaliculata was tested at several concentrations. Biochemical parameters, namely, soluble sugar content, protein, malondialdehyde (MDA), acetylcholinesterase (AChE) activity, alanine aminotransferase (ALT), and aspartate transaminase (AST) were significantly decreased or increased after exposure to PEEE for 48 h (p<0.05). Histological assessment results showed that hepatopancreas tissue structure was destroyed by exposure to PEEE. Gas chromatography-mass spectrometry analysis (GC-MS) was used to identify 15 compounds that could contribute to the molluscicidal efficacy of the PEEE. Molluscicidal assay, biochemical tests and histological assessments suggest that the PEEE from S. canadensis has potential utility as a molluscicide. Title: Selective enzymatic degradation and porous morphology of poly(butylene succinate)/poly(lactic acid) blends Shi K, Bai Z, Su T, Wang Z Ref: Int J Biol Macromol, 126:436, 2018 : PubMed ESTHER: Shi_2018_Int.J.Biol.Macromol_126_436 PubMedSearch: Shi 2018 Int.J.Biol.Macromol 126 436 PubMedID: 30586586 Abstract Poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) were melt-blended in different proportions and selectively degraded by cutinase and proteinase K, respectively. The selective enzymatic degradation process was systematically investigated. The degraded PBS/PLA blends were analyzed via scanning electron microscopy, Fourier-transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. The results of the weight loss of PBS/PLA blends degraded by cutinase and proteinase K suggested that PLA hindered the cutinase-catalyzed degradation of PBS, whereas the addition of PBS in the blends accelerated the degradation of PLA within a specific PBS/PLA ratio. The change in crystallinity after degradation was closely related to the different way of degradation. The characterization of PBS/PLA blends after degradation showed that selective enzymatic degradation could not completely degrade PBS or PLA component. After degradation, the pores formed by proteinase K were more uniform and larger than those formed by cutinase. This work provides a new insight into the selective enzymatic degradation processes of the porous materials, which will be used in tissue engineering or oil-water separation in the future. Title: Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats Wang Z, Chen Z, Yang J, Yang Z, Yin J, Duan X, Shen H, Li H, Chen G Ref: Journal of Cerebral Blood Flow & Metabolism, :271678X18762637, 2018 : PubMed ESTHER: Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637 PubMedSearch: Wang 2018 J.Cereb.Blood.Flow.Metab 271678X18762637 PubMedID: 29513122 Abstract Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1-nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH. Title: Tricellular junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis Wang Z, Bosveld F, Bellache Y Ref: Journal of Cell Science, 131:, 2018 : PubMed ESTHER: Wang_2018_J.Cell.Sci_131_ PubMedSearch: Wang 2018 J.Cell.Sci 131 PubMedID: 29739875 Abstract In epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored de novo formation of tricellular septate junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis. Title: Complex role of titanium dioxide nanoparticles in the trophic transfer of arsenic from Nannochloropsis maritima to Artemia salina nauplii Yang F, Zeng L, Luo Z, Wang Z, Huang F, Wang Q, Drobne D, Yan C Ref: Aquat Toxicol, 198:231, 2018 : PubMed ESTHER: Yang_2018_Aquat.Toxicol_198_231 PubMedSearch: Yang 2018 Aquat.Toxicol 198 231 PubMedID: 29558708 Abstract Increasing concern has been focused on the potential risks associated with the trophic transfer to aquatic organisms of ambient contaminants in the presence of titanium dioxide nanoparticles (nano-TiO2). This study investigated the influence of nano-TiO2 on the trophic transfer of arsenic (As) from the microalgae Nannochloropsis maritima to the brine shrimp Artemia salina nauplii. We found that nano-TiO2 could significantly facilitate As sorption on N. maritima within an exposure period of 24h, and this sorption subsequently led to higher As trophic transfer from the algae to A. salina according to trophic transfer factors (TTFAs+nano-TiO2>TTFAs). However, after 48h of depuration, the retention of As in A. salina fed As-nano-TiO2-contaminated algae was even lower than that in A. salina fed As-contaminated algae at the same exposure concentrations. This result indicates that the increased food chain transfer of As in the presence of nano-TiO2 can be explained by adsorption of As onto nano-TiO2 in contaminated food (algae), but the bioavailability of As in A. salina is reduced after the introduction of nanoparticles. Although the stress enzyme activities of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in A. salina at a lower As concentration treatment in the presence of nano-TiO2 were not significantly changed, they increased with higher exposure concentrations of As with or without nano-TiO2. Our study highlighted the complex role of nanomaterials in the transfer of ambient contaminants via trophic chains and the potential of nano-TiO2 to reduce the bioavailability of As via trophic transfer to saltwater zooplankton. Title: Neurotrophins and cholinergic enzyme regulated by calpain-2: New insights into neuronal apoptosis induced by polybrominated diphenyl ether-153 Zhang H, Yang X, Li X, Zhang Z, Hou L, Wang Z, Niu Q, Wang T Ref: Toxicol Lett, 291:29, 2018 : PubMed ESTHER: Zhang_2018_Toxicol.Lett_291_29 PubMedSearch: Zhang 2018 Toxicol.Lett 291 29 PubMedID: 29621559 Abstract Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (mRNA and protein) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the levels (protein contents and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors. Results showed that the neuronal apoptosis induced by BDE-153 was dependent on p53, and dependent on more calpain-2 than caspase-3 in the cerebral cortex of rats. Following the BDE-153 treatment, the protein contents and mRNA levels of BDNF, GDNF, NGF, NT-3, and NT-4, as well as the AchE and ChaT activities were significantly decreased in the cerebral cortex and primary neurons when compared to the untreated group. When pretreated primary neurons with calpain inhibitor PD150606 or cyclin-dependent kinase (cdk5, the downstream complex of calpain) inhibitor Roscovitine, the neurotrophins contents and activities of ChaT and AchE were reverted, along with the improvement of neuron survival compared with BDE-153 treatment alone. We conclude that neurotrophins and cholinergic enzymes were regulated by the calpain-2 activation and its downstream cdk5 pathway, and which was involved in the neuronal apoptosis induced by the BDE-153 treatment. Title: Kinetic resolution of N-acetyl-DL-alanine methyl ester using immobilized Escherichia coli cells bearing recombinant esterase from Bacillus cereus Zheng J, Lan X, Huang L, Zhang Y, Wang Z Ref: Chirality, 30:907, 2018 : PubMed ESTHER: Zheng_2018_Chirality_30_907 PubMedSearch: Zheng 2018 Chirality 30 907 PubMedID: 29676476 Abstract D-alanine is widely used in medicine, food, additives, cosmetics, and other consumer items. Esterase derived from Bacillus cereus WZZ001 exhibits high hydrolytic activity and stereoselectivity. In this study, we expressed the esterase gene in Escherichia coli BL21 (DE3). We analyzed the biocatalytic resolution of N-acetyl-DL-alanine methyl ester by immobilized whole E. coli BL21 (DE3) cells, which were prepared through embedding and cross-linking. We analyzed biocatalytic resolution under the optimal conditions of pH of 7.0, temperature of 40 degrees C and substrate concentration of at 700 mM with an enantiomeric excess of 99.99% and e.e.p of 99.50%. The immobilized recombinant B. cereus esterase E. coli BL21 (DE3) cells exhibited excellent reusability and retained 86.04% of their initial activity after 15 cycles of repeated reactions. The immobilized cells are efficient and stable biocatalysts for the preparation of N-acetyl-D-alanine methyl esters. Title: Protective and Detoxifying Enzyme Activity and ABCG Subfamily Gene Expression in Sogatella furcifera Under Insecticide Stress Zhou C, Yang H, Wang Z, Long GY, Jin DC Ref: Front Physiol, 9:1890, 2018 : PubMed ESTHER: Zhou_2018_Front.Physiol_9_1890 PubMedSearch: Zhou 2018 Front.Physiol 9 1890 PubMedID: 30670985 Abstract Sogatella furcifera, an important migratory pest of rice, has substantial detrimental effects on rice production. To clarify the mechanism whereby S. furcifera responds to insecticide stress, we measured the activity of its protective [superoxide dismutase (SOD); peroxidase (POD); catalase (CAT)] and detoxifying [carboxylesterase (CarE); glutathione S-transferase (GST); mixed-function oxidase (MFO)] enzymes and the expression levels of its ATP-binding cassette subfamily G (ABCG) transporter genes in response to sublethal concentrations (LC10 and LC25) of the insecticides thiamethoxam, buprofezin, and abamectin. On the bases of the transcriptome data and the ABCG genes of Laodelphax striatellus, we obtained 14 full-length ABCG sequences for S. furcifera. RT-qPCR results showed that 13, 12, and 9 sfABCG genes were upregulated in the presence of thiamethoxam, buprofezin, and abamectin, respectively, at LC10. Moreover, 13 and 7 sfABCG genes were upregulated following treatment with thiamethoxam and abamectin, respectively, at LC25. Enzyme activity assays showed that although thiamethoxam, buprofezin, and abamectin induced GST, CarE, CAT, POD, and SOD activity, they did so at different concentrations and exposure times. The activity of MFO was generally inhibited with prolonged exposure to the three insecticides, with the inhibitory effect being most significant at 72 h. These results indicate that S. furcifera differs in its response to different types or concentrations of insecticides. Taken together, our results lay the foundations for gaining a deeper understanding of the mechanisms underlying the adaptation of S. furcifera to different types of insecticides, which would be of considerable significance for the development of effective pest management strategies. Title: De novo transcriptome and expression profile analyses of the Asian corn borer (Ostrinia furnacalis) reveals relevant flubendiamide response genes Cui L, Rui C, Yang D, Wang Z, Yuan H Ref: BMC Genomics, 18:20, 2017 : PubMed ESTHER: Cui_2017_BMC.Genomics_18_20 PubMedSearch: Cui 2017 BMC.Genomics 18 20 PubMedID: 28056803 Abstract BACKGROUND: The Asian corn borer (ACB), Ostrinia furnacalis (Guenee), has become the most damaging insect pest of corn in Asia. However, the lack of genome or transcriptome information heavily hinders our further understanding of ACB in every aspect at a molecular level and on a genome-wide scale. Here, we used the Ion Torrent Personal Genome Machine (PGM) Sequencer to explore the ACB transcriptome and to identify relevant genes in response to flubendiamide, showing high selective activity against ACB. Title: Efficient kinetic resolution of (+/-)-menthol by a lipase from Thermomyces lanuginosus De Yan H, Li Q, Wang Z Ref: Biotechnol Appl Biochem, 64:87, 2017 : PubMed ESTHER: De Yan_2017_Biotechnol.Appl.Biochem_64_87 PubMedSearch: De Yan 2017 Biotechnol.Appl.Biochem 64 87 PubMedID: 26549685 Gene_locus related to this paper: humla-1lipa Abstract A lipase from Thermomyces lanuginosus (Lipozyme TL IM) exhibited high enantioselectivity for kinetic resolution of (+/-)-menthol in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied. The optimum reaction conditions for the transesterification reaction were found with vinyl acetate in the solvent of methyl tert-butyl ether with a vinyl acetate:(+/-)-menthol molar ratio of 5:1 and an enzyme concentration of 200 g/L at 30 degreeC. In these conditions, (-)-menthyl acetate with 99.3% enantiomeric excess was obtained, whereas the conversion was 34.7% with the reaction time of 12 H at the substrate concentration of 0.5 M. In addition, the enzyme allowed the substrate loading to be increased up to 1.5 M without the decrease of the enantioselectivity. These results indicated that Lipozyme TL IM was a promising biocatalyst in the resolution of (+/-)-menthol. Title: Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern Huo YY, Li S, Huang J, Rong Z, Wang Z, Li Z, Ji R, Kuang S, Cui HL and Xu XW <1 more author(s)> Huo YY, Li S, Huang J, Rong Z, Wang Z, Li Z, Ji R, Kuang S, Cui HL, Li J, Xu XW (- 1) Ref: Sci Rep, 7:4422, 2017 : PubMed ESTHER: Huo_2017_Sci.Rep_7_4422 PubMedSearch: Huo 2017 Sci.Rep 7 4422 PubMedID: 28667306 Gene_locus related to this paper: pelhb-g4rfi7 Abstract Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1.66 A. Compared with other homologs in the family, significant differences were observed in the amino acid sequence, three-dimensional structure, and substrate-binding pattern. Residue Arg79 undergoes configuration switching when binding to the substrate and forms a unique wall, leading to a relatively closed cavity in the substrate-binding pocket compared with the relatively more open and longer clefts in other homologs. Moreover, the mutant Met122Ala showed much stronger substrate affinity and higher catalytic efficiency because less steric repulsion acted on the substrates. Taken together, these results showed that, in PE8, Arg79 and Met122 play important roles in substrate binding and the binding pocket shaping, respectively. Our study provides new insight into the catalytic mechanism of LPCE, which may facilitate the development of structure-based therapeutics and other biocatalytic applications. Title: Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice Liu W, Zhu Y, Wang Y, Qi S, Ma C, Li S, Jiang B, Cheng X, Wang Z and Wang C <1 more author(s)> Liu W, Zhu Y, Wang Y, Qi S, Ma C, Li S, Jiang B, Cheng X, Wang Z, Xuan Z, Wang C (- 1) Ref: J Ethnopharmacol, 204:95, 2017 : PubMed ESTHER: Liu_2017_J.Ethnopharmacol_204_95 PubMedSearch: Liu 2017 J.Ethnopharmacol 204 95 PubMedID: 28442406 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND Title: De Novo Genome and Transcriptome Assembly of the Canadian Beaver (Castor canadensis) Lok S, Paton TA, Wang Z, Kaur G, Walker S, Yuen RK, Sung WW, Whitney J, Buchanan JA and Scherer SW <27 more author(s)> Lok S, Paton TA, Wang Z, Kaur G, Walker S, Yuen RK, Sung WW, Whitney J, Buchanan JA, Trost B, Singh N, Apresto B, Chen N, Coole M, Dawson TJ, Ho K, Hu Z, Pullenayegum S, Samler K, Shipstone A, Tsoi F, Wang T, Pereira SL, Rostami P, Ryan CA, Tong AH, Ng K, Sundaravadanam Y, Simpson JT, Lim BK, Engstrom MD, Dutton CJ, Kerr KC, Franke M, Rapley W, Wintle RF, Scherer SW (- 27) Ref: G3 (Bethesda), 7:755, 2017 : PubMed ESTHER: Lok_2017_G3.(Bethesda)_7_755 PubMedSearch: Lok 2017 G3.(Bethesda) 7 755 PubMedID: 28087693 Gene_locus related to this paper: cascn-a0a250y2s0, cascn-a0a250y135, cascn-a0a250y1i6, cascn-a0a250y2u8, cascn-a0a250xy53, ursma-a0a384cw87, cascn-a0a250y6h8 Abstract The Canadian beaver (Castor canadensis) is the largest indigenous rodent in North America. We report a draft annotated assembly of the beaver genome, the first for a large rodent and the first mammalian genome assembled directly from uncorrected and moderate coverage (< 30 x) long reads generated by single-molecule sequencing. The genome size is 2.7 Gb estimated by k-mer analysis. We assembled the beaver genome using the new Canu assembler optimized for noisy reads. The resulting assembly was refined using Pilon supported by short reads (80 x) and checked for accuracy by congruency against an independent short read assembly. We scaffolded the assembly using the exon-gene models derived from 9805 full-length open reading frames (FL-ORFs) constructed from the beaver leukocyte and muscle transcriptomes. The final assembly comprised 22,515 contigs with an N50 of 278,680 bp and an N50-scaffold of 317,558 bp. Maximum contig and scaffold lengths were 3.3 and 4.2 Mb, respectively, with a combined scaffold length representing 92% of the estimated genome size. The completeness and accuracy of the scaffold assembly was demonstrated by the precise exon placement for 91.1% of the 9805 assembled FL-ORFs and 83.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set used to assess the quality of genome assemblies. Well-represented were genes involved in dentition and enamel deposition, defining characteristics of rodents with which the beaver is well-endowed. The study provides insights for genome assembly and an important genomics resource for Castoridae and rodent evolutionary biology. Title: Genome assembly with in vitro proximity ligation data and whole-genome triplication in lettuce Reyes-Chin-Wo S, Wang Z, Yang X, Kozik A, Arikit S, Song C, Xia L, Froenicke L, Lavelle DO and Michelmore RW <9 more author(s)> Reyes-Chin-Wo S, Wang Z, Yang X, Kozik A, Arikit S, Song C, Xia L, Froenicke L, Lavelle DO, Truco MJ, Xia R, Zhu S, Xu C, Xu H, Xu X, Cox K, Korf I, Meyers BC, Michelmore RW (- 9) Ref: Nat Commun, 8:14953, 2017 : PubMed ESTHER: Reyes-Chin-Wo_2017_Nat.Commun_8_14953 PubMedSearch: Reyes-Chin-Wo 2017 Nat.Commun 8 14953 PubMedID: 28401891 Gene_locus related to this paper: lacsa-a0a2j6jnd3, lacsa-a0a2j6l6y4, lacsa-a0a2j6mjs5, lacsa-a0a2j6mk82, lacsa-a0a2j6k5z4, lacsa-a0a2j6mk08, lacsa-a0a2j6mhc5, lacsa-a0a2j6m8d0, lacsa-a0a2j6mdb6, lacsa-a0a2j6mdh6, lacsa-a0a2j6jnf0, lacsa-a0a2j6mji4, lacsa-a0a2j6ke81, lacsa-a0a2j6jip3, lacsa-a0a2j6jir5, lacsa-a0a2j6ksa7, lacsa-a0a2j6l4a3 Abstract Lettuce (Lactuca sativa) is a major crop and a member of the large, highly successful Compositae family of flowering plants. Here we present a reference assembly for the species and family. This was generated using whole-genome shotgun Illumina reads plus in vitro proximity ligation data to create large superscaffolds; it was validated genetically and superscaffolds were oriented in genetic bins ordered along nine chromosomal pseudomolecules. We identify several genomic features that may have contributed to the success of the family, including genes encoding Cycloidea-like transcription factors, kinases, enzymes involved in rubber biosynthesis and disease resistance proteins that are expanded in the genome. We characterize 21 novel microRNAs, one of which may trigger phasiRNAs from numerous kinase transcripts. We provide evidence for a whole-genome triplication event specific but basal to the Compositae. We detect 26% of the genome in triplicated regions containing 30% of all genes that are enriched for regulatory sequences and depleted for genes involved in defence. Title: In vivo metabolism of organophosphate flame retardants and distribution of their main metabolites in adult zebrafish Wang G, Chen H, Du Z, Li J, Wang Z, Gao S Ref: Sci Total Environ, 590-591:50, 2017 : PubMed ESTHER: Wang_2017_Sci.Total.Environ_590-591_50 PubMedSearch: Wang 2017 Sci.Total.Environ 590-591 50 PubMedID: 28292737 Abstract Understanding the metabolism of chemicals as well as the distribution and depuration of their main metabolites in tissues are essential for evaluating their fate and potential toxicity in vivo. Herein, we investigated the metabolism of six typical organophosphate (OP) flame retardants (tripropyl phosphate (TPRP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tri-p-cresyl phosphate (p-TCP)) in adult zebrafish in laboratory at three levels (0, 1/150 LC50 (environmentally relevant level), and 1/30 LC50 per OP analog). Twenty main metabolites were detected in the liver of OPs-exposed zebrafish using high resolution mass spectrometry (Q-TOF). The reaction pathways involving scission of the ester bond (hydrolysis), cleavage of the ether bond, oxidative hydroxylation, dechlorination, and coupling with glucuronic acid were proposed, and were further confirmed by the frontier electron density and point charge calculations. Tissue distribution of the twenty metabolites revealed that liver and intestine with the highest levels of metabolites were the most active organs for OPs biotransformation among the studied tissues of intestine, liver, roe, brain, muscle, and gill, which showed the importance of hepatobiliary system (liver-bile-intestine) in the metabolism and excretion of OPs in zebrafish. Fast depuration of metabolites from tissues indicated that the formed metabolites might be not persistent in fish, and easily released into water. This study provides comprehensive information on the metabolism of OPs in the tissue of zebrafish, which might give some hints for the exploration of their toxic mechanism in aquatic life. Title: In Vitro Metabolism of Oprozomib, an Oral Proteasome Inhibitor: Role of Epoxide Hydrolases and Cytochrome P450s Wang Z, Fang Y, Teague J, Wong H, Morisseau C, Hammock BD, Rock DA Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 45:712, 2017 : PubMed ESTHER: Wang_2017_Drug.Metab.Dispos_45_712 PubMedSearch: Wang 2017 Drug.Metab.Dispos 45 712 PubMedID: 28428366 Abstract Oprozomib is an oral proteasome inhibitor currently under investigation in patients with hematologic malignancies or solid tumors. Oprozomib elicits potent pharmacological actions by forming a covalent bond with the active site N-terminal threonine of the 20S proteasome. Oprozomib has a short half-life across preclinical species and in patients due to systemic clearance via metabolism. Potential for drug-drug interactions (DDIs) could alter the exposure of this potent therapeutic; therefore, a thorough investigation of pathways responsible for metabolism is required. In the present study, the major drug-metabolizing enzyme responsible for oprozomib metabolism was identified in vitro. A diol of oprozomib was found to be the predominant metabolite in human hepatocytes, which formed via direct epoxide hydrolysis. Using recombinant epoxide hydrolases (EHs) and selective EH inhibitors in liver microsomes, microsomal EH (mEH) but not soluble EH (sEH) was found to be responsible