Author Report for: Zhang QNo contact information in database for Zhang Q
Guo W, Gou X, Yu L, Zhang Q, Yang P, Pang M, Pang X, Pang C, Wei Y, Zhang X Ref: Front Neurol, 14:1129470, 2023 : PubMed ESTHER: Guo_2023_Front.Neurol_14_1129470 PubMedSearch: Guo 2023 Front.Neurol 14 1129470 PubMedID: 37056359 Abstract Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular beta-amyloid (Abeta) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Abeta pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD. Title: Discovery of 1,2,4-Oxadiazole Derivatives Containing Haloalkyl as Potential Acetylcholine Receptor Nematicides Luo L, Ou Y, Zhang Q, Gan X Ref: Int J Mol Sci, 24:, 2023 : PubMed ESTHER: Luo_2023_Int.J.Mol.Sci_24_ PubMedSearch: Luo 2023 Int.J.Mol.Sci 24 PubMedID: 36982843 Abstract Plant-parasitic nematodes pose a serious threat to crops and cause substantial financial losses due to control difficulties. Tioxazafen (3-phenyl-5-thiophen-2-yl-1,2,4-oxadiazole) is a novel broad-spectrum nematicide developed by the Monsanto Company, which shows good prevention effects on many kinds of nematodes. To discover compounds with high nematocidal activities, 48 derivatives of 1,2,4-oxadiazole were obtained by introducing haloalkyl at the 5-position of tioxazafen, and their nematocidal activities were systematically evaluated. The bioassays revealed that most of 1,2,4-oxadiazole derivatives showed remarkable nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci. Notably, compound A1 showed excellent nematocidal activity against B. xylophilus with LC(50) values of 2.4 microg/mL, which was superior to that of avermectin (335.5 microg/mL), tioxazafen (>300 microg/mL), and fosthiazate (436.9 microg/mL). The transcriptome and enzyme activity results indicate that the nematocidal activity of compound A1 was mainly related to the compound which affected the acetylcholine receptor of B. xylophilus. Title: Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery Qu W, Yao Y, Liu Y, Jo H, Zhang Q, Zhao H Ref: Int J Gen Med, 16:1567, 2023 : PubMed ESTHER: Qu_2023_Int.J.Gen.Med_16_1567 PubMedSearch: Qu 2023 Int.J.Gen.Med 16 1567 PubMedID: 37139258 Gene_locus related to this paper: human-CES2 Abstract PURPOSE: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. PATIENTS AND METHODS: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. RESULTS: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. CONCLUSION: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA. Title: A Systematic Review of Clinical Practice Guidelines for Alzheimer's Disease and Strategies for Future Advancements Tahami Monfared AA, Phan NTN, Pearson I, Mauskopf J, Cho M, Zhang Q, Hampel H Ref: Neurol Ther, :, 2023 : PubMed ESTHER: Tahami_2023_Neurol.Ther__ PubMedSearch: Tahami 2023 Neurol.Ther PubMedID: 37261607 Abstract INTRODUCTION: Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving. METHODS: A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease. RESULTS: 53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment. DISCUSSION: The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners. CONCLUSION: Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD. Title: Complete bio-degradation of poly(butylene adipate-co-terephthalate) via engineered cutinases Yang Y, Min J, Xue T, Jiang P, Liu X, Peng R, Huang JW, Qu Y, Li X and Guo RT <6 more author(s)> Yang Y, Min J, Xue T, Jiang P, Liu X, Peng R, Huang JW, Qu Y, Li X, Ma N, Tsai FC, Dai L, Zhang Q, Liu Y, Chen CC, Guo RT (- 6) Ref: Nat Commun, 14:1645, 2023 : PubMed ESTHER: Yang_2023_Nat.Commun_14_1645 PubMedSearch: Yang 2023 Nat.Commun 14 1645 PubMedID: 36964144 Gene_locus related to this paper: idesa-peth, thefu-q6a0i4 Inhibitor(s) related to this paper: Terephthalic-acid, MHET Abstract Poly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production and has accumulated globally as environmental waste. Biodegradation is an attractive strategy to manage PBAT, but an effective PBAT-degrading enzyme is required. Here, we demonstrate that cutinases are highly potent enzymes that can completely decompose PBAT films in 48 h. We further show that the engineered cutinases, by applying a double mutation strategy to render a more flexible substrate-binding pocket exhibit higher decomposition rates. Notably, these variants produce TPA as a major end-product, which is beneficial feature for the future recycling economy. The crystal structures of wild type and double mutation of a cutinase from Thermobifida fusca in complex with a substrate analogue are also solved, elucidating their substrate-binding modes. These structural and biochemical analyses enable us to propose the mechanism of cutinase-mediated PBAT degradation. Title: Near-infrared ratiometric fluorescent strategy for butyrylcholinesterase activity and its application in the detection of pesticide residue in food samples and biological imaging Yuan W, Wan C, Zhang J, Li Q, Zhang P, Zheng K, Zhang Q, Ding C Ref: Spectrochim Acta A Mol Biomol Spectrosc, 297:122719, 2023 : PubMed ESTHER: Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719 PubMedSearch: Yuan 2023 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 297 122719 PubMedID: 37043836 Abstract Butyrylcholinesterase (BChE) is an essential esterase synthesized by the liver, and its level is considered as a vital index for health evaluation. Therefore, it is of great need to develop a highly sensitive and selective tool to monitor BChE activity, which remains a considerable challenge on account of its usage in complex biological systems. A near-infrared (NIR) fluorescent probe was elaborated in this work, employing cyanine backbone to provide the intrinsic NIR fluorescence and avoid interference from bioluminescence. There presented an intriguing structural transformation upon the sensing event to shrink the conjugation in this protocol, leading to an eye-catching fluorescence change from NIR (816 nm) to red (637 nm) region, which gave rise to the proposed ratiometric assay. After an overall investigation, this receptor was verified to be applicable in a wide bio-area with ratiometric pattern, including the cellular level and slice platform. It was worth mentioning that this receptor was also discovered to be capable of monitoring pesticide dichlorvos (DDVP) residue in food samples with high sensitivity and accuracy, with significant potential to be developed as an alternative candidate for monitoring environmental pollution. Title: Rapid detection of carbamate nerve agent analogues using dually functionalized gold nanoclusters Zhang H, Wang X, Xu Z, Ma J, Li ZL, Cheng WM, Jiang H, Zhang Q, Lv J and Liu S <4 more author(s)> Zhang H, Wang X, Xu Z, Ma J, Li ZL, Cheng WM, Jiang H, Zhang Q, Lv J, Xia J, Wang L, Qu G, Yang Y, Liu S (- 4) Ref: Anal Bioanal Chem, :, 2023 : PubMed ESTHER: Zhang_2023_Anal.Bioanal.Chem__ PubMedSearch: Zhang 2023 Anal.Bioanal.Chem PubMedID: 36869898 37266687 Abstract Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs. Title: Knockdown of hepatocyte Perilipin-3 mitigates hepatic steatosis and steatohepatitis caused by hepatocyte CGI-58 deletion in mice Bao X, Ma X, Huang R, Chen J, Xin H, Zhou M, Li L, Tong S, Zhang Q and Zhang Z <4 more author(s)> Bao X, Ma X, Huang R, Chen J, Xin H, Zhou M, Li L, Tong S, Zhang Q, Shui G, Deng F, Yu L, Li MD, Zhang Z (- 4) Ref: J Molecular & Cellular Biology, :, 2022 : PubMed ESTHER: Bao_2022_J.Mol.Cell.Biol__ PubMedSearch: Bao 2022 J.Mol.Cell.Biol PubMedID: 36107452 Abstract Comparative gene identification-58 (CGI-58), also known as alpha/beta hydrolase domain containing 5 (ABHD5), is the co-activator of adipose triglyceride lipase that hydrolyzes triglycerides stored in the cytosolic lipid droplets. Mutations in CGI-58 gene cause Chanarin-Dorfman syndrome (CDS), an autosomal recessive neutral lipid storage disease with ichthyosis. The liver pathology of CDS manifests as steatosis and steatohepatitis, which currently has no effective treatments. Perilipin-3 (Plin3) is a member of the Perilipin-ADRP-TIP47 (PAT) protein family that is essential for lipid droplet biogenesis. The objective of this study was to test a hypothesis that deletion of a major lipid droplet protein alleviates fatty liver pathogenesis caused by CGI-58 deficiency in hepatocytes. Adult CGI-58-floxed mice were injected with adeno-associated vectors simultaneously expressing the Cre recombinase and microRNA against Plin3 under the control of a hepatocyte-specific promoter, followed by high-fat diet (HFD) feeding for 6 weeks. Liver and blood samples were then collected from these animals for histological and biochemical analysis. Plin3 knockdown in hepatocytes prevented steatosis, steatohepatitis, and necroptosis caused by hepatocyte CGI-58 deficiency. Our work is the first to show that inhibiting Plin3 in hepatocytes is sufficient to mitigate hepatocyte CGI-58 deficiency-induced hepatic steatosis and steatohepatitis in mice. Title: Discovering monoacylglycerol lipase inhibitors by a combination of fluorogenic substrate assay and activity-based protein profiling Deng H, Zhang Q, Lei Q, Yang N, Yang K, Jiang J, Yu Z Ref: Front Pharmacol, 13:941522, 2022 : PubMed ESTHER: Deng_2022_Front.Pharmacol_13_941522 PubMedSearch: Deng 2022 Front.Pharmacol 13 941522 PubMedID: 36105202 Abstract The endocannabinoid 2-arachidonoylglycerol (2-AG) is predominantly metabolized by monoacylglycerol lipase (MAGL) in the brain. Selective inhibitors of MAGL provide valuable insights into the role of 2-AG in a variety of (patho)physiological processes and are potential therapeutics for the treatment of diseases such as neurodegenerative disease and inflammation, pain, as well as cancer. Despite a number of MAGL inhibitors been reported, inhibitors with new chemotypes are still required. Here, we developed a substrate-based fluorescence assay by using a new fluorogenic probe AA-HNA and successfully screened a focused library containing 320 natural organic compounds. Furthermore, we applied activity-based protein profiling (ABPP) as an orthogonal method to confirm the inhibitory activity against MAGL in the primary substrate-based screening. Our investigations culminated in the identification of two major compound classes, including quinoid diterpene (23, cryptotanshinone) and beta-carbolines (82 and 93, cis- and trans-isomers), with significant potency towards MAGL and good selectivity over other 2-AG hydrolases (ABHD6 and ABHD12). Moreover, these compounds also showed antiproliferative activities against multiple cancer cells, including A431, H1975, B16-F10, OVCAR-3, and A549. Remarkably, 23 achieved complete inhibition towards endogenous MAGL in most cancer cells determined by ABPP. Our results demonstrate the potential utility of the substrate-based fluorescence assay in combination with ABPP for rapidly discovering MAGL inhibitors, as well as providing an effective approach to identify potential targets for compounds with significant biological activities. Title: miRNA-Mediated Low Expression of EPHX3 Is Associated with Poor Prognosis and Tumor Immune Infiltration in Head and Neck Squamous Cell Carcinomas Ding S, Hong Q, Duan T, Xu Z, He Q, Qiu D, Li L, Yan J, Zhang Q, Mu Z Ref: J Oncol, 2022:7633720, 2022 : PubMed ESTHER: Ding_2022_J.Oncol_2022_7633720 PubMedSearch: Ding 2022 J.Oncol 2022 7633720 PubMedID: 35401746 Abstract The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration. Title: Cirrhosinones A-H, 24-hydroxy cevanine-type alkaloids from Fritillariacirrhosa Dong H, Zhang Y, Wai Ming T, Wang S, Li J, Fu S, Zhang Q, Zeng K, Tu P, Liang H Ref: Phytochemistry, 197:113129, 2022 : PubMed ESTHER: Dong_2022_Phytochemistry_197_113129 PubMedSearch: Dong 2022 Phytochemistry 197 113129 PubMedID: 35176308 Abstract Eight undescribed isosteroidal alkaloids cirrhosinones A-H (1-8), along with six known isosteroidal alkaloids (9-14), were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were determined by HRESIMS and 2D NMR analysis, and their absolute configurations were established by X-ray analysis. Compounds 1-8 possessed a typical cevanine-type alkaloid skeleton with a hydroxyl group rarely substituted at C-24 and compounds 4-8 possessed rare 7alpha or 7beta-hydroxyl groups. This was the first report of both C-7 and C-24 hydroxyl groups substituted cevanine-type alkaloids. In addition, an approach for distinguishing D/E cis and trans conformations of cevanine-type alkaloids by (1)H NMR data was developed. Moreover, the correlations between the relative configurations of 3-OH, 7-OH, 22-C, 24-OH, and 25-Me and the (1)H NMR and (13)C NMR data were also summarized. Compounds 1-9 exhibited moderate NO inhibitory activities in LPS-stimulated BV-2 cells at the concentration of 40 microM. The acetylcholinesterase inhibitory activities of compounds 1-7 and 9-10 were also evaluated and none of them showed acetylcholinesterase inhibitory activities at the concentrations of 20-80 microM. Title: Phytochemical composition, antimicrobial activities, and cholinesterase inhibitory properties of the lichen Usnea diffracta Vain Hao YM, Yan YC, Zhang Q, Liu BQ, Wu CS, Wang LN Ref: Front Chem, 10:1063645, 2022 : PubMed ESTHER: Hao_2022_Front.Chem_10_1063645 PubMedSearch: Hao 2022 Front.Chem 10 1063645 PubMedID: 36688056 Abstract Lichens are important sources of versatile bioactive compounds. Two new dibenzofurans (1-2), a multi-substituted single benzene ring (3), and two organic acid compounds (4-5) along with 25 known compounds (6-30) were isolated from the lichen Usnea diffracta Vain. Their structures were identified by physicochemical properties and spectral analyses. Compounds 1-30 were tested for inhibitory activities against Staphylococcus aureus, Escherichia coli, and Candida albicans by the disk diffusion method and microdilution assay respectively. Compound 3 showed moderate inhibitory activities against S. aureus and E. coli with the inhibition zone (IZ) of 6.2smm and 6.3smm, respectively. Depside 10 exhibited good activity against S.aureus and C. albicans with 6.6smm and 32 microg/ml, respectively. The acetylcholinesterase inhibitory activities of compounds 1, 2, and 6-8 with the characteristic dibenzofuran scaffold were evaluated var anti-AChE assay and a molecular docking study. Compound 2 could better inhibit AChE at the concentration of 0.3smicromol/ml with a value of 61.07 +/- 0.85%. The molecular docking study also demonstrated that compound 2 had the strongest binding affinity among the five dibenzofurans, and the '-CDOCKER Energy' value was 14.4513skcal/mol. Title: Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis Lang B, Han L, Zeng L, Zhang Q, Chen S, Huang L, Jia Z, Yu Q, Zhang L Ref: BMC Pediatr, 22:295, 2022 : PubMed ESTHER: Lang_2022_BMC.Pediatr_22_295 PubMedSearch: Lang 2022 BMC.Pediatr 22 295 PubMedID: 35590273 Abstract BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future. Title: Identification of Novel Organophosphate Esters in Hydroponic Lettuces (Lactuca sativa L.): Biotransformation and Acropetal Translocation Li X, Yao Y, Chen H, Zhang Q, Li C, Zhao L, Guo S, Cheng Z, Wang Y and Sun H <1 more author(s)> Li X, Yao Y, Chen H, Zhang Q, Li C, Zhao L, Guo S, Cheng Z, Wang Y, Wang L, Sun H (- 1) Ref: Environ Sci Technol, :, 2022 : PubMed ESTHER: Li_2022_Environ.Sci.Technol__ PubMedSearch: Li 2022 Environ.Sci.Technol PubMedID: 35849551 Abstract The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log K(ow)) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log K(ow) values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants. Title: PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma Li H, Wu Z, Zhong R, Zhang Q, Chen Q, Shen Y Ref: Med Oncol, 39:250, 2022 : PubMed ESTHER: Li_2022_Med.Oncol_39_250 PubMedSearch: Li 2022 Med.Oncol 39 250 PubMedID: 36209344 Abstract Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC. Title: A carboxylesterase-activatable near-infrared phototheranostic probe for tumor fluorescence imaging and photodynamic therapy Li L, Zhang Q, Li J, Tian Y, Liu W, Diao H Ref: RSC Adv, 12:35477, 2022 : PubMed ESTHER: Li_2022_RSC.Adv_12_35477 PubMedSearch: Li 2022 RSC.Adv 12 35477 PubMedID: 36540215 Abstract Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics. Title: The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects Markowitz JS, De Faria L, Zhang Q, Melchert PW, Frye RF, Klee BO, Qian Y Ref: Med Cannabis Cannabinoids, 5:199, 2022 : PubMed ESTHER: Markowitz_2022_Med.Cannabis.Cannabinoids_5_199 PubMedSearch: Markowitz 2022 Med.Cannabis.Cannabinoids 5 199 PubMedID: 36467779 Abstract INTRODUCTION: Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an over-the-counter supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH). METHODS: In a randomized, placebo-controlled, crossover study, 12 subjects ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry. RESULTS: The C(max) (mean +/- CV) for the CBD group and placebo group was 13.5 +/- 43.7% ng/mL and 12.2 +/- 36.4% ng/mL, respectively. AUC(inf) (ng/mL*h) for the CBD group and placebo group was 70.7 +/- 32.5% and 63.6 +/- 25.4%, respectively. The CBD AUC(0-8h) (mean +/- CV) was 1,542.2 +/- 32% ng/mL*h, and C(max) was 389.2 +/- 39% ng/mL. When compared to MPH only, the geometric mean ratio (CBD/control, 90% CI) for AUC(inf) and C(max) with CBD co-administration was 1.09 (0.89, 1.32) and 1.08 (0.85, 1.37), respectively. DISCUSSION/CONCLUSION: Although the upper bound of bioequivalence was not met, the mean estimates of AUC and C(max) ratios were generally small and unlikely to be of clinical significance. Title: In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones Melchert PW, Qian Y, Zhang Q, Klee BO, Xing C, Markowitz JS Ref: Chemico-Biological Interactions, :109883, 2022 : PubMed ESTHER: Melchert_2022_Chem.Biol.Interact__109883 PubMedSearch: Melchert 2022 Chem.Biol.Interact 109883 PubMedID: 35278473 Abstract Kava refers to the extracts from the rhizome of the plant Piper methysticum which is of particular significance to various indigenous cultures in the South Pacific region. Kavalactones are the active constituents of kava products and are associated with sedative and anxiolytic effects. Kavalactones have been evaluated in vitro for their potential to alter the activity of various CYP450 enzymes but have undergone little systematic investigation as to their potential influence on esterases. This study investigated the inhibition effects of kava and its kavalactones on carboxylesterase 1 (CES1) in an in vitro system and established associated kinetic parameters. Kava and its kavalactones were found to produce reversible inhibition of CES1 to varying degrees. Kavain, dihydrokavain, and desmethoxyyangonin displayed competitive type inhibition, while methysticin, dihydromethysticin, and yangonin displayed a mixed competitive-noncompetitive type inhibition. The inhibition constants (K(i)) values for each of the kavalactones were as follows: methysticin (35.2 microM), dihydromethysticin (68.2 microM), kavain (81.6 microM), dihydrokavain (105.3 microM), yangonin (24.9 microM), and desmethoxyyangonin (25.2 microM). With consideration to the in vitro K(i) for each evaluated kavalactone as well as available clinical kavalactone concentrations in blood circulation, co-administration of CES1 substrate medications and kava products at the recommended daily dose is generally free of drug interaction concerns. However, uncertainty around kavalactone exposure in humans has been noted and a clinically relevant CES1 inhibition by kavain, dihydrokavain, and dihydromethysticin is indeed possible if the kavalactone consumption is higher than 1000 mg in the context of over-the-counter usage. Further clinical studies would be required to assess the possibility of clinically significant kava drug-drug interactions with CES1 substrate medications. Title: Inhibition of Dipeptidyl Peptidase-4 by Flavonoids: Structure-Activity Relationship, Kinetics and Interaction Mechanism Pan J, Zhang Q, Zhang C, Yang W, Liu H, Lv Z, Liu J, Jiao Z Ref: Front Nutr, 9:892426, 2022 : PubMed ESTHER: Pan_2022_Front.Nutr_9_892426 PubMedSearch: Pan 2022 Front.Nutr 9 892426 PubMedID: 35634373 Abstract With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4. Title: Integrative assessment of biomarker responses in Mytilus galloprovincialis exposed to seawater acidification and copper ions Qu Y, Zhang T, Zhang R, Wang X, Zhang Q, Wang Q, Dong Z, Zhao J Ref: Sci Total Environ, 851:158146, 2022 : PubMed ESTHER: Qu_2022_Sci.Total.Environ_851_158146 PubMedSearch: Qu 2022 Sci.Total.Environ 851 158146 PubMedID: 35987231 Abstract The interactive effects of ocean acidification (OA) and copper (Cu) ions on the mussel Mytilus galloprovincialis are not well understood. The underlying mechanisms also remain obscure. In this study, individuals of M. galloprovincialis were exposed for 28 days to 25 microg/L and 50 microg/L Cu ions at two pH levels (ambient level - pH 8.1; acidified level - pH 7.6). The mussels were then monitored for 56 days to determine their recovery ability. Physiological parameters (clearance rate and respiration rate), oxidative stress and neurotoxicity biomarkers (activities of superoxide dismutase, lipid peroxidation, catalase, and acetylcholinesterase), as well as the recovery ability of these parameters, were investigated in two typical tissues (i.e., gills and digestive glands). Results showed that (1) OA affected the bioconcentration of Cu in the gills and digestive glands of the mussels; (2) both OA and Cu can lead to physiological disturbance, oxidative stress, cellular damage, energy metabolism disturbance, and neurotoxicity on M. galloprovincialis; (3) gill is more sensitive to OA and Cu than digestive gland; (4) Most of the biochemical and physiological alternations caused by Cu and OA exposures in M. galloprovincialis can be repaired by the recovery experiments; (5) integrated biomarker response (IBR) analysis demonstrated that both OA and Cu ions exposure caused survival stresses to the mussels, with the highest effect shown in the co-exposure treatment. This study highlights the necessity to include OA along with pollutants in future studies to better elucidate the risks of ecological perturbations. The work also sheds light on the recovery of marine animals after short-term environmental stresses when the natural environment has recovered. Title: Dynamics of allosteric regulation of the phospholipase C-gamma isozymes upon recruitment to membranes Siraliev-Perez E, Stariha JTB, Hoffmann RM, Temple BRS, Zhang Q, Hajicek