for oprozomib diol formation. Coincubation with 2-nonylsulfanyl-propionamide, a selective mEH inhibitor, resulted in a significant decrease in oprozomib disappearance (>80%) with concurrent complete blockage of diol formation in human hepatocytes. On the contrary, a selective sEH inhibitor did not affect oprozomib metabolism. Pretreatment of hepatocytes with the pan-cytochrome P450 (P450) inhibitor 1-aminobenzotriazole resulted in a modest reduction ( approximately 20%) of oprozomib metabolism. These findings indicated that mEH plays a predominant role in oprozomib metabolism. Further studies may be warranted to determine whether drugs that are mEH inhibitors cause clinically significant DDIs with oprozomib. On the other hand, pharmacokinetics of oprozomib is unlikely to be affected by coadministered P450 and sEH inhibitors and/or inducers. Title: Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4 Wang Z, Yang L, Fan H, Wu P, Zhang F, Zhang C, Liu W, Li M Ref: PeerJ, 5:e3283, 2017 : PubMed ESTHER: Wang_2017_PeerJ_5_e3283 PubMedSearch: Wang 2017 PeerJ 5 e3283 PubMedID: 28507818 Abstract Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC50 of 5.76 microM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.) in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic for the treatment of type 2 diabetes. Title: Efficient kinetic resolution of (RS)-1-phenylethanol by a mycelium-bound lipase from a wild-type Aspergillus oryzae strain Yan HD, Wang Z, Qian JQ Ref: Biotechnol Appl Biochem, 64:251, 2017 : PubMed ESTHER: Yan_2017_Biotechnol.Appl.Biochem_64_251 PubMedSearch: Yan 2017 Biotechnol.Appl.Biochem 64 251 PubMedID: 26854002 Abstract A mycelium-bound lipase from Aspergillus oryzae (AOL) exhibited excellent enantioselectivity for kinetic resolution of (RS)-1-phenylethanol ((RS)-1-PE) in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied, including type of acyl donor, solvent, molar ratio, temperature, enzyme amount, and substrate concentration. The optimum reaction conditions were found to be transesterification with vinyl acetate at 30 degrees C in methyl tert-butyl ether with a vinyl acetate: (RS)-1-PE molar ratio of 1:1 and an enzyme concentration of 60 g/L. At the optimum reaction conditions, the conversion could reach above 46% with >99% enantiomeric excess of the product, (R)-1-phenylethyl acetate, when the substrate concentration was below 1.4 M. The enzyme displayed an excellent enantioselectivity with an E-value of >200 and a strong tolerance for high substrate concentration of up to 1.8 M. Those results indicated that AOL was a promising biocatalyst in the kinetic resolution of (RS)-1-PE. Title: Depletion of juvenile hormone esterase extends larval growth in Bombyx mori Zhang Z, Liu X, Shiotsuki T, Wang Z, Xu X, Huang Y, Li M, Li K, Tan A Ref: Insect Biochemistry & Molecular Biology, 81:72, 2017 : PubMed ESTHER: Zhang_2017_Insect.Biochem.Mol.Biol_81_72 PubMedSearch: Zhang 2017 Insect.Biochem.Mol.Biol 81 72 PubMedID: 28057597 Abstract Two major hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulate insect growth and development according to their precisely coordinated titres, which are controlled by both biosynthesis and degradation pathways. Juvenile hormone esterase (JHE) is the primary JH-specific degradation enzyme that plays a key role in regulating JH titers, along with JH epoxide hydrolase (JHEH) and JH diol kinase (JHDK). In the current study, a loss-of-function analysis of JHE in the silkworm, Bombyx mori, was performed by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori JHE (BmJHE) resulted in the extension of larval stages, especially the penultimate and ultimate larval stages, without deleterious effects to silkworm physiology. The expression of JHEH and JHDK was upregulated in mutant animals, indicating the existence of complementary routes in the JH metabolism pathway in which inactivation of one enzyme will activate other enzymes. RNA-Seq analysis of mutant animals revealed that genes involved in protein processing in the endoplasmic reticulum and in amino acid metabolism were affected by BmJHE depletion. Depletion of JHE and subsequent delayed JH metabolism activated genes in the TOR pathway, which are ultimately responsible for extending larval growth. The transgenic Cas9 system used in the current study provides a promising approach for analysing the actions of JH, especially in nondrosophilid insects. Furthermore, prolonging larval stages produced larger larvae and cocoons, which is greatly beneficial to silk production. Title: Bioactive alpha-pyrone meroterpenoids from mangrove endophytic fungus Penicillium sp Ding B, Wang Z, Huang X, Liu Y, Chen W, She Z Ref: Nat Prod Res, :1, 2016 : PubMed ESTHER: Ding_2016_Nat.Prod.Res__1 PubMedSearch: Ding 2016 Nat.Prod.Res 1 PubMedID: 27067533 Abstract Five alpha-pyrone meroterpenoids, including one new 3-epiarigsugacin E (1) and four known compounds, arisugacin D (2), arisugacin B (3), territrem C (4) and terreulactone C (5) were obtained from the marine fungus Penicillium sp. SK5GW1L. Their structures were identified by MS and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low temperature (150 K) single crystal X-ray diffraction with Cu Kalpha radiation. Compounds 3, 4 and 5 showed strong inhibitory activities against acetylcholinesterase (AchE) with IC50 values of 3.03, 0.23 and 0.028 muM, respectively. Title: Nonenzymatic all-solid-state coated wire electrode for acetylcholine determination in vitro He C, Wang Z, Wang Y, Hu R, Li G Ref: Biosensors & Bioelectronics, 85:679, 2016 : PubMed ESTHER: He_2016_Biosens.Bioelectron_85_679 PubMedSearch: He 2016 Biosens.Bioelectron 85 679 PubMedID: 27254787 Abstract A nonenzymatic all-solid-state coated wire acetylcholine electrode was investigated. Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT/PSS) as conducting polymer was coated on one end of a gold wire (0.5mm in diameter). The acetylcholine selective membrane containing heptakis(2,3,6-tri-Omicron-methyl)-beta-cyclodextrin as an ionophore covered the conducting polymer layer. The electrode could work stably in a pH range of 6.5-8.5 and a temperature range of 15-40 degrees C. It covered an acetylcholine concentration range of 10(-5)-10(-1)M with a slope of 54.04+/-1.70mV/decade, while detection limit was 5.69+/-1.06microM. The selectivity, dynamic response, reproducibility and stability were evaluated. The electrode could work properly in the rat brain homogenate to detect different concentrations of acetylcholine. Title: Enzymatic degradation of poly(butylene succinate) by cutinase cloned from Fusarium solani Hu X, Gao Z, Wang Z, Su T, Yang L, Li P Ref: Polymer Degradation and Stability, 134:211, 2016 : PubMed ESTHER: Hu_2016_Polym.Degrad.Stab_134_211 PubMedSearch: Hu 2016 Polym.Degrad.Stab 134 211 Gene_locus related to this paper: fusso-cutas Abstract A gene encoding cutinase from Fusarium solani was cloned and overexpressed in Pichia pastoris. The recombinant cutinase with a molecular weight of 24 kDa was then purified to homogeneity. The enzyme presents degradation capacity for poly(butylene succinate) (PBS) and exhibits the optimum pH and temperature of 8.0 and 50 C, respectively. Enzyme activity is enhanced by K+ and Na+ and inhibited by Zn2+,Fe2+ ,Mn2+, and Co2+. The inhibitions of different chemicals on recombinant enzyme activity were examined. EDTA and b-mercaptoethanol exert significant inhibitory effect. The degradation of PBS films in the presence of the recombinant enzyme was further studied. Results showed that enzymatic degradation is a rapid process, and the PBS fi lms were degraded completely after approximately 6 h. The characteristics of PBS films after degradation were analyzed. With the extension of degradation time, the surfaces of PBS films became rougher and holes appeared with a gradually increasing trend. Differential scanning calorimetry and scanning electron microscopy analyses revealed that both amorphous and crystalline regions of PBS were degraded by the recombinant enzyme. Wide-angle X-ray diffractometer also indicated the crystallinity of PBS has a gradual downward trend with the extension of degradation time. Gel permeation chromatography showed the molecular weight of PBS has no obvious change before and after degradation. Title: Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM Miao H, Ou J, Peng Y, Zhang X, Chen Y, Hao L, Xie G, Wang Z, Pang X and Liang H <6 more author(s)> Miao H, Ou J, Peng Y, Zhang X, Chen Y, Hao L, Xie G, Wang Z, Pang X, Ruan Z, Li J, Yu L, Xue B, Shi H, Shi C, Liang H (- 6) Ref: Nat Commun, 7:11716, 2016 : PubMed ESTHER: Miao_2016_Nat.Commun_7_11716 PubMedSearch: Miao 2016 Nat.Commun 7 11716 PubMedID: 27189574 Abstract Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPvarepsilon, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy. Title: Involvement of Three Esterase Genes from Panonychus citri (McGregor) in Fenpropathrin Resistance Shen XM, Liao CY, Lu XP, Wang Z, Wang JJ, Dou W Ref: Int J Mol Sci, 17:, 2016 : PubMed ESTHER: Shen_2016_Int.J.Mol.Sci_17_ PubMedSearch: Shen 2016 Int.J.Mol.Sci 17 PubMedID: 27548163 Abstract The citrus red mite, Panonychus citri (McGregor), is a major citrus pest with a worldwide distribution and an extensive record of pesticide resistance. However, the underlying molecular mechanism associated with fenpropathrin resistance in this species have not yet been reported. In this study, synergist triphenyl phosphate (TPP) dramatically increased the toxicity of fenpropathrin, suggesting involvement of carboxylesterases (CarEs) in the metabolic detoxification of this insecticide. The subsequent spatiotemporal expression pattern analysis of PcE1, PcE7 and PcE9 showed that three CarEs genes were all over-expressed after insecticide exposure and higher transcripts levels were observed in different field resistant strains of P. citri. Heterologous expression combined with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) cytotoxicity assay in Spodoptera frugiperda (Sf9) cells revealed that PcE1-, PcE7- or PcE9-expressing cells showed significantly higher cytoprotective capability than parental Sf9 cells against fenpropathrin, demonstrating that PcEs probably detoxify fenpropathrin. Moreover, gene silencing through the method of leaf-mediated dsRNA feeding followed by insecticide bioassay increased the mortalities of fenpropathrin-treated mites by 31% (PcE1), 27% (PcE7) and 22% (PcE9), respectively, after individual PcE gene dsRNA treatment. In conclusion, this study provides evidence that PcE1, PcE7 and PcE9 are functional genes mediated in fenpropathrin resistance in P. citri and enrich molecular understanding of CarEs during the resistance development of the mite. Title: Conifer flavonoid compounds inhibit detoxification enzymes and synergize insecticides Wang Z, Zhao Z, Cheng X, Liu S, Wei Q, Scott IM Ref: Pestic Biochem Physiol, 127:1, 2016 : PubMed ESTHER: Wang_2016_Pestic.Biochem.Physiol_127_1 PubMedSearch: Wang 2016 Pestic.Biochem.Physiol 127 1 PubMedID: 26821651 Abstract Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase inhibitors from phytochemicals could provide potential new insecticide synergists. Conifer tree species contain flavonoids, such as taxifolin, that inhibit in vitro GST activity. The objectives were to test the relative effectiveness of taxifolin as an enzyme inhibitor and as an insecticide synergist in combination with the organophosphorous insecticide, Guthion (50% azinphos-methyl), and the botanical insecticide, pyrethrum, using an insecticide-resistant Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say) strain. Both taxifolin and its isomer, quercetin, increased the mortality of 1(st) instar CPB larvae after 48h when combined with Guthion, but not pyrethrum. Taxifolin had greater in vitro esterase inhibition compared with the commonly used esterase inhibitor, S, S, S-tributyl phosphorotrithioate (DEF). An in vivo esterase and GST inhibition effect after ingestion of taxifolin was measured, however DEF caused a greater suppression of esterase activity. This study demonstrated that flavonoid compounds have both in vitro and in vivo esterase inhibition, which is likely responsible for the insecticide synergism observed in insecticide-resistant CPB. Title: Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives Wang Y, Sun Y, Guo Y, Wang Z, Huang L, Li X Ref: J Enzyme Inhib Med Chem, 31:389, 2016 : PubMed ESTHER: Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389 PubMedSearch: Wang 2016 J.Enzyme.Inhib.Med.Chem 31 389 PubMedID: 25798687 Abstract Because of the complexity of Alzheimer's disease (AD), the multi-target-directed ligand (MTDL) strategy is expected to provide superior effects for the treatment of AD, instead of the classic one-drug-one-target strategy. In this context, we focused on the design, synthesis and evaluation of homoisoflavonoid derivatives as dual acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B) inhibitors. Among all the synthesized compounds, compound 10 provided a desired balance of AChE and hMAO-B inhibition activities, with IC50 value of 3.94 and 3.44 muM, respectively. Further studies revealed that compound 10 was a mixed-type inhibitor of AChE and an irreversible inhibitor of hMAO-B, which was also confirmed by molecular modeling studies. Taken together, the data indicated that 10 was a promising dual functional agent for the treatment of AD. Title: Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans Wang Z, Xu S, Du K, Huang F, Chen Z, Zhou K, Ren W, Yang G Ref: Molecular Biology Evolution, 33:3144, 2016 : PubMed ESTHER: Wang_2016_Mol.Biol.Evol_33_3144 PubMedSearch: Wang 2016 Mol.Biol.Evol 33 3144 PubMedID: 27651393 Gene_locus related to this paper: souch-a0a1d8i1n4 Abstract Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans. Title: Dietary methionine level influences growth and lipid metabolism via GCN2 pathway in cobia (Rachycentron canadum) Wang Z, Mai K, Xu W, Zhang Y, Liu Y, Ai Q Ref: Aquaculture, 454:148, 2016 : PubMed ESTHER: Wang_2016_Aquaculture_454_148 PubMedSearch: Wang 2016 Aquaculture 454 148 Abstract This study investigated the effect of dietary methionine level on growth and lipid metabolism via the general control nonderepressible2 kinase (GCN2) pathway in cobia (Rachycentron canadum). Cobia were fed diets with six levels of methionine (0.62%, 0.84%, 1.02%, 1.15%, 1.25% and 1.42% of dry diet) with a constant cystine level (0.42% dry diet). The feeding experiment began in September 2013 and ended in December 2013; during the experiment, cobia were fed ad libitum twice daily (7:00 and 18:00h) for 10weeks. Cobia fed the diet with 1.02% methionine showed elevated weight gain (WG) and feed efficiency ratio (FER) compared with those fed the other diets (P<0.05). The content of liver lipid, total triglyceride, and total cholesterol were first enhanced significantly with increasing dietary methionine level from 0.62% to 1.02%, and then decreased markedly with higher levels of dietary methionine level (1.02% to 1.42%). Crude lipid was markedly elevated when the dietary methionine level was 1.02%, and then plateaued with higher dietary methionine level. The expression of genes associated with hepatic lipid synthesis (sterol regulatory element binding protein-1, peroxisome proliferator activated receptor , fatty acid synthetase, and stearoyl-CoA desaturase-1) were markedly up-regulated in fish fed the diet containing 1.02% methionine, whereas the transcriptional levels of lipolytic genes (peroxisome proliferator activated receptor , carnitine acyl transferase-1, and lipase lipoprotein lipase) were elevated in fish fed the methionine-deficient diet (0.62%; P<0.05). The expression of insulin-like growth factor-I (IGF-I) was suppressed by the methionine-deficient diet, whereas the hepatic mRNA expression levels of genes related to amino acid responses (AAR), i.e., GCN2, activating transcription factor 4 (ATF4), CCAAT enhancer binding protein (C/EBP), and asparagine synthetase (ASNS), were significantly up-regulated. In conclusion, the dietary methionine requirement of cobia was estimated to be 1.04% and 1.15% of dry matter (2.23% and 2.45% dietary protein) on the basis of WG and FER, respectively. Results of this study suggested that methionine deficiency could suppress growth, decrease lipid content, and inhibit expression of IGF-I and some genes related to lipid synthesis in cobia; these changes might be regulated by inducing the expression of genes related to the GCN2 pathway (GCN2, ATF4, C/EBP, and ASNS). Statement of relevance The present study was conducted to investigate the effect of dietary methionine on growth performance, plasma biochemical indexes, lipid content and gene expression involved in lipid metabolism and GCN2 pathway in cobia (Rachycentron canadum). Our findings have showed that methionine deficiency could suppress growth, decrease lipid content and inhibit expressions of IGF-I and some lipid synthesis related genes of cobia, which may be regulated by inducing the mRNA expressions of GCN2 pathway related genes (GCN2, ATF4, C/EBP and ASNS). The results are reliable and of both theoretical and practical importance. The work described has not been submitted elsewhere for publication, in whole or in part, and all the authors listed have approved the manuscript that is enclosed. I have read and have abided by the statement of ethical standards for manuscripts submitted to Aquaculture. Title: Chemical Constituents of Plants from the Genus Phlegmariurus Yang Y, Wang Z, Wu J, Chen Y Ref: Chem Biodivers, 13:269, 2016 : PubMed ESTHER: Yang_2016_Chem.Biodivers_13_269 PubMedSearch: Yang 2016 Chem.Biodivers 13 269 PubMedID: 26916276 Abstract Phlegmariurus is a genus of ca. 200 species in the family Huperziaceae. Up to now, six species of the Phlegmariurus genus have been chemically investigated, and 89 compounds, including Lycopodium alkaloids possessing diverse structures and serratane-type triterpenes, have been isolated. These compounds show potent bioactivities, such as acetylcholinesterase inhibitory and cytotoxic activities. Title: Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus) Yuan L, Li J, Zha J, Wang Z Ref: Environ Pollut, 208:670, 2016 : PubMed ESTHER: Yuan_2016_Environ.Pollut_208_670 PubMedSearch: Yuan 2016 Environ.Pollut 208 670 PubMedID: 26552522 Abstract Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. Title: Characterization of a Desiccation Stress Induced Lipase Gene from Brassica napus L. Zhang H, Zhou J, Zheng X, Zhang Z, Wang Z, Tan X Ref: J Agr Sci Tech, 18:1129, 2016 : PubMed ESTHER: Zhang_2016_J.Agr.Sci.Tech_18_1129 PubMedSearch: Zhang 2016 J.Agr.Sci.Tech 18 1129 Abstract Lipases are known to have important functions in many physiological processes in plants. Here, we cloned a lipase gene via Rapid Amplification of cDNA Ends (RACE) technique from Brassica napus L., designated as BnDIL1 (B. napus Desiccation-Induced Lipase 1). The lipase enzyme activity was confirmed by estimating the lipase activity and reduced lipids content in Saccharomyces cerevisiae (pep4) transformant. Two B. napus lines with different oil contents were employed to examine the transcription profiles of BnDIL1 during the processes of seed morphogenesis, maturation, dormancy, pregermination and germination. The transcription level of lipid degradation pathway was enhanced during the processes of seed maturation, dormancy, pregermination and germination, and was higher in seeds of low oil-contents line than that of high oil-contents line. However, BnDIL1 was significantly activated when seed desiccation started. Both slow desiccation and -fast desiccation- treatments on seedlings dramatically activated the transcription of BnDIL1, while only -slow desiccation- stress, which would induce the cell apoptosis, significantly activated the transcription of lipid degradation gene. This result demonstrated that BnDIL1 in B. napus was desiccation stress dependent gene rather than fatty acids degradation gene. Title: Biocatalytic Resolution of Rac-alpha-Ethyl-2-Oxo-Pyrrolidineacetic Acid Methyl Ester by Immobilized Recombinant Bacillus cereus Esterase Zheng JY, Liu YY, Luo WF, Zheng RC, Ying XX, Wang Z Ref: Appl Biochem Biotechnol, 178:1471, 2016 : PubMed ESTHER: Zheng_2016_Appl.Biochem.Biotechnol_178_1471 PubMedSearch: Zheng 2016 Appl.Biochem.Biotechnol 178 1471 PubMedID: 26695776 Abstract A new esterase-producing strain (Bacillus cereus WZZ001) which exhibiting high hydrolytic activity and excellent enantioselectivity on rac-alpha-ethyl-2-oxo-pyrrolidineacetic acid methyl ester (R, S-1) has been isolated from soil sample by our laboratory. In this study, the stereoselective hydrolysis of (R, S-1) was performed using the recombinant Bacillus cereus esterase which expressed in Escherichia coli BL21 (DE3). Under the optimized conditions of pH 8.0, 35 degrees C, and concentration of substrate 400 mM, a successful enzymatic resolution was achieved with an e.e. s of 99.5 % and conversion of 49 %. Immobilization considerably increased the reusability of the recombinant esterase; the immobilized enzyme showed excellent reusability during 6 cycles of repeated 2 h reactions at 35 degrees C. Thereby, it makes the recombinant B. cereus esterase a usable biocatalyst for industrial application. Title: Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T and Chen X <19 more author(s)> Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T, Ding Y, Nie L, Li Q, Dong WR, Jiang L, Sun B, Zhang X, Li M, Zhang HQ, Xie S, Zhu Y, Jiang X, Wang X, Mu P, Chen W, Yue Z, Wang Z, Wang J, Shao JZ, Chen X (- 19) Ref: PLoS Genet, 11:e1005118, 2015 : PubMed ESTHER: Ao_2015_PLoS.Genet_11_E1005118 PubMedSearch: Ao 2015 PLoS.Genet 11 E1005118 PubMedID: 25835551 Gene_locus related to this paper: larcr-a0a0f8ay25, larcr-a0a0f8cf53, larcr-a0a0f8cir1, larcr-a0a0f8d1j2, larcr-a0a0f8alq6, larcr-a0a0f8bdu4, larcr-a0a0f8abw1, larcr-a0a0f8ahh1, larcr-a0a0f8avc6, larcr-a0a0f8al93, larcr-a0a0f8aed8, larcr-a0a0f7ir14, larcr-a0a0f8aje8, larcr-k9lsm3, larcr-a0a0f8but5, larcr-a0a0f8af44 Abstract The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea. Title: Unraveling adaptation of Pontibacter korlensis to radiation and infertility in desert through complete genome and comparative transcriptomic analysis Dai J, Dai W, Qiu C, Yang Z, Zhang Y, Zhou M, Zhang L, Fang C, Gao Q and Chen X <4 more author(s)> Dai J, Dai W, Qiu C, Yang Z, Zhang Y, Zhou M, Zhang L, Fang C, Gao Q, Yang Q, Li X, Wang Z, Jia Z, Chen X (- 4) Ref: Sci Rep, 5:10929, 2015 : PubMed ESTHER: Dai_2015_Sci.Rep_5_10929 PubMedSearch: Dai 2015 Sci.Rep 5 10929 PubMedID: 26057562 Gene_locus related to this paper: 9bact-a0a0e3zf06, 9bact-a0a0e3zhq7 Abstract The desert is a harsh habitat for flora and microbial life due to its aridness and strong radiation. In this study, we constructed the first complete and deeply annotated genome of the genus Pontibacter (Pontibacter korlensis X14-1(T) = CCTCC AB 206081(T), X14-1). Reconstruction of the sugar metabolism process indicated that strain X14-1 can utilize diverse sugars, including cellulose, starch and sucrose; this result is consistent with previous experiments. Strain X14-1 is also able to resist desiccation and radiation in the desert through well-armed systems related to DNA repair, radical oxygen species (ROS) detoxification and the OstAB and TreYZ pathways for trehalose synthesis. A comparative transcriptomic analysis under gamma radiation revealed that strain X14-1 presents high-efficacy operating responses to radiation, including the robust expression of catalase and the manganese transport protein. Evaluation of 73 novel genes that are differentially expressed showed that some of these genes may contribute to the strain's adaptation to radiation and desiccation through ferric transport and preservation. Title: Resurfaced fluorescent protein as a sensing platform for label-free detection of copper(II) ion and acetylcholinesterase activity Lei C, Wang Z, Nie Z, Deng H, Hu H, Huang Y, Yao S Ref: Analytical Chemistry, 87:1974, 2015 : PubMed ESTHER: Lei_2015_Anal.Chem_87_1974 PubMedSearch: Lei 2015 Anal.Chem 87 1974 PubMedID: 25560517 Abstract Protein engineering by resurfacing is an efficient approach to provide new molecular toolkits for biotechnology and bioanalytical chemistry. H39GFP is a new variant of green fluorescent protein (GFP) containing 39 histidine residues in the primary sequence that was developed by protein resurfacing. Herein, taking H39GFP as the signal reporter, a label-free fluorometric sensor for Cu(2+) sensing was developed based on the unique multivalent metal ion-binding property of H39GFP and fluorescence quenching effect of Cu(2+) by electron transfer. The high affinity of H39GFP with Cu(2+) (Kd, 16.2 nM) leads to rapid detection of Cu(2+) in 5 min with a low detection limit (50 nM). Using acetylthiocholine (ATCh) as the substrate, this H39GFP/Cu(2+) complex-based sensor was further applied for the turn-on fluorescence detection of acetylcholinesterase (AChE) activity. The assay was based on the reaction between Cu(2+) and thiocholine, the hydrolysis product of ATCh by AChE. The proposed sensor is highly sensitive (limit of detection (LOD) = 0.015 mU mL(-1)) and is feasible for screening inhibitors of AChE. Furthermore, the practicability of this method was demonstrated by the detection of pesticide residue (carbaryl) in real food samples. Hence, the successful applications of H39GFP in the detection of metal ion and enzyme activity present the prospect of resurfaced proteins as versatile biosensing platforms. Title: In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor Liu W, Shi X, Yang Y, Cheng X, Liu Q, Han H, Yang B, He C, Wang Y and Wang C <2 more author(s)> Liu W, Shi X, Yang Y, Cheng X, Liu Q, Han H, Yang B, He C, Wang Y, Jiang B, Wang Z, Wang C (- 2) Ref: PLoS ONE, 10:e0122366, 2015 : PubMed ESTHER: Liu_2015_PLoS.One_10_e0122366 PubMedSearch: Liu 2015 PLoS.One 10 e0122366 PubMedID: 25849329 Inhibitor(s) related to this paper: Peganine Abstract Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising anticholinesterase activity in preclinical models and has been in development for treatment of Alzheimer's disease. This study systematically investigated the in vitro and in vivo metabolism of VAS in rat using ultra performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 72 metabolites were found based on a detailed analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-beta-D-glucuronide. The metabolic pathway of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl group and the C-9 site. All 72 metabolites were found in the urine sample, and 15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile, rat liver microsomes, and rat primary hepatocyte incubations, respectively. Results indicated that renal clearance was the major excretion pathway of VAS. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of VAS and its main metabolites were also evaluated. The results indicated that although most metabolites maintained potential inhibitory activity against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic inactivation process in vivo in respect to cholinesterase inhibitory activity. Title: Characterization of large structural genetic mosaicism in human autosomes Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB, Black A, Brinton LA, Chang IS, Chen C and Chanock SJ <188 more author(s)> Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB, Black A, Brinton LA, Chang IS, Chen C, Chen K, Cook LS, Crous Bou M, De Vivo I, Doherty J, Friedenreich CM, Gaudet MM, Haiman CA, Hankinson SE, Hartge P, Henderson BE, Hong YC, Hosgood HD, 3rd, Hsiung CA, Hu W, Hunter DJ, Jessop L, Kim HN, Kim YH, Kim YT, Klein R, Kraft P, Lan Q, Lin D, Liu J, Le Marchand L, Liang X, Lissowska J, Lu L, Magliocco AM, Matsuo K, Olson SH, Orlow I, Park JY, Pooler L, Prescott J, Rastogi R, Risch HA, Schumacher F, Seow A, Setiawan VW, Shen H, Sheng X, Shin MH, Shu XO, VanDen Berg D, Wang JC, Wentzensen N, Wong MP, Wu C, Wu T, Wu YL, Xia L, Yang HP, Yang PC, Zheng W, Zhou B, Abnet CC, Albanes D, Aldrich MC, Amos C, Amundadottir LT, Berndt SI, Blot WJ, Bock CH, Bracci PM, Burdett L, Buring JE, Butler MA, Carreon T, Chatterjee N, Chung CC, Cook MB, Cullen M, Davis FG, Ding T, Duell EJ, Epstein CG, Fan JH, Figueroa JD, Fraumeni JF, Jr., Freedman ND, Fuchs CS, Gao YT, Gapstur SM, Patino-Garcia A, Garcia-Closas M, Gaziano JM, Giles GG, Gillanders EM, Giovannucci EL, Goldin L, Goldstein AM, Greene MH, Hallmans G, Harris CC, Henriksson R, Holly EA, Hoover RN, Hu N, Hutchinson A, Jenab M, Johansen C, Khaw KT, Koh WP, Kolonel LN, Kooperberg C, Krogh V, Kurtz RC, Lacroix A, Landgren A, Landi MT, Li D, Liao LM, Malats N, McGlynn KA, McNeill LH, McWilliams RR, Melin BS, Mirabello L, Peplonska B, Peters U, Petersen GM, Prokunina-Olsson L, Purdue M, Qiao YL, Rabe KG, Rajaraman P, Real FX, Riboli E, Rodriguez-Santiago B, Rothman N, Ruder AM, Savage SA, Schwartz AG, Schwartz KL, Sesso HD, Severi G, Silverman DT, Spitz MR, Stevens VL, Stolzenberg-Solomon R, Stram D, Tang ZZ, Taylor PR, Teras LR, Tobias GS, Viswanathan K, Wacholder S, Wang Z, Weinstein SJ, Wheeler W, White E, Wiencke JK, Wolpin BM, Wu X, Wunder JS, Yu K, Zanetti KA, Zeleniuch-Jacquotte A, Ziegler RG, de Andrade M, Barnes KC, Beaty TH, Bierut LJ, Desch KC, Doheny KF, Feenstra B, Ginsburg D, Heit JA, Kang JH, Laurie CA, Li JZ, Lowe WL, Marazita ML, Melbye M, Mirel DB, Murray JC, Nelson SC, Pasquale LR, Rice K, Wiggs JL, Wise A, Tucker M, Perez-Jurado LA, Laurie CC, Caporaso NE, Yeager M, Chanock SJ (- 188) Ref: American Journal of Human Genetics, 96:487, 2015 : PubMed ESTHER: Machiela_2015_Am.J.Hum.Genet_96_487 PubMedSearch: Machiela 2015 Am.J.Hum.Genet 96 487 PubMedID: 25748358 Abstract Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. Title: The high-resolution crystal structure of human LCAT Piper DE, Romanow WG, Gunawardane RN, Fordstrom P, Masterman S, Pan O, Thibault ST, Zhang R, Meininger D and Walker NP <4 more author(s)> Piper DE, Romanow WG, Gunawardane RN, Fordstrom P, Masterman S, Pan O, Thibault ST, Zhang R, Meininger D, Schwarz M, Wang Z, King C, Zhou M, Walker NP (- 4) Ref: J Lipid Res, 56:1711, 2015 : PubMed ESTHER: Piper_2015_J.Lipid.Res_56_1711 PubMedSearch: Piper 2015 J.Lipid.Res 56 1711 PubMedID: 26195816 Gene_locus related to this paper: human-LCAT Abstract LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. Here we report the 2.65 A crystal structure of the human LCAT protein. Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. The crystal structure reveals that LCAT has an alpha/beta hydrolase core with two additional subdomains that play important roles in LCAT function. Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity. Title: Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats Shen H, Chen Z, Wang Y, Gao A, Li H, Cui Y, Zhang L, Xu X, Wang Z, Chen G Ref: Stroke, 46:2607, 2015 : PubMed ESTHER: Shen_2015_Stroke_46_2607 PubMedSearch: Shen 2015 Stroke 46 2607 PubMedID: 26219651 Abstract BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. Title: Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression Ventura R, Mordec K, Waszczuk J, Wang Z, Lai J, Fridlib M, Buckley D, Kemble G, Heuer TS Ref: EBioMedicine, 2:808, 2015 : PubMed ESTHER: Ventura_2015_EBioMedicine_2_808 PubMedSearch: Ventura 2015 EBioMedicine 2 808 PubMedID: 26425687 Abstract Inhibition of de novo palmitate synthesis via fatty acid synthase (FASN) inhibition provides an unproven approach to cancer therapy with a strong biological rationale. FASN expression increases with tumor progression and associates with chemoresistance, tumor metastasis, and diminished patient survival in numerous tumor types. TVB-3166, an orally-available, reversible, potent, and selective FASN inhibitor induces apoptosis, inhibits anchorage-independent cell growth under lipid-rich conditions, and inhibits in-vivo xenograft tumor growth. Dose-dependent effects are observed between 20-200snM TVB-3166, which agrees with the IC50 in biochemical FASN and cellular palmitate synthesis assays. Mechanistic studies show that FASN inhibition disrupts lipid raft architecture, inhibits biological pathways such as lipid biosynthesis, PI3K-AKT-mTOR and beta-catenin signal transduction, and inhibits expression of oncogenic effectors such as c-Myc; effects that are tumor-cell specific. Our results demonstrate that FASN inhibition has anti-tumor activities in biologically diverse preclinical tumor models and provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers, including those expressing mutant K-Ras, ErbB2, c-Met, and PTEN. The reported findings inform ongoing studies to link mechanisms of action with defined tumor types and advance the discovery of biomarkers supporting development of FASN inhibitors as cancer therapeutics. RESEARCH IN CONTEXT: Fatty acid synthase (FASN) is a vital enzyme in tumor cell biology; the over-expression of FASN is associated with diminished patient prognosis and resistance to many cancer therapies. Our data demonstrate that selective and potent FASN inhibition with TVB-3166 leads to selective death of tumor cells, without significant effect on normal cells, and inhibits in vivo xenograft tumor growth at well-tolerated doses. Candidate biomarkers for selecting tumors highly sensitive to FASN inhibition are identified. These preclinical data provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers. Title: Butyrylcholinesterase K Variant and Alzheimer's Disease Risk: A Meta-Analysis Wang Z, Jiang Y, Wang X, Du Y, Xiao D, Deng Y, Wang J Ref: Med Sci Monit, 21:1408, 2015 : PubMed ESTHER: Wang_2015_Med.Sci.Monit_21_1408 PubMedSearch: Wang 2015 Med.Sci.Monit 21 1408 PubMedID: 25978873 Abstract Background Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. Material and Methods We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE epsilon4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE epsilon4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). Conclusions The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk. Title: Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P and Ye J <6 more author(s)> Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P, Zhang X, Gu Y, Xu Y, Wang Z, Li Z, Zhang H, Ye J (- 6) Ref: Hepatology, 61:870, 2015 : PubMed ESTHER: Wang_2015_Hepatology_61_870 PubMedSearch: Wang 2015 Hepatology 61 870 PubMedID: 25179419 Abstract Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. Title: 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism Wang Z, Chen Z, Xu S, Ren W, Zhou K, Yang G Ref: Sci Rep, 5:14187, 2015 : PubMed ESTHER: Wang_2015_Sci.Rep_5_14187 PubMedSearch: Wang 2015 Sci.Rep 5 14187 PubMedID: 26381091 Gene_locus related to this paper: delle-a0a2y9m8t8, lipve-a0a0n6wyt2 Abstract Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans. Title: FgRIC8 is involved in regulating vegetative growth, conidiation, deoxynivalenol production and virulence in Fusarium graminearum Wu J, Liu Y, Lv W, Yue X, Que Y, Yang N, Zhang Z, Ma Z, Talbot NJ, Wang Z Ref: Fungal Genet Biol, 83:92, 2015 : PubMed ESTHER: Wu_2015_Fungal.Genet.Biol_83_92 PubMedSearch: Wu 2015 Fungal.Genet.Biol 83 92 PubMedID: 26341536 Abstract Proteins of the resistance to inhibitors of cholinesterase 8 (Ric8) group act as guanine nucleotide exchange factors (GEFs) and play important roles in regulating G-protein signaling in animals. In filamentous fungi, putative Ric8 orthologs have so far been identified in Magnaporthe oryzae, Neurospora crassa, Aspergillus nidulans and Aspergillus fumigatus. Here, we report the functional investigation of a potential RIC8 ortholog (FgRIC8) in the wheat head blight pathogen Fusarium graminearum. Targeted gene deletion mutants of FgRIC8 exhibited a significant reduction in vegetative growth, conidiation, pigment production as well as deoxynivalenol (DON) biosynthesis. Pathogenicity assays using a point-inoculated spikelet approach showed that the mutants were severely impaired in virulence on flowering wheat heads. Quantitative RT-PCR analysis revealed that genes encoding F. graminearum Galpha (FgGpa1 and FgGpa3), Gbeta (FgGpb1) and Ggamma (FgGpg1) subunits were significantly down-regulated in Fgric8 mutants. Moreover, we showed that FgRic8 physically interacts with both FgGpa1 and FgGpa3, but not FgGpa2, in yeast two-hybrid assays. The intracellular cAMP levels in Fgric8 mutants were significantly decreased compared to the isogenic wild-type strain. Taken together, our results indicate that FgRic8 plays critical roles in fungal development, secondary metabolism and virulence in F. graminearum and may act as a regulator of G protein alpha subunits. Title: Comprehensive characterization of a time-course transcriptional response induced by autotoxins in Panax ginseng using RNA-Seq Wu B, Long Q, Gao Y, Wang Z, Shao T, Liu Y, Li Y, Ding W Ref: BMC Genomics, 16:1010, 2015 : PubMed ESTHER: Wu_2015_BMC.Genomics_16_1010 PubMedSearch: Wu 2015 BMC.Genomics 16 1010 PubMedID: 26608743 Abstract BACKGROUND: As a valuable medicinal plant, the yield of Panax ginseng is seriously affected by autotoxicity, which is a common phenomenon due to continuous cropping. However, the mechanism of autotoxicity in P. ginseng is still unknown. Title: Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation Yang Y, Cheng X, Liu W, Chou G, Wang Z, Wang C Ref: J Ethnopharmacol, 168:279, 2015 : PubMed ESTHER: Yang_2015_J.Ethnopharmacol_168_279 PubMedSearch: Yang 2015 J.Ethnopharmacol 168 279 PubMedID: 25862961 Inhibitor(s) related to this paper: Peganine Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. AIM OF THE STUDY: The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). MATERIALS AND Title: Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y and Wan P <17 more author(s)> Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y, Li W, Chen Y, Zhang Y, Ai D, Zhao J, Shang C, Ma Y, Wu B, Wang M, Gao L, Sun D, Zhang P, Guo F, Wang W, Wang J, Varshney RK, Ling HQ, Wan P (- 17) Ref: Proc Natl Acad Sci U S A, 112:13213, 2015 : PubMed ESTHER: Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213 PubMedSearch: Yang 2015 Proc.Natl.Acad.Sci.U.S.A 112 13213 PubMedID: 26460024 Gene_locus related to this paper: phaan-a0a0l9ttq5, phaan-a0a0l9vh69, phaan-a0a0l9vh89, phaan-a0a0s3tc53, vigrr-a0a1s3v914, phaan-a0a0s3s998, phaan-a0a0s3siv8, phaan-a0a0l9uys5, phaan-a0a0s3rp07, phaan-a0a0s3rbq0, vigrr-a0a1s3tul4, phaan-a0a0s3smk7, phaan-a0a0s3slm9, phaan-a0a0l9ujf5, phaan-a0a0l9til9, phaan-a0a0l9uqr2, phaan-a0a0l9v1m8, phaan-a0a0l9uc60, phaan-a0a0l9ucr8 Abstract Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean. Title: [Effects of lingonberry extraction on the mice cognitive function damaged by chronic stress] Zuo C, Li W, Wang L, Zhu J, Wang Z Ref: Wei Sheng Yan Jiu, 44:943, 2015 : PubMed ESTHER: Zuo_2015_Wei.Sheng.Yan.Jiu_44_943 PubMedSearch: Zuo 2015 Wei.Sheng.Yan.Jiu 44 943 PubMedID: 26738388 Abstract OBJECTIVE: To study the effects of lingonberry extraction on mice cognitive impairment caused by chronic stress. Title: Comparative genomic and transcriptomic analysis of wangiella dermatitidis, a major cause of phaeohyphomycosis and a model black yeast human pathogen Chen Z, Martinez DA, Gujja S, Sykes SM, Zeng Q, Szaniszlo PJ, Wang Z, Cuomo CA Ref: G3 (Bethesda), 4:561, 2014 : PubMed ESTHER: Chen_2014_G3.(Bethesda)_4_561 PubMedSearch: Chen 2014 G3.(Bethesda) 4 561 PubMedID: 24496724 Gene_locus related to this paper: exodn-h6bmp3, exodn-h6btr2, exodn-h6c4y3 Abstract Black or dark brown (phaeoid) fungi cause cutaneous, subcutaneous, and systemic infections in humans. Black fungi thrive in stressful conditions such as intense light, high radiation, and very low pH. Wangiella (Exophiala) dermatitidis is arguably the most studied phaeoid fungal pathogen of humans. Here, we report our comparative analysis of the genome of W. dermatitidis and the transcriptional response to low pH stress. This revealed that W. dermatitidis has lost the ability to synthesize alpha-glucan, a cell wall compound many pathogenic fungi use to evade the host immune system. In contrast, W. dermatitidis contains a similar profile of chitin synthase genes as related fungi and strongly induces genes involved in cell wall synthesis in response to pH stress. The large portfolio of transporters may provide W. dermatitidis with an enhanced ability to remove harmful products as well as to survive on diverse nutrient sources. The genome encodes three independent pathways for producing melanin, an ability linked to pathogenesis; these are active during pH stress, potentially to produce a barrier to accumulated oxidative damage that might occur under stress conditions. In addition, a full set of fungal light-sensing genes is present, including as part of a carotenoid biosynthesis gene cluster. Finally, we identify a two-gene cluster involved in nucleotide sugar metabolism conserved with a subset of fungi and characterize a horizontal transfer event of this cluster between fungi and algal viruses. This work reveals how W. dermatitidis has adapted to stress and survives in diverse environments, including during human infections. Title: Rapid and sensitive detection of the inhibitive activities of acetyl- and butyryl-cholinesterases inhibitors by UPLC-ESI-MS/MS Liu W, Yang Y, Cheng X, Gong C, Li S, He D, Yang L, Wang Z, Wang C Ref: J Pharm Biomed Anal, 94:215, 2014 : PubMed ESTHER: Liu_2014_J.Pharm.Biomed.Anal_94_215 PubMedSearch: Liu 2014 J.Pharm.Biomed.Anal 94 215 PubMedID: 24631841 Abstract Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are legitimate therapeutic targets for Alzheimer's disease. The classical approach for screening potential AChE/BChE inhibitors was developed by Ellman. However, the background color of compounds or plant extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Rapid, selective, and sensitive ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry method was developed and used for the detection of AChE and BChE inhibition by directly determining the common product, choline (Ch). Proper separation was achieved for choline and chlormequat (internal standard) within 1.2min via isocratic elution (0.1% fromic acid:methanol=98:2) on an HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of the intra- and inter-day precisions were below 7.34 and 9.09%, respectively, whereas the mean accuracy for the quality control samples was 100.31+/-10.93%. The method exhibited the advantages of small total reaction volume (100muL), short analysis time (1.2min), high sensitivity (LOQ of 0.036muM for Ch), and low cost (little consumption enzymes of 0.0035 and 0.008unitmL(-1) for AChE and BChE, and substrates of 5.505 and 7.152muM for ACh and BCh in individual inhibition, respectively), and without matrix effect (90.00-105.03%). The developed method was successfully applied for detecting the AChE and BChE inhibitive activities for model drugs, including galanthamine, tacrine, neostigmine methylsulfate, eserine, as well as beta-carboline and quinazoline alkaloids from Peganum harmala. Title: Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears Liu S, Lorenzen ED, Fumagalli M, Li B, Harris K, Xiong Z, Zhou L, Korneliussen TS, Somel M and Wang J <19 more author(s)> Liu S, Lorenzen ED, Fumagalli M, Li B, Harris K, Xiong Z, Zhou L, Korneliussen TS, Somel M, Babbitt C, Wray G, Li J, He W, Wang Z, Fu W, Xiang X, Morgan CC, Doherty A, O'Connell MJ, McInerney JO, Born EW, Dalen L, Dietz R, Orlando L, Sonne C, Zhang G, Nielsen R, Willerslev E, Wang J (- 19) Ref: Cell, 157:785, 2014 : PubMed ESTHER: Liu_2014_Cell_157_785 PubMedSearch: Liu 2014 Cell 157 