N, Jenkins ML, Burke JE, Sondek J Ref: Elife, 11:, 2022 : PubMed ESTHER: Siraliev-Perez_2022_Elife_11_ PubMedSearch: Siraliev-Perez 2022 Elife 11 PubMedID: 35708309 Abstract Numerous receptor tyrosine kinases and immune receptors activate phospholipase C-gamma (PLC-gamma) isozymes at membranes to control diverse cellular processes including phagocytosis, migration, proliferation, and differentiation. The molecular details of this process are not well understood. Using hydrogen-deuterium exchange mass spectrometry, we show that PLC-gamma1 is relatively inert to lipid vesicles that contain its substrate, phosphatidylinositol 4,5-bisphosphate (PIP(2)), unless first bound to the kinase domain of the fibroblast growth factor receptor (FGFR1). Exchange occurs throughout PLC-gamma1 and is exaggerated in PLC-gamma1 containing an oncogenic substitution (D1165H) that allosterically activates the lipase. These data support a model whereby initial complex formation shifts the conformational equilibrium of PLC-gamma1 to favor activation. This receptor-induced priming of PLC-gamma1 also explains the capacity of a kinase-inactive fragment of FGFR1 to modestly enhance the lipase activity of PLC-gamma1 operating on lipid vesicles but not a soluble analog of PIP(2) and highlights potential cooperativity between receptor engagement and membrane proximity. Priming is expected to be greatly enhanced for receptors embedded in membranes and nearly universal for the myriad of receptors and co-receptors that bind the PLC-gamma isozymes. Title: Highly stable acetylcholinesterase electrochemical biosensor based on polymerized ionic liquids microgel for pesticides detection Wan Y, Wang H, Zhang L, Chen Y, Li S, Zhou J, Zhang Q, Xia L Ref: Mikrochim Acta, 189:300, 2022 : PubMed ESTHER: Wan_2022_Mikrochim.Acta_189_300 PubMedSearch: Wan 2022 Mikrochim.Acta 189 300 PubMedID: 35904635 Abstract A highly stable electrochemical biosensor for pesticide detection was developed. For the first time polymeric ionic liquids (PILs) were introduced to construct an acetylcholinesterase (AChE) biosensor . AChE was entrapped in PILs microspheres through an emulsion polymerization reaction, where negatively charged Au nanoparticles (Au NPs) can be immobilized by the positively charged PILs, leading to improved catalytic performance. The results suggest that the positively charged PILs not only provide a biocompatible microenvironment around the enzyme molecule, stabilizing its biological activity and preventing its leakage, but also act as a modifiable interface allowing other components with electron transport properties to be loaded onto the polymer substrate, thus providing an efficient electron transport channel for the entrapped enzyme. More notably, when AChE was immobilized in a positively charged environment, the active site is closer to the electrode, promoting faster electron transfer. The detection limits of the constructed electrochemical biosensor AChE@PILs@Au NPs/GCE toward carbaryl and dichlorvos (DDVP) were 5.0 x 10(-2) ng ml(-1) and 3.9 x 10(-2) ng ml(-1), in a wide linear range of 6.3 x 10(-2)-8.8 x 10(2) ng ml(-1) and 1.3 x 10(-1)-1.4 x 10(3) ng ml(-1), respectively. More importantly, the biosensor has high thermal and storage stability, which facilitates rapid field analysis of fruits and vegetables in a variety of climates. In addition, the biosensor reported has good repeatability and selectivity and has high accuracy in the analysis of peaches, tap water, and other types of samples. 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: Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women Zhang B, Yu L, Cheng M, Zhang Q, Wu J, Yang J, Liu Q, Lu S, Zhao X and Zhao P <3 more author(s)> Zhang B, Yu L, Cheng M, Zhang Q, Wu J, Yang J, Liu Q, Lu S, Zhao X, Deng K, Liu Y, Wang J, Zhao P (- 3) Ref: Food Sci Nutr, 10:3, 2022 : PubMed ESTHER: Zhang_2022_Food.Sci.Nutr_10_3 PubMedSearch: Zhang 2022 Food.Sci.Nutr 10 3 PubMedID: 35035905 Abstract To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues. Title: 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: In vitro evaluation of the impact of Covid-19 therapeutic agents on the hydrolysis of the antiviral prodrug remdesivir Zhang Q, Melchert PW, Markowitz JS Ref: Chemico-Biological Interactions, 365:110097, 2022 : PubMed ESTHER: Zhang_2022_Chem.Biol.Interact_365_110097 PubMedSearch: Zhang 2022 Chem.Biol.Interact 365 110097 PubMedID: 35964681 Inhibitor(s) related to this paper: Remdesivir Abstract Remdesivir (RDV, Veklury(a)) is an FDA-approved prodrug for the treatment of hospitalized patients with COVID-19. Recent in vitro studies have indicated that human carboxylesterase 1 (CES1) is the major metabolic enzyme catalyzing RDV activation. COVID-19 treatment for hospitalized patients typically also involves a number of antibiotics and anti-inflammatory drugs. Further, individuals who are carriers of a CES1 variant (polymorphism in exon 4 codon 143 [G143E]) may experience impairment in their ability to metabolize therapeutic agents which are CES1 substrates. The present study assessed the potential influence of nine therapeutic agents (hydroxychloroquine, ivermectin, erythromycin, clarithromycin, roxithromycin, trimethoprim, ciprofloxacin, vancomycin, and dexamethasone) commonly used in treating COVID-19 and 5 known CES1 inhibitors on the metabolism of RDV. Additionally, we further analyzed the mechanism of inhibition of cannabidiol (CBD), as well as the impact of the G143E polymorphism on RDV metabolism. An in vitro S9 fraction incubation method and in vitro to in vivo pharmacokinetic scaling were utilized. None of the nine therapeutic agents evaluated produced significant inhibition of RDV hydrolysis; CBD was found to inhibit RDV hydrolysis by a mixed type of competitive and noncompetitive partial inhibition mechanism. In vitro to in vivo modeling suggested a possible reduction of RDV clearance and increase of AUC when coadministration with CBD. The same scaling method also suggested a potentially lower clearance and higher AUC in the presence of the G143E variant. In conclusion, a potential CES1-mediated DDI between RDV and the nine assessed medications appears unlikely. However, a potential CES1-mediated DDI between RDV and CBD may be possible with sufficient exposure to the cannabinoid. Patients carrying the CES1 G143E variant may exhibit a slower biotransformation and clearance of RDV. Further clinical studies would be required to evaluate and characterize the clinical significance of a CBD-RDV interaction. Title: Genetic manipulation of the interconversion between diacylglycerols and triacylglycerols in Rhodosporidium toruloides Zhang Y, Zhang S, Chu Y, Zhang Q, Zhou R, Yu D, Wang S, Lyu L, Xu G, Zhao ZK Ref: Front Bioeng Biotechnol, 10:1034972, 2022 : PubMed ESTHER: Zhang_2022_Front.Bioeng.Biotechnol_10_1034972 PubMedSearch: Zhang 2022 Front.Bioeng.Biotechnol 10 1034972 PubMedID: 36394004 Abstract The basidiomycetous yeast Rhodosporidium toruloides (R. toruloides) is an excellent producer for neutral lipids, including triacylglycerols (TAG). Partially because genetic tools for this yeast were less developed, limited efforts were shown to explore its capacity for the production of higher-value lipids such as diacylglycerols (DAG). Here, four genes linked to the interconversion between DAG and TAG were manipulated to promote the production of DAG and free fatty acids (FFA). Among them, three TAG synthesis-related genes, DGA1, LRO1, and ARE1, were down-regulated successively via the RNA interference technology, and an endogenous TAG lipase encoded by TGL5 was fused with LDP1 and over-expressed to convert TAG into DAG and FFA. Results showed that those engineered R. toruloides strains grew normally under nutrient-rich conditions but notably slower than the parental strain NP11 in the lipid production stage. When cultivated in nitrogen-limited media, engineered strains were able to produce total lipids with improved contents of DAG and FFA by up to two-fold and three-fold, respectively. Further correlation analysis between lipid composition and cell density indicated that the formation of TAG correlated positively with cell growth; however, other lipids including DAG did negatively. This study offered valuable information and strains to engineer R. toruloides for advanced production of fatty acid derivatives. Title: Whole genome sequencing and analysis of fenvalerate degrading bacteria Citrobacter freundii CD-9 Zhou X, Lei D, Tang J, Wu M, Ye H, Zhang Q Ref: AMB Express, 12:51, 2022 : PubMed ESTHER: Zhou_2022_AMB.Express_12_51 PubMedSearch: Zhou 2022 AMB.Express 12 51 PubMedID: 35523901 Abstract Citrobacter freundii CD-9 is a Gram-negative bacteria sourced from factory sludge that can use fenvalerate as its sole carbon source and has a broad degradation spectrum for pyrethroid pesticides. The whole genome of CD-9 sequenced using Illumina HiSeq PE150 was reported in this study. The CD-9 genome size was 5.33 Mb and the G + C content was 51.55%. A total of 5291 coding genes, 9 5s-rRNA, and 79 tRNA were predicted bioinformatically. 3586 genes annotated to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database that can be involved in 173 metabolic pathways, including various microbial metabolic pathways that degrade exogenous chemicals, especially those that degrade aromatic compounds, and also produce a variety of bioactive substances. Fifty genes related to pyrethroid degradation were identified in the C. freundii CD-9 genome, including 9 dioxygenase, 25 hydrolase, and 16 esterase genes. Notably, RT-qPCR results showed that from the predicted 13 genes related to fenvalerate degradation, the expression of six genes, including esterase, HAD family hydrolase, lipolytic enzyme, and gentisic acid dioxygenase, was induced in the presence of fenvalerate. In this study, the key genes and degradation mechanism of C. freundii CD-9 were analyzed and the results provide scientific evidence to support its application in environmental bioremediation. It can establish application models for different environmental pollution management by constructing genetically engineered bacteria for efficient fenvalerate or developing enzyme formulations that can be industrially produced. Title: Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients Zhou Q, Yu L, Yin C, Zhang Q, Wang X, Kang K, Shao D, Wang Q Ref: Aging Clin Exp Res, :, 2022 : PubMed ESTHER: Zhou_2022_Aging.Clin.Exp.Res__ PubMedSearch: Zhou 2022 Aging.Clin.Exp.Res PubMedID: 35809206 Abstract BACKGROUND: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could decrease the incidence of delayed neurocognitive recovery (dNCR) in elderly adults after total joint arthroplasty (TJA). METHODS: A prospective, randomized, double-blind, sham-controlled trial was designed. In total, 124 elderly patients undergoing TJA were enrolled and randomly assigned to taVNS group (n = 62), who received taVNS at 1 h before anesthetic induction until the end of surgery, or sham stimulation (SS) group (n = 62), who received SS in the same manner. Neuropsychological batteries were performed before and at 1 week after surgery to assess the incidence of dNCR. Blood samples were collected before surgery and at 1 day after surgery to detect the activity of cholinesterase (AChE and BChE), as well as the levels of inflammatory factors (TNF-alpha, IL-1beta, IL-6, and HMGB1) and brain damage factor S100beta. RESULTS: Of 124 patients, 119 completed 1 week neuropsychological tests. The incidence of dNCR was significantly decreased in taVNS group [10% (6/60)] compared with the SS group [27.1% (16/59)] (P < 0.05). Patients who received taVNS had lower blood levels of AChE, BChE, IL-6, HMGB1, and S100beta after surgery (P < 0.05), as compared with those in the SS group. There was no difference in TNF-alpha between the two groups. CONCLUSION: The taVNS can decrease the incidence of dNCR after TJA in elderly patients, which may be related to the inhibition of inflammatory cytokine production and the reduction of cholinesterase activity. Title: Insights into mechanisms involved in the uptake, translocation, and metabolism of phthalate esters in Chinese cabbage (Brassica rapa var. chinensis) Cheng Z, Wang Y, Qiao B, Zhang Q, Sun H Ref: Sci Total Environ, 768:144945, 2021 : PubMed ESTHER: Cheng_2021_Sci.Total.Environ_768_144945 PubMedSearch: Cheng 2021 Sci.Total.Environ 768 144945 PubMedID: 33736326 Abstract In the present study, the uptake and translocation mechanisms of phthalate esters (PAEs) and their primary mono esters metabolites (mPAEs), and the mechanisms of PAEs metabolism in plants were elucidated. The objectives of this study were to: (i) elucidate the fractionation of PAEs and mPAEs in Chinese cabbage (Brassica rapa var. chinensis) by hydroponic experiment, (ii) investigate the PAEs and mPAEs uptake mechanisms in root by inhibitor experiments, (iii) explain the molecular mechanisms of PAE interactions with the plant macromolecules by proteomics analysis and molecular docking, and (iv) reveal the involvement of carboxylesterase in the plant metabolism of PAEs. The results demonstrated that both the apoplastic and symplastic pathways contributed to the uptake of di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP) by vacuum-infiltration-centrifugation method. The energy-dependent active process was involved for the uptake of DnBP, DEHP, MnBP, and MEHP. The passive uptake pathways of anion mPAEs and neutral PAEs differ. Aquaporins contributed to the uptake of anion MnBP and MEHP, and slow-type anion channel was also responsible for the uptake of anion MEHP. Molecular interactions of PAEs and macromolecules were further characterized by proteomic analysis and molecular docking. PAEs were transferred via non-specific lipid transfer protein by binding hydroponic amino acid residues. The carboxylesterase enzyme was attributed to the metabolism of PAEs to form mPAEs by using crude enzyme extract and commercial pure enzyme. This study provides both experimental and theoretical evidence for uptake, accumulation, and metabolism of PAEs in plants. Title: ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis Ding Y, Wang X, Ji J, Zhang X, Chen M, Li S, Zhang Q, Liu P Ref: ACS Chem Neurosci, :, 2021 : PubMed ESTHER: Ding_2021_ACS.Chem.Neurosci__ PubMedSearch: Ding 2021 ACS.Chem.Neurosci PubMedID: 33517657 Abstract Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects. Title: Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis Wang S, Yang H, Guo R, Wang L, Zhang Y, Lv J, Zhao X, Zhang J, Fang H and Gao F <5 more author(s)> Wang S, Yang H, Guo R, Wang L, Zhang Y, Lv J, Zhao X, Zhang J, Fang H, Zhang Q, Yang J, Cui X, Gao P, Chang T, Gao F (- 5) Ref: Front Immunol, 12:753247, 2021 : PubMed ESTHER: Wang_2021_Front.Immunol_12_753247 PubMedSearch: Wang 2021 Front.Immunol 12 753247 PubMedID: 34956185 Abstract This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms. Title: Absolute protein assay for the simultaneous quantification of two epoxide hydrolases in rats by mass spectrometry-based targeted proteomics Wu T, Xi X, Chen Y, Jiang C, Zhang Q, Dai G, Bai Y, Zhang W, Ni T and Xu M <2 more author(s)> Wu T, Xi X, Chen Y, Jiang C, Zhang Q, Dai G, Bai Y, Zhang W, Ni T, Zou J, Ju W, Xu M (- 2) Ref: J Sep Sci, :, 2021 : PubMed ESTHER: Wu_2021_J.Sep.Sci__ PubMedSearch: Wu 2021 J.Sep.Sci PubMedID: 34008891 Abstract Epoxide hydrolases catalyze the hydrolysis of both exogenous and endogenous epoxides to the corresponding vicinal diols by adding water. Microsomal and soluble epoxide hydrolase are two main mammalian enzymes that have been intensely characterized. The purpose of this investigation was to develop and validate a proteomics assay allowing the simultaneous quantification of microsomal and soluble epoxide hydrolase in rats. Protein quantification was realized through targeted proteomics, using liquid chromatography with tandem mass spectrometry for the determination of trypsin-specific surrogate peptides after digestion. Stable isotope-labeled peptides were used as the internal standards. The chromatography of the surrogate peptides was performed on an Agilent SB C(18) column (100 mm x 4.6 mm, 1.8 microm) with gradient elution. Acetonitrile containing 0.1% formic acid and 0.1% formic acid aqueous solution were used as mobile phases. A multiple reaction monitoring method in a positive ionization mode was used for the simultaneous detection of the peptides. The method was validated concerning the specificity, linearity, within-day and between-day accuracy and precision, matrix effect, stability, and digestion efficiency. The developed assay was successfully used to quantify the protein levels of microsomal and soluble epoxide hydrolase in rat liver, kidney, and heart S9 samples. This article is protected by copyright. All rights reserved. Title: Fluorescent Determination of Butyrylcholinesterase Activity and Its Application in Biological Imaging and Pesticide Residue Detection Zhang Q, Fu C, Guo X, Gao J, Zhang P, Ding C Ref: ACS Sens, :, 2021 : PubMed ESTHER: Zhang_2021_ACS.Sens__ PubMedSearch: Zhang 2021 ACS.Sens PubMedID: 33503372 Abstract Butyrylcholinesterase (BChE) is an essential human cholinesterase relevant to liver conditions and neurodegenerative diseases, which makes it a pivotal biomarker of health. It therefore remains challenging and highly desired to elaborate efficient chemical tools for BChE with simple operations and satisfactory working performance. In this work, a background-free detection strategy was built by virtue of the judicious coupling of a specific BChE-enzymatic reaction and in situ cyclization. High sensitivity with a low limit of detection (LOD) of 0.075 microg/mL could be readily achieved from the blank background and the as-produced emissive indicators, and the specific reaction site contributed to the high selectivity over other bio-species even acetylcholinesterase (AChE). In addition to the multifaceted spectral experiments to verify the sensing mechanism, this work assumed comprehensive studies on the application. The bio-investigation ranged from cells to an organism, declaring a noteworthy prospect in disease diagnosis, especially for Alzheimer's disease (AD), a common neurodegenerative disease with over-expressed BChE. Moreover, its excellent work for inhibition efficacy elucidation was also proved with the accuracy IC(50) of tacrine for BChE (8.6 nM), giving rise to an expanded application for trace pesticide determination. Title: Smart nanozyme of silver hexacyanoferrate with versatile bio-regulated activities for probing different targets Zhang L, Zhang Q, Liu Q, Wu X, Dong Y, Wang GL Ref: Talanta, 228:122268, 2021 : PubMed ESTHER: Zhang_2021_Talanta_228_122268 PubMedSearch: Zhang 2021 Talanta 228 122268 PubMedID: 33773716 Abstract Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag(4)[Fe(CN)(6)]), was constructed in situ via the rapid, direct reaction between silver(I) and K(4)[Fe(CN)(6)]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 microM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity. Title: Evaluation of the effect of high protein supply on diaphragm atrophy in critically ill patients receiving prolonged mechanical ventilation Zhang Q, Zhou J, Zhu D, Zhou S Ref: Nutr Clin Pract, :, 2021 : PubMed ESTHER: Zhang_2021_Nutr.Clin.Pract__ PubMedSearch: Zhang 2021 Nutr.Clin.Pract PubMedID: 34101252 Abstract BACKGROUND: Our aim was to evaluate the effect of high protein to the target of 2.0 g/kg/d on diaphragm atrophy and clinical prognosis of patients receiving prolonged mechanical ventilation (MV). METHODS: This prospective, randomized, controlled, single-center study included 41 patients who were treated with <=7 days' MV. The patients were randomly divided into a standard nutrition treatment (SNT) group and intensive nutrition treatment (INT) group, followed by evaluation of computer tomography-analyzed diaphragm volume, the level of butyrylcholinesterase (BChE) as a muscle mass indicator, and respiratory mechanics indices weekly to observe and compare the differences between the groups. RESULTS: In the INT group, the actual protein (1.70 +/- 0.21 vs 1.06 +/- 0.21 g/kg/d, P < .001) and calorie intake (33.46 +/- 2.78 vs 25.75 +/- 4.81 kcal/kg/d, P < .001) were significantly different from those of the SNT group. Compared with the SNT group, the INT group's diaphragm atrophy improved in the fourth and fifth weeks (all P < .05). The BChE after the third week was higher (all P < .05). No significant differences in respiratory mechanical indices and clinical outcomes were found in the surviving patients between the groups. CONCLUSION: INT improved the diaphragm atrophy and muscle mass of critically ill patients receiving prolonged MV. There was no evidence that increasing protein to the target amount of 2.0 g/kg/d is related to improvement in clinical prognosis for patients receiving prolonged MV. Title: AND-Logic Strategy for Accurate Analysis of Alzheimer's Disease via Fluorescent Probe Lighted Up by Two Specific Biomarkers Zhang P, Fu C, Liu H, Guo X, Zhang Q, Gao J, Chen W, Yuan W, Ding C Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Zhang_2021_Anal.Chem__ PubMedSearch: Zhang 2021 Anal.Chem PubMedID: 34353021 Abstract Alzheimer's disease (AD) has become a global threat to the elderly health with a short survival time after diagnosis. Due to the asymptomatic stage during the early development, patients are usually diagnosed at the middle or late stage. Therefore, an efficient tool for AD early diagnosis deserves considerable attention, which could make a significant contribution to the treatment intervention. A fluorescent probe has been widely applied for detecting and visualizing species of interest in vitro and in vivo, and the proper reaction between the probe and analytes is responsible for the fluorescence change to provide a lighting-on or ratiometric responsive pattern with satisfactory sensing behavior. In this work, we report the first attempt to build up an AND-logic probe P2 for AD accuracy diagnosis taking butyrylcholinesterase (BChE) and reactive oxygen species (ROSs) as dual targets. Upon the co-stimulation by these two factors through enzymatic hydrolysis and redox reaction, the NIR emission could be readily turned on. This AND sensing pattern avoided the false-positive response effectively, and other diseases sharing one biomarker could hardly induce a NIR fluorescence response. The sensing assay has also been confirmed to