785 PubMedID: 24813606 Gene_locus related to this paper: ursma-a0a384cw87, ursma-a0a384cqm7, ursma-a0a452vbh6, ursma-a0a384cyu0 Abstract Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans. Title: Study on the interaction of catalase with pesticides by flow injection chemiluminescence and molecular docking Tan X, Wang Z, Chen D, Luo K, Xiong X, Song Z Ref: Chemosphere, 108:26, 2014 : PubMed ESTHER: Tan_2014_Chemosphere_108_26 PubMedSearch: Tan 2014 Chemosphere 108 26 PubMedID: 24875908 Abstract The interaction mechanisms of catalase (CAT) with pesticides (including organophosphates: disulfoton, isofenphos-methyl, malathion, isocarbophos, dimethoate, dipterex, methamidophos and acephate; carbamates: carbaryl and methomyl; pyrethroids: fenvalerate and deltamethrin) were first investigated by flow injection (FI) chemiluminescence (CL) analysis and molecular docking. By homemade FI-CL model of lg[(I0-I)/I]=lgK+nlg[D], it was found that the binding processes of pesticides to CAT were spontaneous with the apparent binding constants K of 10(3)-10(5) L mol(-1) and the numbers of binding sites about 1.0. The binding abilities of pesticides to CAT followed the order: fenvalerate>deltamethrin>disulfoton>isofenphos-methyl>carbaryl>malathion>isocarbo phos>dimethoate>dipterex>acephate>methomyl>methamidophos, which was generally similar to the order of determination sensitivity of pesticides. The thermodynamic parameters revealed that CAT bound with hydrophobic pesticides by hydrophobic interaction force, and with hydrophilic pesticides by hydrogen bond and van der Waals force. The pesticides to CAT molecular docking study showed that pesticides could enter into the cavity locating among the four subdomains of CAT, giving the specific amino acid residues and hydrogen bonds involved in CAT-pesticides interaction. It was also found that the lgK values of pesticides to CAT increased regularly with increasing lgP, Mr, MR and MV, suggesting that the hydrophobicity and steric property of pesticide played essential roles in its binding to CAT. Title: Structural and functional characterization of a novel alpha/beta hydrolase from cariogenic pathogen Streptococcus mutans Wang Z, Li L, Su XD Ref: Proteins, 82:695, 2014 : PubMed ESTHER: Wang_2014_Proteins_82_695 PubMedSearch: Wang 2014 Proteins 82 695 PubMedID: 24115105 Gene_locus related to this paper: strmu-SMU.1393C Abstract The protein Smu.1393c from Streptococcus mutans is annotated as a putative alpha/beta hydrolase, but it has low sequence identity to the structure-known alpha/beta hydrolases. Here we present the crystal structure of Smu.1393c at 2.0 A resolution. Smu.1393c has a fully open alkaline substrate pocket, whose conformation is unique among other similar hydrolase structures. Three residues, Ser101, His251, and Glu125, were identified as the active center of Smu.1393c. By screening a series of artificial hydrolase substrates, we demonstrated Smu.1393c had low carboxylesterase activity towards short-chain carboxyl esters, which provided a clue for exploring the in vivo function of Smu.1393c. Proteins 2014; 82:695-700. (c) 2013 Wiley Periodicals, Inc. Title: Lignin binding to pancreatic lipase and its influence on enzymatic activity Zhang J, Xiao L, Yang Y, Wang Z, Li G Ref: Food Chem, 149:99, 2014 : PubMed ESTHER: Zhang_2014_Food.Chem_149_99 PubMedSearch: Zhang 2014 Food.Chem 149 99 PubMedID: 24295682 Abstract In this paper, we find that the effect of lignin on pancreatic lipase (PL) is dependent on reaction medium and substrate used. Experimental results reveal that lignin can gradually bind to PL to form a PL-lignin complex, resulting in an increased activity of the enzyme. The binding process is spontaneous and the PL-lignin complex formation is an endothermic reaction induced by hydrophobic and electrostatic interaction. There is a non-radiation energy transfer from PL to lignin during the binding process, and the binding of lignin to PL conforms to a secondary exponential decay function. Moreover, the alpha-helix content of the enzyme will be changed and the rigidity of its side chain will be enhanced due to the formation of lignin-PL complex. This study has not only provided the activation effect of lignin on PL, but also given an insight into the interaction between lignin and the enzyme, which would benefit the application of lignin in the pharmacy and food industry, as well as other fields. Title: Enzymatic resolution of ibuprofen in an organic solvent under ultrasound irradiation Zhao D, Yue H, Chen G, Jiang L, Zhang H, Wang Z, Liu G Ref: Biotechnol Appl Biochem, 61:655, 2014 : PubMed ESTHER: Zhao_2014_Biotechnol.Appl.Biochem_61_655 PubMedSearch: Zhao 2014 Biotechnol.Appl.Biochem 61 655 PubMedID: 24698427 Abstract Ultrasound has been successfully adopted to improve the biocatalytic properties of APE1547 (a novel esterase from the archaeon Aeropyrum pernix K1) in the resolution of ibuprofen. After optimizing the conditions (ultrasound power, 200 W; temperature, 35 degrees C), the best biocatalytic performance of APE1547 (enzyme activity, 5.39 micromol/H/mg; E value, 130.8) was obtained. Compared with the conventional reaction in an orbital shaker, the enzyme activity was significantly enhanced about 90-fold, and the enantioselectivity was enhanced about fourfold after an ultrasound. The results of scanning electron microscopy clearly indicated that the activation effect of ultrasound on APE1547 originated mainly in the morphological change of the enzyme powder. Both lower particle size and conformational change of APE1547 under ultrasound might be helpful to enhance the enantioselectivity. In addition, APE1547 kept its best performance under the low-power ultrasound for at least five reaction cycles. Title: Purification, Characterization, and Sensitivity to Pesticides of Carboxylesterase From Dendrolimus superans (Lepidoptera: Lasiocampidae) Zou C, Cao C, Zhang G, Wang Z Ref: J Insect Sci, 14:, 2014 : PubMed ESTHER: Zou_2014_J.Insect.Sci_14_ PubMedSearch: Zou 2014 J.Insect.Sci 14 PubMedID: 25525114 Abstract Through a combination of steps including centrifugation, ammonium sulfate gradient precipitation, sephadex G-25 gel chromatography, diethylaminoethyl cellulose 52 ion-exchange chromatography and hydroxyapatite affinity chromatography, carboxylesterase (CarE, EC3.1.1.1) from sixth instar larch caterpillar moth, Dendrolimus superans (Lepidoptera: Lasiocampidae) larvae was purified and its biochemical properties were compared between crude homogenate and purified CarE. The final purified CarE after hydroxyapatite chromatography had a specific activity of 52.019 mumol/(min.mg protein), 138.348-fold of crude homogenate, and the yield of 2.782%. The molecular weight of the purified CarE was approximately 84.78 kDa by SDS-PAGE. Three pesticides (dichlorvos, lambda-cyhalothrin, and avermectins) showed different inhibition to crude CarE and purified CarE, respectively. In vitro median inhibitory concentration indicated that the sensitivity of CarE (both crude homogenate and final purified CarE) to pesticides was in decreasing order of dichlorvos > avermectins > lambda-cyhalothrin. By the kinetic analysis, the substrates alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA) showed lesser affinity to crude extract than purified CarE. The results also indicated that both crude homogenate and purified CarE had more affinity to alpha-NA than to beta-NA, and the Kcat and Vmax values of crude extract were lower than purified CarE using alpha-NA or beta-NA as substrate. Title: Remote brain network changes after unilateral cortical impact injury and their modulation by acetylcholinesterase inhibition Holschneider DP, Guo Y, Wang Z, Roch M, Scremin OU Ref: Journal of Neurotrauma, 30:907, 2013 : PubMed ESTHER: Holschneider_2013_J.Neurotrauma_30_907 PubMedSearch: Holschneider 2013 J.Neurotrauma 30 907 PubMedID: 23343118 Abstract We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [(14)C]-iodoantipyrine. Quantitative autoradiographs were analyzed by statistical parametric mapping and functional connectivity (FC) analysis. CCI resulted in functional deficits in the ipsilesional basal ganglia, with increased activation contralesionally. Recruitment was also observed, especially contralesionally, of the red nucleus, superior colliculus, pedunculopontine tegmental nucleus, thalamus (ventrolateral n., central medial n.), cerebellum, and sensory cortex. FC decreased significantly within ipsi- and contralesional motor circuits and between hemispheres, but increased between midline cerebellum and select regions of the basal ganglia within each hemisphere. Physostigmine significantly increased functional brain activation in the cerebellar thalamocortical pathway (midline cerebellum-->ventrolateral thalamus-->motor cortex), subthalamic nucleus/zona incerta, and red nucleus and bilateral sensory cortex. In conclusion, CCI resulted in increased functional recruitment of contralesional motor cortex and bilateral subcortical motor regions, as well as recruitment of the cerebellar-thalamocortical circuit and contralesional sensory cortex. This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation. Title: Draft genome of the wheat A-genome progenitor Triticum urartu Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L and Zhang A <39 more author(s)> Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L, Tao Y, Gao C, Wu H, Li Y, Cui Y, Guo X, Zheng S, Wang B, Yu K, Liang Q, Yang W, Lou X, Chen J, Feng M, Jian J, Zhang X, Luo G, Jiang Y, Liu J, Wang Z, Sha Y, Zhang B, Tang D, Shen Q, Xue P, Zou S, Wang X, Liu X, Wang F, Yang Y, An X, Dong Z, Zhang K, Luo MC, Dvorak J, Tong Y, Yang H, Li Z, Wang D, Zhang A (- 39) Ref: Nature, 496:87, 2013 : PubMed ESTHER: Ling_2013_Nature_496_87 PubMedSearch: Ling 2013 Nature 496 87 PubMedID: 23535596 Gene_locus related to this paper: triua-m8a764, triua-m8ag96, triua-m7zp69, wheat-w5d1z6, wheat-w5d232, wheat-w5bnf5, triua-t1nm05, wheat-w5cae4, triua-m7ytf7, wheat-w5f1j8, triua-m8ad49, wheat-a0a077s1q2, wheat-a0a3b6c2m6, triua-m7zi26, wheat-a0a3b6at77 Abstract Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat. Title: Acetylcholinesterase-catalyzed hydrolysis allows ultrasensitive detection of pathogens with the naked eye Liu D, Wang Z, Jin A, Huang X, Sun X, Wang F, Yan Q, Ge S, Xia N and Chen X <3 more author(s)> Liu D, Wang Z, Jin A, Huang X, Sun X, Wang F, Yan Q, Ge S, Xia N, Niu G, Liu G, Hight Walker AR, Chen X (- 3) Ref: Angew Chem Int Ed Engl, 52:14065, 2013 : PubMed ESTHER: Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065 PubMedSearch: Liu 2013 Angew.Chem.Int.Ed.Engl 52 14065 PubMedID: 24155243 Abstract Seeing is believing: A rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction has been developed. Owing to signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of the assay is based on solution color change, which can be easily observed by the naked eye alone. Title: The assessment of environmental pollution along the coast of Beibu Gulf, northern South China Sea: an integrated biomarker approach in the clam Meretrix meretrix Meng F, Wang Z, Cheng F, Du X, Fu W, Wang Q, Yi X, Li Y, Zhou Y Ref: Mar Environ Research, 85:64, 2013 : PubMed ESTHER: Meng_2013_Mar.Environ.Res_85_64 PubMedSearch: Meng 2013 Mar.Environ.Res 85 64 PubMedID: 23422511 Abstract The clam Meretrix meretrix was used as a biomonitor to implement an environmental monitoring program along the coast of Beibu Gulf in October 2011. This program not only analyzed biomarkers including acetylcholinesterase, glutathione peroxidase, glutathione S-transferase, catalase and superoxide dismutase activities, total glutathione content and lipid peroxidation level in M. meretrix but also adopted a multi-biomarker approach - integrated biomarker response (IBR) to assess the environmental quality in this ecosystem. In addition, the metal (Hg, As, Cu, Pb, Zn, Cd and Cr) and polychlorinated biphenyls (PCBs) content in the surface sediment at the study area were also measured. The results showed that IBR index was able to distinguish a space trend between sampling sites with different degrees of anthropogenic environmental stress. Integrated contamination degree were displayed in the form of star plots and compared to IBR plots. There was a visual consistency between the pollution level and IBR variation. Based on the results, it was proved that the IBR method coupled with chemical analysis was quite useful for the assessment of environmental pollution in the coastal system. Title: An Inhibitory Antibody against Dipeptidyl Peptidase IV Improves Glucose Tolerance in Vivo Tang J, Majeti J, Sudom A, Xiong Y, Lu M, Liu Q, Higbee J, Zhang Y, Wang Y and Wang Z <12 more author(s)> Tang J, Majeti J, Sudom A, Xiong Y, Lu M, Liu Q, Higbee J, Zhang Y, Wang Y, Wang W, Cao P, Xia Z, Johnstone S, Min X, Yang X, Shao H, Yu T, Sharkov N, Walker N, Tu H, Shen W, Wang Z (- 12) Ref: Journal of Biological Chemistry, 288:1307, 2013 : PubMed ESTHER: Tang_2013_J.Biol.Chem_288_1307 PubMedSearch: Tang 2013 J.Biol.Chem 288 1307 PubMedID: 23184939 Gene_locus related to this paper: ratno-dpp4 Abstract Dipeptidyl peptidase IV (DPP-IV) degrades the incretin hormone glucagon-like peptide 1 (GLP-1). Small molecule DPP-IV inhibitors have been used as treatments for type 2 diabetes to improve glucose tolerance. However, each of the marketed small molecule drugs has its own limitation in terms of efficacy and side effects. To search for an alternative strategy of inhibiting DPP-IV activity, we generated a panel of tight binding inhibitory mouse monoclonal antibodies (mAbs) against rat DPP-IV. When tested in vitro, these mAbs partially inhibited the GLP-1 cleavage activity of purified enzyme and rat plasma. To understand the partial inhibition, we solved the co-crystal structure of one of the mAb Fabs (Ab1) in complex with rat DPP-IV. Although Ab1 does not bind at the active site, it partially blocks the side opening, which prevents the large substrates such as GLP-1 from accessing the active site, but not small molecules such as sitagliptin. When Ab1 was tested in vivo, it reduced plasma glucose and increased plasma GLP-1 concentration during an oral glucose tolerance test in rats. Together, we demonstrated the feasibility of using mAbs to inhibit DPP-IV activity and to improve glucose tolerance in a diabetic rat model. 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: Draft Genome Sequence of the Fast-Growing Marine Bacterium Vibrio natriegens Strain ATCC 14048 Wang Z, Lin B, Hervey WJt, Vora GJ Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Wang_2013_Genome.Announc_1_e00589 PubMedSearch: Wang 2013 Genome.Announc 1 e00589 PubMedID: 23929482 Gene_locus related to this paper: 9vibr-h2ift0, vibna-s6lg09, vibna-s6l8z7, 9vibr-h2ihh3 Abstract Vibrio natriegens bacteria are Gram-negative aquatic microorganisms that are found primarily in coastal seawater and sediments and are perhaps best known for their high growth rates (generation time of <10 min). In this study, we report the first sequenced genome of this species, that of the type strain Vibrio natriegens ATCC 14048, a salt marsh mud isolate from Sapelo Island, GA. Title: Vibrio campbellii hmgA-mediated pyomelanization impairs quorum sensing, virulence, and cellular fitness Wang Z, Lin B, Mostaghim A, Rubin RA, Glaser ER, Mittraparp-Arthorn P, Thompson JR, Vuddhakul V, Vora GJ Ref: Front Microbiol, 4:379, 2013 : PubMed ESTHER: Wang_2013_Front.Microbiol_4_379 PubMedSearch: Wang 2013 Front.Microbiol 4 379 PubMedID: 24376440 Gene_locus related to this paper: vibcb-a7n1h5, vibcy-a6awa8 Abstract Melanization due to the inactivation of the homogentisate-1,2-dioxygenase gene (hmgA) has been demonstrated to increase stress resistance, persistence, and virulence in some bacterial species but such pigmented mutants have not been observed in pathogenic members of the Vibrio Harveyi clade. In this study, we used Vibrio campbellii ATCC BAA-1116 as model organism to understand how melanization affected cellular phenotype, metabolism, and virulence. An in-frame deletion of the hmgA gene resulted in the overproduction of a pigment in cell culture supernatants and cellular membranes that was identified as pyomelanin. Unlike previous demonstrations in Vibrio cholerae, Burkholderia cepacia, and Pseudomonas aeruginosa, the pigmented V. campbellii mutant did not show increased UV resistance and was found to be ~2.7 times less virulent than the wild type strain in Penaeus monodon shrimp virulence assays. However, the extracted pyomelanin pigment did confer a higher resistance to oxidative stress when incubated with wild type cells. Microarray-based transcriptomic analyses revealed that the hmgA gene deletion and subsequent pyomelanin production negatively effected the expression of 129 genes primarily involved in energy production, amino acid, and lipid metabolism, and protein translation and turnover. This transcriptional response was mediated in part by an impairment of the quorum sensing regulon as transcripts of the quorum sensing high cell density master regulator LuxR and other operonic members of this regulon were significantly less abundant in the hmgA mutant. Taken together, the results suggest that the pyomelanization of V. campbellii sufficiently impairs the metabolic activities of this organism and renders it less fit and virulent than its isogenic wild type strain. Title: The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan Wang Z, Pascual-Anaya J, Zadissa A, Li W, Niimura Y, Huang Z, Li C, White S, Xiong Z and Irie N <22 more author(s)> Wang Z, Pascual-Anaya J, Zadissa A, Li W, Niimura Y, Huang Z, Li C, White S, Xiong Z, Fang D, Wang B, Ming Y, Chen Y, Zheng Y, Kuraku S, Pignatelli M, Herrero J, Beal K, Nozawa M, Li Q, Wang J, Zhang H, Yu L, Shigenobu S, Liu J, Flicek P, Searle S, Kuratani S, Yin Y, Aken B, Zhang G, Irie N (- 22) Ref: Nat Genet, 45:701, 2013 : PubMed ESTHER: Wang_2013_Nat.Genet_45_701 PubMedSearch: Wang 2013 Nat.Genet 45 701 PubMedID: 23624526 Gene_locus related to this paper: chemy-m7c042, chemy-m7bp40, chemy-m7cgq9, chemy-m7bs15, chemy-m7c0b2, chemy-m7bkv2, chemy-m7bnk5, chemy-m7bzy6 Abstract The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split approximately 267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell. Title: The genome of the hydatid tapeworm Echinococcus granulosus Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y and Wang S <21 more author(s)> Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y, Liu J, Kang H, Chen J, Wang L, Chen A, Yu S, Gao Z, Jin L, Gu W, Wang Z, Zhao L, Shi B, Wen H, Lin R, Jones MK, Brejova B, Vinar T, Zhao G, McManus DP, Chen Z, Zhou Y, Wang S (- 21) Ref: Nat Genet, 45:1168, 2013 : PubMed ESTHER: Zheng_2013_Nat.Genet_45_1168 PubMedSearch: Zheng 2013 Nat.Genet 45 1168 PubMedID: 24013640 Gene_locus related to this paper: echgr-k4epc5, echmu-u6hbw4, echgr-w6ugl0, echgr-w6u7y4, echgr-w6vaq5, echgr-a0a068wxj3, echgr-a0a068wgw1, echgr-a0a068wl60 Abstract Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control. Title: Draft genome sequence of the shrimp pathogen Vibrio harveyi CAIM 1792 Espinoza-Valles I, Soto-Rodriguez S, Edwards RA, Wang Z, Vora GJ, Gomez-Gil B Ref: Journal of Bacteriology, 194:2104, 2012 : PubMed ESTHER: Espinoza-Valles_2012_J.Bacteriol_194_2104 PubMedSearch: Espinoza-Valles 2012 J.Bacteriol 194 2104 PubMedID: 22461546 Gene_locus related to this paper: vibcb-a7n1h5, 9vibr-k5vek9 Abstract Vibrio harveyi is a Gram-negative bacterium found in tropical and temperate marine environments as a free-living organism or in association with aquatic animals. We report the first sequenced genome of a Vibrio harveyi strain, CAIM 1792, the etiologic agent of the "bright red" syndrome of the Pacific white shrimp Litopenaeus vannamei. Title: Genome sequences of wild and domestic bactrian camels Jirimutu, Wang Z, Ding G, Chen G, Sun Y, Sun Z, Zhang H, Wang L, Hasi S and Meng H <57 more author(s)> Jirimutu, Wang Z, Ding G, Chen G, Sun Y, Sun Z, Zhang H, Wang L, Hasi S, Zhang Y, Li J, Shi Y, Xu Z, He C, Yu S, Li S, Zhang W, Batmunkh M, Ts B, Narenbatu, Unierhu, Bat-Ireedui S, Gao H, Baysgalan B, Li Q, Jia Z, Turigenbayila, Subudenggerile, Narenmanduhu, Wang J, Pan L, Chen Y, Ganerdene Y, Dabxilt, Erdemt, Altansha, Altansukh, Liu T, Cao M, Aruuntsever, Bayart, Hosblig, He F, Zha-ti A, Zheng G, Qiu F, Zhao L, Zhao W, Liu B, Li C, Tang X, Guo C, Liu W, Ming L, Temuulen, Cui A, Li Y, Gao J, Wurentaodi, Niu S, Sun T, Zhai Z, Zhang M, Chen C, Baldan T, Bayaer T, Meng H (- 57) Ref: Nat Commun, 3:1202, 2012 : PubMed ESTHER: Jirimutu_2012_Nat.Commun_3_1202 PubMedSearch: Jirimutu 2012 Nat.Commun 3 1202 PubMedID: 23149746 Gene_locus related to this paper: 9ceta-s9yik4, 9ceta-s9yb99, 9ceta-s9x0n3, 9ceta-s9xqa3, 9ceta-s9xi02, camfr-s9wiw9, camfr-s9x3r3, camfr-s9xce1, camfr-s9xcr2, camfr-s9yuz0, camfr-s9xlc8, camfr-s9w5f6, camfr-s9xmm4 Abstract Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 x 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system. Title: A highly sensitive gold-nanoparticle-based assay for acetylcholinesterase in cerebrospinal fluid of transgenic mice with Alzheimer's disease Liu D, Chen W, Tian Y, He S, Zheng W, Sun J, Wang Z, Jiang X Ref: Adv Healthc Mater, 1:90, 2012 : PubMed ESTHER: Liu_2012_Adv.Healthc.Mater_1_90 PubMedSearch: Liu 2012 Adv.Healthc.Mater 1 90 PubMedID: 23184691 Abstract A highly sensitive, selective, and dual-readout (colorimetric and fluorometric) assay for acetylcholinesterase (AChE) based on Rhodamine B-modified gold nanoparticle is reported. Due to its good sensitivity and selectivity, the assay can be used for monitoring AChE levels in the cerebrospinal fluid of transgenic mice with Alzheimer's disease. Title: A highly sensitive, dual-readout assay based on gold nanoparticles for organophosphorus and carbamate pesticides Liu D, Chen W, Wei J, Li X, Wang Z, Jiang X Ref: Analytical Chemistry, 84:4185, 2012 : PubMed ESTHER: Liu_2012_Anal.Chem_84_4185 PubMedSearch: Liu 2012 Anal.Chem 84 4185 PubMedID: 22475016 Abstract This report presents a highly sensitive, rhodamine B-covered gold nanoparticle (RB-AuNP) -based assay with dual readouts (colorimetric and fluorometric) for detecting organophosphorus and carbamate pesticides in complex solutions. The detection mechanism is based on the fact that these pesticides can inhibit the activity of acetylcholinesterase (AChE), thus preventing the generation of thiocholine (which turns the RB-AuNP solutions blue and unquenches the fluorescence of RB simultaneously). The color of the RB-AuNP solution remains red and the fluorescence of RB remains quenched. By use of this dual-readout assay, the lowest detectable concentrations for several kinds of pesticides including carbaryl, diazinon, malathion, and phorate were measured to be 0.1, 0.1, 0.3, and 1 mug/L, respectively, all of which are much lower than the maximum residue limits (MRL) as reported in the European Union pesticides database as well as those from the U.S. Department Agriculture (USDA). This assay allows detection of pesticides in real samples such as agricultural products and river water. The results in detecting pesticide residues collected from food samples via this method agree well with those from high-performance liquid chromatography (HPLC). This simple assay is therefore suitable for sensing pesticides in complex samples, especially in combination with other portable platforms. Title: Complete genome sequence of Paenibacillus mucilaginosus 3016, a bacterium functional as microbial fertilizer Ma M, Wang Z, Li L, Jiang X, Guan D, Cao F, Chen H, Wang X, Shen D and Li J <1 more author(s)> Ma M, Wang Z, Li L, Jiang X, Guan D, Cao F, Chen H, Wang X, Shen D, Du B, Li J (- 1) Ref: Journal of Bacteriology, 194:2777, 2012 : PubMed ESTHER: Ma_2012_J.Bacteriol_194_2777 PubMedSearch: Ma 2012 J.Bacteriol 194 2777 PubMedID: 22535950 Gene_locus related to this paper: paemk-f8fjj7, paemk-f8fd43, paemk-f8fl06, 9bacl-h6ntc5 Abstract Paenibacillus mucilaginosus is a ubiquitous functional bacterium in microbial fertilizer. Here we report the complete sequence of P. mucilaginosus 3016. Multiple sets of functional genes have been found in the genome. To the best of our knowledge, this is the first announcement about the complete genome sequence of a P. mucilaginosus strain. Title: Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres Paterson AH, Wendel JF, Gundlach H, Guo H, Jenkins J, Jin D, Llewellyn D, Showmaker KC, Shu S and Schmutz J <64 more author(s)> Paterson AH, Wendel JF, Gundlach H, Guo H, Jenkins J, Jin D, Llewellyn D, Showmaker KC, Shu S, Udall J, Yoo MJ, Byers R, Chen W, Doron-Faigenboim A, Duke MV, Gong L, Grimwood J, Grover C, Grupp K, Hu G, Lee TH, Li J, Lin L, Liu T, Marler BS, Page JT, Roberts AW, Romanel E, Sanders WS, Szadkowski E, Tan X, Tang H, Xu C, Wang J, Wang Z, Zhang D, Zhang L, Ashrafi H, Bedon F, Bowers JE, Brubaker CL, Chee PW, Das S, Gingle AR, Haigler CH, Harker D, Hoffmann LV, Hovav R, Jones DC, Lemke C, Mansoor S, ur Rahman M, Rainville LN, Rambani A, Reddy UK, Rong JK, Saranga Y, Scheffler BE, Scheffler JA, Stelly DM, Triplett BA, Van Deynze A, Vaslin MF, Waghmare VN, Walford SA, Wright RJ, Zaki EA, Zhang T, Dennis ES, Mayer KF, Peterson DG, Rokhsar DS, Wang X, Schmutz J (- 64) Ref: Nature, 492:423, 2012 : PubMed ESTHER: Paterson_2012_Nature_492_423 PubMedSearch: Paterson 2012 Nature 492 423 PubMedID: 23257886 Gene_locus related to this paper: gosra-a0a0d2qg22, gosra-a0a0d2w3z1, gosra-a0a0d2uuz7, gosra-a0a0d2rxs2, gosra-a0a0d2sdk0, gosra-a0a0d2tng2, gosra-a0a0d2twz7, gosra-a0a0d2vdc5, gosra-a0a0d2vj24, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8kis4, gosra-a0a0d2pul0, gosra-a0a0d2p3f2, gosra-a0a0d2ril5, gosra-a0a0d2s7d5, gosra-a0a0d2t9b3, gosra-a0a0d2tw88, gosra-a0a0d2umz5, gosra-a0a0d2pzd7 Abstract Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups. Title: The yak genome and adaptation to life at high altitude Qiu Q, Zhang G, Ma T, Qian W, Wang J, Ye Z, Cao C, Hu Q, Kim J and Liu J <35 more author(s)> Qiu Q, Zhang G, Ma T, Qian W, Wang J, Ye Z, Cao C, Hu Q, Kim J, Larkin DM, Auvil L, Capitanu B, Ma J, Lewin HA, Qian X, Lang Y, Zhou R, Wang L, Wang K, Xia J, Liao S, Pan S, Lu X, Hou H, Wang Y, Zang X, Yin Y, Ma H, Zhang J, Wang Z, Zhang Y, Zhang D, Yonezawa T, Hasegawa M, Zhong Y, Liu W, Huang Z, Zhang S, Long R, Yang H, Lenstra JA, Cooper DN, Wu Y, Shi P, Liu J (- 35) Ref: Nat Genet, 44:946, 2012 : PubMed ESTHER: Qiu_2012_Nat.Genet_44_946 PubMedSearch: Qiu 2012 Nat.Genet 44 946 PubMedID: 22751099 Gene_locus related to this paper: bosmu-l8ic43, bovin-2neur, bovin-balip, bovin-BCHE, bovin-e1bbv2, bovin-e1bn79, bovin-est8, bovin-f1mi11, bovin-f1n385, bovin-g3mxp5, bovin-lipli, bovin-lipr2, bovin-q2kj30, bovin-q3sz79, bovin-q3t0r6, bovin-ABHDA, bovin-q08dw9, bovin-ABHD16B, bovin-SPG21, bovin-TEX30, 9ceta-l8iwv2, 9ceta-l8idy3, 9ceta-l8hsi3, bovin-e1bjq9, bovin-f1mc21, 9ceta-l8hyl8, bovin-LIPG, bovin-a0a3q1nm09, bovin-f1n2i5 Abstract Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans. Title: Three-dimensional ordered macroporous (3DOM) composite for electrochemical study on acetylcholinesterase inhibition induced by endogenous neurotoxin Teng Y, Fu Y, Xu L, Lin B, Wang Z, Xu Z, Jin L, Zhang W Ref: J Phys Chem B, 116:11180, 2012 : PubMed ESTHER: Teng_2012_J.Phys.Chem.B_116_11180 PubMedSearch: Teng 2012 J.Phys.Chem.B 116 11180 PubMedID: 22946763 Abstract In this paper, an electrochemical acetylcholinesterase (AChE) inhibition assay based on three-dimensional ordered macroporous (3DOM) composite was conducted. The 3DOM composite was first fabricated on the glassy carbon electrode by electropolymerization of aniline in the presence of ionic liquid (IL) on a sacrificial silica nanospheres template. After the silica nanospheres were etched, an IL-doped polyaniline (IL-PANI) film with 3DOM morphology was formed. Then, gold nanoparticles (AuNPs) were decorated on the IL-PANI film by electrodeposition. The immobilized AChE on the 3DOM composite displayed favorable affinity to substrate acetylthiocholine chloride (ATCh), and the 3DOM composite showed excellent electrocatalytic effect on thiocholine, the hydrolysis product of ATCh. The presence of IL and AuNPs could improve the sensitivity by accelerating the electron transfer. The designed AChE biosensor was successfully applied to evaluate the AChE inhibition induced by endogenous neurotoxin 1(R),2N-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-NMSal]. The results demonstrate that (R)-NMSal exerts a considerable effect on AChE activity, and the inhibition is reversible. The developed method offers a new approach for AChE inhibition assay, which is of great benefit in understanding the mechanism behind neurotoxin-induced neurodegenerative disorders. Title: The genome of flax (Linum usitatissimum) assembled de novo from short shotgun sequence reads Wang Z, Hobson N, Galindo L, Zhu S, Shi D, McDill J, Yang L, Hawkins S, Neutelings G and Deyholos MK <13 more author(s)> Wang Z, Hobson N, Galindo L, Zhu S, Shi D, McDill J, Yang L, Hawkins S, Neutelings G, Datla R, Lambert G, Galbraith DW, Grassa CJ, Geraldes A, Cronk QC, Cullis C, Dash PK, Kumar PA, Cloutier S, Sharpe AG, Wong GK, Wang J, Deyholos MK (- 13) Ref: Plant J, 72:461, 2012 : PubMed ESTHER: Wang_2012_Plant.J_72_461 PubMedSearch: Wang 2012 Plant.J 72 461 PubMedID: 22757964 Gene_locus related to this paper: linus-i6xnh8 Abstract Flax (Linum usitatissimum) is an ancient crop that is widely cultivated as a source of fiber, oil and medicinally relevant compounds. To accelerate crop improvement, we performed whole-genome shotgun sequencing of the nuclear genome of flax. Seven paired-end libraries ranging in size from 300 bp to 10 kb were sequenced using an Illumina genome analyzer. A de novo assembly, comprised exclusively of deep-coverage (approximately 94x raw, approximately 69x filtered) short-sequence reads (44-100 bp), produced a set of scaffolds with N(50) =694 kb, including contigs with N(50)=20.1 kb. The contig assembly contained 302 Mb of non-redundant sequence representing an estimated 81% genome coverage. Up to 96% of published flax ESTs aligned to the whole-genome shotgun scaffolds. However, comparisons with independently sequenced BACs and fosmids showed some mis-assembly of regions at the genome scale. A total of 43384 protein-coding genes were predicted in the whole-genome shotgun assembly, and up to 93% of published flax ESTs, and 86% of A. thaliana genes aligned to these predicted genes, indicating excellent coverage and accuracy at the gene level. Analysis of the synonymous substitution rates (K(s) ) observed within duplicate gene pairs was consistent with a recent (5-9 MYA) whole-genome duplication in flax. Within the predicted proteome, we observed enrichment of many conserved domains (Pfam-A) that may contribute to the unique properties of this crop, including agglutinin proteins. Together these results show that de novo assembly, based solely on whole-genome shotgun short-sequence reads, is an efficient means of obtaining nearly complete genome sequence information for some plant species. Title: Classification of acetylcholinesterase inhibitors and decoys by a support vector machine Wang K, Hu X, Wang Z, Yan A Ref: Comb Chem High Throughput Screen, 15:492, 2012 : PubMed ESTHER: Wang_2012_Comb.Chem.High.Throughput.Screen_15_492 PubMedSearch: Wang 2012 Comb.Chem.High.Throughput.Screen 15 492 PubMedID: 22263859 Abstract Acetylcholinesterase has long been considered as a target for Alzheimer disease therapy. In this work, several classification models were built for the purpose of distinguishing acetylcholinesterase inhibitors (AChEIs) and decoys. Each molecule was initially represented by 211 ADRIANA.Code and 334 MOE descriptors. Correlation analysis, F-score and attribute selection methods in Weka were used to find the best reduced set of descriptors, respectively. Additionally, models were built using a Support Vector Machine and evaluated by 5-, 10-fold and leave-one-out cross-validation. The best model gave a Matthews Correlation Coefficient (MCC) of 0.99 and a prediction accuracy (Q) of 99.66% for the test set. The best model also gave good result on an external test set of 86 compounds (Q=96.51%, MCC=0.93). The descriptors selected by our models suggest that H-bond and hydrophobicity interactions are important for the classification of AChEIs and decoys. Title: Concentrations of plasma metabolites, hormones, and mRNA abundance of adipose leptin and hormone-sensitive lipase in ketotic and nonketotic dairy cows Xia C, Wang Z, Xu C, Zhang HY Ref: J Vet Intern Med, 26:415, 2012 : PubMed ESTHER: Xia_2012_J.Vet.Intern.Med_26_415 PubMedSearch: Xia 2012 J.Vet.Intern.Med 26 415 PubMedID: 22296673 Abstract BACKGROUND: Ketosis is an important metabolic disorder of dairy cows during the transition period. There have been many reports on the etiology of ketosis in periparturient cows, but little is known about its molecular etiology. OBJECTIVES: The objective of this study was to clarify the status of fat mobilization and mRNA abundance of leptin and hormone-sensitive lipase in cows with spontaneous clinical ketosis. ANIMALS: Ten ketotic Holstein cows and 10 nonketotic Holstein cows were used as the experimental animals. METHODS: Six blood biochemical parameters were evaluated by means of individual analysis method for 2 groups of cows. The mRNA abundance of leptin and hormone-sensitive lipase in tail fat tissue from 2 groups of cows was measured by real-time (RT)-PCR, with a fluorescent Taqman probe and a standard curve. RESULTS: The plasma concentrations of glucose (P = 0.01), and leptin (P = 0.03), insulin (P = 0.05), and the ratio of insulin to glucagon (P = 0.04) were lower in ketotic compared with nonketotic cows, whereas there were marked increases in the plasma concentrations of nonesterified fatty acid and beta-hydroxybutyric acid (P = 0.005). The mRNA abundance of leptin (P = 0.04) and hormone-sensitive lipase (P = 0.02) in the fat tissue of ketotic cows was lower relative to that of nonketotic cows. CONCLUSIONS AND CLINICAL IMPORTANCE: The ketotic cows showed characteristics of type I ketosis and some adaptive changes to negative energy balance in the plasma leptin concentration and mRNA abundance of fat leptin and hormone-sensitive lipase. Title: Acetylcholinesterase responsive polymeric supra-amphiphiles for controlled self-assembly and disassembly Xing Y, Wang C, Han P, Wang Z, Zhang X Ref: Langmuir, 28:6032, 2012 : PubMed ESTHER: Xing_2012_Langmuir_28_6032 PubMedSearch: Xing 2012 Langmuir 28 6032 PubMedID: 22404254 Abstract We have fabricated enzyme responsive polymeric supra-amphiphiles by mixing a block copolymer of poly(ethylene glycol)-block-poly(acrylic acid) with myristoylcholine chloride in water. The polymeric supra-amphiphiles self-assemble into spherical aggregates with sizes varying from about 40 to 150 nm. Moreover, the spherical aggregates can be disassembled triggered by acetylcholinesterase, an enzyme which can cut off the ester linkage of myristoylcholine chloride. Nile red can be loaded into the spherical aggregates and released in several hours upon the treatment of acetylcholinesterase. The releasing rate is rather fast considering that it takes more than 150 h for Nile red to diffuse out of the spherical aggregates without addition of acetylcholinesterase. It is anticipated that the new enzyme responsive polymeric supra-amphiphile may be explored as a carrier for drug delivery. Title: Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells via stimulating the gene expression of brain-derived neurotrophic factor Zhang R, Wang Z, Howson PA, Xia Z, Zhou S, Wu E, Hu Y Ref: Neuroscience, 210:275, 2012 : PubMed ESTHER: Zhang_2012_Neurosci_210_275 PubMedSearch: Zhang 2012 Neurosci 210 275 PubMedID: 22441042 Abstract The development of drugs that attenuate neurodegeneration is important for the treatment of Alzheimer's disease (AD). We previously found that smilagenin (SMI), a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in animal models, is neither a cholinesterase inhibitor nor a glutamate receptor antagonist, but can significantly elevate the declined muscarinic receptor (M receptor) density. In this article, to clarify whether SMI represents a new approach for treating neurodegeneration disease, we first demonstrate that SMI pretreatment significantly attenuates the neurodegenerative changes induced by beta amyloid 25-35 (Abeta(25-35)) in cultured rat cortical neurons, including decreased cholinergic neuron number, shortened neurite outgrowth length, and declined M receptor density. Brain-derived neurotrophic factor (BDNF) protein levels in the culture medium were also decreased by Abeta(25-35) and significantly elevated by SMI. Parallel experiments revealed that when the trk receptors were inhibited by K252a or the action of BDNF was inhibited by a neutralizing anti-BDNF antibody, the effects of SMI on the Abeta(25-35)-induced neurodegeneration in rat cortical neurons were almost completely abolished. In the all-trans retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells, the BDNF transcription rate measured by a nuclear run-on assay was significantly suppressed by Abeta(25-35) and elevated by SMI, but the BDNF degradation rate measured by half-life determination was unchanged by Abeta(25-35) and SMI. Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR (qRT-PCR) showed that the IV and VI transcripts of BDNF mRNA were significantly decreased by Abeta(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates Abeta(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y cells mainly through stimulating BDNF mRNA transcription implicating that SMI may represent a novel therapeutic strategy for AD. Title: Sequencing the genome of Marssonina brunnea reveals fungus-poplar co-evolution Zhu S, Cao YZ, Jiang C, Tan BY, Wang Z, Feng S, Zhang L, Su XH, Brejova B and Zhou Y <6 more author(s)> Zhu S, Cao YZ, Jiang C, Tan BY, Wang Z, Feng S, Zhang L, Su XH, Brejova B, Vinar T, Xu M, Wang MX, Zhang SG, Huang MR, Wu R, Zhou Y (- 6) Ref: BMC Genomics, 13:382, 2012 : PubMed ESTHER: Zhu_2012_BMC.Genomics_13_382 PubMedSearch: Zhu 2012 BMC.Genomics 13 382 PubMedID: 22876864 Gene_locus related to this paper: marbu-k1wj37, marbu-k1xt94, marbu-k1wdc0, marbu-k1wht2, marbu-k1wj82, marbu-k1wkk6, marbu-k1wnk8, marbu-k1wpc4, marbu-k1wrg1, marbu-k1wsf4, marbu-k1wtx1, marbu-k1x087, marbu-k1x383, marbu-k1x3g3, marbu-k1x464, marbu-k1x8c9, marbu-k1xi08, marbu-k1xzh8, marbu-k1y283, marbu-k1x918, marbu-k1wzc0, marbu-k1xu92, marbu-k1xws5 Abstract BACKGROUND: The fungus Marssonina brunnea is a causal pathogen of Marssonina leaf spot that devastates poplar plantations by defoliating susceptible trees before normal fall leaf drop. Title: A naked-eye visible and fluorescence turn-on probe for acetyl-cholinesterase assay and thiols as well as imaging of living cells Cui K, Chen Z, Wang Z, Zhang G, Zhang D Ref: Analyst, 136:191, 2011 : PubMed ESTHER: Cui_2011_Analyst_136_191 PubMedSearch: Cui 2011 Analyst 136 191 PubMedID: 20927440 Abstract A resorufin derivative with a DBS group (probe 1) was designed and investigated for the detection of acetylcholinesterase (AChE) and inhibitor screening. The new assay is based on cascade enzymatic and chemical reactions of ATC, AChE and probe 1, and it can be carried out in a dual-signal detection mode. Moreover, the results show that probe 1 can be used for cell fluorescence staining. Title: [The comparison of clinical manifestation of organophosphorus pesticide poisoning (OPP) between oral exposure and occupational exposure in field work] Hu XZ, Lu ZQ, Sun LF, Wang Z Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 29:378, 2011 : PubMed ESTHER: Hu_2011_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_29_378 PubMedSearch: Hu 2011 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 29 378 PubMedID: 21972539 Abstract OBJECTIVE: To investigate the differences of clinical manifestation and therapy of organophosphorus pesticide poisoning (OPP) between oral exposure and occupational exposure in field work. METHODS: From July 2007 to July 2010, 85 patients with acute severe OPP were treated in a hospital, which were divided into oral poisoning group (51 cases) and non-oral poisoning group (34 cases). The differences of clinical manifestations, curative effects and prognosis between two groups were compared. RESULTS: The rates of myoclonus and ataxia in cases with moderate poisoning of oral poisoning group were 86.4% and 90.9%, which were significantly higher than those (50.0% and 55.0%) of non-oral poisoning group (P<0.05 or P< 0.01). The rates of myoclonus, lung fluid and coma in cases with severe poisoning of oral poisoning group were 100.0%, 89.7% and 93.1%, respectively, which were significantly higher than those (71.4%, 64.3% and 50.0%) of non-oral poisoning group (P<0.05). The mean detoxification hours in cases with moderate poisoning and cases with severe poisoning of non-oral poisoning group were (35.0 +/- 6.2) and (45.0 +/- 11.1) hours which were significantly lower than those [(49.0 +/- 7.7) and (77.0 +/- 10.3) hours] in cases with moderate poisoning and cases with severe poisoning of oral poisoning group (P<0.05). In 24, 48 and 72 h after treatment, the cholinesterase (ChE) activities of non-oral poisoning group were higher than those of oral poisoning group (P< 0.05 or P<0.01). The used doses of pyraloxime methylchloride (PAM-Cl) or atropine and the used total dose of atropine in non-oral poisoning group were lower than those in oral poisoning group (P<0.05 or P<0.01). CONCLUSIONS: The clinical manifestation of non-oral poisoning group is different from the clinical manifestation of oral poisoning group due to the high morbidity of OPP occurred at field site in summer. The used doses of atropine and PAM-Cl are less and the ChE activity recovers quickly for non-oral poisoning group. Title: The draft genome of the parasitic nematode Trichinella spiralis Mitreva M, Jasmer DP, Zarlenga DS, Wang Z, Abubucker S, Martin J, Taylor CM, Yin Y, Fulton L and Wilson RK <11 more author(s)> Mitreva M, Jasmer DP, Zarlenga DS, Wang Z, Abubucker S, Martin J, Taylor CM, Yin Y, Fulton L, Minx P, Yang SP, Warren WC, Fulton RS, Bhonagiri V, Zhang X, Hallsworth-Pepin K, Clifton SW, McCarter JP, Appleton J, Mardis ER, Wilson RK (- 11) Ref: Nat Genet, 43:228, 2011 : PubMed ESTHER: Mitreva_2011_Nat.Genet_43_228 PubMedSearch: Mitreva 2011 Nat.Genet 43 228 PubMedID: 21336279 Gene_locus related to this paper: trisp-ACHE1, trisp-e5ryh1, trisp-e5s2p1, trisp-e5s3s1, trisp-e5s5l6, trisp-e5s7y8, trisp-e5s8m6, trisp-e5s9j3, trisp-e5s254, trisp-e5s773, trisp-e5sav1, trisp-e5sbp4, trisp-e5sgg4, trisp-e5sgu8, trisp-e5snw0, trisp-e5sr61, trisp-e5ss42, trisp-e5sgh2, 9bila-a0a0v0tgw4.1, 9bila-a0a0v0tws5 Abstract Genome evolution studies for the phylum Nematoda have been limited by focusing on comparisons involving Caenorhabditis elegans. We report a draft genome sequence of Trichinella spiralis, a food-borne zoonotic parasite, which is the most common cause of human trichinellosis. This parasitic nematode is an extant member of a clade that diverged early in the evolution of the phylum, enabling identification of archetypical genes and molecular signatures exclusive to nematodes. We sequenced the 64-Mb nuclear genome, which is estimated to contain 15,808 protein-coding genes, at approximately 35-fold coverage using whole-genome shotgun and hierarchal map-assisted sequencing. Comparative genome analyses support intrachromosomal rearrangements across the phylum, disproportionate numbers of protein family