be feasible in vitro and in vivo with good sensibility and selectivity. It is worth mentioning that the probe structure has been optimized in terms of the linkage length. This study shows that probe P2 with a connecting arm of medium length (one methylene, n = 1) has superior sensing performance, promising to provide a reference for the relative structure design. Title: Computational biotransformation of polyethylene terephthalate by depolymerase: A QM/MM approach Zheng M, Li Y, Dong W, Feng S, Zhang Q, Wang W Ref: J Hazard Mater, 423:127017, 2021 : PubMed ESTHER: Zheng_2021_J.Hazard.Mater_423_127017 PubMedSearch: Zheng 2021 J.Hazard.Mater 423 127017 PubMedID: 34464862 Gene_locus related to this paper: 9bact-g9by57 Abstract Despite increasing environmental concerns on ever-lasting Polyethylene Terephthalate (PET), its global production is continuously growing. Effective strategies that can completely remove PET from environment are urgently desired. Here biotransformation processes of PET by one of the most effective enzymes, leaf-branch compost cutinase (LCC), were systematically explored with Molecular Dynamics and Quantum Mechanics/Molecular Mechanics approaches. We found that four concerted steps are required to complete the whole catalytic cycle. The last concerted step, deacylation, was determined as the rate-determining step with Boltzmann-weighted average barrier of 13.6 kcal/mol and arithmetic average of 16.1 +/- 2.9 kcal/mol. Interestingly, unprecedented fluctuations of hydrogen bond length during LCC catalyzed transformation process toward PET were found. This fluctuation was also observed in enzyme IsPETase, indicating that it may widely exist in other catalytic triad (Ser-His-Asp) containing enzymes as well. In addition, possible features (bond, angle, dihedral angle and charge) that influence the catalytic reaction were identified and correlations between activation energies and key features were established. Our results present new insights into catalytic mechanism of hydrolases and shed light on the efficient recycling of the ever-lasting PET. Title: In situ and real-time insight into Rhizopus chinensis lipase under high pressure and temperature: Conformational traits and biobehavioural analysis Chen G, Zhang Q, Chen H, Lu Q, Miao M, Campanella OH, Feng B Ref: Int J Biol Macromol, 154:1314, 2020 : PubMed ESTHER: Chen_2020_Int.J.Biol.Macromol_154_1314 PubMedSearch: Chen 2020 Int.J.Biol.Macromol 154 1314 PubMedID: 31733249 Abstract An in situ and real-time investigation was performed using an optical cell system and in-silico analysis to reveal the impacts of pressure and temperature on the conformational state and behaviours of Rhizopus chinensis lipase (RCL). The fluorescence intensity (FI) of RCL increased remarkably under high pressure, and part of this increase was recovered after depressurization. This result displayed the partially reversible conformational change of RCL, which may be associated with the local change of Trp224 near the catalytic centre. High temperature caused a significant loss of secondary structure, whereas the alpha-helical segments including the lid were preserved by high pressure even at temperatures over 60 degreesC. The parameters of enzymatic reaction monitored by UV showed that the hydrolysis rate was remarkably enhanced by the pressure of 200 MPa. In the pressure range of 0.1-200 MPa, the active volume measured by the in situ system decreased from -2.85 to -6.73 mL/mol with the temperature increasing from 20 degreesC to 40 degreesC. The high catalytic capacity of the lipase under high pressure and high temperature was primarily attributed to pressure protection on RCL. Title: Biodegradation mechanism of polycaprolactone by a novel esterase MGS0156: a QM/MM approach Feng S, Yue Y, Chen J, Zhou J, Li Y, Zhang Q Ref: Environ Sci Process Impacts, 22:2332, 2020 : PubMed ESTHER: Feng_2020_Environ.Sci.Process.Impacts_22_2332 PubMedSearch: Feng 2020 Environ.Sci.Process.Impacts 22 2332 PubMedID: 33146659 Gene_locus related to this paper: 9zzzz-A0A0G3FEJ8 Abstract Nowadays micro-plastic pollution has become one of the most serious global environmental problems. A potential strategy in managing micro-plastic waste is enzyme-catalyzed degradation. MGS0156 is a hydrolase screened from environmental metagenomes, which can efficiently degrade commercial plastics such as polycaprolactone, polylactide, etc. Here a combined molecular dynamics, molecular mechanics Poisson-Boltzmann surface area, and quantum mechanics/molecular mechanism method was used to reveal the enzymatic depolymerization mechanism. By systematically analyzing the binding processes of nine oligomers (from a monomer to tetramer), we found that longer oligomers have relatively stronger binding energy. The degradation process involves two concerted elementary steps: triad-assisted nucleophilic attack and C-O bond cleavage. C-O bond cleavage is the rate determining step with an average barrier of 15.7 kcal mol-1, which is consistent with the experimentally determined kcat (1101 s-1, corresponds to 13.3 kcal mol-1). The electrostatic influence analysis of twenty amino acids highlights His231 and Asp237 as potential mutation targets for designing more efficient MGS0156 mutants. Title: Preparation of Lipase-Electrospun SiO(2) Nanofiber Membrane Bioreactors and Their Targeted Catalytic Ability at the Macroscopic Oil-Water Interface Kuang L, Zhang Q, Li J, Tian H Ref: Journal of Agricultural and Food Chemistry, 68:8362, 2020 : PubMed ESTHER: Kuang_2020_J.Agric.Food.Chem_68_8362 PubMedSearch: Kuang 2020 J.Agric.Food.Chem 68 8362 PubMedID: 32649192 Abstract Lipase is one of the most widely used enzymes in biocatalysis. Because of the special structure of the catalytic active center, lipases show high catalytic activity at oil-water interfaces. Hence, the interface plays a key role in activating and modulating lipase biocatalysis. Compared with traditional catalytic systems that offer interfaces, such as emulsions, a lipase-membrane bioreactor exhibits many obvious advantages when at the macroscopic oil-water system. In our current research, a series of new Burkholderia cepacia lipase (BCL)-SiO(2) nanofiber membrane (NFM) bioreactors prepared via combined electrospinning and immobilization strategies were reported. These SiO(2) NFMs assisted BCL in reaching the oil-water interface for efficient catalysis. The enzyme loading capacity and catalytic efficiency of BCL-SiO(2) NFMs varied with the surface hydrophobicity of the electrospun NFMs. As the hydrophobicity increased, the activity decreased from 2.43-fold to 0.74-fold that of free BCL. However, the lipase-loading capacity increased obviously when the hydrophobicity of the SiO(2) NFMs increased from 0 to 143 degrees, and no significant change was observed when the hydrophobicity of the SiO(2) NFMs increased from 143 to 153 degrees. The gel trapping technique proved that the hydrolytic activity of the different BCL-SiO(2) NFM bioreactors depends on the contact area of the membrane at the oil-water interface. BCL-SiO(2) NFM, BCL-SiO(2) NFM-C(12), and BCL-SiO(2) NFM-C(18) retained 32, 83, and 42% of activity, respectively, after five cycles of reuse. The current work was a useful exploration of the construction and modification of lipase-membrane reactors based on electrospun inorganic silicon. Title: The influence mechanism of temperature on solid phase denitrification based on denitrification performance, carbon balance, and microbial analysis Shen Q, Ji F, Wei J, Fang D, Zhang Q, Jiang L, Cai A, Kuang L Ref: Sci Total Environ, 732:139333, 2020 : PubMed ESTHER: Shen_2020_Sci.Total.Environ_732_139333 PubMedSearch: Shen 2020 Sci.Total.Environ 732 139333 PubMedID: 32438161 Abstract In this work, the influence mechanism of temperature on solid phase denitrification (SPD) was investigated using a pilot-scale reactor supported with polycaprolactone (PCL). The results showed that under nitrate loads of ~31.5 mg N/(L.h), as temperature decreased from 30 degrees C to 13 degrees C, the nitrate removal efficiency declined from 94% to 57%. Furthermore, denitrification rate constants were input into Arrhenius equation and the resulting temperature coefficient was 1.04. Significantly nitrite accumulation and less effluent COD residue occurred at low-temperatures. Via stoichiometry, the sludge yield coefficient and COD demand for nitrate removal both increased as a function of increasing temperature; and were calculated at 20 degrees C as 0.069 g MLVSS/(g COD.d) and 3.265 g COD/g N, respectively. Carbon balance analysis indicated that the COD release rate (upsilon) at 30 degrees C was twice that at 13 degrees C. LEfSe analysis demonstrated that Desulfomicrobium, Desulfovibrio, and Meganema were abundant at low-temperature, while Simplicispira, Aquabacterium, and Acidovorax were enriched at high-temperature. Besides, carboxylesterase (PCL depolymerase) was more abundant at high-temperature, implying an association with a fast upsilon. Moreover, nar was enriched at low-temperature, while nir was depleted, which led to nitrite accumulation. These results provide reference for SPD design parameter estimation and/or optimal operation strategy. Title: Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease Wei X, Adak S, Zayed M, Yin L, Feng C, Speck SL, Kathayat RS, Zhang Q, Dickinson BC, Semenkovich CF Ref: Circulation Research, 127:249, 2020 : PubMed ESTHER: Wei_2020_Circ.Res_127_249 PubMedSearch: Wei 2020 Circ.Res 127 249 PubMedID: 32233916 Abstract RATIONALE: Peripheral artery disease, common in metabolic syndrome and diabetes mellitus, responds poorly to medical interventions and is characterized by chronic vessel immaturity leading to lower extremity amputations. OBJECTIVE: To define the role of reversible palmitoylation at the endothelium in the maintenance of vascular maturity. METHODS AND RESULTS: Endothelial knockout of the depalmitoylation enzyme APT-1 (acyl-protein thioesterase 1) in mice impaired recovery from chronic hindlimb ischemia, a model of peripheral artery disease. Endothelial APT-1 deficiency decreased fibronectin processing, disrupted adherens junctions, and inhibited in vitro lumen formation. In an unbiased palmitoylation proteomic screen of endothelial cells from genetically modified mice, R-Ras, known to promote vessel maturation, was preferentially affected by APT-1 deficiency. R-Ras was validated as an APT-1 substrate, and click chemistry analyses demonstrated increased R-Ras palmitoylation in cells with APT-1 deficiency. APT-1 enzyme activity was decreased in endothelial cells from db/db mice. Hyperglycemia decreased APT-1 activity in human umbilical vein endothelial cells, due, in part, to altered acetylation of the APT-1 protein. Click chemistry analyses demonstrated increased R-Ras palmitoylation in the setting of hyperglycemia. Altered R-Ras trafficking, increased R-Ras palmitoylation, and fibronectin retention were found in diabetes mellitus models. Loss of R-Ras depalmitoylation caused by APT-1 deficiency constrained R-Ras membrane trafficking, as shown by total internal reflection fluorescence imaging. To rescue cellular phenotypes, we generated an R-Ras molecule with an inserted hydrophilic domain to circumvent membrane rigidity caused by defective palmitoylation turnover. This modification corrected R-Ras membrane trafficking, restored fibronectin processing, increased adherens junctions, and rescued defective lumen formation induced by APT-1 deficiency. CONCLUSIONS: These results suggest that endothelial depalmitoylation is regulated by the metabolic milieu and controls plasma membrane partitioning to maintain vascular homeostasis. Title: Cascade Reaction System Integrating Single-Atom Nanozymes with Abundant Cu Sites for Enhanced Biosensing Wu Y, Wu J, Jiao L, Xu W, Wang H, Wei X, Gu W, Ren G, Zhang N and Zhu C <3 more author(s)> Wu Y, Wu J, Jiao L, Xu W, Wang H, Wei X, Gu W, Ren G, Zhang N, Zhang Q, Huang L, Gu L, Zhu C (- 3) Ref: Analytical Chemistry, :, 2020 : PubMed ESTHER: Wu_2020_Anal.Chem__ PubMedSearch: Wu 2020 Anal.Chem PubMedID: 31941278 Abstract Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the de-velopment of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple mod-el of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were syn-thesized through a salt-template strategy. With the densely distributed active Cu atoms (~5.1 wt%), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxi-dase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organo-phosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems. Title: Gene cloning, expression, purification and characterization of a sn-1,3 extracellular lipase from Aspergillus niger GZUF36 Xing S, Zhu R, Li C, He L, Zeng X, Zhang Q Ref: J Food Sci Technol, 57:2669, 2020 : PubMed ESTHER: Xing_2020_J.Food.Sci.Technol_57_2669 PubMedSearch: Xing 2020 J.Food.Sci.Technol 57 2669 PubMedID: 32549617 Gene_locus related to this paper: aspng-EXANL1 Abstract Sn-1,3 extracellular Aspergillus niger GZUF36 lipase (EXANL1) has wide application potential in the food industry. However, the A. niger strain has defects such as easy degradation and instability in the expression of sn-1,3 lipase. To obtain a stable expression of this lipase and its subsequent enzymatic properties, the gene encoding EXANL1 was cloned and expressed in Escherichia coli BL21 (DE3) cells using pET-28a as the expression vector. The temperature-induced conditions were optimized, and we successfully achieved its active expression in E. coli. These conditions significantly influenced the active expression of EXANL1 (P < 0.05), and the highest enzyme activity of the supernatant of lysis cells expressed at 20 degreesC was at 7.02 +/- 0.05 U/mL. The expressed recombinant EXANL1 was purified using Ni-NTA, showing an estimated relative molecular mass of 35 kDa. The recombinant EXANL1 exhibited maximum activity at 35 degreesC and pH 4.0, with a wide acid pH range. Thin-layer chromatography analysis showed that the enzyme displayed sn-1,3 positional selectivity toward triolein. The recombinant EXANL1 could maintain its relative activities (> 80%) after 24 h of incubation at pH 3-10, suggesting its suitability for a wide range of industrial applications. After comparing these properties with those of the other A. niger lipases, we found that some key amino acids may play a decisive role in enzymology. This work laid a foundation for the stable expression of the EXANL1 gene and its potential industrial application. Title: The genome evolution and low-phosphorus adaptation in white lupin Xu W, Zhang Q, Yuan W, Xu F, Muhammad Aslam M, Miao R, Li Y, Wang Q, Li X and Cheng F <3 more author(s)> Xu W, Zhang Q, Yuan W, Xu F, Muhammad Aslam M, Miao R, Li Y, Wang Q, Li X, Zhang X, Zhang K, Xia T, Cheng F (- 3) Ref: Nat Commun, 11:1069, 2020 : PubMed ESTHER: Xu_2020_Nat.Commun_11_1069 PubMedSearch: Xu 2020 Nat.Commun 11 1069 PubMedID: 32103018 Gene_locus related to this paper: lupal-a0a6a5lz53, lupal-a0a6a5mjk3 Abstract White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin. Title: Rationally design and chemical modification: Getting a new and efficient biocatalyst for Henry reaction Yu Z, Zhang Q, Tang H, Xu G Ref: Enzyme Microb Technol, 142:109695, 2020 : PubMed ESTHER: Yu_2020_Enzyme.Microb.Technol_142_109695 PubMedSearch: Yu 2020 Enzyme.Microb.Technol 142 109695 PubMedID: 33220873 Gene_locus related to this paper: rhidl-lipas Abstract A robust biocatalyst for green Henry reaction was achieved. Based on the fact that Henry reaction requires a base for proton transfer, we firstly proposed that the catalytic triad of lipase could play this role. The distance between the substrate and the catalytic center and the surrounding amino acid interaction network were used as the criterion. Benzaldehyde and nitromethane were used as the model reaction, RNL (Lipase from Rhizopus niveus) was considered to be the best Henry reaction catalyst via a molecular dynamics simulation. Then experiments demonstrated that RNL has a yield of 48 % using model substrate in water. Further, in order to increase product yield, the chemical modifier 1, 2-cyclohexanedione (CHD) was used to modify Arg on RNL. As a result, RNL (CHD) increased the activity of catalyzing Henry reaction and had a broad spectrum of substrates, the yield of the product was as high as 67-99 %. Title: Copper(II) complex as a turn on fluorescent sensing platform for acetylcholinesterase activity with high sensitivity Zhang P, Fu C, Xiao Y, Zhang Q, Ding C Ref: Talanta, 208:120406, 2020 : PubMed ESTHER: Zhang_2020_Talanta_208_120406 PubMedSearch: Zhang 2020 Talanta 208 120406 PubMedID: 31816742 Abstract Acetylcholinesterase (AChE) is an important enzyme associated with many nervous diseases, demonstrating the great need for smarter sensing platform with improved sensitivity, selectivity and simplified operation. A "turn on" fluorometric assay is described herein for AChE activity detection, according to the specific enzyme catalyzed reaction of acetylcholine (ATCh) by AChE, which generates thiocholine (TCh) as the product. The well-designed fluorescent probe HBTP possesses ESIPT (Excited State Intramolecular Proton Transfer) nature, leading to a larger Stokes shift, which could be quenched upon coordination with Cu(2+). The fluorescence-silent HBTP-Cu(2+) complex could be broken by TCh generated from reaction of ATCh with AChE, giving rise to HBTP release which originates from competitive coordination of TCh with Cu(2+). This complex probe HBTP-Cu(2+) offers a limit detection as low as 0.02 mUmL(-1), which is lower than most reported literatures. Furthermore, both HBTP-Cu(2+) and HBTP show little toxicity to live cells and is available in visualizing cellular AChE activity. Title: A Comparison of the Resolution of Selective (+/-)-Glycidyl Butyrate by Using Free and Nano-SiO(2) Immobilized Porcine Pancreatic Lipase Zhang Q, Qian J, Guo H, Zhang W, Kuang C Ref: J Nanosci Nanotechnol, 20:6168, 2020 : PubMed ESTHER: Zhang_2020_J.Nanosci.Nanotechnol_20_6168 PubMedSearch: Zhang 2020 J.Nanosci.Nanotechnol 20 6168 PubMedID: 32384967 Abstract To explore the hydrolyzed properties of nano-SiO(2) immobilized porcine pancreatic lipase, the selective hydrolysis of immobilized lipase for glycidyl butyrate was compared with the free enzyme. The hydrolysis selectivity of the immobilized biocatalyst was evaluated and compared with the free enzyme using the enantiomeric excess (ee) of resolving racemic glycidyl butyrate as the indicator. The enantiomeric excess of the immobilized biocatalyst could be increased by 4.5%-10.0% which compared with the free enzyme under every single technological condition. The ee was improved from 84.7% for free enzyme to 91.6% for the immobilized enzyme with 61.2% conversion. Compared with free enzyme, the conversion rate of the immobilized enzyme was increased slightly, but the % enantiomeric excess of the immobilized enzyme was increased greatly. Title: Approach to Cognitive Impairment in Parkinson's Disease Zhang Q, Aldridge GM, Narayanan NS, Anderson SW, Uc EY Ref: Neurotherapeutics, 17:1495, 2020 : PubMed ESTHER: Zhang_2020_Neurotherapeutics_17_1495 PubMedSearch: Zhang 2020 Neurotherapeutics 17 1495 PubMedID: 33205381 Abstract Cognitive dysfunction is common in Parkinson's disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer disease duration, which is usually accompanied by immobility, hallucinations/psychosis, and dysautonomia. Dopaminergic medications and deep brain stimulation help motor dysfunction, but may have potential cognitive side effects. Central acetylcholinesterase inhibitors, and possibly memantine, provide modest and temporary symptomatic relief for dementia, although there is no evidence-based treatment for MCI. There is no proven disease-modifying treatment for cognitive impairment in PD. The symptomatic and disease-modifying role of physical exercise, cognitive training, and neuromodulation on cognitive impairment in PD is under investigation. Multidisciplinary approaches to cognitive impairment with effective treatment of comorbidities, proper rehabilitation, and maintenance of good support systems in addition to pharmaceutical treatment may improve the quality of life of the patients and caregivers. Title: Structures and esterolytic reactivity of novel binuclear copper(ii) complexes with reduced l-serine Schiff bases as mimic carboxylesterases Zhang Q, Shu J, Zhang Y, Xu Z, Yue J, Liu X, Xu B, Chen Z, Jiang W Ref: Dalton Trans, 49:10261, 2020 : PubMed ESTHER: Zhang_2020_Dalton.Trans_49_10261 PubMedSearch: Zhang 2020 Dalton.Trans 49 10261 PubMedID: 32672259 Abstract Three novel binuclear copper(ii) complexes with reduced l-serine Schiff bases were synthesized and their structures were analyzed with single-crystal X-ray diffraction and DFT calculations. The crystal data revealed that all of these binuclear complexes are chiral. Both 5-halogenated (bromo- and chloro-) binuclear complexes exhibit right-handed helix structural character. Interestingly, the 5-methyl-containing analogue has a two-dimensional pore structure. In this paper, the esterolysis reactivity of the as-prepared complexes shows that in the hydrolysis of p-nitrophenyl acetate (PNPA) these three complexes provide 26, 18, 40-fold rate acceleration as compared to the spontaneous hydrolysis of PNPA at pH 7.0, respectively. Under selected conditions, in excess buffered aqueous solution a rate enhancement by three orders of magnitude was observed for the catalytic hydrolysis of another carboxylic ester, p-nitrophenyl picolinate (PNPP). These complexes efficiently promoted PNPP hydrolysis in a micellar solution of cetyltrimethylammonium bromide (CTAB), giving rise to a rate enhancement in excess of four orders of magnitude, which is approximately 2.0-3.2 times higher than that in the buffer. Title: Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties Zhang W, Zhang Y, Qiu H, Guo Y, Wan H, Zhang X, Scossa F, Alseekh S, Zhang Q and Wen W <11 more author(s)> Zhang W, Zhang Y, Qiu H, Guo Y, Wan H, Zhang X, Scossa F, Alseekh S, Zhang Q, Wang P, Xu L, Schmidt MH, Jia X, Li D, Zhu A, Guo F, Chen W, Ni D, Usadel B, Fernie AR, Wen W (- 11) Ref: Nat Commun, 11:3719, 2020 : PubMed ESTHER: Zhang_2020_Nat.Commun_11_3719 PubMedSearch: Zhang 2020 Nat.Commun 11 3719 PubMedID: 32709943 Gene_locus related to this paper: camsi-a0a7j7g2i2 Abstract Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds. Title: Degradation mechanism for Zearalenone