deaths over births in parasitic compared to a non-parasitic nematode and a preponderance of gene-loss and -gain events in nematodes relative to Drosophila melanogaster. This genome sequence and the identified pan-phylum characteristics will contribute to genome evolution studies of Nematoda as well as strategies to combat global parasites of humans, food animals and crops. Title: Cloning and characterization of the biosynthetic gene cluster of the bacterial RNA polymerase inhibitor tirandamycin from marine-derived Streptomyces sp. SCSIO1666 Mo X, Wang Z, Wang B, Ma J, Huang H, Tian X, Zhang S, Zhang C, Ju J Ref: Biochemical & Biophysical Research Communications, 406:341, 2011 : PubMed ESTHER: Mo_2011_Biochem.Biophys.Res.Commun_406_341 PubMedSearch: Mo 2011 Biochem.Biophys.Res.Commun 406 341 PubMedID: 21329667 Gene_locus related to this paper: 9actn-f1di35 Abstract Tirandamycins are bacterial RNA polymerase inhibitors holding great potential for antibacterial agent design. To elucidate the biosynthetic machinery and generate new derivatives, the tirandamycin biosynthetic gene cluster was cloned and sequenced from marine-derived Streptomyces sp. SCSIO1666. The biosynthetic gene cluster of tirandamycin spans a DNA region of ~56kb and consists of 15 open reading frames (ORFs) which encode three type I polyketide synthases (TrdAI, AII, AIII), one non-ribosomal peptide synthetase (TrdD), one phosphopantetheinyl transferase (TrdM), one Type II thioesterase (TrdB), one FAD-dependent oxidoreductase (TrdL), one cytochrome P450 monooxygenase (TrdI), three proteins related to resistance and regulations (TrdHJK), and four proteins with unknown function (TrdCEFG). To investigate the roles of the genes played in the biosynthetic machinery, seven genes (trdAI and trdBDFHIK) were inactivated via in frame replacement with an apramycin gene cassette using -RED recombination technology. The trdAI and trdD mutants targeting the ketosynthase and adenylation domain of TrdAI and TrdD, respectively, abolished the production of tirandamycins, confirming their involvement in the tirandamycin biosynthesis. TrdH showed high homology to LuxR family transcriptional regulatory proteins, disruption of which abolished the production of tirandamycins, indicating that TrdH is a positive regulator for tirandamycin biosynthesis. On the other hand, TrdK showed high homology to TetR-family transcriptional regulatory proteins, disruption of which significantly increased the yields of tirandamycins almost one-fold, implicating that TrdK is a negative regulator for tirandamycin biosynthesis. Disruption of the gene trdI resulted in the accumulation of the intermediate tirandamycin C (3) and a trace amount of new product tirandamycin C2 (5). A model of tirandamycin biosynthesis was proposed based on bioinformatics analyses, gene inactivation experiments and intermediates isolated from the mutants. These findings set the stage for further study of the tirandamycin biosynthetic mechanism and rationally engineer new tirandamycin analogues. Title: Whole-genome sequences of four Mycobacterium bovis BCG vaccine strains Pan Y, Yang X, Duan J, Lu N, Leung AS, Tran V, Hu Y, Wu N, Liu D and Zhu B <6 more author(s)> Pan Y, Yang X, Duan J, Lu N, Leung AS, Tran V, Hu Y, Wu N, Liu D, Wang Z, Yu X, Chen C, Zhang Y, Wan K, Liu J, Zhu B (- 6) Ref: Journal of Bacteriology, 193:3152, 2011 : PubMed ESTHER: Pan_2011_J.Bacteriol_193_3152 PubMedSearch: Pan 2011 J.Bacteriol 193 3152 PubMedID: 21478353 Gene_locus related to this paper: myctu-RV1215C Abstract Mycobacterium bovis Bacille Calmette-Guerin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines. Title: Increased fat mass and insulin resistance in mice lacking pancreatic lipase-related protein 1 Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L and Fei J <2 more author(s)> Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L, Sun X, Wang Z, Fei J (- 2) Ref: J Nutr Biochem, 22:691, 2011 : PubMed ESTHER: Ren_2011_J.Nutr.Biochem_22_691 PubMedSearch: Ren 2011 J.Nutr.Biochem 22 691 PubMedID: 21115337 Gene_locus related to this paper: human-PNLIPRP1, mouse-1plrp Abstract Pancreatic triglyceride lipase (PTL) and its cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase-related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. The lipase activity of PLRP2 has been confirmed, whereas no known triglyceride lipase activity has been detected with PLRP1 up to now. To explore the biological functions of PLRP1 in vivo, we generated Plrp1 knockout (KO) mice in our laboratory. Here we show that the Plrp1 KO mice displayed mature-onset obesity with increased fat mass, impaired glucose clearance and the resultant insulin resistance. When fed on high-fat (HF) diet, the Plrp1 KO mice exhibited an increased weight gain, fat mass and severe insulin resistance compared with wild-type mice. Pancreatic juice extracted from Plrp1 KO mice had greater ability to hydrolyze triglyceride than that from the wild-type littermates. We propose that PLRP1 may function as a metabolic inhibitor in vivo of PLT-colipase-mediated dietary triglyceride digestion and provides potential anti-obesity targets for developing new drugs. Title: The genome of the mesopolyploid crop species Brassica rapa Wang X, Wang H, Wang J, Sun R, Wu J, Liu S, Bai Y, Mun JH, Bancroft I and Zhang Z <88 more author(s)> Wang X, Wang H, Wang J, Sun R, Wu J, Liu S, Bai Y, Mun JH, Bancroft I, Cheng F, Huang S, Li X, Hua W, Freeling M, Pires JC, Paterson AH, Chalhoub B, Wang B, Hayward A, Sharpe AG, Park BS, Weisshaar B, Liu B, Li B, Tong C, Song C, Duran C, Peng C, Geng C, Koh C, Lin C, Edwards D, Mu D, Shen D, Soumpourou E, Li F, Fraser F, Conant G, Lassalle G, King GJ, Bonnema G, Tang H, Belcram H, Zhou H, Hirakawa H, Abe H, Guo H, Jin H, Parkin IA, Batley J, Kim JS, Just J, Li J, Xu J, Deng J, Kim JA, Yu J, Meng J, Min J, Poulain J, Hatakeyama K, Wu K, Wang L, Fang L, Trick M, Links MG, Zhao M, Jin M, Ramchiary N, Drou N, Berkman PJ, Cai Q, Huang Q, Li R, Tabata S, Cheng S, Zhang S, Sato S, Sun S, Kwon SJ, Choi SR, Lee TH, Fan W, Zhao X, Tan X, Xu X, Wang Y, Qiu Y, Yin Y, Li Y, Du Y, Liao Y, Lim Y, Narusaka Y, Wang Z, Li Z, Xiong Z, Zhang Z (- 88) Ref: Nat Genet, 43:1035, 2011 : PubMed ESTHER: Wang_2011_Nat.Genet_43_1035 PubMedSearch: Wang 2011 Nat.Genet 43 1035 PubMedID: 21873998 Gene_locus related to this paper: braol-Q8GTM3, braol-Q8GTM4, brarp-m4ei94, brarp-m4c988, brana-a0a078j4a9, brana-a0a078e1m0, brana-a0a078cd75, brarp-m4dwa6, brana-a0a078j4f0, brana-a0a078cus4, brana-a0a078f8c2, brana-a0a078jql1, brana-a0a078dgj3, brana-a0a078hw50, brana-a0a078cuu0, brana-a0a078dfa9, brana-a0a078ic91, brarp-m4ctw3, brana-a0a078ca65, brana-a0a078ctc8, brana-a0a078h021, brana-a0a078jx23, brarp-m4da84, brarp-m4dwr7, brana-a0a078dh94, brana-a0a078h612, brana-a0a078j2t3, braol-a0a0d3dpb2, braol-a0a0d3dx76, brana-a0a078jxa8, brana-a0a078i2k3, brarp-m4cwq4, brarp-m4dcj8, brarp-m4eh17, brarp-m4eey4, brarp-m4dnj8, brarp-m4ey83, brarp-m4ey84 Abstract We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops. Title: Genomic insights into an obligate epibiotic bacterial predator: Micavibrio aeruginosavorus ARL-13 Wang Z, Kadouri DE, Wu M Ref: BMC Genomics, 12:453, 2011 : PubMed ESTHER: Wang_2011_BMC.Genomics_12_453 PubMedSearch: Wang 2011 BMC.Genomics 12 453 PubMedID: 21936919 Gene_locus related to this paper: micaa-g2kq08 Abstract BACKGROUND: Although bacterial predators play important roles in the dynamics of natural microbial communities, little is known about the molecular mechanism of bacterial predation and the evolution of diverse predatory lifestyles. Title: Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y and Wang X <32 more author(s)> Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y, van Gool AJ, Du H, Chen J, Chen R, Zhang P, Huang Z, Thompson JR, Meng Y, Bai Y, Wang J, Zhuo M, Wang T, Huang Y, Wei L, Li J, Wang Z, Hu H, Yang P, Le L, Stenson PD, Li B, Liu X, Ball EV, An N, Huang Q, Fan W, Zhang X, Wang W, Katze MG, Su B, Nielsen R, Yang H, Wang X (- 32) Ref: Nat Biotechnol, 29:1019, 2011 : PubMed ESTHER: Yan_2011_Nat.Biotechnol_29_1019 PubMedSearch: Yan 2011 Nat.Biotechnol 29 1019 PubMedID: 22002653 Gene_locus related to this paper: macfa-BCHE, macfa-g7nzc0, macfa-g7nze2, macfa-g7p4b9, macfa-g7pa87, macfa-g7pd01, macfa-g7q259, macfa-3neur, macfa-g8f585, macfa-KANSL3, macfa-q4r8p0, macfa-SPG21, macfa-TEX30, macmu-3neur, macmu-ACHE, macmu-BCHE, macmu-f6sz31, macmu-f6the6, macmu-f6zkq5, macmu-f7buk8, macmu-f7cfi8, macmu-f7flv1, macmu-f7ggk1, macmu-f7hir7, macmu-g7n054, macmu-g7npb8, macmu-g7nq39, macmu-KANSL3, macmu-TEX30, macfa-g7pgg6, macmu-g7n4x3, macfa-g7nzx2, macfa-g8f4f7, macmu-f7ba84, macfa-g7psx7, macmu-h9er02, macfa-g8f3k0, macfa-a0a2k5w1n7, macmu-g7mxj6, macfa-g7pbk1, macfa-a0a2k5urk5, macfa-a0a2k5wye4, macfa-g7pe14, macmu-f7hkw9, macmu-f7hm08, macmu-g7mke4, macfa-g7nxn9, macmu-a0a1d5rh04, macmu-h9fud6, macfa-g8f3e1, macfa-i7gcw6, macmu-f6qwx1, macmu-f7h4t2, macfa-a0a2k5wkd0, macfa-a0a2k5v7v4, macfa-g7p7y3, macfa-a0a2k5uqq3, macmu-i2cu80, macfa-g8f5i1, macmu-f7h550, macmu-f7gkb9, macfa-a0a2k5tui1 Abstract The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. Title: Chronic administration of Liu Wei Dihuang protects rat's brain against D-galactose-induced impairment of cholinergic system Zhang WW, Sun QX, Liu YH, Gao W, Li YH, Lu K, Wang Z Ref: Sheng Li Xue Bao, 63:245, 2011 : PubMed ESTHER: Zhang_2011_Sheng.Li.Xue.Bao_63_245 PubMedSearch: Zhang 2011 Sheng.Li.Xue.Bao 63 245 PubMedID: 21681343 Abstract This study was aimed to investigate the protective effect of Liu Wei Dihuang (LWDH) against D-galactose (D-gal)-induced brain injury in rats and the existence of sex-dependent differences in LWDH protection. Sixty-four rats evenly composed of males and females were randomly assigned into 4 groups (n = 8): normal saline (NS) + NS (N + N), NS + LWDH (N + L), D-gal + NS (D + N) and D-gal + LWDH (D + L) groups. Rats in D + N and D + L groups received daily injection of D-gal (100 mg/kg, s.c.) for six weeks to establish the aging model, while rats in N + N and N + L groups were injected with the same volume of NS. From the third week, rats in N + L and D + L groups were orally administered with a decoction of LWDH for subsequent six weeks. Rats in N + N and D + N groups were orally administered just with the same volume of NS simultaneously. Morris water maze test was employed to evaluate the ability of learning and memory of the rats in all the groups. Acetylcholine (ACh) content, activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in visual cortex were assayed. Hematoxylin and eosin (HE) staining were used to observe the morphologic injury in hippocampus and visual cortex, and immunohistochemistry was performed to evaluate ChAT and AChE expression levels in the visual cortex. The results showed that the rats in D + N groups exhibited a longer escape latency to platform, lower swimming speed, less percent of target quadrant search time and platform crossings, compared with N + N groups, suggesting the establishment of aging model, while LWDH improved these indexes in D-gal-treated rats. Compared with D + N groups, LWDH increased ACh content and ChAT activity, and decreased AChE activity in visual cortex. Remarkable loss of neurons was found in hippocampus and visual cortex of aging rats, and the injury was significantly attenuated by LWDH. Immunohistochemistry showed D-gal-induced decreases of ChAT and AChE expressions were restored by LWDH. Furthermore, under the neural protection of LWDH, the improvement on platform crossings in male aging rats was better than that in female ones, while in ChAT expression and neuron density in visual cortex, female aging rats obtained more amelioration. These results suggest LWDH can markedly reverse the D-gal-induced cognitive impairments and neuronal damage in both hippocampus and visual cortex, which are achieved at least partly through restoring cholinergic system in central nervous system. Moreover, there is some sex difference in protective effects of LWDH against D-gal-induced impairment. Title: Distribution of CuO nanoparticles in juvenile carp (Cyprinus carpio) and their potential toxicity Zhao J, Wang Z, Liu X, Xie X, Zhang K, Xing B Ref: J Hazard Mater, 197:304, 2011 : PubMed ESTHER: Zhao_2011_J.Hazard.Mater_197_304 PubMedSearch: Zhao 2011 J.Hazard.Mater 197 304 PubMedID: 22014442 Abstract Adverse effect of engineered nanoparticles (NPs) on the aquatic environment and organisms has recently drawn much attention. This paper reports on the toxicity of CuO NPs to juvenile carp (Cyprinus carpio) and their distribution in the fish. CuO NPs and its counterpart bulk particles (BPs) (10, 50, 100, 200, 300, 500 and 1000 mg L(-1)) exhibited no acute toxicity (96 h), while during the 30 day sub-acute toxicity test, carp growth was significantly inhibited by CuO NPs (100 mg L(-1)) in comparison to control, CuO BPs and Cu(2+) groups. CuO NPs (or released Cu(2+) ions inside the fish body) could distribute in various tissues/organs and followed an order: intestine>gill>muscle>skin and scale>liver>brain. For time-related distribution, Cu content (expressed on a dry mass basis) in intestine, gill and liver increased faster (within 1 day) and they had obviously higher Cu content than other tissues/organs at all exposure times. CuO NPs could be excreted by carp to lower their toxicity. Cholinesterase activity was inhibited during CuO NPs exposure, suggesting NPs exposure could have potential neurotoxicity, and free Cu(2+) ions dissolved inside the carp body was responsible for the cholinesterase inhibition. Finally, actual suspended NPs concentrations should be used instead of initially added concentrations whenever possible in nanotoxicity studies. Title: Regulation of M1-receptor mRNA stability by smilagenin and its significance in improving memory of aged rats Hu Y, Wang Z, Zhang R, Wu P, Xia Z, Orsi A, Rees D Ref: Neurobiology of Aging, 31:1010, 2010 : PubMed ESTHER: Hu_2010_Neurobiol.Aging_31_1010 PubMedSearch: Hu 2010 Neurobiol.Aging 31 1010 PubMedID: 18676061 Abstract The purpose of this work is to study the effect of smilagenin on the mRNA stability of muscarinic receptor subtype 1 (M(1); m1 mRNA) in aged rat brains and its significance in improving memory. The Y-maze avoidance task showed that oral administration of smilagenin significantly improved spatial memory performance in aged rats. Mechanistic studies showed that smilagenin was neither a ligand of the M receptors nor a cholinesterase inhibitor, while radioligand binding assays revealed that smilagenin significantly increased the M(1)-receptor density. The increase of M(1)-receptor density correlated with memory improvement. Real-time polymerase chain reaction (RT-PCR) revealed that the m1 mRNA in m1 gene-transfected CHO cells increased significantly, and the average half-life of m1 mRNA was approximately doubled by smilagenin treatment. These results suggest that smilagenin improves memory of aged rats at least partially by increasing the stability of m1 mRNA. However since the ChAT activity in the cortex of aged rats was also elevated by smilagenin, it cannot be excluded that the increase of intrinsic acetylcholine excretion also plays a role in the memory-improvement effect of smilagenin. Title: Adsorption and inhibition of butyrylcholinesterase by different engineered nanoparticles Wang Z, Zhang K, Zhao J, Liu X, Xing B Ref: Chemosphere, 79:86, 2010 : PubMed ESTHER: Wang_2010_Chemosphere_79_86 PubMedSearch: Wang 2010 Chemosphere 79 86 PubMedID: 20089293 Abstract Butyrylcholinesterase (BChE), an important enzyme present in brain, serum and nervous system, is sensitive to neurotoxin. Engineered nanoparticles (NPs) may enter the mammalian body and be toxic. To investigate the potential neurotoxicity of different NPs and the interaction between NPs and BChE, three metal NPs (Cu-C, Cu and Al), three oxides NPs (SiO(2), TiO(2) and Al(2)O(3)), two carbon nanotubes (MWCNT and SWCNT) and two micro-scaled particles (Cu and activated carbon) were used to test their adsorption and inhibition on human serum BChE. At 800mgL(-1), adsorption and inhibition of BChE by MWCNT were the highest, 97% and 96%, respectively, while Al NPs showed the lowest adsorption (6.8%) and inhibition rates (3.3%). Ions could be dissolved in all metal and oxide NPs suspensions except TiO(2) NPs. In comparison to other ions, Cu(2+) released in Cu and Cu-C suspensions had the highest BChE activity reduction, 39.1% and 42.6%, respectively. The contribution of dissolved ions to the total inhibition by NPs suspension followed a decreasing sequence of Al (66%)>Cu (46%)>Cu-C (45%)>Al(2)O(3) (44%)>SS1[SiO(2)] (25%)>SP1[SiO(2)] (4%), suggesting that the inhibition of BChE may partly result from ion dissolution from NPs. The inhibition of BChE by micro-scaled activated carbon and Cu particles was significantly lower than that of their nano-scaled particles. The inhibition of BChE by MWCNT, SWCNT, TiO(2) (HR3) and Cu NPs showed concentration-response relationships. Their median inhibitory concentrations (IC(50)) were 97, 49, 206 and 1.54mgL(-1), respectively. These results indicate that these four NPs may have neurotoxicity and BChE may be potentially used as a biomarker of NPs in the environment. Title: Application of ultrasound-assisted surfactant-enhanced emulsification microextraction for the determination of some organophosphorus pesticides in water samples Wu C, Liu N, Wu Q, Wang C, Wang Z Ref: Anal Chim Acta, 679:56, 2010 : PubMed ESTHER: Wu_2010_Anal.Chim.Acta_679_56 PubMedSearch: Wu 2010 Anal.Chim.Acta 679 56 PubMedID: 20951857 Abstract An ultrasound-assisted surfactant-enhanced emulsification microextraction (UASEME) was developed as a new approach for the extraction of organophosphorus pesticides (OPs) in water samples prior to high-performance liquid chromatography with diode array detection (HPLC-DAD). The use of a surfactant as an emulsifier in the UASEME method could enhance the dispersion of water-immiscible extraction solvent into aqueous phase and is favorable for the mass-transfer of the analytes from aqueous phase to the organic phase. Several variables that affect the extraction efficiency, including the kind and volume of the extraction solvent, the type and concentration of the surfactant, salt addition, ultrasound emulsification time and temperature, were investigated and optimized. Under the optimum experimental conditions, the calibration curve was linear in the concentration range from 1 to 200 ng mL(-1) for the seven OPs (isocarbophos, phosmet, parathion, parathion-methyl, fenitrothion, fonofos and phoxim), with the correlation coefficients (r) varying from 0.9973 to 0.9998. High enrichment factors were achieved ranging from 210 to 242. The established UASEME-HPLC-DAD method has been successfully applied for the determination of the OPs in real water samples. The limits of detection were in the range between 0.1 and 0.3 ng mL(-1). The recoveries of the target analytes over the three spiked concentration levels of the compounds (10, 50, and 100 ng mL(-1), respectively) in rain, reservoir and well water samples were between 83% and 106% with the relative standard deviations varying from 3.3% to 5.6%. Title: Enantiospecific total synthesis of the important biogenetic intermediates along the ajmaline pathway, (+)-polyneuridine and (+)-polyneuridine aldehyde, as well as 16-epivellosimine and macusine A Yin W, Kabir MS, Wang Z, Rallapalli SK, Ma J, Cook JM Ref: J Org Chem, 75:3339, 2010 : PubMed ESTHER: Yin_2010_J.Org.Chem_75_3339 PubMedSearch: Yin 2010 J.Org.Chem 75 3339 PubMedID: 20392128 Abstract The first stereospecific synthesis of polyneuridine aldehyde (6), 16-epivellosimine (7), (+)-polyneuridine (8), and (+)-macusine A (9) has been accomplished from commercially available d-(+)-tryptophan methyl ester. d-(+)-Tryptophan has served here both as the chiral auxiliary and the starting material for the synthesis of the common intermediate, (+)-vellosimine (13). This alkaloid was available in enantiospecific fashion in seven reaction vessels in 27% overall yield from d-(+)-trytophan methyl ester (14) via a combination of the asymmetric Pictet-Spengler reaction, Dieckmann cyclization, and a stereocontrolled intramolecular enolate-driven palladium-mediated cross-coupling reaction. A new process for this stereocontrolled intramolecular cross-coupling has been developed via a copper-mediated process. The initial results of this investigation indicated that an enolate-driven palladium-mediated cross-coupling reaction can be accomplished by a copper-mediated process which is less expensive and much easier to work up. An enantiospecific total synthesis of (+)-polyneuridine aldehyde (6), which has been proposed as an important biogenetic intermediate in the biosynthesis of quebrachidine (2), was then accomplished in an overall yield of 14.1% in 13 reaction vessels from d-(+)-tryptophan methyl ester (14). Aldehyde 13 was protected as the N(a)-Boc aldehyde 32 and then converted into the prochiral C(16)-quaternary diol 12 via the practical Tollens' reaction and deprotection. The DDQ-mediated oxidative cyclization and TFA/Et(3)SiH reductive cleavage served as protection/deprotection steps to provide a versatile entry into the three alkaloids polyneuridine aldehyde (6), polyneuridine (8), and macusine A (9) from the quarternary diol 12. The oxidation of the 16-hydroxymethyl group present in the axial position was achieved with the Corey-Kim reagent to provide the desired beta-axial aldehydes, polyneuridine aldehyde (6), and 16-epivellosimine (7) with 100% diastereoselectivity. Title: Bio-resolution of glycidyl (o, m, p)-methylphenyl ethers by Bacillus megaterium Zhang Z, Sheng Y, Jiang K, Wang Z, Zheng Y, Zhu Q Ref: Biotechnol Lett, 32:513, 2010 : PubMed