ring-cleavage by Zearalenone hydrolase RmZHD: A QM/MM study Zhou J, Zhu L, Chen J, Wang W, Zhang R, Li Y, Zhang Q Ref: Sci Total Environ, 709:135897, 2020 : PubMed ESTHER: Zhou_2020_Sci.Total.Environ_709_135897 PubMedSearch: Zhou 2020 Sci.Total.Environ 709 135897 PubMedID: 31887512 Gene_locus related to this paper: 9euro-a0a0d2ilk1 Abstract The danger of zearalenone (ZEN) as an endocrine disruptor to humans and the environment has aroused increasing attention. In this study, we implemented the quantum mechanics/molecular mechanics (QM/MM) method to investigate the degradation mechanism of ZEN hydrolase (RmZHD) toward ZEN at the atomic level. The degradation process involves two concerted reaction pathways, where the active site contains a Ser-His-Glu triplet as a proton donor. With the Boltzmann-weighted average potential barriers of 18.1 and 21.5 kcal/mol, the process undergoes proton transfer and nucleophilic-substituted ring opening to form a hydroxyl product. Non-covalent interaction analyses elucidated hydrogen bonding between key amino acids with ZEN. The electrostatic influence analysis of 16 amino acids proposes residues Asp34 and His128 as the possible mutation target for future mutation design of enzyme RmZHD. An in-depth investigation of the protein environment of RmZHD can improve the bioremediation efficiency of endocrine disrupting chemicals. Title: Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease Bai P, Wang K, Zhang P, Shi J, Cheng X, Zhang Q, Zheng C, Cheng Y, Yang J and Sang Z <1 more author(s)> Bai P, Wang K, Zhang P, Shi J, Cheng X, Zhang Q, Zheng C, Cheng Y, Yang J, Lu X, Sang Z (- 1) Ref: Eur Journal of Medicinal Chemistry, 183:111737, 2019 : PubMed ESTHER: Bai_2019_Eur.J.Med.Chem_183_111737 PubMedSearch: Bai 2019 Eur.J.Med.Chem 183 111737 PubMedID: 31581002 Abstract A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50=1.3+/-0.01muM) and butyrylcholinesterase (IC50=1.2+/-0.09muM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57+/-0.01muM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Abeta1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu(2+)-induced Abeta1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Abeta1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD. Title: Protection effect of polyols on Rhizopus chinensis lipase counteracting the deactivation from high pressure and high temperature treatment Chen G, Zhang Q, Lu Q, Feng B Ref: Int J Biol Macromol, 127:555, 2019 : PubMed ESTHER: Chen_2019_Int.J.Biol.Macromol_127_555 PubMedSearch: Chen 2019 Int.J.Biol.Macromol 127 555 PubMedID: 30664969 Abstract The influence of polyols on Rhizopus chinensis lipase (RCL) was investigated under high pressure. The poor stability of RCL was observed at 500MPa at 60 degrees C without polyols which protected RCL against the loss of activity. The lipase is more stable in phosphate buffer than in tris buffer despite the protection of polyols. The activity was maintained 63% by the sorbitol of 2mol/L in Tris-HCl buffer but 73% in phosphate buffer after the treatment at 500MPa and 60 degrees C for 25min. The same protective effects could be observed at 1mol/L of sorbitol, erythritol, xylitol, and mannitol. However, further increase of hydroxyl group number could not significantly improve the enzyme stability. The protection of polyols on RCL appears to depend on both of the polyol nature and the hydroxyl group number. Together with fluorescence spectra, circular dichroism spectra indicated that the chaotic conformation of RCL under high pressure became more ordered with 1mol/L sorbitol. The results showed that sorbitol effectively stabilized the lipase conformation including the hydrophobic core under extreme conditions. It might be attributed to the interaction of polyols with RCL surface to modify intra-/intermolecular hydrogen bonds, maintaining the hydrophobic interactions within RCL. Title: Prognostic Impact of Carboxylesterase 2 in Cholangiocarcinoma Goeppert B, Renner M, Singer S, Albrecht T, Zhang Q, Mehrabi A, Pathil A, Springfeld C, Kohler B and Utku N <8 more author(s)> Goeppert B, Renner M, Singer S, Albrecht T, Zhang Q, Mehrabi A, Pathil A, Springfeld C, Kohler B, Rupp C, Weiss KH, Kuhl AA, Arsenic R, Pape UF, Vogel A, Schirmacher P, Roessler S, Utku N (- 8) Ref: Sci Rep, 9:4338, 2019 : PubMed ESTHER: Goeppert_2019_Sci.Rep_9_4338 PubMedSearch: Goeppert 2019 Sci.Rep 9 4338 PubMedID: 30867471 Gene_locus related to this paper: human-CES2 Abstract Carboxylesterase 2 (CES2) is instrumental for conversion of ester-containing prodrugs in cancer treatment. Novel treatment strategies are exceedingly needed for cholangiocarcinoma (CCA) patients. Here, we assessed CES2 expression by immunohistochemistry in a CCA cohort comprising 171 non-liver fluke associated, intrahepatic (n = 72) and extrahepatic (perihilar: n = 56; distal: n = 43) CCAs. Additionally, 80 samples of high-grade biliary intraepithelial neoplastic tissues and 158 corresponding samples of histological normal, non-neoplastic biliary tract tissues were included. CES2 expression was highest in non-neoplastic biliary tissue and significantly decreased in CCA. Patients showing any CES2 expression in tumor cells had a significantly better overall survival compared to negative cases (p = 0.008). This survival benefit was also maintained after stratification of CES2-positive cases, by comparing low, medium and high CES2 expression levels (p-trend = 0.0006). Evaluation of CCA subtypes showed the survival difference to be restricted to extrahepatic tumors. Correlation of CES2 expression with data of tumor-infiltrating immune cells showed that particularly CD8+ T cells were more frequently detected in CES2-positive CCAs. Furthermore, treatment of CCA cell lines with the prodrug Irinotecan reduced cell viability, increased cytotoxicity and modulated inflammatory gene expression. In conclusion, reduced CES2 expression is associated with poor outcome and low CD8+ T cell infiltration in CCA patients. Further clinical studies could show, whether CES2 expression may serve as a predictive marker in patients treated with prodrugs converted by CES2. Title: Glucoconjugated Monoterpene Indole Alkaloids from Uncaria rhynchophylla Guo Q, Si X, Shi Y, Yang H, Liu X, Liang H, Tu P, Zhang Q Ref: Journal of Natural Products, 82:3288, 2019 : PubMed ESTHER: Guo_2019_J.Nat.Prod_82_3288 PubMedSearch: Guo 2019 J.Nat.Prod 82 3288 PubMedID: 31804070 Abstract Twenty-six glucoconjugated monoterpene indole alkaloids, including 12 new compounds, rhynchophyllosides A-L (1-12), and 14 known ones, 13-26, were obtained from the hook-bearing stems of Uncaria rhynchophylla (Miq.) Miq. ex Havil. Their structures were unambiguously elucidated by analyses of UV, MS, NMR, ECD, and single-crystal X-ray diffraction data. The ESI-MS(n) behavior of the new glucoalkaloids was also elucidated. Although comprising the same glucosyl moiety, the aglycone skeletons and glucosidic numbers and linkage varied greatly, implying the diversity in biosynthetic pathways. This is the first report of such structurally diverse glucoconjugated monoterpene indole alkaloids from U. rhynchophylla. Compound 1 represents a new subtype of oxindole alkaloid with a seven-membered D-ring, 10 is a rare monoterpene indole alkaloid with the glucosyl moiety located at C-9, 4 and 5 are the first two oxindole alkaloid diglycosides, and 11 and 12 represent the first two examples of alkaloids with a quinolone nucleus from the genus Uncaria. Compound 10 exhibited moderate acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 10.5 muM. Molecular docking was performed to explore the binding mode of inhibitor 10 at the active site of AChE. Title: Enantioselective Hydrolysis of Styrene Oxide and Benzyl Glycidyl Ether by a Variant of Epoxide Hydrolase from Agromyces mediolanus Jin H, Li Y, Zhang Q, Lin S, Yang Z, Ding G Ref: Mar Drugs, 17:, 2019 : PubMed ESTHER: Jin_2019_Mar.Drugs_17_ PubMedSearch: Jin 2019 Mar.Drugs 17 PubMedID: 31226863 Abstract Enantiopure epoxides are versatile synthetic intermediates for producing optically active pharmaceuticals. In an effort to provide more options for the preparation of enantiopure epoxides, a variant of the epoxide hydrolase (vEH-Am) gene from a marine microorganism Agromyces mediolanus was synthesized and expressed in Escherichia coli. Recombiant vEH-Am displayed a molecular weight of 43 kDa and showed high stability with a half-life of 51.1 h at 30 degrees C. The purified vEH-Am exhibited high enantioselectivity towards styrene oxide (SO) and benzyl glycidyl ether (BGE). The vEH-Am preferentially converted (S)-SO, leaving (R)-SO with the enantiomeric excess (ee) >99%. However, (R)-BGE was preferentially hydrolyzed by vEH-Am, resulting in (S)-BGE with >99% ee. To investigate the origin of regioselectivity, the interactions between vEH-Am and enantiomers of SO and BGE were analyzed by molecular docking simulation. In addition, it was observed that the yields of (R)-SO and (S)-BGE decreased with the increase of substrate concentrations. The yield of (R)-SO was significantly increased by adding 2% (v/v) Tween-20 or intermittent supplementation of the substrate. To our knowledge, vEH-Am displayed the highest enantioselectivity for the kinetic resolution of racemic BGE among the known EHs, suggesting promising applications of vEH-Am in the preparation of optically active BGE. Title: Molluscicidal activity and physiological toxicity of quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits on Oncomelania hupensis Ke W, Tu C, Cao D, Lin X, Sun Q, Zhang Q Ref: PLoS Negl Trop Dis, 13:e0007740, 2019 : PubMed ESTHER: Ke_2019_PLoS.Negl.Trop.Dis_13_e0007740 PubMedSearch: Ke 2019 PLoS.Negl.Trop.Dis 13 e0007740 PubMedID: 31603908 Abstract Schistosomiasis is a serious worldwide parasitic disease. One of the best ways to control schistosomiasis is to control the population of Oncomelania hupensis snails. We sought to identify a high-efficiency biogenic molluscicide against Oncomelania with low toxicity, to avoid chemical molluscicide contamination and toxicity in aquatic organisms. We extracted quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits. Molluscicidal activity of the QBAs against Oncomelania was determined using bioassay. Our results showed that the extracted QBAs had a strong molluscicidal effect. In treatment of O. hupensis with QBAs for 48 h and 72 h, the lethal concentration (LC50) was 2.89 mg/L and 1.29 mg/L, respectively. The molluscicidal activity of QBAs was close to that of niclosamide (ethanolamine salt), indicating that QBAs have potential development value as novel biogenic molluscicides. We also analyzed physiological toxicity mechanisms by examining the activity of several important detoxification enzymes. We measured the effect of the extracted QBAs on the activities of glutathione S-transferase (GST), carboxylesterase (CarE), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the liver of O. hupensis. We found that the effects of QBAs on detoxification metabolism in O. hupensis were time and concentration dependent. The activities of GST, CarE, AKP, and ACP in the liver of snails increased significantly in the early stage of treatment (24 h), but decreased sharply in later stages (120 h), compared with these activities in controls. GST, CarE, AKP, and ACP activity in the liver of snails treated with LC50 QBAs for 120 h decreased by 62.3%, 78.1%, 59.2%, and 68.6%, respectively. Our results indicate that these enzymes were seriously inhibited by the extracted QBAs and the detoxification and metabolic functions of the liver gradually weakened, leading to poisoning, which could be the main cause of death in O. hupensis snails. Title: Lipase member H is a downstream molecular target of hypoxia inducible factor-1alpha and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines Li Y, Zhou X, Zhang Q, Chen E, Sun Y, Ye D, Wang O, Zhang X, Lyu J Ref: Cancer Manag Res, 11:931, 2019 : PubMed ESTHER: Li_2019_Cancer.Manag.Res_11_931 PubMedSearch: Li 2019 Cancer.Manag.Res 11 931 PubMedID: 30774423 Abstract Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. Materials and methods: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. Results: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial-mesenchymal transition pathway in PTC. Conclusion: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future. Title: Clinical analysis of Chinese anti-low-density-lipoprotein-receptor-associated protein 4 antibodies in patients with myasthenia gravis Li M, Han J, Zhang Y, Lv J, Zhang J, Zhao X, Ren L, Fang H, Yang J and Gao F <4 more author(s)> Li M, Han J, Zhang Y, Lv J, Zhang J, Zhao X, Ren L, Fang H, Yang J, Cui X, Zhang Q, Li Q, Du Y, Gao F (- 4) Ref: Eur Journal of Neurology, 26:1296, 2019 : PubMed ESTHER: Li_2019_Eur.J.Neurol_26_1296 PubMedSearch: Li 2019 Eur.J.Neurol 26 1296 PubMedID: 31050101 Abstract BACKGROUND AND PURPOSE: Low-density-lipoprotein-receptor-associated protein 4 (LRP4) autoantibodies have recently been detected in myasthenia gravis (MG), but little is known about the clinical characteristics associated with this serological type. In this study, the clinical features of Chinese patients with anti-LRP4 antibody-positive MG were characterized. METHODS: A total of 2172 MG serum samples were collected from patients in various parts of China. An enzyme-linked immunosorbent assay was used to detect acetylcholine receptor (AChR) antibody and titin antibody, and cell-based assays were used to detect muscle-specific kinase antibody and LRP4 antibody. Clinical data for patients with MG were collected from different provinces in China. RESULTS: In total, 16 (0.8%) patients with LRP4-MG were found amongst 2172 total patients, including three patients with AChR/LRP4-MG. Additionally, 13 (2.9%) patients with LRP4-MG were found amongst 455 patients with double seronegative MG. The ratio of males to females for these 13 patients was 1:1.6, and 53.8% patients were children. A total of 91.7% of cases exhibited initial ocular involvement, and 58.3% of cases exhibited simple eye muscle involvement. Responses to acetylcholinesterase inhibitors and prednisone were observed. CONCLUSION: The expanded sample confirmed that the positive rate of LRP4 antibodies in China is lower than that in western countries. Our results highlighted the differences between LRP4-MG and other antibody groups. Children and female patients with LRP4-MG have a higher prevalence, often involving the ocular muscles and limb muscles. The clinical symptoms are mild, and satisfactory responses to treatment are often achieved. Title: Selenepezil, a Selenium-Containing Compound, Exerts Neuroprotective Effect via Modulation of the Keap1-Nrf2-ARE Pathway and Attenuates Abeta-Induced Cognitive Impairment in Vivo Yan J, Pang Y, Zhuang J, Lin H, Zhang Q, Han L, Ke P, Huang X Ref: ACS Chem Neurosci, 10:2903, 2019 : PubMed ESTHER: Yan_2019_ACS.Chem.Neurosci_10_2903 PubMedSearch: Yan 2019 ACS.Chem.Neurosci 10 2903 PubMedID: 31035749 Inhibitor(s) related to this paper: Selenepezil Abstract Oxidative stress is a major risk factor for neurodegenerative disease. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is one of the most potent defensive systems against oxidative stress. Selenepezil, a selenium-based compound, was previously found to exhibit excellent acetylcholinesterase (AChE) inhibition, to mimic endogenous glutathione peroxidase (GPx) activity, and to exhibit scavenging activity for hydrogen peroxide in vitro. However, none of these activities have been evaluated in a cellular model, and detailed molecular mechanisms are not elucidated. Moreover, whether selenepezil ameliorates memory deficits in vivo remains unknown. This study validated the cytoprotective effect of selenepezil against 6-hydroxydopamine (6-OHDA)- or H2O2-induced SH-SY5Y cell damage via alleviation or neutralization of intracellular microtubule disorder, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and cell apoptosis. Our study clearly demonstrated that selenepezil pretreatment exhibited remarkable cytoprotective effect in a Nrf2-dependent manner via activating the Keap1-Nrf2-ARE pathway and stimulating the transcription of Nrf2-ARE-regulated cytoprotective genes. Moreover, selenepezil.HCl exerts neuroprotective effect via attenuating Abeta-induced cognitive impairment in Alzheimer's disease (AD) rat and was more active than the reference drug donepezil. In summary, selenepezil deserves further consideration for AD therapy. Title: Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem-leaf saponins using ultrafiltration (UF)-LC-ESI-MS(2) Yang Y, Liang X, Jin P, Li N, Zhang Q, Yan W, Zhang H, Sun J Ref: Phytochem Anal, 30:26, 2019 : PubMed ESTHER: Yang_2019_Phytochem.Anal_30_26 PubMedSearch: Yang 2019 Phytochem.Anal 30 26 PubMedID: 30159954 Abstract INTRODUCTION: Previous studies have demonstrated that several ginsenosides have remarkable inhibitory effect on acetylcholinesterase (AChE). In the present study, ginseng stem-leaf saponins (GSLS) can improve learning and memory of Alzheimer's disease patients. However, much comprehensive information regarding AChE inhibition of GSLS and its metabolites is yet unknown. OBJECTIVE: The present study aims to screen and determine the potential of AChE inhibitors (AChEIs) from GSLS. METHODOLOGY: The active fraction of the GSLS detected in vitro AChE inhibition assays was selected as a starting material for the screening of the potential of AChEIs using ultrafiltration liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (UF-LC-ESI-MS(2) ). RESULTS: The results showed that 31 ginsenosides were identified with analysis using rapid resolution liquid chromatography with a diode array detector combined with electrospray ionisation tandem mass spectrometry (RRLC-DAD-ESI-MS(2) ) from the active fraction, and there are 27 compounds with AChE binding activity. Among them, 11 ginsenosides were evaluated and confirmed using in vitro enzymatic assay, and ginsenosides F1 , Rd, Rk3 , 20(S)-Rg3 , F2 and Rb2 were found to possess strong AChE inhibitory activities. CONCLUSION: The proposed UF-LC-ESI-MS(2) method was a powerful tool for the discovery of AChEIs from traditional Chinese medicine (TCM). Title: A Flexible Acetylcholinesterase-Modified Graphene for Chiral Pesticide Sensor Zhang Y, Liu X, Qiu S, Zhang Q, Tang W, Liu H, Guo Y, Ma Y, Guo X, Liu Y Ref: Journal of the American Chemical Society, 141:14643, 2019 : PubMed ESTHER: Zhang_2019_J.Am.Chem.Soc_141_14643 PubMedSearch: Zhang 2019 J.Am.Chem.Soc 141 14643 PubMedID: 31448915 Abstract Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for chiral recognition, which is very important in biological systems, graphene sensors remain unable to discriminate enantiomers. Here, using chiral pesticide molecules as an example, we realized a highly sensitive graphene chiral sensor by modification with acetylcholinesterase (AChE). Quantum chemical simulations indicate that the inhibition effect of the enantiomer on AChE was transferred to graphene, which allowed for the electrical detection of chiral molecules. Under an operating voltage of 1 V, the sensitivity of the device reached 0.34 mug/L and 0.32 mug/L for (+)/(-)-methamidophos, respectively, which is much higher than by circular dichroism (6.90 mg/L and 5.16 mg/L, respectively). Furthermore, real-time, rapid detection was realized by combining with smartphones and wireless transmission. Title: Hydroxy-alpha-sanshool isolated from Zanthoxylum bungeanum attenuates learning and memory impairments in scopolamine-treated mice Zhang M, Xie M, Wei D, Wang L, Hu M, Zhang Q, He Z, Peng W, Wu C Ref: Food Funct, 10:7315, 2019 : PubMed ESTHER: Zhang_2019_Food.Funct_10_7315 PubMedSearch: Zhang 2019 Food.Funct 10 7315 PubMedID: 31637395 Abstract Learning and memory impairments are common symptoms of dementia in neurodegenerative disorders. Occasionally, we found that Zanthoxylum bungeanum pericarps (ZBP) significantly activated the spontaneous activity of the hippocampus (HIPP) and paraHIPP (P < 0.001, uncorrected), implying the potential ability of ZBP to improve cognitive impairments. Thus, this study aimed to investigate the improving effect of hydroxy-alpha-sanshool (HAS), a characteristic ingredient of ZBP, against scopolamine (1 mg kg(-1), i.p.)