ESTHER: Zhang_2010_Biotechnol.Lett_32_513 PubMedSearch: Zhang 2010 Biotechnol.Lett 32 513 PubMedID: 20013303 Abstract A newly isolated Bacillus megaterium with epoxide hydrolase activity resolved racemic glycidyl (o, m, p)-methylphenyl ethers to give enantiopure epoxides in 84-99% enantiomeric excess and with 21-73 enantiomeric ratios. The (S)-enantiomer was obtained from rac-glycidyl (o or m)-methylphenyl ether while the (R)-epoxides was obtained from glycidyl p-methylphenyl ether. The observations are explained at the level by enzyme-substrate docking studies. Title: Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: potential sources of metabolic drug interactions Zhu HJ, Appel DI, Peterson YK, Wang Z, Markowitz JS Ref: Toxicology, 270:59, 2010 : PubMed ESTHER: Zhu_2010_Toxicology_270_59 PubMedSearch: Zhu 2010 Toxicology 270 59 PubMedID: 20097249 Abstract A series of studies were designed and carried out in order to explore the potential for the major human hepatic hydrolase, carboxylesterase 1 (hCES1), to serve as a target of metabolic inhibition by a variety of medications. The risk of adverse drug-drug interaction(s) is present when metabolic inhibitors are combined with known or suspected substrates of a given enzyme. In the present report the abundantly expressed hepatic enzyme, hCES1, was examined as a potential target of metabolic inhibition by a number of routinely prescribed medications. hCES1 has been seldom assessed in this regard despite its role in the metabolism and detoxification of many compounds. The psychostimulant methylphenidate (MPH) was chosen as an hCES1 selective substrate. In vitro studies were performed using previously developed cell lines which overexpress hCES1 with both p-nitrophenyl acetate and d-MPH serving as known substrates. Aripiprazole, perphenazine, thioridazine, and fluoxetine were determined to be the potent hCES1 inhibitors. A complementary animal study followed in vitro screening studies to further evaluate the inhibitory effect of aripiprazole on CES1 activity in FVB mice. The results suggest that the concurrent administration of racemic (i.e. dl-) MPH with aripiprazole significantly increased the plasma concentrations of both total MPH as well as the less active l-isomer. The ratio of d-MPH and l-MPH plasma concentrations was significantly decreased in the mice treated with aripiprazole compared to the control animals, indicating an overall decrease of CES1 catalytic activity in aripiprazole treated animals. Additionally, a quantitative structure-activity relationship based analysis identified a number of structural similarities of CES1 inhibitors. In conclusion, drug-drug interactions with MPH are likely mediated via CES1 inhibition as a result of concomitant drug therapies. CES1 inhibition represents an overlooked and little studied source of variability in MPH disposition, tolerability, and response. Title: Therapeutic potential of lipase inhibitor orlistat in Alzheimer's disease Du J, Wang Z Ref: Med Hypotheses, 73:662, 2009 : PubMed ESTHER: Du_2009_Med.Hypotheses_73_662 PubMedSearch: Du 2009 Med.Hypotheses 73 662 PubMedID: 19505770 Abstract Emerging evidences indicate that elevated cholesterol and triglyceride levels precede Alzheimer's disease (AD) pathology. High caloric intake based on saturated fat raises hyperlipidaemia and also promotes AD pathology. As a result, strategy that limits the absorption of dietary fat and attenuates hyperlipidemia could be a useful medication for protective treatment of AD. As an active site-directed inhibitor of digestive lipases, orlistat effectively reduces dietary fat absorption and decreases total cholesterol and triglyceride levels in plasma. Orlistat also potently inhibits lipoprotein lipase, monoacylglycerol lipase and diacylglycerol lipase, which are also involved in AD causation. Taken together, orlistat inhibits lipases activities, thereby reduces dietary fat intake and ameliorates hyperlipidemia, which indicates a therapeutic potential of orlistat in protecting against AD pathology. Title: The genome sequence of taurine cattle: a window to ruminant biology and evolution Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, Weinstock GM, Adelson DL, Eichler EE, Elnitski L and Zhao FQ <297 more author(s)> Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, Weinstock GM, Adelson DL, Eichler EE, Elnitski L, Guigo R, Hamernik DL, Kappes SM, Lewin HA, Lynn DJ, Nicholas FW, Reymond A, Rijnkels M, Skow LC, Zdobnov EM, Schook L, Womack J, Alioto T, Antonarakis SE, Astashyn A, Chapple CE, Chen HC, Chrast J, Camara F, Ermolaeva O, Henrichsen CN, Hlavina W, Kapustin Y, Kiryutin B, Kitts P, Kokocinski F, Landrum M, Maglott D, Pruitt K, Sapojnikov V, Searle SM, Solovyev V, Souvorov A, Ucla C, Wyss C, Anzola JM, Gerlach D, Elhaik E, Graur D, Reese JT, Edgar RC, McEwan JC, Payne GM, Raison JM, Junier T, Kriventseva EV, Eyras E, Plass M, Donthu R, Larkin DM, Reecy J, Yang MQ, Chen L, Cheng Z, Chitko-McKown CG, Liu GE, Matukumalli LK, Song J, Zhu B, Bradley DG, Brinkman FS, Lau LP, Whiteside MD, Walker A, Wheeler TT, Casey T, German JB, Lemay DG, Maqbool NJ, Molenaar AJ, Seo S, Stothard P, Baldwin CL, Baxter R, Brinkmeyer-Langford CL, Brown WC, Childers CP, Connelley T, Ellis SA, Fritz K, Glass EJ, Herzig CT, Iivanainen A, Lahmers KK, Bennett AK, Dickens CM, Gilbert JG, Hagen DE, Salih H, Aerts J, Caetano AR, Dalrymple B, Garcia JF, Gill CA, Hiendleder SG, Memili E, Spurlock D, Williams JL, Alexander L, Brownstein MJ, Guan L, Holt RA, Jones SJ, Marra MA, Moore R, Moore SS, Roberts A, Taniguchi M, Waterman RC, Chacko J, Chandrabose MM, Cree A, Dao MD, Dinh HH, Gabisi RA, Hines S, Hume J, Jhangiani SN, Joshi V, Kovar CL, Lewis LR, Liu YS, Lopez J, Morgan MB, Nguyen NB, Okwuonu GO, Ruiz SJ, Santibanez J, Wright RA, Buhay C, Ding Y, Dugan-Rocha S, Herdandez J, Holder M, Sabo A, Egan A, Goodell J, Wilczek-Boney K, Fowler GR, Hitchens ME, Lozado RJ, Moen C, Steffen D, Warren JT, Zhang J, Chiu R, Schein JE, Durbin KJ, Havlak P, Jiang H, Liu Y, Qin X, Ren Y, Shen Y, Song H, Bell SN, Davis C, Johnson AJ, Lee S, Nazareth LV, Patel BM, Pu LL, Vattathil S, Williams RL, Jr., Curry S, Hamilton C, Sodergren E, Wheeler DA, Barris W, Bennett GL, Eggen A, Green RD, Harhay GP, Hobbs M, Jann O, Keele JW, Kent MP, Lien S, McKay SD, McWilliam S, Ratnakumar A, Schnabel RD, Smith T, Snelling WM, Sonstegard TS, Stone RT, Sugimoto Y, Takasuga A, Taylor JF, Van Tassell CP, Macneil MD, Abatepaulo AR, Abbey CA, Ahola V, Almeida IG, Amadio AF, Anatriello E, Bahadue SM, Biase FH, Boldt CR, Carroll JA, Carvalho WA, Cervelatti EP, Chacko E, Chapin JE, Cheng Y, Choi J, Colley AJ, de Campos TA, De Donato M, Santos IK, de Oliveira CJ, Deobald H, Devinoy E, Donohue KE, Dovc P, Eberlein A, Fitzsimmons CJ, Franzin AM, Garcia GR, Genini S, Gladney CJ, Grant JR, Greaser ML, Green JA, Hadsell DL, Hakimov HA, Halgren R, Harrow JL, Hart EA, Hastings N, Hernandez M, Hu ZL, Ingham A, Iso-Touru T, Jamis C, Jensen K, Kapetis D, Kerr T, Khalil SS, Khatib H, Kolbehdari D, Kumar CG, Kumar D, Leach R, Lee JC, Li C, Logan KM, Malinverni R, Marques E, Martin WF, Martins NF, Maruyama SR, Mazza R, McLean KL, Medrano JF, Moreno BT, More DD, Muntean CT, Nandakumar HP, Nogueira MF, Olsaker I, Pant SD, Panzitta F, Pastor RC, Poli MA, Poslusny N, Rachagani S, Ranganathan S, Razpet A, Riggs PK, Rincon G, Rodriguez-Osorio N, Rodriguez-Zas SL, Romero NE, Rosenwald A, Sando L, Schmutz SM, Shen L, Sherman L, Southey BR, Lutzow YS, Sweedler JV, Tammen I, Telugu BP, Urbanski JM, Utsunomiya YT, Verschoor CP, Waardenberg AJ, Wang Z, Ward R, Weikard R, Welsh TH, Jr., White SN, Wilming LG, Wunderlich KR, Yang J, Zhao FQ (- 297) Ref: Science, 324:522, 2009 : PubMed ESTHER: Elsik_2009_Science_324_522 PubMedSearch: Elsik 2009 Science 324 522 PubMedID: 19390049 Gene_locus related to this paper: bovin-2neur, bovin-a0jnh8, bovin-a5d7b7, bovin-ACHE, bovin-balip, bovin-dpp4, bovin-dpp6, bovin-e1bi31, bovin-e1bn79, bovin-est8, bovin-f1mbd6, bovin-f1mi11, bovin-f1mr65, bovin-f1n1l4, bovin-g3mxp5, bovin-q0vcc8, bovin-q2kj30, bovin-q3t0r6, bovin-thyro Abstract To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production. Title: Adsorption and inhibition of acetylcholinesterase by different nanoparticles Wang Z, Zhao J, Li F, Gao D, Xing B Ref: Chemosphere, 77:67, 2009 : PubMed ESTHER: Wang_2009_Chemosphere_77_67 PubMedSearch: Wang 2009 Chemosphere 77 67 PubMedID: 19540550 Abstract Manufactured nanoparticles can be toxic via interactions with proteins and enzymes. Acetylcholinesterase (AChE) is a key enzyme present in the brain, blood and nervous system. Therefore, adsorption and inhibition of AChE by eight nanoparticles, SiO(2), TiO(2), Al(2)O(3), Al, Cu, Cu-C (carbon-coated copper), multi-walled carbon nanotubes (MWCNT) and single-walled carbon nanotubes (SWCNT), were examined. A modified Ellman assay was used to measure AChE activity because nanoparticles could adsorb the yellowish product, 5'-mercapto-2'-nitrobenzoic acid (5-MNBA) during the color development. Adsorption and inhibition rates by nanoparticles were estimated by decrease of AChE activities compared to controls. Carbon nanotubes had high affinity for AChE adsorption, the highest being SWCNT (94%). Nano SiO(2) and Al(2)O(3) showed the lowest adsorption. Inhibition by the tested nanoparticles was primarily caused by adsorption. However, Cu(2+) release in Cu and Cu-C nanoparticle suspensions caused 40% and 45% of AChE activity reduction, respectively. AChE inhibition by bulk Cu and activated carbon particles was also measured for comparison, showing that the inhibition by bulk particles was lower than their counterpart nanoparticles. For bulk Cu particles, AChE inhibition was primarily caused by dissolved ions, but mainly by adsorption for activated carbon. AChE inhibition by Cu, Cu-C, MWCNT and SWCNT had dose-response relationships, and their median inhibitory concentrations (IC(50)) were 4, 17, 156 and 96mgL(-1), respectively, showing that these nanoparticles may have neurotoxicity and AChE may have potential to be used as a biomarker for nanoparticles. Title: Carboxylesterase 2 is downregulated in colorectal cancer following progression of the disease Tang X, Wu H, Wu Z, Wang G, Wang Z, Zhu D Ref: Cancer Invest, 26:178, 2008 : PubMed ESTHER: Tang_2008_Cancer.Invest_26_178 PubMedSearch: Tang 2008 Cancer.Invest 26 178 PubMedID: 18259949 Abstract Expression of carboxylesterase 2 in colorectal tumor tissues and serum carboxylesterase 2 levels at different stages of the disease were investigated by Western blotting. Carboxylesterase 2 was decreasing in tumor tissues from TNM stages 0 through IV (n = 20); the expression of carboxylesterase 2 was similar between "normal" and tumor tissues (n = 20); serum carboxylesterase 2 levels were similar among patients at different stages of the disease. These results indicate that local expression of carboxylesterase 2 is downregulated following progression of the disease; carboxylesterase 2 expression is altered in histology "normal" tissues from stages I through IV before histopathological changes. Title: The genome of a lepidopteran model insect, the silkworm Bombyx mori Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J and Morishita S <88 more author(s)> Xia Q, Wang J, Zhou Z, Li R, Fan W, Cheng D, Cheng T, Qin J, Duana J, Xu H, Li Q, Li N, Wang M, Dai F, Liu C, Lin Y, Zhao P, Zhang H, Liu S, Zha X, Li C, Zhao A, Pan M, Pan G, Shen Y, Gao Z, Wang Z, Wang G, Wu Z, Hou Y, Chai C, Yu Q, He N, Zhang Z, Li S, Yang H, Lu C, Xiang Z, Mita K, Kasahara M, Nakatani Y, Yamamoto K, Abe H, Ahsan B, Daimoni T, Doi K, Fujii T, Fujiwara H, Fujiyama A, Futahashi R, Hashimotol S, Ishibashi J, Iwami M, Kadono-Okuda K, Kanamori H, Kataoka H, Katsuma S, Kawaoka S, Kawasaki H, Kohara Y, Kozaki T, Kuroshu RM, Kuwazaki S, Matsushima K, Minami H, Nagayasu Y, Nakagawa T, Narukawa J, Nohata J, Ohishi K, Ono Y, Osanai-Futahashi M, Ozaki K, Qu W, Roller L, Sasaki S, Sasaki T, Seino A, Shimomura M, Shin-I T, Shinoda T, Shiotsuki T, Suetsugu Y, Sugano S, Suwa M, Suzuki Y, Takiya S, Tamura T, Tanaka H, Tanaka Y, Touhara K, Yamada T, Yamakawa M, Yamanaka N, Yoshikawa H, Zhong YS, Shimada T, Morishita S (- 88) Ref: Insect Biochemistry & Molecular Biology, 38:1036, 2008 : PubMed ESTHER: Xia_2008_Insect.Biochem.Mol.Biol_38_1036 PubMedSearch: Xia 2008 Insect.Biochem.Mol.Biol 38 1036 PubMedID: 19121390 Gene_locus related to this paper: bommo-a0mnw6, bommo-a1yw85, bommo-a9ls22, bommo-ACHE1, bommo-ACHE2, bommo-b0fgv8, bommo-b1q137, bommo-b1q139, bommo-b1q140, bommo-b1q141, bommo-b2zdz0, bommo-b3gef6, bommo-b3gef7, bommo-b3gs55, bommo-b3gs56, bommo-d2ktu3, bommo-d2ktu5, bommo-d9ile0, bommo-e1cga5, bommo-e1cga6, bommo-g8fpz6, bommo-h9iu43, bommo-h9iu46, bommo-h9iu47.1, bommo-h9iu47.2, bommo-h9iue5, bommo-h9ivg2, bommo-h9iwj7, bommo-h9iwj8, bommo-h9ix58, bommo-h9ixi1.1, bommo-h9ixi1.2, bommo-h9iy47, bommo-h9izw1, bommo-h9j0s4, bommo-h9j1y0, bommo-h9j3r0, bommo-h9j3w6, bommo-h9j3w7, bommo-h9j5t0, bommo-h9j8g3, bommo-h9j9k9, bommo-h9j066, bommo-h9j067, bommo-h9j593, bommo-h9j594, bommo-h9j990, bommo-h9jde8, bommo-h9jde9, bommo-h9jdf0, bommo-h9jds4, bommo-h9jle7, bommo-h9jn83, bommo-h9jn85, bommo-h9jrg2, bommo-h9jyh9, bommo-JHE, bommo-m1rmh6, bommo-q1hq05, bommo-q4tte1, bommo-h9j592, bommo-h9j604, bommo-h9jpm8, bommo-h9iss4, bommo-h9j2c7 Abstract Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes. Title: Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamins C and E Yu F, Wang Z, Ju B, Wang Y, Wang J, Bai D Ref: Exp Toxicol Pathol, 59:415, 2008 : PubMed ESTHER: Yu_2008_Exp.Toxicol.Pathol_59_415 PubMedSearch: Yu 2008 Exp.Toxicol.Pathol 59 415 PubMedID: 18222074 Abstract Organophosphorus insecticide poisoning is widely investigated, and a growing number of evidence indicates its effects to cause ocular lesions, but the mechanisms of its ocular effects are not well elucidated. Here, effects of organophosphorus insecticide chlorpyrifos on mouse retina in vivo and protection of combination of vitamins C and E were reported. Cell apoptosis, lipid peroxidation and DNA damage were increased, and activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were decreased in retina of chlorpyrifos-administrated mice (63mg/kg, single treatment, via oral gavage). Pretreatment of combination of antioxidants vitamin C (250mg/kg) and vitamin E (150mg/kg) (once daily for 6 days, hypodermic injecting) significantly attenuated these effects of chlorpyrifos, demonstrating oxidative stress was involved in chlorpyrifos-induced cell apoptosis in mouse retina. Moreover, chlorpyrifos treatment inhibited acetylcholinesterase activity and promoted [Ca(2+)](i) level in mouse retinal cells, which were also attenuated by combination of vitamins C and E. These results may have implications for treatment of organophosphorus insecticide poisoning in retina with combination of vitamins C and E. Title: Neuroendocrine secretory protein 55 (NESP55) immunoreactivity in male and female rat superior cervical ganglion and other sympathetic ganglia Li Y, Wang Z, Dahlstrom A Ref: Auton Neurosci, 132:52, 2007 : PubMed ESTHER: Li_2007_Auton.Neurosci_132_52 PubMedSearch: Li 2007 Auton.Neurosci 132 52 PubMedID: 17185044 Abstract Neuroendocrine secretory protein 55 (NESP55) is a soluble, acidic and heat-stable protein, belonging to the class of chromogranins. It is expressed specifically in endocrine cells and the nervous system, and is probably involved in both constitutive and regulated secretion. In the present study, we investigated the distribution of NESP55 in various rat sympathetic ganglia by immunohistochemistry. The expression of NESP55-IR was detected in a subpopulation of principal neurons in the rat SCG, which was also TH positive, and, thus, adrenergic. In the rat stellate ganglion, more than two thirds of NESP55 positive neurons were adrenergic. Colocalization of NESP55 and calcitonin gene-related peptide (CGRP) in cholinergic neurons was also observed. In the rat thoracic chain, however, the majority of NESP55 positive neurons appeared to lack TH. No detectable NESP55-IR was found in the mouse SCG. Furthermore, in the sexually dimorphic SCG, it was demonstrated that, 80% of the NESP55 positive principal neurons were also NPY positive in the male rat, while a slightly higher, but statistically significant proportion, 87%, was found in the female. Whether or not this small difference is physiologically significant is unknown. The present data provide basic knowledge about the expression of NESP55 in the sympathetic autonomic nervous system of rat, which may further our understanding of the functional significance of NESP55. Title: Methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives: a new class of acetylcholinesterase inhibitors Wen H, Zhou Y, Lin C, Ge H, Ma L, Wang Z, Peng W, Song H Ref: Bioorganic & Medicinal Chemistry Lett, 17:2123, 2007 : PubMed ESTHER: Wen_2007_Bioorg.Med.Chem.Lett_17_2123 PubMedSearch: Wen 2007 Bioorg.Med.Chem.Lett 17 2123 PubMedID: 17317172 Abstract A new class of inhibitors of acetylcholinesterase (methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives) is described. Compounds 4b and 4i were found to be more potent than galanthamine in inhibiting acetylcholinesterase. Title: Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons Wang Z, Kai L, Day M, Ronesi J, Yin HH, Ding J, Tkatch T, Lovinger DM, Surmeier DJ Ref: Neuron, 50:443, 2006 : PubMed ESTHER: Wang_2006_Neuron_50_443 PubMedSearch: Wang 2006 Neuron 50 443 PubMedID: 16675398 Abstract Long-term depression (LTD) of the synapse formed between cortical pyramidal neurons and striatal medium spiny neurons is central to many theories of motor plasticity and associative learning. The induction of LTD at this synapse is thought to depend upon D(2) dopamine receptors localized in the postsynaptic membrane. If this were true, LTD should be inducible in neurons from only one of the two projection systems of the striatum. Using transgenic mice in which neurons that contribute to these two systems are labeled, we show that this is not the case. Rather, in both cell types, the D(2) receptor dependence of LTD induction reflects the need to lower M(1) muscarinic receptor activity-a goal accomplished by D(2) receptors on cholinergic interneurons. In addition to reconciling discordant tracts of the striatal literature, these findings point to cholinergic interneurons as key mediators of dopamine-dependent striatal plasticity and learning. Title: Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors Feng S, Wang Z, He X, Zheng S, Xia Y, Jiang H, Tang X, Bai D Ref: Journal of Medicinal Chemistry, 48:655, 2005 : PubMed ESTHER: Feng_2005_J.Med.Chem_48_655 PubMedSearch: Feng 2005 J.Med.Chem 48 655 PubMedID: 15689148 Abstract By targeting dual active sites of AChE, a series of bis-huperzine B analogues with various lengths of the tether were designed, synthesized, and tested for their inhibition and selectivity. The most potent bis-huperzine B (5g) exhibited 3900-fold increase in AChE inhibition and 930-fold greater in selectivity for AChE vs BuChE than its parent huperzine B. Title: The genome of the protist parasite Entamoeba histolytica Loftus B, Anderson I, Davies R, Alsmark UC, Samuelson J, Amedeo P, Roncaglia P, Berriman M, Hirt RP and Hall N <44 more author(s)> Loftus B, Anderson I, Davies R, Alsmark UC, Samuelson J, Amedeo P, Roncaglia P, Berriman M, Hirt RP, Mann BJ, Nozaki T, Suh B, Pop M, Duchene M, Ackers J, Tannich E, Leippe M, Hofer M, Bruchhaus I, Willhoeft U, Bhattacharya A, Chillingworth T, Churcher C, Hance Z, Harris B, Harris D, Jagels K, Moule S, Mungall K, Ormond D, Squares R, Whitehead S, Quail MA, Rabbinowitsch E, Norbertczak H, Price C, Wang Z, Guillen N, Gilchrist C, Stroup SE, Bhattacharya S, Lohia A, Foster PG, Sicheritz-Ponten T, Weber C, Singh U, Mukherjee C, El-Sayed NM, Petri WA, Jr., Clark CG, Embley TM, Barrell B, Fraser CM, Hall N (- 44) Ref: Nature, 433:865, 2005 : PubMed ESTHER: Loftus_2005_Nature_433_865 PubMedSearch: Loftus 2005 Nature 433 865 PubMedID: 15729342 Gene_locus related to this paper: entds-b0efg6, entds-b0egj2, enthi-b1n4x1, enthi-b1n449, enthi-b1n456, enthi-c4lsp4, enthi-c4lte6, enthi-c4lu03, enthi-c4lu54, enthi-c4lve4, enthi-c4lwe1, enthi-c4m0c3, enthi-c4m0e4, enthi-c4m1e7, enthi-c4m2a9, enthi-c4m2i4, enthi-c4m3r1, enthi-c4m4l3, enthi-c4m6g0, enthi-c4m6k3, enthi-c4m7k7, enthi-c4m7n4, enthi-c4m7v0, enthi-c4m8y5, enthi-c4m793, enthi-c4mb48, enthi-DPP, enthi-q50rh1, enthi-q50ya6, enthi-q51a37, enthi-q51aw6, enthi-q51ch3, enthi-q51cz6, enthi-q51ds3, enthi-q513q8, enthi-q513w3, enthi-q519v1 Abstract Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen. Title: Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm Wang Z, Wang F, Wang WQ, Gao Q, Wei WL, Yang Y, Wang GY Ref: World J Gastroenterol, 10:550, 2004 : PubMed ESTHER: Wang_2004_World.J.Gastroenterol_10_550 PubMedSearch: Wang 2004 World.J.Gastroenterol 10 550 PubMedID: 14966915 Gene_locus related to this paper: human-NDRG1 Abstract AIM: To study the function of N-myc downstream-regulated gene 1 (NDRG1) in colorectal carcinogenesis and its correlation with tumor lymph node metastasis. Title: Inhibitory effect of tellimagrandin I on chemically induced differentiation of human leukemia K562 cells Yi Z, Wang Z, Li H, Liu M Ref: Toxicol Lett, 147:109, 2004 : PubMed ESTHER: Yi_2004_Toxicol.Lett_147_109 PubMedSearch: Yi 2004 Toxicol.Lett 147 109 PubMedID: 14757314 Abstract Tellimagrandin I is a hydrolysable tannin compound widely present in plants. In this study, the effect of tellimagrandin I on chemically induced erythroid and megakaryocytic differentiation was investigated using K562 cells as differentiation model. It was found that tellimagrandin I not only inhibited the hemoglobin synthesis in butyric acid (BA)- and hemin-induced K562 cells with IC50 of 3 and 40microM, respectively, but also inhibited other erythroid differentiation marker including acetylcholinesterase (AChE) and glycophorin A (GPA) in BA-induced K562 cells. Tellimagrandin I also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of CD61 protein, a megakaryocytic marker. RT-PCR analysis showed that tellimagrandin I decreased the expression of erythroid genes (gamma-globin and porphobilinogen deaminase (PBGD)) and related transcription factors (GATA-1 and NF-E2) in BA-induced K562 cells, whereas tellimagrandin I induced the overexpresison of GATA-2 transcription factor that played negative regulation on erythroid differentiation. These results indicated that tellimagrandin I had inhibitory effects on erythroid and megakaryocytic differentiation, which suggested that tannins like tellimagrandin I might influence the anti-tumor efficiency of some drugs and the hematopoiesis processes. Title: Effects of chebulinic acid on differentiation of human leukemia K562 cells Yi ZC, Wang Z, Li HX, Liu MJ, Wu RC, Wang XH Ref: Acta Pharmacol Sin, 25:231, 2004 : PubMed ESTHER: Yi_2004_Acta.Pharmacol.Sin_25_231 PubMedSearch: Yi 2004 Acta.Pharmacol.Sin 25 231 PubMedID: 14769215 Abstract AIM: To study effects of chebulinic acid on erythroid and megakaryocytic differentiation in K562 cells. Title: Highly enantioselective hydrolysis of alicyclic meso-epoxides with a bacterial epoxide hydrolase from Sphingomonas sp. HXN-200: simple syntheses of alicyclic vicinal trans-diols Chang D, Wang Z, Heringa MF, Wirthner R, Witholt B, Li Z Ref: Chem Commun (Camb), :960, 2003 : PubMed ESTHER: Chang_2003_Chem.Commun.