-induced learning and memory deficits. HAS (5 mg kg(-1), p.o.) markedly reversed scopolamine-induced cognitive impairments, as indicated by its performance in the passive avoidance test and Morris water maze test (P < 0.01). Furthermore, HAS (2.5 and 5.0 mg kg(-1), p.o.) also dose-dependently prevented changes in hippocampal neuronal morphology and apoptosis, inhibited acetylcholinesterase (AChE) activity, increased the acetylcholine (ACh) content, and increased the protein and mRNA expression of brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding (p-CREB) compared with those in the model group (P < 0.05 & P < 0.01). These findings demonstrated that HAS attenuated scopolamine-induced cognitive impairments mainly by enhancing the activity of the cholinergic system and increasing the CREB/BDNF signalling pathway. Title: Effects of acute and chronic exposures of fluoxetine on the Chinese fish, topmouth gudgeon Pseudorasbora parva Chen H, Zeng X, Mu L, Hou L, Yang B, Zhao J, Schlenk D, Dong W, Xie L, Zhang Q Ref: Ecotoxicology & Environmental Safety, 160:104, 2018 : PubMed ESTHER: Chen_2018_Ecotoxicol.Environ.Saf_160_104 PubMedSearch: Chen 2018 Ecotoxicol.Environ.Saf 160 104 PubMedID: 29793199 Abstract Fluoxetine is a selective serotonin reuptake inhibitor used as an antidepressant and has been frequently detected in aquatic environments. However, its effects in fish from Asia remain relatively less studied. In this study, the topmouth gudgeon Pseudorasbora parva was exposed to 0, 50, and 200microg/L of fluoxetine for 4h and 42 d. The effects of fluoxetine on biometrics were compared to biochemical endpoints indicative of stress in different fish tissues (brain, liver, gills and intestine) following exposures. In fish exposed for 42 d, lipid peroxidation endpoints were enhanced 80% in the liver and gills. Acetylcholinesterase (AChE) activity was increased 40% after exposure to 50microg/L and 55% at 200microg/L following 4h exposure. In contrast AChE was increased 26% (at 50microg/L) after 42 d of exposures. Enhanced ethoxyresorufin-O-deethylase activity (EROD) was detected only in fish exposed to 50microg/L of fluoxetine for 4h. The activity of alpha-glucosidase (alpha-Glu) was also induced (at 200microg/L) after 4h of exposure. After 4h of exposure, the activities of proteases in the intestine were generally inhibited at 200microg/L. Both 4h and 42 d exposures resulted in an increased hepatosomatic index (HSI) but did not affect the condition factor (CF). Our results demonstrate that fluoxetine significantly altered biochemical endpoints in P. parva after acute exposure and the morphological changes in liver size were not observed until 42d of exposure. Title: Characterization, in vitro binding properties, and inhibitory activity on pancreatic lipase of beta-glucans from different Qingke (Tibetan hulless barley) cultivars Guo H, Lin S, Lu M, Gong JDB, Wang L, Zhang Q, Lin DR, Qin W, Wu DT Ref: Int J Biol Macromol, 120:2517, 2018 : PubMed ESTHER: Guo_2018_Int.J.Biol.Macromol_120_2517 PubMedSearch: Guo 2018 Int.J.Biol.Macromol 120 2517 PubMedID: 30195000 Abstract In order to explore Qingke beta-glucans as functional food ingredients for prevention of obesity, the physicochemical structures, in vitro binding properties, and inhibitory activities on pancreatic lipase of beta-glucans from three different Qingke cultivars, including Ganyucang (black), Dingqing (blue), and Zangqing 320 (white), were investigated and compared. Results showed that molecular weights, particle sizes, and intrinsic viscosities of beta-glucans from colored (black and blue) Qingke cultivars were much higher than those of white Qingke beta-glucans, respectively. In addition, the constituent monosaccharides of beta-glucans from colored Qingke cultivars were determined as arabinose, xylose, glucose, and galactose, and glucose was the dominant monosaccharide. Furthermore, colored Qingke beta-glucans exerted strong fat binding, cholesterol binding, and bile-acid binding capacities, as well as inhibitory activities on pancreatic lipase, which were much higher than those of white Qingke beta-glucans. Indeed, the fat binding, cholesterol binding, and bile-acid binding capacities, as well as the inhibitory activities on pancreatic lipase of Qingke beta-glucans were positively associated with their molecular weights and intrinsic viscosities. Results are beneficial for better understanding of the structure-function relationship of Qingke beta-glucans, and beta-glucans from colored Qingke cultivars (Ganyucang and Dingqing) could be further explored as functional food ingredients for prevention of obesity. Title: Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum Guo Y, Zhang N, Sun W, Duan X, Zhang Q, Zhou Q, Chen C, Zhu H, Luo Z and Zhang Y <3 more author(s)> Guo Y, Zhang N, Sun W, Duan X, Zhang Q, Zhou Q, Chen C, Zhu H, Luo Z, Liu J, Li XN, Xue Y, Zhang Y (- 3) Ref: Org Biomol Chem, 16:8130, 2018 : PubMed ESTHER: Guo_2018_Org.Biomol.Chem_16_8130 PubMedSearch: Guo 2018 Org.Biomol.Chem 16 8130 PubMedID: 30334059 Abstract Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 muM) and simultaneously inhibited BACE1 (at a concentration of 5 muM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed. Title: Insecticidal Mechanism of Wintergreen Oil Against the Health Pest Paederus fuscipes (Coleoptera: Staphylinidae) Liu Z, Zhang Q, Wu X, Yu W, Guo S Ref: Journal of Medical Entomology, 55:155, 2018 : PubMed ESTHER: Liu_2018_J.Med.Entomol_55_155 PubMedSearch: Liu 2018 J.Med.Entomol 55 155 PubMedID: 29029320 Abstract Paederus fuscipes, a health pest, causes dermatitis linearis in humans. Wintergreen oil exhibits optimal insecticidal activity against P. fuscipes. However, the insecticidal mechanism remains unclear not only in P. fuscipes but also in other pests. In this study, we explored the insecticidal mechanism of wintergreen oil in terms of its effect on the activity of acetylcholinesterase (AChE) enzyme and detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and mixed function oxidase); such effect was studied by fumigation both in vivo and in vitro in P. fuscipes male and female adults. In the in vivo and in vitro experiments on male and female adults, wintergreen oil did not significantly affect the activities of the three detoxifying enzymes. Hence, the mode of action of wintergreen oil may be unrelated to the three detoxifying enzymes. Wintergreen oil significantly inhibited AChE activity. When wintergreen oil was tested at different times in vivo, the highest inhibition rates were 41.99% (male) and 40.91% (female). When different doses of wintergreen oil were used for in vivo treatment, the highest inhibition rates were 33.78% (male) and 43.33% (female). When wintergreen oil was tested in vitro, the highest inhibition rates were 31.06% (male) and 35.57% (female). In vitro with chlorpyrifos as a positive control, the AChE activity of 3-mul wintergreen oil treatment was significantly lower than that of 10 mg/liter chlorpyrifos in both P. fuscipes male and female adults. The results demonstrated that AChE is a potential key factor, maybe a target enzyme, in the mechanism of wintergreen oil against P. fuscipes. Title: A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants Pilkington SM, Crowhurst R, Hilario E, Nardozza S, Fraser L, Peng Y, Gunaseelan K, Simpson R, Tahir J and Schaffer RJ <89 more author(s)> Pilkington SM, Crowhurst R, Hilario E, Nardozza S, Fraser L, Peng Y, Gunaseelan K, Simpson R, Tahir J, Deroles SC, Templeton K, Luo Z, Davy M, Cheng C, McNeilage M, Scaglione D, Liu Y, Zhang Q, Datson P, De Silva N, Gardiner SE, Bassett H, Chagne D, McCallum J, Dzierzon H, Deng C, Wang YY, Barron L, Manako K, Bowen J, Foster TM, Erridge ZA, Tiffin H, Waite CN, Davies KM, Grierson EP, Laing WA, Kirk R, Chen X, Wood M, Montefiori M, Brummell DA, Schwinn KE, Catanach A, Fullerton C, Li D, Meiyalaghan S, Nieuwenhuizen N, Read N, Prakash R, Hunter D, Zhang H, McKenzie M, Knabel M, Harris A, Allan AC, Gleave A, Chen A, Janssen BJ, Plunkett B, Ampomah-Dwamena C, Voogd C, Leif D, Lafferty D, Souleyre EJF, Varkonyi-Gasic E, Gambi F, Hanley J, Yao JL, Cheung J, David KM, Warren B, Marsh K, Snowden KC, Lin-Wang K, Brian L, Martinez-Sanchez M, Wang M, Ileperuma N, Macnee N, Campin R, McAtee P, Drummond RSM, Espley RV, Ireland HS, Wu R, Atkinson RG, Karunairetnam S, Bulley S, Chunkath S, Hanley Z, Storey R, Thrimawithana AH, Thomson S, David C, Testolin R, Huang H, Hellens RP, Schaffer RJ (- 89) Ref: BMC Genomics, 19:257, 2018 : PubMed ESTHER: Pilkington_2018_BMC.Genomics_19_257 PubMedSearch: Pilkington 2018 BMC.Genomics 19 257 PubMedID: 29661190 Gene_locus related to this paper: actde-CXE3, actde-CXE5, actch-a0a2r6p9v4, actch-a0a2r6phk8, actch-a0a2r6pty2, actch-q0zpu6, actcc-a0a2r6q553, actcc-a0a2r6quq2, actcc-a0a2r6q2m9, actcc-a0a2r6q2n7, actcc-a0a2r6ru97, actcc-a0a2r6r3e8, actcc-a0a2r6qy24, actcc-a0a2r6pzy5, actcc-a0a2r6p5n3, actcc-a0a2r6qdp0, actcc-a0a2r6qgs9 Abstract BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis. Title: Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane Wang J, Tang X, Li Y, Zhang R, Zhu L, Chen J, Sun Y, Zhang Q, Wang W Ref: Phys Chem Chem Phys, 20:20540, 2018 : PubMed ESTHER: Wang_2018_Phys.Chem.Chem.Phys_20_20540 PubMedSearch: Wang 2018 Phys.Chem.Chem.Phys 20 20540 PubMedID: 30051124 Abstract The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts. Title: Duplication of a Pks gene cluster and subsequent functional diversification facilitate environmental adaptation in Metarhizium species Zeng G, Zhang P, Zhang Q, Zhao H, Li Z, Zhang X, Wang C, Yin WB, Fang W Ref: PLoS Genet, 14:e1007472, 2018 : PubMed ESTHER: Zeng_2018_PLoS.Genet_14_E1007472 PubMedSearch: Zeng 2018 PLoS.Genet 14 E1007472 PubMedID: 29958281 Gene_locus related to this paper: metaq-pks1, metra-pks2, metmf-pks2, metaf-pks1, metbs-pks2, metas-pks1, metaq-pks2 Abstract The ecological importance of the duplication and diversification of gene clusters that synthesize secondary metabolites in fungi remains poorly understood. Here, we demonstrated that the duplication and subsequent diversification of a gene cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal genus Metarhizium. Diversification occurred in the promoter regions and the exon-intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes have distinct expression patterns, with Pks1 highly expressed during conidiation and Pks2 highly expressed during infection. Different upstream signaling pathways were found to regulate the two Pks genes. Pks1 is positively regulated by Hog1-MAPK, Slt2-MAPK and Mr-OPY2, while Pks2 is positively regulated by Fus3-MAPK and negatively regulated by Mr-OPY2. Pks1 and Pks2 have been subjected to positive selection and synthesize different secondary metabolites. PKS1 is involved in synthesis of an anthraquinone derivative, and contributes to conidial pigmentation, which plays an important role in fungal tolerance to UV radiation and extreme temperatures. Disruption of the Pks2 gene delayed formation of infectious structures and increased the time taken to kill insects, indicating that Pks2 contributes to pathogenesis. Thus, the duplication of a Pks gene cluster and its subsequent functional diversification has increased the adaptive flexibility of Metarhizium species. Title: Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors Zhang Q, Hu Y, Wu D, Ma S, Wang J, Rao J, Xu L, Xu H, Shao H and Wang S <1 more author(s)> Zhang Q, Hu Y, Wu D, Ma S, Wang J, Rao J, Xu L, Xu H, Shao H, Guo Z, Wang S (- 1) Ref: Talanta, 183:258, 2018 : PubMed ESTHER: Zhang_2018_Talanta_183_258 PubMedSearch: Zhang 2018 Talanta 183 258 PubMedID: 29567174 Abstract A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H2O2), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H2O2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H2O2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC50 of donepezil and tacrine were estimated to be 1.4nM and 3.5nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity. Title: A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3 Zhang Q, Xiao X, Zheng J, Li M, Yu M, Ping F, Wang T, Wang X Ref: Biomed Res Int, 2018:3109251, 2018 : PubMed ESTHER: Zhang_2018_Biomed.Res.Int_2018_3109251 PubMedSearch: Zhang 2018 Biomed.Res.Int 2018 3109251 PubMedID: 29951533 Abstract The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20 mg/kg/d). The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3 (Angptl3) and betaine-homocysteine S-methyltransferase (Bhmt) expression and activated paraoxonase-1 (Pon1) in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin in vivo. Title: Arabidopsis phospholipase Dalpha1 and Ddelta oppositely modulate EDS1- and SA-independent basal resistance against adapted powdery mildew Zhang Q, Berkey R, Blakeslee JJ, Lin J, Ma X, King H, Liddle A, Guo L, Munnik T and Xiao S <1 more author(s)> Zhang Q, Berkey R, Blakeslee JJ, Lin J, Ma X, King H, Liddle A, Guo L, Munnik T, Wang X, Xiao S (- 1) Ref: J Exp Bot, 69:3675, 2018 : PubMed ESTHER: Zhang_2018_J.Exp.Bot_69_3675 PubMedSearch: Zhang 2018 J.Exp.Bot 69 3675 PubMedID: 29912376 Abstract Plants use a tightly regulated immune system to fight off various pathogens. Phospholipase D (PLD) and its product, phosphatidic acid, have been shown to influence plant immunity; however, the underlying mechanisms remain unclear. Here, we show that the Arabidopsis mutants pldalpha1 and plddelta, respectively, exhibited enhanced resistance and enhanced susceptibility to both well-adapted and poorly adapted powdery mildew pathogens, and a virulent oomycete pathogen, indicating that PLDalpha1 negatively while PLDdelta positively modulates post-penetration resistance. The pldalpha1delta double mutant showed a similar infection phenotype to pldalpha1, genetically placing PLDalpha1 downstream of PLDdelta. Detailed genetic analyses of plddelta with mutations in genes for salicylic acid (SA) synthesis (SID2) and/or signaling (EDS1 and PAD4), measurement of SA and jasmonic acid (JA) levels, and expression of their respective reporter genes indicate that PLDdelta contributes to basal resistance independent of EDS1/PAD4, SA, and JAsignaling. Interestingly, while PLDalpha1-enhanced green fluorescent protein (eGFP) was mainly found in the tonoplast before and after haustorium invasion, PLDdelta-eGFP's focal accumulation to the plasma membrane around the fungal penetration site appeared to be suppressed by adapted powdery mildew. Together, our results demonstrate that PLDalpha1 and PLDdelta oppositely modulate basal, post-penetration resistance against powdery mildew through a non-canonical mechanism that is independent of EDS1/PAD4, SA, and JA. Title: VHL and Hypoxia Signaling: Beyond HIF in Cancer Zhang J, Zhang Q Ref: Biomedicines, 6:, 2018 : PubMed ESTHER: Zhang_2018_Biomedicines_6_ PubMedSearch: Zhang 2018 Biomedicines 6 PubMedID: 29562667 Abstract Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor alpha (including HIF1alpha and HIF2alpha) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-kappaB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer. Title: Enzymatic synthesis of lysophosphatidylcholine with n-3 polyunsaturated fatty acid from sn-glycero-3-phosphatidylcholine in a solvent-free system Liu Y, Zhang Q, Guo Y, Liu J, Xu J, Li Z, Wang J, Wang Y, Xue C Ref: Food Chem, 226:165, 2017 : PubMed ESTHER: Liu_2017_Food.Chem_226_165 PubMedSearch: Liu 2017 Food.Chem 226 165 PubMedID: 28254008 Abstract The n-3 polyunsaturated fatty acids (PUFA)-rich lysophosphatidylcholine (LPC) was successfully synthesized by Thermomyces lanuginosus lipase (TL IM)-catalyzed esterification of glycerylphosphorylcholine (GPC) and n-3 PUFA-rich fatty acids in a solvent-free system. Effects of reaction temperature, enzyme loading and substrate mole ratio on the yield of LPC and incorporation of n-3 PUFA were evaluated. The acyl-specificities of five enzymes were tested for direct esterification of n-3 PUFA, and Lipozyme TL IM was found to be more effective than others for production of LPC with n-3 PUFA. Substrate mole ratio and reaction temperature, however, had no significant effect on the incorporation. The maximal yield of LPC was obtained under the following conditions: temperature 45 degC, enzyme loading 15% by weight and substrate mole ratio (GPC/n-3 PUFA) 1:20. Furthermore, the composition of products were further investigated in the study. The 1-acyl-sn-glycero-3-lysophosphatidylcholine (2-LPC) was predominant in the mixtures at early stages of reaction, whereas less increment of 2-acyl-sn-glycero-3-lysophosphatidylcholine (1-LPC) and PC was observed at later stages. Title: Enantioselectivity of haloalkane dehalogenase LinB on the degradation of 1,2-dichloropropane: A QM/MM study Tang X, Zhang R, Li Y, Zhang Q, Wang W Ref: Bioorg Chem, 73:16, 2017 : PubMed ESTHER: Tang_2017_Bioorg.Chem_73_16 PubMedSearch: Tang 2017 Bioorg.Chem 73 16 PubMedID: 28527381 Abstract The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8kcal/mol for the (R)-isomer and 24.0kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP. Title: Abundance and Significance of Neuroligin-1 and Neurexin II in the Enteric Nervous System of Embryonic Rats Wang D, Pan J, Song G, Gao N, Zheng Y, Zhang Q, Li A Ref: Biomed Res Int, 2017:1209360, 2017 : PubMed ESTHER: Wang_2017_Biomed.Res.Int_2017_1209360 PubMedSearch: Wang 2017 Biomed.Res.Int 2017 1209360 PubMedID: 28194405 Abstract Aim. To investigate the abundance of neuroligin-1 and neurexin II in the enteric nervous system (ENS) of rats on different embryonic days and to explore their potential significance. Methods. The full-thickness colon specimens proximal to the ileocecal junction of rats on embryonic days 16, 18, and 20 and of newborns within 24 hours (E16, E18, E20, and Ep0) were studied, respectively. qRT-PCR was applied for detecting the expressions of neuroligin-1 and neurexin II on mRNA, and western blotting was employed for detecting their further expressions on the whole tissue. Finally, the histological appearance of neuroligin-1 and neurexin IIalpha was elucidated using immunohistochemical staining. Results. qRT-PCR showed that the neuroligin-1 and neurexin II mRNA expressions of groups E16, E18, E20, and Ep0 increased gradually with the growth of embryonic rats (P < 0.05). Western blotting confirmed the increasing tendency. In immunohistochemical staining, proteins neuroligin-1 and neurexin IIalpha positive cells concentrated mostly in the myenteric nerve plexus of the colon and their expressions depend on the embryonic time. Conclusion. Neuroligin-1 and neurexin II were both expressed in the ENS and have temporal correlation with the development of ENS, during which neuronal intestinal malformations (NIM) may occur due to their disruptions and consequent abnormal ENS development. Title: Organophosphate esters in sediment cores from coastal Laizhou Bay of the Bohai Sea, China Wang Y, Wu X, Zhang Q, Hou M, Zhao H, Xie Q, Du J, Chen J Ref: Sci Total Environ, 607-608:103, 2017 : PubMed ESTHER: Wang_2017_Sci.Total.Environ_607-608_103 PubMedSearch: Wang 2017 Sci.Total.Environ 607-608 103 PubMedID: 28688252 Abstract Concentrations and vertical distributions of organophosphate esters (OPEs) were investigated in the sediment cores collected from the Laizhou Bay, Bohai Sea of China. The total concentrations of OPEs in the sediment core (CA) collected near the Yellow River Estuary were in the range of 11.8-102ng/g, while the total concentrations in the sediment core (CB) near a mariculture area were 6.65-41.5ng/g. Significantly high concentrations of OPEs were found in the sediments near the Yellow River Estuary than those in the mariculture area. Vertical distributions in the sediment cores demonstrated a recent increase of OPE emissions, especially for tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), and tris (2-chloroisopropyl) phosphate (TCPP). Generally, TCEP and TCPP were the dominant congeners in the sediment cores, while the profiles of TnBP were increase in the surface 0-20cm layers of the CA core. OPEs in the CA core may be remarkably influenced by the discharge of Yellow River, whereas OPEs in the CB core may originate from the transport through seawater. The remarkable increase of OPE flame retardants in the surface sediments raises the concern about their emissions and risks to the environment and indicates the need for further monitoring. Title: Pharmacophore-based design and discovery of (-)-meptazinol carbamates as dual modulators of cholinesterase and amyloidogenesis Xie Q, Zheng Z, Shao B, Fu W, Xia Z, Li W, Sun J, Zheng W, Zhang W and Qiu Z <4 more author(s)> Xie Q, Zheng Z, Shao B, Fu W, Xia Z, Li W, Sun J, Zheng W, Zhang W, Sheng W, Zhang Q, Chen H, Wang H, Qiu Z (- 4) Ref: J Enzyme Inhib Med Chem, 32:659, 2017 : PubMed ESTHER: Xie_2017_J.Enzyme.Inhib.Med.Chem_32_659 PubMedSearch: Xie 2017 J.Enzyme.Inhib.Med.Chem 32 659 PubMedID: 28274151 Abstract Multifunctional carbamate-type acetylcholinesterase (AChE) inhibitors with anti-amyloidogenic properties like phenserine are potential therapeutic agents for Alzheimer's disease (AD). We reported here the design of new carbamates using pharmacophore model strategy to modulate both cholinesterase and amyloidogenesis. A five-feature pharmacophore model was generated based on 25 carbamate-type training set compounds. (-)-Meptazinol carbamates that superimposed well upon the model were designed and synthesized, which exhibited nanomolar AChE inhibitory potency and good anti-amyloidogenic properties in in vitro test. The phenylcarbamate 43 was highly potent (IC50 31.6 nM) and slightly selective for AChE, and showed low acute toxicity. In enzyme kinetics assay, 43 exhibited uncompetitive inhibition and reacted by pseudo-irreversible mechanism. 43 also showed amyloid-beta (Abeta) lowering effects (51.9% decrease of Abeta42) superior to phenserine (31% decrease of total Abeta) in SH-SY5Y-APP695 cells at 50 microM. The dual actions of 43 on cholinergic and amyloidogenic pathways indicated potential uses as symptomatic and disease-modifying agents. Title: Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells Yang H, Liu C, Chen B, An J, Zhang R, Zhang Q, Zhao J, He B, Hao DJ Ref: Molecular Neurobiology, 54:788, 2017 : PubMed ESTHER: Yang_2017_Mol.Neurobiol_54_788 PubMedSearch: Yang 2017 Mol.Neurobiol 54 788 PubMedID: 27566610 Abstract Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration medicine. Therefore, it is essential to establish a suitable cell reservoir as an issue-free alternative. Here, we demonstrate that spermatogonial stem cells (SSCs) derived from rat testis robustly give rise to terminally differentiated, functionally mature spinal cord neurons by using an optimized differentiation protocol. After performing a 3-week in vitro differentiation procedure, most cells exhibited neural morphological features and were Tuj-1 positive. Of note, approximately 60 % of the obtained cells coexpressed choline acetyltransferase (CHAT), acetylcholinesterase (AchE), and calcitonin gene-related peptide (CGRP). More importantly, apart from acquisition of neural antigenic and biochemical properties, nearly all neurons efficiently exhibited in vitro functionality similar to wild-type neurons, such as synapse formation, increased neuronal calcium influx, and electrophysiology. This is the first report revealing consistent and reproducible generation of large amounts of functional neurons from SSCs. Collectively, this system is suitable for studies of SSC transdifferentiation into neuronal cells and can provide sufficient neurons for the treatment of spinal cord injury as well as for genetic and small molecule screenings. Title: Genome-wide identification of pathogenicity, conidiation and colony sectorization genes in Metarhizium robertsii Zeng G, Chen X, Zhang X, Zhang Q, Xu C, Mi W, Guo N, Zhao H, You Y and Fang W <4 more author(s)> Zeng G, Chen X, Zhang X, Zhang Q, Xu C, Mi W, Guo N, Zhao H, You Y, Dryburgh FJ, Bidochka MJ, St Leger RJ, Zhang L, Fang W (- 4) Ref: Environ Microbiol, 19:3896, 2017 : PubMed ESTHER: Zeng_2017_Environ.Microbiol_19_3896 PubMedSearch: Zeng 2017 Environ.Microbiol 19 3896 PubMedID: 28447400 Gene_locus related to this paper: metaf-pks1 Abstract Metarhizium robertsii occupies a wide array of ecological niches and has diverse lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders it an unusually effective model for studying genetic mechanisms for fungal adaptation. Here over 20,000 M. robertsii T-DNA mutants were screened in order to elucidate genetic mechanism by which M. robertsii replicates and persists in diverse niches. About 287 conidiation, colony sectorization or pathogenicity loci, many of which have not been reported in other fungi were identified. By analysing a series of conidial pigmentation mutants, a new fungal pigmentation gene cluster, which contains Mr-Pks1, Mr-EthD and Mlac1 was identified. A conserved conidiation regulatory pathway containing Mr-BrlA, Mr-AbaA and Mr-WetA regulates expression of these pigmentation genes. During conidiation Mr-BlrA up-regulates Mr-AbaA, which in turn controls Mr-WetA. It was found that Hog1-MAPK regulates fungal conidiation by controlling the conidiation regulatory pathway, and that all three pigmentation genes exercise feedback regulation of conidiation. This work provided the foundation for deeper understanding of the genetic processes behind M. robertsii adaptive phenotypes, and advances our insights into conidiation and pigmentation in this fungus. Title: Neuroprotective Effects of Acetylcholinesterase Inhibitory Peptides from Anchovy (Coilia mystus) against Glutamate-Induced Toxicity in PC12 Cells Zhao T, Su G, Wang S, Zhang Q, Zhang J, Zheng L, Sun B, Zhao M Ref: Journal of Agricultural and Food Chemistry, 65:11192, 2017 : PubMed ESTHER: Zhao_2017_J.Agric.Food.Chem_65_11192 PubMedSearch: Zhao 2017 J.Agric.Food.Chem 65 11192 PubMedID: 29190426 Abstract Ameliorations of cholinergic system dysfunction and oxidative stress in neurodegenerative diseases were main approaches to improve memory disorder. Our previous investigation showed that anchovy protein hydrolysate (APH) could attenuate scopolamine-induced memory deficits in mice by regulating acetylcholinesterase (AChE) activity. Therefore, peptides with AChE inhibitory activity in APH were explored and identified in this study, and their possible neuroprotective mechanisms on glutamate induced apoptosis in PC12 were also elucidated. Two peptides with strong AChE inhibitory capacity were identified as Pro-Ala-Tyr-Cys-Ser (PAYCS) and Cys-Val-Gly-Ser-Tyr (CVGSY) by ultraperformance liquid chromatography coupled with tandem mass spectrometry. The AChE inhibitory was 23.68 +/- 0.97% and 6.08 +/- 0.41%, respectively. Treatment with PAYCS and CVGSY could significantly (p < 0.05) increase cells viability, reduce lactate dehydrogenase release, reactive oxygen species (ROS) production, malondialdehyde content, and the ratio of Bax/Bcl-2 of glutamate-induced apoptosis PC12 cells (82.78 +/- 6.58 and 109.94 +/- 7.16% of control, respectively) as well as increase superoxide dismutase and GSH-px activities. In addition, both the peptides could inhibit Ca(2+) influx but have no effects on mitochondrial membrane potential. Results indicated that AChE inhibitory peptides (PAYCS and CVGSY) possibly protected the PC12 cells against glutamate-induced apoptosis via inhibiting ROS production and Ca(2+) influx. PAYCS and CVGSY might be considered as nutraceuticals for alleviating memory deficits. Title: Down-regulation of fibronectin and the correlated expression of neuroligin in hirschsprung disease Zheng Y, Lv X, Wang D, Gao N, Zhang Q, Li A Ref: Neurogastroenterol Motil, 29:, 2017 : PubMed ESTHER: Zheng_2017_Neurogastroenterol.Motil_29_ PubMedSearch: Zheng 2017 Neurogastroenterol.Motil 29 PubMedID: 28656720 Abstract AIM: The goal of this study was to investigate the expression of fibronectin (FN) and the correlated abundance of neuroligins (NLs) in the enteric nervous system (ENS) and to find a novel diagnostic marker in the serum of Hirschsprung disease (HSCR) patients. METHODS: The expression levels of FN, neuroligin-1 and neuroligin-2 were detected in 114 children with or without HSCR. The expression and localization of the NLs and FN were assessed morphologically by immunohistochemical staining. Western blot analysis and real-time fluorescence quantitative PCR (qPCR) were performed to examine the correlated expression of the NLs and FN in aganglionic, transitional, and normal ganglionic colon tissues. An enzyme-linked immunosorbent assay (ELISA) was performed to evaluate and compare serum FN levels between HSCR and non-HSCRand between long-type HSCR and short-type HSCR. RESULTS: These studies showed that both neuroligin-1 and neuroligin-2 were expressed at low levels in aganglionic segments and at intermediate levels in transitional segments compared to their high level of expression in normal tissue. In contrast, FN expression was negatively correlated, with expression in these three samples transitioning from highest to lowest. The serum FN level was higher in HSCR than in non-HSCR, but no significant difference between short-type HSCR and long-type HSCR was observed. CONCLUSION: FN affects the expression of both neuroligin-1 and neuroligin-2 in HSCR, which may lead to the hypoplasia of ganglion cells in the ENS. This correlation may play a key role in the pathogenesis, diagnosis, or classification of HSCR. Title: MAPK cascade-mediated regulation of pathogenicity, conidiation and tolerance to abiotic stresses in the entomopathogenic fungus Metarhizium robertsii Chen X, Xu C, Qian Y, Liu R, Zhang Q, Zeng G, Zhang X, Zhao H, Fang W Ref: Environ Microbiol, 18:1048, 2016 : PubMed ESTHER: Chen_2016_Environ.Microbiol_18_1048 PubMedSearch: Chen 2016 Environ.Microbiol 18 1048 PubMedID: 26714892 Gene_locus related to this paper: metra-pks2 Abstract Metarhizium robertsii has been used as a model to study fungal pathogenesis in insects, and its pathogenicity has many parallels with plant and mammal pathogenic fungi. MAPK (Mitogen-activated protein kinase) cascades play pivotal roles in cellular regulation in fungi, but their functions have not been characterized in M. robertsii. In this study, we identified the full complement of MAPK cascade components in M. robertsii and dissected their regulatory roles in pathogenesis, conidiation and stress tolerance. The nine components of the Fus3, Hog1 and Slt2-MAPK cascades are all involved in conidiation. The Fus3- and Hog1-MAPK cascades are necessary for tolerance to hyperosmotic stress, and the Slt2- and Fus3-MAPK cascades both mediate cell wall integrity. The Hog1 and Slt2-MAPK cascades contribute to pathogenicity; the Fus3-MAPK cascade is indispensable for fungal pathogenesis. During its life cycle, M. robertsii experiences multiple microenvironments as it transverses the cuticle into the haemocoel. RNA-seq analysis revealed that MAPK cascades collectively play a major role in regulating the adaptation of M. robertsii to the microenvironmental change from the cuticle to the haemolymph. The three MAPKs each regulate their own distinctive subset of genes during penetration of the cuticle and haemocoel colonization, but they function redundantly to regulate adaptation to microenvironmental change. Title: Postconditioning with sevoflurane ameliorates spatial learning and memory deficit after hemorrhage shock and resuscitation in rats Hu X, Wang J, Zhang Q, Duan X, Chen Z, Zhang Y Ref: J Surg Res, 206:307, 2016 : PubMed ESTHER: Hu_2016_J.Surg.Res_206_307 PubMedSearch: Hu 2016 J.Surg.Res 206 307 PubMedID: 27884324 Abstract BACKGROUND: Severe hemorrhage shock and resuscitation are a systemic ischemia-reperfusion phenomenon which can induce learning and memory deficit in human and rats. Sevoflurane postconditioning has been proved to offer neuroprotection under different setting of cerebral ischemia-reperfusion in rats. The aim of this study was to investigate whether sevoflurane postconditioning could improve spatial learning and memory ability after hemorrhage shock and resuscitation in rats. Title: Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans Wang H, Rangan VS, Sung MC, Passmore D, Kempe T, Wang X, Thevanayagam L, Pan C, Rao C and Yang Z <6 more author(s)> Wang H, Rangan VS, Sung MC, Passmore D, Kempe T, Wang X, Thevanayagam L, Pan C, Rao C, Srinivasan M, Zhang Q, Gangwar S, Deshpande S, Cardarelli P, Marathe P, Yang Z (- 6) Ref: Biopharmaceutics & Drug Disposition, 37:93, 2016 : PubMed ESTHER: Wang_2016_Biopharm.Drug.Dispos_37_93 PubMedSearch: Wang 2016 Biopharm.Drug.Dispos 37 93 PubMedID: 25869904 Abstract CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that is transiently expressed on activated T- and B-lymphocytes. Aberrant expression of CD70 was identified in both solid tumors and haematologic malignancies. BMS-936561 (alphaCD70_MED-A) is an antibody-drug conjugate composed of a fully human anti-CD70 monoclonal antibody (alphaCD70) conjugated with a duocarmycin derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide linker. MED-A is a carbamate prodrug that is activated by carboxylesterase to its active form, MED-B, to exert its DNA alkylation activity. In vitro serum stability studies suggested the efficiencies of hydrolyzing the carbamate-protecting group in alphaCD70_MED-A followed a rank order of mouse > rat > > monkey > dog ~ human. Pharmacokinetics of alphaCD70_MED-A was evaluated in mice, monkeys, and dogs after single intravenous doses. In mice, alphaCD70_MED-A was cleared rapidly, with no detectable exposures after 15 min following dosing. In contrast, alphaCD70_MED-A was much more stable in monkeys and dogs. The clearance of alphaCD70_MED-A in monkeys was 58 mL/d/kg, ~2-fold faster than that in dogs (31 mL/d/kg). The human PK profiles of the total alphaCD70 and alphaCD70_MED-A were predicted using allometrically scaled monkeys PK parameters of alphaCD70 and the carbamate hydrolysis rate constant estimated in dogs. Comparing the predicted and observed human PK from the phase I study, the dose-normalized concentration-time profiles of alphaCD70_MED-A and the total alphaCD70 were largely within the 5(th) -95(th) percentile of the predicted profiles. Copyright (c) 2015 John Wiley & Sons, Ltd. Title: Artificial hydrolase based on carbon nanotubes conjugated with peptides Zhang Q, He X, Han A, Tu Q, Fang G, Liu J, Wang S, Li H Ref: Nanoscale, 8:16851, 2016 : PubMed ESTHER: Zhang_2016_Nanoscale_8_16851 PubMedSearch: Zhang 2016 Nanoscale 8 16851 PubMedID: 27714071 Abstract An artificial enzyme was constructed by attaching short peptides with active sites (SHELKLKLKL, WLKLKLKL) onto carbon nanotubes (CNT). It was found that the combination of SHE amino acids was essential to form a catalytic triad. W was also incorporated into this artificial enzyme and acted as a substrate binding site, thus producing an enzyme model with synergism of 67.7% catalytic groups and 32.3% binding groups, CNT-(SHE/W)2:1-LKLKLKL. When the peptide SHELKLKLKL was attached with the catalytic triad site close to the surface of CNT, the composite had higher activity than a leucine-attached system terminated with the catalytic triad site, suggesting that CNT not only served as a platform for attaching active amino acids, but also created a hydrophobic microenvironment and facilitated the proton transfer process to enhance the catalytic activity. The artificial enzyme exhibited Michaelis-Menten behaviour, indicating that it was indeed a mimic of the corresponding natural enzyme. This work showed that a well-designed combination of CNT and short peptides containing active sites can mimic a natural enzyme. Title: Surface display of the thermophilic lipase Tm1350 on the spore of Bacillus subtilis by the CotB anchor protein Chen H, Tian R, Ni Z, Zhang Q, Zhang T, Chen Z, Chen K, Yang S Ref: Extremophiles, 19:799, 2015 : PubMed ESTHER: Chen_2015_Extremophiles_19_799 PubMedSearch: Chen 2015 Extremophiles 19 799 PubMedID: 26026992 Abstract Lipases expressed in microbial hosts have great commercial value, but their applications are restricted by the high costs of production and harsh conditions used in industrial processes, such as high temperature and alkaline environment. In this study, an Escherichia coli-Bacillus subtilis shuttle vector (pHS-cotB-Tm1350) was constructed for the spore surface display of the lipase Tm1350 from hyperthermophilic bacterium Thermotoga maritima MSB8. Successful display of the CotB-Tm1350 fusion protein on spore surface was confirmed by Western blot analysis and activity measurements. The optimal catalytic temperature and pH of the spore surface-displayed Tm1350 were 80 degreesC and 9, respectively, which were higher than non-immobilized Tm1350 (70 degreesC and pH 7.5). Analysis of thermal and pH stability showed that spore surface-displayed Tm1350 retained 81 or 70 % of its original activity after 8 h of incubation at pH 8 or pH 9 (70 degreesC), which were 18 % higher than the retained activity of the non-immobilized Tm1350 under the same conditions. Meanwhile, recycling experiments showed that the recombinant spores could be used for up to three reaction cycles without a significant decrease in the catalytic rate (84 %). These results suggested that enzyme display on the surface of the B. subtilis spore could serve as an effective approach for enzyme immobilization, which has potential applications in the harsh biochemical industry. Title: Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis He T, Hu J, Yan G, Li L, Zhang D, Zhang Q, Chen B, Huang Y Ref: Clinical Science (Lond), 129:49, 2015 : PubMed ESTHER: He_2015_Clin.Sci.(Lond)_129_49 PubMedSearch: He 2015 Clin.Sci.(Lond) 129 49 PubMedID: 25700221 Abstract The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis. Title: Expression, purification and characterization of a functional, recombinant, cold-active lipase (LipA) from psychrotrophic Yersinia enterocolitica Ji X, Li S, Wang B, Zhang Q, Lin L, Dong Z, Wei Y Ref: Protein Expr Purif, 115:125, 2015 : PubMed ESTHER: Ji_2015_Protein.Expr.Purif_115_125 PubMedSearch: Ji 2015 Protein.Expr.Purif 115 125 PubMedID: 26256062 Abstract A novel cold-active lipase gene encoding 294 amino acid residues was obtained from the Yersinia enterocolitica strain KM1. Sequence alignment and phylogenetic analysis revealed that this novel lipase is a new member of the bacterial lipase family I.1. The lipase shares the conserved GXSXG motif and catalytic triad Ser85-Asp239-His261. The recombinant protein LipA was solubly and heterogeneously expressed in Escherichia coli, purified by Ni-affinity chromatography, and then characterized. LipA was active over a broad range spanning 15-60 degrees C with an optimum activity at 25 degrees C and across a wide pH range from 5.0 to 11.0 with an optimum activity at pH 7.5. The molecular weight was estimated to be 34.2KDa. The lipase could be activated by Mg(2+) and a low concentration (10%) of ethanol, dimethyl sulfoxide, methanol and acetonitrile, whereas it was strongly inhibited by Zn(2+), Cu(2+) and Mn(2+). This cold-active lipase may be a good candidate for detergents and biocatalysts at low temperature. Title: Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology Jia J, Yang X, Wu Z, Zhang Q, Lin Z, Guo H, Lin CS, Wang J, Wang Y Ref: Biomed Res Int, 2015:497462, 2015 : PubMed ESTHER: Jia_2015_Biomed.Res.Int_2015_497462 PubMedSearch: Jia 2015 Biomed.Res.Int 2015 497462 PubMedID: 26366414 Abstract Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production. Title: Effects of electroacupuncture on recovery of the electrophysiological properties of the rabbit gastrocnemius after contusion: an in vivo animal study Liu S, Wang R, Luo D, Xu Q, Xiao C, Lin P, Yu Z, Zhao X, Cai R and Wang Y <2 more author(s)> Liu S, Wang R, Luo D, Xu Q, Xiao C, Lin P, Yu Z, Zhao X, Cai R, Ma J, Zhang Q, Wang Y (- 2) Ref: BMC Complement Altern Med, 15:69, 2015 : PubMed ESTHER: Liu_2015_BMC.Complement.Altern.Med_15_69 PubMedSearch: Liu 2015 BMC.Complement.Altern.Med 15 69 PubMedID: 25887510 Abstract BACKGROUND: Our preliminary studies indicated that electroacupuncture (EA) at the ST36 and Ashi acupoints could promote regeneration of the rabbit gastrocnemius (GM) by improving microcirculation perfusion, promoting the recovery of myofiber structures, and inhibiting excessive fibrosis. However, the effects of EA on recovery of the electrophysiological properties of the GM after contusion are not yet clear. Thus, the purpose of this study was to investigate the effects of EA at the Zusanli (ST36) and Ashi acupoints with regard to recovery of the electrophysiological properties of the rabbit GM after contusion. Title: Expression and Characterization of a Novel Thermo-Alkalistable Lipase from Hyperthermophilic Bacterium Thermotoga maritima Tian R, Chen H, Ni Z, Zhang Q, Zhang Z, Zhang T, Zhang C, Yang S Ref: Appl Biochem Biotechnol, 176:1482, 2015 : PubMed ESTHER: Tian_2015_Appl.Biochem.Biotechnol_176_1482 PubMedSearch: Tian 2015 Appl.Biochem.Biotechnol 176 1482 PubMedID: 25957275 Abstract A gene coding for lipase (Tm1350) from the hyperthermophilic bacterium Thermotoga maritima MSB8 was cloned and overexpressed by Escherichia coli. The enzyme can degrade substrates with both short and long acyl chain lengths. The apparent Km and Vmax values for p-nitrophenyl butyrate were 8 mM and 333 U/mg, respectively. The enzyme displayed optimal activity at pH 7.5 and 70 degrees C, maintained 66 % of the original activity after 8 h of incubation, and its half-lives at pHs 9 and 10 were 8 and 1 h. The activity of Tm1350 was stimulated up to 131 or 151 % of the original activity by incubating with 4 M urea or 20 % (v/v) methanol, and 90.1 or 70.2 % of the activity was maintained after 8 h incubation of the enzyme in 20 or 75 % (v/v) of the methanol, showing potential for biodiesel production. The activity of the enzyme without cysteine residue was stimulated up to 618 and 550 % of the original activity by incubating with dithiothreitol (DTT) and reduced glutathione (GSH) at a concentration of 1 mM. However, the circular dichroism spectra of the enzyme have no obvious change after DTT treatment. It is speculated that DTT interacts with potential residues in some key active sites without influence of structure. Title: Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo Zhang Q, Li J, Liu C, Song C, Li P, Yin F, Xiao Y, Jiang W, Zong A and Wang F <1 more author(s)> Zhang Q, Li J, Liu C, Song C, Li P, Yin F, Xiao Y, Jiang W, Zong A, Zhang X, Wang F (- 1) Ref: Neuroscience, 305:169, 2015 : PubMed ESTHER: Zhang_2015_Neurosci_305_169 PubMedSearch: Zhang 2015 Neurosci 305 169 PubMedID: 26254241 Abstract In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Abeta)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Abeta25-35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Abeta1-40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Abeta peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer's disease. Title: Intranasal H102 Peptide-Loaded Liposomes for Brain Delivery to Treat Alzheimer's Disease Zheng X, Shao X, Zhang C, Tan Y, Liu Q, Wan X, Zhang Q, Xu S, Jiang X Ref: Pharm Res, 32:3837, 2015 : PubMed ESTHER: Zheng_2015_Pharm.Res_32_3837 PubMedSearch: Zheng 2015 Pharm.Res 32 3837 PubMedID: 26113236 Abstract PURPOSE: H102, a novel beta-sheet breaker peptide, was encapsulated into liposomes to reduce its degradation and increase its brain penetration through intranasal administration for the treatment of Alzheimer's disease (AD). Title: Identification and characterization of a new erythromycin biosynthetic gene cluster in Actinopolyspora erythraea YIM90600, a novel erythronolide-producing halophilic actinomycete isolated from salt field Chen D, Feng J, Huang L, Zhang Q, Wu J, Zhu X, Duan Y, Xu Z Ref: PLoS ONE, 9:e108129, 2014 : PubMed ESTHER: Chen_2014_PLoS.ONE_9_E108129 PubMedSearch: Chen 2014 PLoS.ONE 9 E108129 PubMedID: 25250723 Gene_locus related to this paper: 9acto-a0a099d7w4, 9actn-a0a099d934 Abstract Erythromycins (Ers) are clinically potent macrolide antibiotics in treating pathogenic bacterial infections. Microorganisms capable of producing Ers, represented by Saccharopolyspora erythraea, are mainly soil-dwelling actinomycetes. So far, Actinopolyspora erythraea YIM90600, a halophilic actinomycete isolated from Baicheng salt field, is the only known Er-producing extremophile. In this study, we have reported the draft genome sequence of Ac. erythraea YIM90600, genome mining of which has revealed a new Er biosynthetic gene cluster encoding several novel Er metabolites. This Er gene cluster shares high identity and similarity with the one of Sa. erythraea NRRL2338, except for two absent genes, eryBI and eryG. By correlating genotype and chemotype, the biosynthetic pathways of 3'-demethyl-erythromycin C, erythronolide H (EH) and erythronolide I have been proposed. The formation of EH is supposed to be sequentially biosynthesized via C-6/C-18 epoxidation and C-14 hydroxylation from 6-deoxyerythronolide B. Although an in vitro enzymatic activity assay has provided limited evidence for the involvement of the cytochrome P450 oxidase EryFAc (derived from Ac. erythraea YIM90600) in the catalysis of a two-step oxidation, resulting in an epoxy moiety, the attempt to construct an EH-producing Sa. erythraea mutant via gene complementation was not successful. Characterization of EryKAc (derived from Ac. erythraea YIM90600) in vitro has confirmed its unique role as a C-12 hydroxylase, rather than a C-14 hydroxylase of the erythronolide. Genomic characterization of the halophile Ac. erythraea YIM90600 will assist us to explore the great potential of extremophiles, and promote the understanding of EH formation, which will shed new insights into the biosynthesis of Er metabolites. Title: The coffee genome provides insight into the convergent evolution of caffeine biosynthesis Denoeud F, Carretero-Paulet L, Dereeper A, Droc G, Guyot R, Pietrella M, Zheng C, Alberti A, Anthony F and Lashermes P <54 more author(s)> Denoeud F, Carretero-Paulet L, Dereeper A, Droc G, Guyot R, Pietrella M, Zheng C, Alberti A, Anthony F, Aprea G, Aury JM, Bento P, Bernard M, Bocs S, Campa C, Cenci A, Combes MC, Crouzillat D, Da Silva C, Daddiego L, De Bellis F, Dussert S, Garsmeur O, Gayraud T, Guignon V, Jahn K, Jamilloux V, Joet T, Labadie K, Lan T, Leclercq J, Lepelley M, Leroy T, Li LT, Librado P, Lopez L, Munoz A, Noel B, Pallavicini A, Perrotta G, Poncet V, Pot D, Priyono, Rigoreau M, Rouard M, Rozas J, Tranchant-Dubreuil C, VanBuren R, Zhang Q, Andrade AC, Argout X, Bertrand B, de Kochko A, Graziosi G, Henry RJ, Jayarama, Ming R, Nagai C, Rounsley S, Sankoff D, Giuliano G, Albert VA, Wincker P, Lashermes P (- 54) Ref: Science, 345:1181, 2014 : PubMed ESTHER: Denoeud_2014_Science_345_1181 PubMedSearch: Denoeud 2014 Science 345 1181 PubMedID: 25190796 Gene_locus related to this paper: cofca-a0a068vi93, cofca-a0a068uy77, cofca-a0a068tzh7, cofca-a0a068tuj7, cofca-a0a068v983, cofca-a0a068tnj0, cofca-a0a068tyf7, cofca-a0a068u1v4.1, cofca-a0a068vks5, cofar-a0a6p6xcv5 Abstract Coffee is a valuable beverage crop due to its