(Camb)__960 PubMedSearch: Chang 2003 Chem.Commun.(Camb) 960 PubMedID: 12744319 Abstract Hydrolysis of N-benzyloxycarbonyl-3,4-epoxy-pyrrolidine and cyclohexene oxide with the epoxide hydrolase of Sphingomonas sp. HXN-200, respectively, gave the corresponding vicinal trans-diols in high ee and yield, representing the first example of enantioselective hydrolysis of a meso-epoxide with a bacterial epoxide hydrolase. Title: Presence and release of SR-17 (chromogranin B(586-602)) in the porcine splenic nerve and its enzymatic degradation by CD26/dipeptidyl peptidase IV Depreitere J, Durinx C, Wang Z, Coen E, Lambeir AM, Scharpe S, De Potter W, Nouwen EJ Ref: Regul Pept, 106:71, 2002 : PubMed ESTHER: Depreitere_2002_Regul.Pept_106_71 PubMedSearch: Depreitere 2002 Regul.Pept 106 71 PubMedID: 12047913 Abstract Using the pig splenic nerve as a model, we investigated the proteolytic processing of porcine chromogranin B (CgB) during its axonal transport. An ELISA was developed for SR-17 (CgB(586-602)), a novel CgB-derived peptide, originally found in the adrenal medulla. The results demonstrate that CgB is processed in an early stage during its axonal transport. Immunohistochemical data, based on a rabbit anti-SR-17 antiserum, show that the spleen CgB/SR-17 is exclusively present in the nerve endings. No SR-17 immunoreactivity (IR) was found in splenocytes. We also provide evidence that SR-17 is co-released with noradrenaline (NA) upon electrical stimulation of the splenic nerve. Its release is frequency-dependent and strongly enhanced in the presence of the alpha-blocking agent phentolamine. In addition, we show that the new CgB-peptide can serve as a substrate for the lymphocyte surface glycoprotein CD26, also known as dipeptidyl peptidase IV (DPP IV), generating a new peptide ER-15 (CgB(588-602)). Title: Effects of low intensity radiofrequency electromagnetic fields on electrical activity in rat hippocampal slices Tattersall JE, Scott IR, Wood SJ, Nettell JJ, Bevir MK, Wang Z, Somasiri NP, Chen X Ref: Brain Research, 904:43, 2001 : PubMed ESTHER: Tattersall_2001_Brain.Res_904_43 PubMedSearch: Tattersall 2001 Brain.Res 904 43 PubMedID: 11516410 Abstract Slices of rat hippocampus were exposed to 700 MHz continuous wave radiofrequency (RF) fields (25.2-71.0 V m(-1), 5-15 min exposure) in a stripline waveguide. At low field intensities, the predominant effect on the electrically evoked field potential in CA1 was a potentiation of the amplitude of the population spike by up to 20%, but higher intensity fields could produce either increases or decreases of up to 120 and 80%, respectively, in the amplitude of the population spike. To eliminate the possibility of RF-induced artefacts due to the metal stimulating electrode, the effect of RF exposure on spontaneous epileptiform activity induced in CA3 by 4-aminopyridine (50-100 microM) was investigated. Exposure to RF fields (50.0 V m(-1)) reduced or abolished epileptiform bursting in 36% of slices tested. The maximum field intensity used in these experiments, 71.0 V m(-1), was calculated to produce a specific absorption rate (SAR) of between 0.0016 and 0.0044 W kg(-1) in the slices. Measurements with a Luxtron fibreoptic probe confirmed that there was no detectable temperature change (+/- 0.1 degrees C) during a 15 min exposure to this field intensity. Furthermore, imposed temperature changes of up to 1 degrees C failed to mimic the effects of RF exposure. These results suggest that low-intensity RF fields can modulate the excitability of hippocampal tissue in vitro in the absence of gross thermal effects. The changes in excitability may be consistent with reported behavioural effects of RF fields. Title: The sequence of the human genome Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA and Zhu X <264 more author(s)> Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (- 264) Ref: Science, 291:1304, 2001 : PubMed ESTHER: Venter_2001_Science_291_1304 PubMedSearch: Venter 2001 Science 291 1304 PubMedID: 11181995 Gene_locus related to this paper: human-AADAC, human-ABHD1, human-ABHD10, human-ABHD11, human-ACHE, human-BCHE, human-LDAH, human-ABHD18, human-CMBL, human-ABHD17A, human-KANSL3, human-LIPA, human-LYPLAL1, human-NDRG2, human-NLGN3, human-NLGN4X, human-NLGN4Y, human-PAFAH2, human-PREPL, human-RBBP9, human-SPG21 Abstract A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. Title: O-ethyl and o-methyl n-(2,3,4,6-tetra-o-acetyl-beta-d-glucopyranosyl)thiocarbamate Zhang S, Wang Z, Li M, Jiao K, Razak IA, Shanmuga Sundara Raj S, Fun HK Ref: Acta Crystallographica C, 57:566, 2001 : PubMed ESTHER: Zhang_2001_Acta.Crystallogr.C_57_566 PubMedSearch: Zhang 2001 Acta.Crystallogr.C 57 566 PubMedID: 11353253 Abstract In both the title structures, O-ethyl N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)thiocarbamate, C(17)H(25)NO(10)S, and O-methyl N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)thiocarbamate, C(16)H(23)NO(10)S, the hexopyranosyl ring adopts the (4)C(1) conformation. All the ring substituents are in equatorial positions. The acetoxymethyl group is in a gauche-gauche conformation. The S atom is in a synperiplanar conformation, while the C-N-C-O linkage is antiperiplanar. N-H.O intermolecular hydrogen bonds link the molecules into infinite chains and these are connected by C-H.O interactions. Title: The DNA sequence of human chromosome 22 Dunham I, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP and O'Brien KP <207 more author(s)> Dunham I, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage AK, Bagguley C, Bailey J, Barlow KF, Bates KN, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Buck D, Burgess J, Burrill WD, Burton J, Carder C, Carter NP, Chen Y, Clark G, Clegg SM, Cobley VE, Cole CG, Collier RE, Connor R, Conroy D, Corby NR, Coville GJ, Cox AV, Davis J, Dawson E, Dhami PD, Dockree C, Dodsworth SJ, Durbin RM, Ellington AG, Evans KL, Fey JM, Fleming K, French L, Garner AA, Gilbert JGR, Goward ME, Grafham DV, Griffiths MND, Hall C, Hall RE, Hall-Tamlyn G, Heathcott RW, Ho S, Holmes S, Hunt SE, Jones MC, Kershaw J, Kimberley AM, King A, Laird GK, Langford CF, Leversha MA, Lloyd C, Lloyd DM, Martyn ID, Mashreghi-Mohammadi M, Matthews LH, Mccann OT, Mcclay J, Mclaren S, McMurray AA, Milne SA, Mortimore BJ, Odell CN, Pavitt R, Pearce AV, Pearson D, Phillimore BJCT, Phillips SH, Plumb RW, Ramsay H, Ramsey Y, Rogers L, Ross MT, Scott CE, Sehra HK, Skuce CD, Smalley S, Smith ML, Soderlund C, Spragon L, Steward CA, Sulston JE, Swann RM, Vaudin M, Wall M, Wallis JM, Whiteley MN, Willey DL, Williams L, Williams SA, Williamson H, Wilmer TE, Wilming L, Wright CL, Hubbard T, Bentley DR, Beck S, Rogers J, Shimizu N, Minoshima S, Kawasaki K, Sasaki T, Asakawa S, Kudoh J, Shintani A, Shibuya K, Yoshizaki Y, Aoki N, Mitsuyama S, Roe BA, Chen F, Chu L, Crabtree J, Deschamps S, Do A, Do T, Dorman A, Fang F, Fu Y, Hu P, Hua A, Kenton S, Lai H, Lao HI, Lewis J, Lewis S, Lin S-P, Loh P, Malaj E, Nguyen T, Pan H, Phan S, Qi S, Qian Y, Ray L, Ren Q, Shaull S, Sloan D, Song L, Wang Q, Wang Y, Wang Z, White J, Willingham D, Wu H, Yao Z, Zhan M, Zhang G, Chissoe S, Murray J, Miller N, Minx P, Fulton R, Johnson D, Bemis G, Bentley D, Bradshaw H, Bourne S, Cordes M, Du Z, Fulton L, Goela D, Graves T, Hawkins J, Hinds K, Kemp K, Latreille P, Layman D, Ozersky P, Rohlfing T, Scheet P, Walker C, Wamsley A, Wohldmann P, Pepin K, Nelson J, Korf I, Bedell JA, Hillier L, Mardis E, Waterston R, Wilson R, Emanuel BS, Shaikh T, Kurahashi H, Saitta S, Budarf ML, McDermid HE, Johnson A, Wong ACC, Morrow BE, Edelmann L, Kim UJ, Shizuya H, Simon MI, Dumanski JP, Peyrard M, Kedra D, Seroussi E, Fransson I, Tapia I, Bruder CE, O'Brien KP (- 207) Ref: Nature, 402:489, 1999 : PubMed ESTHER: Dunham_1999_Nature_402_489 PubMedSearch: Dunham 1999 Nature 402 489 PubMedID: 10591208 Gene_locus related to this paper: human-CES5A, human-SERHL2 Abstract Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome. Title: Paraoxonase polymorphism and its effect on male reproductive outcomes among Chinese pesticide factory workers Padungtod C, Niu T, Wang Z, Savitz DA, Christiani DC, Ryan LM, Xu X Ref: American Journal of Industrial Medicine, 36:379, 1999 : PubMed ESTHER: Padungtod_1999_Am.J.Ind.Med_36_379 PubMedSearch: Padungtod 1999 Am.J.Ind.Med 36 379 PubMedID: 10470002 Abstract BACKGROUND Serum paraoxonase has been associated with the metabolism of organophosphate pesticides in humans. Molecular analysis of the human paraoxonase gene (PON1) has revealed that Arg192 homozygotes have a greater detoxifying capability than Gln192 homozygotes. We examined the effects of PON1 genotypes on male reproductive outcomes and its interaction with exposure to organophosphate pesticides. METHODS: We studied 60 Chinese pesticide-factory workers and 89 textile-factory workers who were unexposed to pesticides. The respective allele frequencies of Arg192 and Gln192 were 0.62 and 0.38. Pesticide exposure among 36 exposed subjects and 12 unexposed subjects, regardless of gender, was assessed by personal measurement of pesticide residues over an entire 8-hr shift and measurement of urinary p-nitrophenol level over a 24-hr period. We analyzed semen and hormone data collected from male subjects. RESULTS: When the three PON1 genotypes were analyzed separately, a gene dose effect was not detected. We used the unexposed Arg192 homo/heterozygotes as the reference group, and re-analyzed the data. Exposed Arg192 homo/heterozygotes had significantly lower sperm count (chi 2 = 9.01, P < 0.01) and lower percentage of sperm with normal morphology (chi 2 = 4.18, P < 0.05) than the reference group. Both unexposed Gln192 homozygotes (chi 2 = 4.90, P < 0.05) and exposed Arg192 homo/heterozygotes (chi 2 = 10.00, P < 0.01) showed significantly lower sperm concentrations than the reference group. In addition, exposed Arg192 homo/heterozygotes had significantly higher serum LH levels (chi 2 = 7.94, P < 0.01) than the reference group. CONCLUSIONS: Because of a small sample size, our findings are highly preliminary. Nevertheless, it calls for further investigation of the interaction between the PON1 genotype and organophosphate pesticide exposure on male reproductive outcomes. Title: Poster: Functional and molecular identification and characterization of cardiac M3 and M4 muscarinic acetylcholine receptors Shi H, Wang H, Wang Z Ref: Life Sciences, 64:583, 1999 : PubMed Title: Poster: Pharmacological and molecular characterization of muscarinic acetylcholine receptor subtypes in human heart Wang H, Shi H, Deng X, Wang Z Ref: Life Sciences, 64:590, 1999 : PubMed Title: Poster: Choline alters cardiac function by activating M3 muscarinic acetylcholine receptors (mAChRs) in cardiac myocytes Wang Z, Shi H, Wang H Ref: Life Sciences, 64:580, 1999 : PubMed Title: Poster: Modulation of K+ currents by muscarinic acetylcholine receptor agonists in canine atrial myocytes Yang X, Shi H, Wang H, Wang Z Ref: Life Sciences, 64:576, 1999 : PubMed Title: The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis Brown DD, Wang Z, Furlow JD, Kanamori A, Schwartzman RA, Remo BF, Pinder A Ref: Proc Natl Acad Sci U S A, 93:1924, 1996 : PubMed ESTHER: Brown_1996_Proc.Natl.Acad.Sci.U.S.A_93_1924 PubMedSearch: Brown 1996 Proc.Natl.Acad.Sci.U.S.A 93 1924 PubMedID: 8700860 Gene_locus related to this paper: xenla-Q91651 Abstract Genes that are up- and down-regulated by thyroid hormone in the tail resorption program of Xenopus laevis have been isolated by a gene expression screen, sequenced, and identified in the GenBank data base. The entire program is estimated to consist of fewer than 35 up-regulated and fewer than 10 down-regulated genes; 17 and 4 of them, respectively, have been isolated and characterized. Up-regulated genes whose function can be predicted on the basis of their sequence include four transcription factors (including one of the thyroid hormone receptors), an extracellular matrix component (fibronectin) and membrane receptor (integrin), four proteinases, a deiodinase that degrades thyroid hormone, and a protein that binds the hypothalamic corticotropin-releasing factor, which has been implicated in controlling thyroid hormone synthesis in Xenopus tadpoles. All four down-regulated genes encode extracellular proteins that are expressed in tadpole epidermis. This survey of the program provides insights into the biology of metamorphosis. Title: Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels Cohen JC, Wang Z, Grundy SM, Stoesz MR, Guerra R Ref: J Clinical Investigation, 94:2377, 1994 : PubMed ESTHER: Cohen_1994_J.Clin.Invest_94_2377 PubMedSearch: Cohen 1994 J.Clin.Invest 94 2377 PubMedID: 7989594 Abstract Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical-by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci. Title: [Study on Na(+)-K(+)-ATPase of the spiral ganglion neuron and acetylcholinesterase of the cochlea efferent nerve after electric stimulation in the scale media]. [Chinese] Wang Z, Shen Y Ref: Chinese Journal of Otorhinolaryngology, 29:92, 1994 : PubMed ESTHER: Wang_1994_Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi_29_92 PubMedSearch: Wang 1994 Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi 29 92 PubMedID: 7803098 Abstract In this study, it was found the concentration of Na(+)-K(+)-ATPase of the spiral ganglion neuron (SGN) increased 3 months after electric stimulation (0.1 mA) for 3 hours. However, current at 1.0 mA would destroy the enzyme production mechanism of SGN. Therefore 0.4 mA might be thought as a critical level because the concentration of the enzyme decreased with just above this level of stimulation. We suggest that the appropriate intensity range of the current stimulation of SGN should be controlled from 0.1 mA-0.4 mA. Acetylcholinesterase of the cochlea efferent nerve would increase with weak current stimulation (0.1 mA) which might play an important role in the protection of SGN during ototoxicity. This experimental results led to the conclusion that Na(+)-K(+)-ATPase of the SGN could be taken as an objective indicator presenting the functional changes of SGN quantitatively. Title: Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R-ACPD Wang Z, McCormick DA Ref: Journal of Neuroscience, 13:2199, 1993 : PubMed ESTHER: Wang_1993_J.Neurosci_13_2199 PubMedSearch: Wang 1993 J.Neurosci 13 2199 PubMedID: 8386756 Abstract The ionic mechanisms by which the firing mode of layer V burst-generating neurons is modulated by noradrenergic, cholinergic, and glutamate metabotropic receptors were investigated with intracellular and extracellular recordings obtained in slices of guinea pig sensorimotor and primary visual cortices maintained in vitro. Extracellular and intracellular recordings revealed that a subset of layer V cells spontaneously generated bursts of three to six action potentials with an interburst frequency of 0.2-4 Hz. Depolarization of these cells with the intracellular injection of current inhibited burst firing and switched the cells to the tonic, single-spike mode of action potential generation. Intracellular recording from retrogradely labeled layer V pyramidal cells that project to either the superior colliculus or pontine nuclei revealed that a substantial portion of these are burst-generating cells. Application of norepinephrine (NE), the glutamate metabotropic receptor agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD), or ACh to layer V burst-generating cells resulted in depolarization and a subsequent shift in firing pattern from spontaneously bursting to single-spike activity. Pharmacological analysis of these responses indicated that they are mediated by the alpha 1-adrenoceptor for NE and the muscarinic subtype for ACh. Thus, the NE response was mimicked by the alpha-agonist phenylephrine but not by the beta-agonist isoprenaline, and was completely blocked by the alpha 1-antagonist prazosin but not by the alpha 2-antagonist yohimbine or the beta-antagonist propranolol. Finally, the ACh effect could be mimicked by the muscarinic agonist acetyl-beta-methylcholine (MCh) and was blocked by the muscarinic antagonist scopolamine. Intracellular recordings revealed that the NE-, MCh-, and ACPD-induced responses in bursting neurons are due to the direct activation of receptors on these cells, since block of synaptic transmission with local application of TTX or bath application of low [Ca2+]o and raised [Mg2+]o did not block the postsynaptic responses. Voltage-clamp analysis of the currents involved in the depolarizing responses of bursting cells revealed that activation of alpha 1-adrenergic, muscarinic, or glutamate metabotropic receptors resulted in a decrease in a potassium conductance that consisted of both a voltage-independent component and a voltage- and Ca(2+)-sensitive component. These results suggest that increased activity in noradrenergic, cholinergic, and glutamatergic pathways may control the firing mode of layer V corticotectal and corticopontine pyramidal cells by determining the resting membrane potential through modulation of both voltage-dependent and voltage-independent K+ conductances. Title: Poster: Muscarinic autoreceptors on cholinergic nerves innervating horse trachea are not of the M1, M2, or M3 subtypes Wang Z, Yu M, Robinson NE Ref: Life Sciences, 52(5-6):567, 1993 : PubMed Title: Serotonin and noradrenaline excite GABAergic neurones of the guinea-pig and cat nucleus reticularis thalami McCormick DA, Wang Z Ref: Journal of Physiology, 442:235, 1991 : PubMed ESTHER: McCormick_1991_J.Physiol_442_235 PubMedSearch: McCormick 1991 J.Physiol 442 235 PubMedID: 1665858 Abstract 1. The actions of serotonin (5-HT) and noradrenaline (NA) in the cat perigeniculate nucleus (PGN) and the guinea-pig nucleus reticularis thalami (NRT) were investigated with extracellular and intracellular recordings obtained from neurones in thalamic slices maintained in vitro. 2. Single, local application of either 5-HT or NA resulted in pronounced (5-50 Hz) and prolonged (2-10 min) excitation associated with the occurrence of single-spike activity. Serotoninergic excitation was specifically blocked by the 5-HT2/5-HT1C antagonists ketanserin and ritanserin, but not by the 5-HT1A antagonist pindolol or the 5-HT3 antagonist ICS 205-930. Furthermore, the 5-HT response was mimicked by alpha-methyl-5-HT, but not by the 5-HT1A agonist 8-hydroxydipropylaminotetralin (8-OHDPAT) or the 5-HT3 agonist 2-methyl-5-HT. Together, these results indicate that this excitatory response is mediated through 5-HT2 receptors with the possible involvement of 5-HT1C receptors. 3. Noradrenergic excitation was specifically blocked by the alpha 1-antagonist prazosin, but not by the beta-antagonist propranolol or the alpha 2-antagonist yohimbine. Similarly, the response was mimicked by the alpha-agonist phenylephrine, but not by the beta-agonist isoprenaline. These results indicate that the noradrenergic excitation is mediated by alpha 1-adrenoceptors. 4. Block of synaptic transmission either by lowering external calcium concentration ([Ca2+]o) to 0.5 mM and raising external magnesium concentration ([Mg2+]o) to 10 mM or by local application of tetrodotoxin failed to block the excitatory or depolarizing response to 5-HT or NA indicating that these responses are direct and not mediated through the release of other neurotransmitters. 5. Intracellular recordings revealed that the 5-HT- and NA-induced excitations are mediated by a pronounced slow depolarization associated with an apparent decrease in input conductance and an increase in the membrane time constant. Current versus voltage plots obtained under voltage clamp before and during the presence of 5-HT and NA revealed that these neurotransmitters induced an inward current which reversed to an outward current at -107 and -110 mV, respectively, in 2.5 mM external potassium concentration ([K+]o). This reversal potential was identical to that associated with an increase in potassium conductance activated by acetylcholine (-110 mV) in the same neurones. Plots of the amplitude of the 5-HT- or NA-induced current versus membrane potential revealed a linear relationship in the voltage range from -140 to -60 mV. |