characteristic flavor, aroma, and the stimulating effects of caffeine. We generated a high-quality draft genome of the species Coffea canephora, which displays a conserved chromosomal gene order among asterid angiosperms. Although it shows no sign of the whole-genome triplication identified in Solanaceae species such as tomato, the genome includes several species-specific gene family expansions, among them N-methyltransferases (NMTs) involved in caffeine production, defense-related genes, and alkaloid and flavonoid enzymes involved in secondary compound synthesis. Comparative analyses of caffeine NMTs demonstrate that these genes expanded through sequential tandem duplications independently of genes from cacao and tea, suggesting that caffeine in eudicots is of polyphyletic origin. Title: Purification and characterization of a hydrolysis-resistant lipase from Aspergillus terreus Shi H, Meng Y, Yang M, Zhang Q Ref: Biotechnol Appl Biochem, 61:165, 2014 : PubMed ESTHER: Shi_2014_Biotechnol.Appl.Biochem_61_165 PubMedSearch: Shi 2014 Biotechnol.Appl.Biochem 61 165 PubMedID: 23855368 Abstract Lipase from Aspergillus terreus was purified to homogeneity using ammonium sulfate precipitation and chromatographies with Q-Sepharose and Sephacryl S-200. It showed a single band on SDS-PAGE and IEF-PAGE with a relative molecular mass of 37.2 kDa and pI of 3.2. Its glycoprotein nature was confirmed with the percentage of saccharides of 5.02% and 3.88% determined by the phenol/sulfuric acid and anthrone/ sulfuric acid methods, respectively. The lipase hydrolyzed both plant oils and animal oils, with the K(m) value for substrate p-NPP of 16.42 mM at pH 6.0, 50 degrees C. The enzyme was tolerant in a wide range of pH (pH 3-12) with optimum activity at pH 4.0. It remained stable under the highest temperature of 65 degrees C, with maximal activity at 50 degrees C. Ca(2)(+), Co(2)(+), Mn(2)(+), and Ni(2)(+) stimulated enzyme activity, but Hg(2)(+) caused inhibition. Detected detergents had no obvious effect on enzyme activity, except SDS, which stimulated the activity at lower concentrations but inhibited the activity at higher concentrations. The inhibitory effect on enzyme activity of phenylmethanesulfonyl fluoride revealed that the Ser was involved in catalysis. Saccharides had no obvious effect on enzyme activity but could enhance its thermostability. Furthermore, the enzyme was resistant to trypsin digestion. Title: The Down-Regulation of Neuroligin-2 and the Correlative Clinical Significance of Serum GABA Over-Expression in Hirschsprung's Disease Yang H, Niu J, Wang J, Zhang F, Zhang Q, Zhang W, Li A Ref: Neurochem Res, 39:1451, 2014 : PubMed ESTHER: Yang_2014_Neurochem.Res_39_1451 PubMedSearch: Yang 2014 Neurochem.Res 39 1451 PubMedID: 24842555 Abstract The goal of this study was to investigate the expression level of neuroligin-2 in different colon tissue segments of children with Hirschsprung's disease (HSCR) and the correlative clinical significance of serum Gamma-Aminobutyric Acid (serum GABA) in HSCR. Neuroligin-2 was assessed by Immunohistochemistry staining method on routine paraffin section from different colon tissue segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Western-blot analysis and real-time fluorescence quantitative PCR(qRT-PCR) were applied to compare and evaluate the expression levels of neuroligin-2 from three segments of HSCR, and we used Enzyme-linked Immunosorbent Assay (ELISA) method to detect and compare the serum GABA between HSCR and non-HSCR. Immunohistochemistry staining demonstrated that intensive neuroligin-2 staining was detected in the ganglion cells in the ganglionic colonic and transitional colonic segments from the HSCR children; however, neuroligin-2 staining was down-regulated significantly in the aganglionic colonic segments. The expression levels of neuroligin-2 mRNA and protein in the aganglionic colonic segment were decreased compared to the ganglionic colonic segment and transitional colonic segment (P < 0.05). And the level of serum GABA was significantly higher in HSCR than that in non-HSCR. The expression of neuroligin-2 varies from different segments of HSCR. The down-regulation of neuroligin-2 in aganglionic colonic segments may be correlated with the excessive intestine contraction and further result in HSCR. The over-expression of serum GABA may be considered as a new diagnostic method of HSCR. Title: The interaction between OsMADS57 and OsTB1 modulates rice tillering via DWARF14 Guo S, Xu Y, Liu H, Mao Z, Zhang C, Ma Y, Zhang Q, Meng Z, Chong K Ref: Nat Commun, 4:1566, 2013 : PubMed ESTHER: Guo_2013_Nat.Commun_4_1566 PubMedSearch: Guo 2013 Nat.Commun 4 1566 PubMedID: 23463009 Abstract Rice tillering is a multigenic trait that influences grain yield, but its regulation molecular module is poorly understood. Here we report that OsMADS57 interacts with OsTB1 (TEOSINTE BRANCHED1) and targets D14 (Dwarf14) to control the outgrowth of axillary buds in rice. An activation-tagged mutant osmads57-1 and OsMADS57-overexpression lines showed increased tillers, whereas OsMADS57 antisense lines had fewer tillers. OsMIR444a-overexpressing lines exhibited suppressed OsMADS57 expression and tillering. Furthermore, osmads57-1 was insensitive to strigolactone treatment to inhibit axillary bud outgrowth, and OsMADS57's function in tillering was dependent on D14. D14 expression was downregulated in osmads57-1, but upregulated in antisense and OsMIR444a-overexpressing lines. OsMADS57 bound to the CArG motif [C(A/T)TTAAAAAG] in the promoter and directly suppressed D14 expression. Interaction of OsMADS57 with OsTB1 reduced OsMADS57 inhibition of D14 transcription. Therefore, OsMIR444a-regulated OsMADS57, together with OsTB1, target D14 to control tillering. This regulation mechanism could have important application in rice molecular breeding programs focused on high grain yield. Title: Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) Ming R, VanBuren R, Liu Y, Yang M, Han Y, Li LT, Zhang Q, Kim MJ, Schatz MC and Shen-Miller J <60 more author(s)> Ming R, VanBuren R, Liu Y, Yang M, Han Y, Li LT, Zhang Q, Kim MJ, Schatz MC, Campbell M, Li J, Bowers JE, Tang H, Lyons E, Ferguson AA, Narzisi G, Nelson DR, Blaby-Haas CE, Gschwend AR, Jiao Y, Der JP, Zeng F, Han J, Min XJ, Hudson KA, Singh R, Grennan AK, Karpowicz SJ, Watling JR, Ito K, Robinson SA, Hudson ME, Yu Q, Mockler TC, Carroll A, Zheng Y, Sunkar R, Jia R, Chen N, Arro J, Wai CM, Wafula E, Spence A, Xu L, Zhang J, Peery R, Haus MJ, Xiong W, Walsh JA, Wu J, Wang ML, Zhu YJ, Paull RE, Britt AB, Du C, Downie SR, Schuler MA, Michael TP, Long SP, Ort DR, Schopf JW, Gang DR, Jiang N, Yandell M, dePamphilis CW, Merchant SS, Paterson AH, Buchanan BB, Li S, Shen-Miller J (- 60) Ref: Genome Biol, 14:R41, 2013 : PubMed ESTHER: Ming_2013_Genome.Biol_14_R41 PubMedSearch: Ming 2013 Genome.Biol 14 R41 PubMedID: 23663246 Gene_locus related to this paper: nelnu-a0a1u8aj84, nelnu-a0a1u8bpe4, nelnu-a0a1u7z9m9, nelnu-a0a1u7ywy5, nelnu-a0a1u8aik2, nelnu-a0a1u7zmb5, nelnu-a0a1u8a7m7, nelnu-a0a1u8b0n9, nelnu-a0a1u8b461, nelnu-a0a1u7zzj3, nelnu-a0a1u8ave7, nelnu-a0a1u7yn26 Abstract BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots. Title: Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease Zhang Q, Wang J, Li A, Liu H, Zhang W, Cui X, Wang K Ref: Mol Biol Rep, 40:2969, 2013 : PubMed ESTHER: Zhang_2013_Mol.Biol.Rep_40_2969 PubMedSearch: Zhang 2013 Mol.Biol.Rep 40 2969 PubMedID: 23264101 Abstract To investigate the expression levels of neurexins and neuroligins in the enteric nervous system (ENS) in Hirschsprung Disease (HSCR). Longitudinal muscles with adherent mesenteric plexus were obtained by dissection of the fresh gut wall of mice, guinea pigs, and humans. Double labeling of neurexin I and Hu (a neuron marker), neuroligin 1 and Hu, neurexin I and synaptophysin (a presynaptic marker), and neuroligin 1 and PSD95 (a postsynaptic marker) was performed by immunofluorescence staining. Images were merged to determine the relative localizations of the proteins. Expression levels of neurexin and neuroligin in different segments of the ENS in HSCR were investigated by immunohistochemistry. Neurexin and neuroligin were detected in the mesenteric plexus of mice, guinea pigs, and humans with HSCR. Neurexin was located in the presynapse, whereas neuroligin was located in the postsynapse. Expression levels of neurexin and neuroligin were significant in the ganglionic colonic segment of HSCR, moderate in the transitional segment, and negative in the aganglionic colonic segment. The expressions of neurexin and neuroligin in the transitional segments were significantly down-regulated compared with the levels in the normal segments (P < 0.05). Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR. Title: Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X and Meng J <2 more author(s)> Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X, Allard M, Brown E, Meng J (- 2) Ref: Genome Announc, 1:E00213, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00213 PubMedSearch: Zhang 2013 Genome.Announc 1 E00213 PubMedID: 23661485 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China. Title: Enhancement of nose-to-brain delivery of basic fibroblast growth factor for improving rat memory impairments induced by co-injection of beta-amyloid and ibotenic acid into the bilateral hippocampus Feng C, Zhang C, Shao X, Liu Q, Qian Y, Feng L, Chen J, Zha Y, Zhang Q, Jiang X Ref: Int J Pharm, 423:226, 2012 : PubMed ESTHER: Feng_2012_Int.J.Pharm_423_226 PubMedSearch: Feng 2012 Int.J.Pharm 423 226 PubMedID: 22193058 Abstract Basic fibroblast growth factor (bFGF) delivery to the brain of animals appears to be an emerging potential therapeutic approach to neurodegenerative diseases, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion. A nasal spray of bFGF had been developed previously and the objective of the present study was to investigate whether bFGF nasal spray could enhance brain uptake of bFGF and ameliorate memory impairment induced by co-injection of beta-amyloid(25-35) and ibotenic acid into bilateral hippocampus of rats. The results of brain uptake study showed that the AUC(0-12h) of bFGF nasal spray in olfactory bulb, cerebrum, cerebellum and hippocampus was respectively 2.47, 2.38, 2.56 and 2.19 times that of intravenous bFGF solution, and 1.11, 1.95, 1.40 and 1.93 times that of intranasal bFGF solution, indicating that intranasal administration of bFGF nasal spray was an effective means of delivering bFGF to the brain, especially to cerebrum and hippocampus. In Morris water maze tasks, intravenous administration of bFGF solution at high dose (40 mug/kg) showed little improvement on spatial memory impairment. In contrast, bFGF solution of the same dose following intranasal administration could significantly ameliorate spatial memory impairment. bFGF nasal spray obviously improved spatial memory impairment even at a dose half (20 mug/kg) of bFGF solution, recovered their acetylcholinesterase and choline acetyltransferase activity to the sham control level, and alleviated neuronal degeneration in rat hippocampus, indicating neuroprotective effects on the central nerve system. In a word, bFGF nasal spray may be a new formulation of great potential for treating AD. Title: Intranasal administration of TAT-haFGF(14-154) attenuates disease progression in a mouse model of Alzheimer's disease Lou G, Zhang Q, Xiao F, Xiang Q, Su Z, Zhang L, Yang P, Yang Y, Zheng Q, Huang Y Ref: Neuroscience, 223:225, 2012 : PubMed ESTHER: Lou_2012_Neurosci_223_225 PubMedSearch: Lou 2012 Neurosci 223 225 PubMedID: 22885230 Abstract Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 ug/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced beta-amyloid protein(1-42) (Abeta(1-42)) deposits as well as the levels of Abeta soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Abeta pathology and oxidative stress. Title: A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-beta(2)(5)(-)(3)(5)-treated rats following intranasal administration Wu H, Li J, Zhang Q, Yan X, Guo L, Gao X, Qiu M, Jiang X, Lai R, Chen H Ref: Eur J Pharm Biopharm, 80:368, 2012 : PubMed ESTHER: Wu_2012_Eur.J.Pharm.Biopharm_80_368 PubMedSearch: Wu 2012 Eur.J.Pharm.Biopharm 80 368 PubMedID: 22061263 Abstract Because of the immunogenicity and toxicity in vivo of large molecules such as lectins, the application of these molecules is remarkably restricted in drug delivery systems. In this study, to improve the brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, Odorranalectin (OL, 1700 Da), a novel non-immunogenic small peptide, was selected to establish an OL-modified cubosomes (Cubs) system. The streptavidin (SA)-conjugated Cubs were prepared by incorporating maleimide-PEG-oleate and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothiolane thiolated SA; mono-biotinylated OL was then coupled with the SA-modified Cubs. The OL-decorated Cubs (OL-Cubs) devised via a non-covalent SA-biotin "bridge" made it easy to conjugate OL and determine the number of ligands on the surface of the Cubs using sensitive chemiluminescent detection. Retention of the bio-recognitive activity of OL after covalent coupling was verified by hemagglutination testing. Nose-to-brain delivery characteristic of OL-Cubs was investigated by in vivo fluorescent biodistribution using coumarin-6 as a marker. The relative uptake of coumarin carried by OL-Cubs was 1.66- to 3.46-fold in brain tissues compared to that incorporated in the Cubs. Besides, Gly14-Humanin (S14G-HN) as a model peptide drug was loaded into cubosomes and evaluated for its pharmacodynamics on Alzheimer's disease (AD) rats following intranasal administration by Morris water maze test and acetylcholinesterase activity determination. The results suggested that OL functionalization enhanced the therapeutic effects of S14G-HN-loaded cubosomes on AD. Thus, OL-Cubs might offer a novel effective and noninvasive system for brain drug delivery, especially for peptides and proteins. Title: [Inhibitory effect of icariin on acetylcholinesterase] Zhang YD, Cai YN, Zhang Q, Qi ZL, Gao QQ Ref: Yao Xue Xue Bao, 47:1141, 2012 : PubMed ESTHER: Zhang_2012_Yao.Xue.Xue.Bao_47_1141 PubMedSearch: Zhang 2012 Yao.Xue.Xue.Bao 47 1141 PubMedID: 23227542 Abstract Acetylcholinesterase (AChE) inhibitors are mainly used in the treatment of Alzheimer's disease (AD). The inhibitory effect of icariin on the activity of AChE was investigated by inhibition kinetics. The binding interaction and binding sites between icariin and AChE were also studied by using fluorimetry and molecular docking, respectively. The results showed that icariin could potently inhibit the activity of AChE, the IC50 value was determined to be 3.50 x 10(-8) mol x L(-1), and the determined IC50 value to tacrine was 0.75 x 10(-8) mol x L(-1). Kinetic analyses showed that icariin is a reversible and mixed type AChE inhibitor. The inhibition constants K1 and K(IS) were determined to be 2.67 x 10(-8) and 4.43 x 10(-8) mol x L(-1), respectively. Icariin binds selectively to the AChE peripheral anionic site via hydrogen bonds and Van der Waals forces. Title: Affinity binding-guided fluorescent nanobiosensor for acetylcholinesterase inhibitors via distance modulation between the fluorophore and metallic nanoparticle Zhang Y, Hei T, Cai Y, Gao Q, Zhang Q Ref: Analytical Chemistry, 84:2830, 2012 : PubMed ESTHER: Zhang_2012_Anal.Chem_84_2830 PubMedSearch: Zhang 2012 Anal.Chem 84 2830 PubMedID: 22339669 Abstract The magnitude of fluorescence enhancement was found to depend strongly on the distance between fluorophores and metal nanostructures in metal-enhanced fluorescence (MEF). However, the precise placement of the particle in front of the molecule with nanometer accuracy and distance control is a great challenge. We describe a method using acetylcholinesterase (AChE) to modulate the distance between a gold nanoparticle (AuNP) and the fluorophore 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) (DDAO). We found that DDAO is a reversible mixed type-I AChE inhibitor. DDAO binds to the peripheral anionic site and penetrates into the active gorge site of AChE via inhibition kinetics test and molecular docking study. The affinity ligand DDAO bound to AChE which was immobilized onto AuNPs, and its fluorescence was sharply enhanced due to MEF. The fluorescence was reduced by distance variations between the AuNP and DDAO, which resulted from other inhibitors competitively binding with AChE and partly or completely displacing DDAO. Experimental results show that changes in fluorescence intensity are related to the concentration of inhibitors present in the solution. In addition, the nanobiosensor has high sensitivity, with detection limits as low as 0.4 muM for paraoxon and 10 nM for tacrine, and also exhibits different reduction efficiencies for the two types of inhibitor. Thus, instead of an inhibition test, a new type of affinity binding-guided fluorescent nanobiosensor was fabricated to detect AChE inhibitors, determine AChE inhibitor binding mode, and screen more potent AChE inhibitors. The proposed strategy may be applied to other proteins or protein domains via changes in the affinity ligand. Title: Genome sequencing reveals insights into physiology and longevity of the naked mole rat Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV, Han L, Marino SM, Sun X, Turanov AA and Gladyshev VN <26 more author(s)> Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV, Han L, Marino SM, Sun X, Turanov AA, Yang P, Yim SH, Zhao X, Kasaikina MV, Stoletzki N, Peng C, Polak P, Xiong Z, Kiezun A, Zhu Y, Chen Y, Kryukov GV, Zhang Q, Peshkin L, Yang L, Bronson RT, Buffenstein R, Wang B, Han C, Li Q, Chen L, Zhao W, Sunyaev SR, Park TJ, Zhang G, Wang J, Gladyshev VN (- 26) Ref: Nature, 479:223, 2011 : PubMed ESTHER: Kim_2011_Nature_479_223 PubMedSearch: Kim 2011 Nature 479 223 PubMedID: 21993625 Gene_locus related to this paper: hetga-g5amh8, hetga-g5an68, hetga-g5anw7, hetga-g5as32, hetga-g5atg6, hetga-g5b5b7, hetga-g5b9m6, hetga-g5bdh8, hetga-g5bmv3, hetga-g5bp66, hetga-g5bp67, hetga-g5bp68, hetga-g5bpp3, hetga-g5bsd4, hetga-g5bul0, hetga-g5bw29, hetga-g5bze3, hetga-g5c6q5, hetga-g5bfw4, hetga-g5b832, hetga-g5c6q8, hetga-g5bj87, hetga-a0a0p6jix7, hetga-g5c108, hetga-g5c109, hetga-g5c110, hetga-g5arh0, hetga-g5aua1, hetga-g5are8, hetga-g5ax31, hetga-a0a0p6jud6, hetga-g5b7v3, hetga-a0a0p6jw61, hetga-a0a0p6jdl4, hetga-g5bg83, hetga-g5bcu5, hetga-g5bvp0, hetga-g5b8m7, hetga-g5b709, hetga-g5bt99, hetga-g5b4q4 Abstract The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research. Title: Natural variation in GS5 plays an important role in regulating grain size and yield in rice Li Y, Fan C, Xing Y, Jiang Y, Luo L, Sun L, Shao D, Xu C, Li X and Zhang Q <2 more author(s)> Li Y, Fan C, Xing Y, Jiang Y, Luo L, Sun L, Shao D, Xu C, Li X, Xiao J, He Y, Zhang Q (- 2) Ref: Nat Genet, 43:1266, 2011 : PubMed ESTHER: Li_2011_Nat.Genet_43_1266 PubMedSearch: Li 2011 Nat.Genet 43 1266 PubMedID: 22019783 Gene_locus related to this paper: orysa-q5w727 Abstract Increasing crop yield is one of the most important goals of plant science research. Grain size is a major determinant of grain yield in cereals and is a target trait for both domestication and artificial breeding(1). We showed that the quantitative trait locus (QTL) GS5 in rice controls grain size by regulating grain width, filling and weight. GS5 encodes a putative serine carboxypeptidase and functions as a positive regulator of grain size, such that higher expression of GS5 is correlated with larger grain size. Sequencing of the promoter region in 51 rice accessions from a wide geographic range identified three haplotypes that seem to be associated with grain width. The results suggest that natural variation in GS5 contributes to grain size diversity in rice and may be useful in improving yield in rice and, potentially, other crops(2). Title: Visual detection of organophosphorus pesticides represented by mathamidophos using Au nanoparticles as colorimetric probe Li H, Guo J, Ping H, Liu L, Zhang M, Guan F, Sun C, Zhang Q Ref: Talanta, 87:93, 2011 : PubMed ESTHER: Li_2011_Talanta_87_93 PubMedSearch: Li 2011 Talanta 87 93 PubMedID: 22099654 Abstract With citrate-coated Au nanoparticles as colorimetric probe, a novel visual method for rapid assay of organophosphorus pesticides has been developed. The assay principle is based on catalytic hydrolysis of acetylthiocholine into thiocholine by acetylcholinesterase, which induces the aggregation of Au nanoparticles and the color change from claret-red to purple or even grey. The original plasmon absorption of Au nanoparticles at 522 nm decreases, and simultaneously, a new absorption band appears at 675 nm. The irreversible inhibition of organophosphorus pesticides on acetylcholinesterase prevents aggregation of Au nanoparticles. Under optimum conditions, the absorbance at 522 nm of Au nanoparticles is related linearly to the concentration of mathamidophos in the range of 0.02-1.42 mug/mL with a detection limit of 1.40 ng/mL. This colorimetric method has been successfully utilized to detect mathamidophos in vegetables with satisfactory results. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for the analysis of organophosphorus pesticides. Title: In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain Liu Q, Shao X, Chen J, Shen Y, Feng C, Gao X, Zhao Y, Li J, Zhang Q, Jiang X Ref: Toxicol Appl Pharmacol, 251:79, 2011 : PubMed ESTHER: Liu_2011_Toxicol.Appl.Pharmacol_251_79 PubMedSearch: Liu 2011 Toxicol.Appl.Pharmacol 251 79 PubMedID: 21163285 Abstract Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-alpha level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain. Title: Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase Shen LL, Liu H, Peng J, Gan L, Lu L, Zhang Q, Li L, He F, Jiang Y Ref: Mol Biol Rep, 38:553, 2011 : PubMed ESTHER: Shen_2011_Mol.Biol.Rep_38_553 PubMedSearch: Shen 2011 Mol.Biol.Rep 38 553 PubMedID: 20373033 Abstract The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid. Title: [Correlation research of isolated liver tissue pathology and clinical diagnosis in patients with chronic severe hepatitis B] Sun J, Yu HW, Liu Z, Liu H, Zhang Q, Yao QW, Feng YM, Li J, Meng QH Ref: Zhonghua Gan Zang Bing Za Zhi, 19:603, 2011 : PubMed ESTHER: Sun_2011_Zhonghua.Gan.Zang.Bing.Za.Zhi_19_603 PubMedSearch: Sun 2011 Zhonghua.Gan.Zang.Bing.Za.Zhi 19 603 PubMedID: 22152318 Abstract To study the coincidence rate of clinical diagonisis with pathological diagnosis for chronic severe hepatitis, and to screen out clinical indicators consistent with pathological diagnosis. Fifty-one patients diagnosed as chronic severe hepatitis and underwent liver transplantation in Beijing You'an hospital from November 2004 to June 2009 participated in this study. The clinical data were selected as following: ALT, AST, urea nitrogen, creatinine, glucose, cholinesterase, total cholesterol, Glutamyl endopeptidase, alkaline phosphatase, serum potassium, serum sodium, prothrombin activity and blood ammonia level. The width of the portal vein and splenic vein thickness were measured by color Doppler ultrasound and were compared in different groups. Data were ananlyzed with independent sample t test and F test. The coincidence rate between clinical and pathological diagnoses in this study was 64.7%. ALT and AST levels for Chronic severe hepatitis and decompensated cirrhosis were 675.0+/-510.0 U/L, 67.00+/-45.0 U/L ( P is less than to 0.01) and 392.0 +/-370.0 U/L, 103.0+/-59.0 U/L (P is less than to 0.01) respectively, with statistically significant difference existed. The mean level of ALT in Chronic severe hepatitis group was significantly different in the situations of onset less than 30 days or more than 30 days (means were 761.0+/-743.0 U/L and 117.0+/-112.0 U/L, P is less than to 0.01). The rate of the phenomenon of enzyme isolated bile in the chronic severe hepatitis and decompensated cirrhosis group were 78.9% and 0 respectively. The coincidence rate of clinical with pathological diagnoses for Chronic Severe Hepatitis was low, increased ALT and AST levels would help improve the diagnostic accuracy. Title: Genome sequencing reveals unique mutations in characteristic metabolic pathways and the transfer of virulence genes between V. mimicus and V. cholerae Wang D, Wang H, Zhou Y, Zhang Q, Zhang F, Du P, Wang S, Chen C, Kan B Ref: PLoS ONE, 6:e21299, 2011 : PubMed ESTHER: Wang_2011_PLoS.ONE_6_E21299 PubMedSearch: Wang 2011 PLoS.ONE 6 E21299 PubMedID: 21731695 Gene_locus related to this paper: vibmi-d0gt41, vibmi-u4zh77, vibmi-g0sil5 Abstract Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes. Title: Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M and Yu Z <1 more author(s)> He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M, Wang S, Yu Z (- 1) Ref: Journal of Bacteriology, 192:4074, 2010 : PubMed ESTHER: He_2010_J.Bacteriol_192_4074 PubMedSearch: He 2010 J.Bacteriol 192 4074 PubMedID: 20525827 Gene_locus related to this paper: bacan-BA3703, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1677, bacce-BC1788, bacce-BC2141, bacce-BC2171, bacce-BC2456, bacce-BC2458, bacce-BC3133, bacce-BC4102, bacce-BC4854, bacce-BC4862, bacce-BC5130, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: Discovery of novel alpha7 nicotinic receptor antagonists Peng Y, Zhang Q, Snyder GL, Zhu H, Yao W, Tomesch J, Papke RL, O'Callaghan JP, Welsh WJ, Wennogle LP Ref: Bioorganic & Medicinal Chemistry Lett, 20:4825, 2010 : PubMed ESTHER: Peng_2010_Bioorg.Med.Chem.Lett_20_4825 PubMedSearch: Peng 2010 Bioorg.Med.Chem.Lett 20 4825 PubMedID: 20638843 Abstract Two distinct families of small molecules were discovered as novel alpha7 nicotinic acetylcholine receptor (nAChR) antagonists by pharmacophore-based virtual screening. These novel antagonists exhibited selectivity for the neuronal alpha7 subtype over other nAChRs and good brain penetration. Neuroprotection was demonstrated by representative compounds 7i and 8 in a mouse seizure-like behavior model induced by the nerve agent diisopropylfluorophosphate (DFP). These novel nAChR antagonists have potential use as antidote for organophosphorus nerve agent intoxication. Title: Enantioselective interaction with acetylcholinesterase of an organophosphate insecticide fenamiphos Wang C, Zhang N, Li L, Zhang Q, Zhao M, Liu W Ref: Chirality, 22:612, 2010 : PubMed ESTHER: Wang_2010_Chirality_22_612 PubMedSearch: Wang 2010 Chirality 22 612 PubMedID: 19899158 Inhibitor(s) related to this paper: Fenamiphos Abstract Enantioselectivity in the environmental behavior and ecotoxicity of chiral pesticide is widely observed. However, the investigation of the enantioselective mechanisms remains limited. In this study, we used fenamiphos (FAP), an organophosphorus insecticide, to study enantioselectivity in toxicity to arthropods and the inhibition potential towards acetylcholinesterase (AChE) in the rat pheochromocytoma 12 (PC 12) cell line. Furthermore, we carried out molecular docking to help explain the mechanisms of enantioselective toxicity of FAP. The two enantiomers of FAP were successfully separated and identified as R-(+)-FAP and S-(-)-FAP. Toxicological assays revealed that R-(+)-FAP was 2.4-fold more toxic than S-(-)-FAP to Daphnia magna and approximately threefold more to PC12 cells. Based on molecular docking results, dynamic simulation shows that strong hydrophobic interactions and a key hydrogen bond can only exist between R-(+)-FAP and AChE, which helps explain the preference of R-(+) binding to AChE over that of the S-(-)-enantiomer, and supports our biological results. Our present study considers the impact of stereochemistry on ecotoxicological effects and, ultimately, on development of environmentally safe, insecticidally efficient pesticides. Title: Nerve agent exposure elicits site-specific changes in protein phosphorylation in mouse brain Zhu H, O'Brien JJ, O'Callaghan JP, Miller DB, Zhang Q, Rana M, Tsui T, Peng Y, Tomesch J and Snyder GL <2 more author(s)> Zhu H, O'Brien JJ, O'Callaghan JP, Miller DB, Zhang Q, Rana M, Tsui T, Peng Y, Tomesch J, Hendrick JP, Wennogle LP, Snyder GL (- 2) Ref: Brain Research, 1342:11, 2010 : PubMed ESTHER: Zhu_2010_Brain.Res_1342_11 PubMedSearch: Zhu 2010 Brain.Res 1342 11 PubMedID: 20423708 Abstract Organophosphorus (OP) compounds cause toxic symptoms, including convulsions, coma, and death, as the result of irreversible inhibition of acetylcholinesterase (AChE). The development of effective treatments to block these effects and attenuate long-term cognitive and motor disabilities that result from OP intoxication is hampered by a limited understanding of the CNS pathways responsible for these actions. We employed a candidate method (called CNSProfile) to identify changes in the phosphorylation state of key neuronal phosphoproteins evoked by the OP compound, diisopropyl fluorophosphate (DFP). Focused microwave fixation was used to preserve the phosphorylation state of phosphoproteins in brains of DFP-treated mice; hippocampus and striatum were analyzed by immunoblotting with a panel of phospho-specific antibodies. DFP exposure elicited comparable effects on phosphorylation of brain phosphoproteins in both C57BL/6 and FVB mice. DFP treatment significantly altered phosphorylation at regulatory residues on glutamate receptors, including Serine897 (S897) of the NR1 NMDA receptor. NR1 phosphorylation was bi-directionally regulated after DFP in striatum versus hippocampus. NR1 phosphorylation was reduced in striatum, but elevated in hippocampus, compared with controls. DARPP-32 phosphorylation in striatum was selectively increased at the Cdk5 kinase substrate, Threonine75 (T75). Phencynonate hydrochloride, a muscarinic cholinergic antagonist, prevented seizure-like behaviors and the observed changes in phosphorylation induced by DFP. The data reveal region-specific effects of nerve agent exposure on intracellular signaling pathways that correlate with seizure-like behavior and which are reversed by the muscarinic receptor blockade. This approach identifies specific targets for nerve agents, including substrates for Cdk5 kinase, which may be the basis for new anti-convulsant therapies. Title: Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi Akiyoshi DE, Morrison HG, Lei S, Feng X, Zhang Q, Corradi N, Mayanja H, Tumwine JK, Keeling PJ and Tzipori S <1 more author(s)> Akiyoshi DE, Morrison HG, Lei S, Feng X, Zhang Q, Corradi N, Mayanja H, Tumwine JK, Keeling PJ, Weiss LM, Tzipori S (- 1) Ref: PLoS Pathog, 5:e1000261, 2009 : PubMed ESTHER: Akiyoshi_2009_PLoS.Pathog_5_E1000261 PubMedSearch: Akiyoshi 2009 PLoS.Pathog 5 E1000261 PubMedID: 19132089 Gene_locus related to this paper: entbh-b7xjm2 Abstract Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence. Title: Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in Pichia pastoris Gao Z, Bai G, Chen J, Zhang Q, Pan P, Bai F, Geng P Ref: Biosci Biotechnol Biochem, 73:688, 2009 : PubMed ESTHER: Gao_2009_Biosci.Biotechnol.Biochem_73_688 PubMedSearch: Gao 2009 Biosci.Biotechnol.Biochem 73 688 PubMedID: 19270384 Abstract Glucagon-like peptide-1 (GLP-1) has considerable potential as a possible therapeutic agent for type-2 diabetes. Unfortunately, this glucoincretin is short lived due to degradation by dipeptidyl-peptidase IV and rapid clearance by renal filtration. In this study, we attempted to extend GLP-1 action through the attachment of a lysine residue at the N-terminal of GLP-1 (named KGLP-1), and to make a fusion protein with human serum albumin (HSA) in Pichia pastoris. The protein, designated KGLP-1/HSA, was purified by an immunomagnetic separation technique. High performance liquid chromatography (HPLC) showed that the purified protein had an overall purity of 92.0%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the expected molecular mass of 70,297.8 Da. Additionally, the N-terminal sequence of KGLP-1/HSA was confirmed by N-terminal sequencing. The stability and biological activity of KGLP-1/HSA were then evaluated in vitro and in vivo. The findings indicated that fusion KGLP-1/HSA preserved the action of native GLP-1, and the active duration was greatly prolonged. Title: Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications Liao R, Duan L, Lei C, Pan H, Ding Y, Zhang Q, Chen D, Shen B, Yu Y, Liu W Ref: Chemical Biology, 16:141, 2009 : PubMed ESTHER: Liao_2009_Chem.Biol_16_141 PubMedSearch: Liao 2009 Chem.Biol 16 141 PubMedID: 19246004 Gene_locus related to this paper: 9acto-c0jrv0, 9acto-c0jrv6, strlu-c0jry1, 9actn-c0jrw3, strlu-c0l0l7 Abstract Thiopeptides, with potent activity against various drug-resistant pathogens, contain a characteristic macrocyclic core consisting of multiple thiazoles, dehydroamino acids, and a 6-membered nitrogen heterocycle. Their biosynthetic pathways remain elusive, in spite of great efforts by in vivo feeding experiments. Here, cloning, sequencing, and characterization of the thiostrepton and siomycin A gene clusters unveiled a biosynthetic paradigm for the thiopeptide specific core formation, featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. The paradigm generality for thiopeptide biosynthesis was supported by genome mining and ultimate confirmation of the thiocillin I production in Bacillus cereus ATCC 14579, a strain that was previously unknown as a thiopeptide producer. These findings set the stage to accelerate the discovery of thiopeptides by prediction at the genetic level and to generate structural diversity by applying combinatorial biosynthesis methods. Title: Invasive mechanism and management strategy of Bemisia tabaci (Gennadius) biotype B: progress report of 973 Program on invasive alien species in China Wan F, Zhang G, Liu S, Luo C, Chu D, Zhang Y, Zang L, Jiu M, Lu Z and Lei Z <6 more author(s)> Wan F, Zhang G, Liu S, Luo C, Chu D, Zhang Y, Zang L, Jiu M, Lu Z, Cui X, Zhang L, Zhang F, Zhang Q, Liu W, Liang P, Lei Z (- 6) Ref: Sci China C Life Sciences, 52:88, 2009 : PubMed ESTHER: Wan_2009_Sci.China.C.Life.Sci_52_88 PubMedSearch: Wan 2009 Sci.China.C.Life.Sci 52 88 PubMedID: 19152088 Abstract Bemisia tabaci (Gennadius) biotype B, called a "superbug", is one of the most harmful biotypes of this species complex worldwide. In this report, the invasive mechanism and management of B. tabaci biotype B, based on our 5-year studies, are presented. Six B. tabaci biotypes, B, Q, ZHJ1, ZHJ2, ZHJ3 and FJ1, have been identified in China. Biotype B dominates the other biotypes in many regions of the country. Genetic diversity in biotype B might be induced by host plant, geographical conditions, and/or insecticidal application. The activities of CarE (carboxylesterase) and GSTs (glutathione-S-transferase) in biotype B reared on cucumber and squash were greater than on other host plants, which might have increased its resistance to insecticides. The higher activities of detoxification enzymes in biotype B might be induced by the secondary metabolites in host plants. Higher adaptive ability of biotype B adults to adverse conditions might be linked to the expression of heat shock protein genes. The indigenous B. tabaci biotypes were displaced by the biotype B within 225 d. The asymmetric mating interactions and mutualism between biotype B and begomoviruses via its host plants speed up widespread invasion and displacement of other biotypes. B. tabaci biotype B displaced Trialeurodes vaporariorum (Westwood) after 4-7 generations under glasshouse conditions. Greater adaptive ability of the biotype B to adverse conditions and its rapid population increase might be the reasons of its successful displacement of T. vaporariorum. Greater ability of the biotype B to switch to different host plants may enrich its host plants, which might enable it to better compete with T. vaporariorum. Native predatory natural enemies possess greater ability to suppress B. tabaci under field conditions. The kairomones in the 3rd and 4th instars of biotype B may provide an important stimulus in host searching and location by its parasitoids. The present results provide useful information in explaining the mechanisms of genetic diversity, evolution and molecular eco-adaptation of biotype B. Furthermore, it provides a base for sustainable management of B. tabaci using biological and ecological measures. Title: Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework Yu Y, Duan L, Zhang Q, Liao R, Ding Y, Pan H, Wendt-Pienkowski E, Tang G, Shen B, Liu W Ref: ACS Chemical Biology, 4:855, 2009 : PubMed ESTHER: Yu_2009_ACS.Chem.Biol_4_855 PubMedSearch: Yu 2009 ACS.Chem.Biol 4 855 PubMedID: 19678698 Gene_locus related to this paper: stras-c6fx50 Abstract Nosiheptide (NOS), belonging to the e series of thiopeptide antibiotics that exhibit potent activity against various bacterial pathogens, bears a unique indole side ring system and regiospecific hydroxyl groups on the characteristic macrocyclic core. Here, cloning, sequencing, and characterization of the nos gene cluster from Streptomyces actuosus ATCC 25421 as a model for this series of thiopeptides has unveiled new insights into their biosynthesis. Bioinformatics-based sequence analysis and in vivo investigation into the gene functions show that NOS biosynthesis shares a common strategy with recently characterized b or c series thiopeptides for forming the characteristic macrocyclic core, which features a ribosomally synthesized precursor peptide with conserved posttranslational modifications. However, it apparently proceeds via a different route for tailoring the thiopeptide framework, allowing the final product to exhibit the distinct structural characteristics of e series thiopeptides, such as the indole side ring system. Chemical complementation supports the notion that the S-adenosylmethionine-dependent protein NosL may play a central role in converting tryptophan to the key 3-methylindole moiety by an unusual carbon side chain rearrangement, most likely via a radical-initiated mechanism. Characterization of the indole side ring-opened analogue of NOS from the nosN mutant strain is consistent with the proposed methyltransferase activity of its encoded protein, shedding light into the timing of the individual steps for indole side ring biosynthesis. These results also suggest the feasibility of engineering novel thiopeptides for drug discovery by manipulating the NOS biosynthetic machinery. Title: The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation Zhang Q, Liang C, Yu YA, Chen N, Dandekar T, Szalay AA Ref: Mol Genet Genomics, 282:417, 2009 : PubMed ESTHER: Zhang_2009_Mol.Genet.Genomics_282_417 PubMedSearch: Zhang 2009 Mol.Genet.Genomics 282 417 PubMedID: 19701652 Gene_locus related to this paper: cowvi-M5L Abstract As a new anticancer treatment option, vaccinia virus (VACV) has shown remarkable antitumor activities (oncolysis) in preclinical studies, but potential infection of other organs remains a safety concern. We present here genome comparisons between the de novo sequence of GLV-1h68, a recombinant VACV, and other VACVs. The identified differences in open reading frames (ORFs) include genes encoding host-range selection, virulence and immune modulation proteins, e.g., ankyrin-like proteins, serine proteinase inhibitor SPI-2/CrmA, tumor necrosis factor (TNF) receptor homolog CrmC, semaphorin-like and interleukin-1 receptor homolog proteins. Phylogenetic analyses indicate that GLV-1h68 is closest to Lister strains but has lost several ORFs present in its parental LIVP strain, including genes encoding CrmE and a viral Golgi anti-apoptotic protein, v-GAAP. The reduced pathogenicity of GLV-1h68 is confirmed in male mice bearing C6 rat glioma and in immunocompetent mice bearing B16-F10 murine melanoma. The contribution of foreign gene expression cassettes in the F14.5L, J2R and A56R loci is analyzed, in particular the contribution of F14.5L inactivation to the reduced virulence is demonstrated by comparing the virulence of GLV-1h68 with its F14.5L-null and revertant viruses. GLV-1h68 is a promising engineered VACV variant for anticancer therapy with tumor-specific replication, reduced pathogenicity and benign tissue tropism. Title: Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics Fang J, Zhang Y, Huang L, Jia X, Zhang Q, Zhang X, Tang G, Liu W Ref: Journal of Bacteriology, 190:6014, 2008 : PubMed ESTHER: Fang_2008_J.Bacteriol_190_6014 PubMedSearch: Fang 2008 J.Bacteriol 190 6014 PubMedID: 18586939 Gene_locus related to this paper: micch-b5l6l6 Abstract Tetrocarcin A (TCA), produced by Micromonospora chalcea NRRL 11289, is a spirotetronate antibiotic with potent antitumor activity and versatile modes of action. In this study, the biosynthetic gene cluster of TCA was cloned and localized to a 108-kb contiguous DNA region. In silico sequence analysis revealed 36 putative genes that constitute this cluster (including 11 for unusual sugar biosynthesis, 13 for aglycone formation, and 4 for glycosylations) and allowed us to propose the biosynthetic pathway of TCA. The formation of D-tetronitrose, L-amicetose, and L-digitoxose may begin with D-glucose-1-phosphate, share early enzymatic steps, and branch into different pathways by competitive actions of specific enzymes. Tetronolide biosynthesis involves the incorporation of a 3-C unit with a polyketide intermediate to form the characteristic spirotetronate moiety and trans-decalin system. Further substitution of tetronolide with five deoxysugars (one being a deoxynitrosugar) was likely due to the activities of four glycosyltransferases. In vitro characterization of the first enzymatic step by utilization of 1,3-biphosphoglycerate as the substrate and in vivo cross-complementation of the bifunctional fused gene tcaD3 (with the functions of chlD3 and chlD4) to Delta chlD3 and Delta chlD4 in chlorothricin biosynthesis supported the highly conserved tetronate biosynthetic strategy in the spirotetronate family. Deletion of a large DNA fragment encoding polyketide synthases resulted in a non-TCA-producing strain, providing a clear background for the identification of novel analogs. These findings provide insights into spirotetronate biosynthesis and demonstrate that combinatorial-biosynthesis methods can be applied to the TCA biosynthetic machinery to generate structural diversity. Title: Influences of Cu or Cd on the neurotoxicity induced by petroleum hydrocarbons in ragworm Perinereis aibuhitensis Zhang Q, Zhou Q, Wang J, Sun S, Hua T, Ren L Ref: J Environ Sci (China), 20:364, 2008 : PubMed ESTHER: Zhang_2008_J.Environ.Sci.(China)_20_364 PubMedSearch: Zhang 2008 J.Environ.Sci.(China) 20 364 PubMedID: 18595406 Abstract The ecotoxicological effects of heavy metals and petroleum hydrocarbons (PHCs) on ragworms are still vague. The relationships between toxicological indices (mortality and acetylcholinesterase (AChE) activity) and concentrations of toxicants (Cu, Cd, and PHCs) were examined in the estuary keystone species Perinereis aibuhitensis in laboratory conditions. The results of single toxicant indicated that three toxicants had potentially physiological toxicity to P. aibuhitensis. The estimated 4-d and 10-d LC50 for Cu, Cd, and PHCs was derived from the relationships between mortality and toxicants concentrations. Notable changes in the morphological signs and symptoms of P. aibuhitensis exposed to PHCs were observed. The AChE activity of P. aibuhitensis was more sensitive to the toxicity of PHCs than the others. The results of combined toxicants implied that the combined toxicity of Cu or Cd and PHCs to P. aibuhitensis was related to the concentration combination of toxicants. Compared to single PHCs treatment, the addition of Cu or Cd significantly mitigated the neurotoxicity of PHCs to AChE activity in P. aibuhitensis, which showed an antagonistic effect. Title: One-step purification of a fusion protein of glucagon-like peptide-1 and human serum albumin expressed in pichia pastoris by an immunomagnetic separation technique Chen J, Bai G, Cao Y, Gao Z, Zhang Q, Zhu Y, Yang W Ref: Biosci Biotechnol Biochem, 71:2655, 2007 : PubMed ESTHER: Chen_2007_Biosci.Biotechnol.Biochem_71_2655 PubMedSearch: Chen 2007 Biosci.Biotechnol.Biochem 71 2655 PubMedID: 17986790 Abstract Glucagon-like peptide-1 (GLP-1) has great therapeutic potential to treat diabetes type 2, mainly due to its unique glucose-dependent stimulation of insulin secretion profiles, but its clinical application is limited by its short half-life in vivo, which resultes from degradation by dipeptidyl peptidase IV and/or renal clearance. Developing long-acting GLP-1 analogs is therefore an important step toward using them therapeutically. In this study, the GLP-1/human serum albumin (HSA) fusion protein gene was cloned into the secretor type expression vector pPIC9K and subsequently expressed in Pichia pastoris. The expression quantity reached 58.5 mg/l in small-scale incubation. After optimization and characterization, the GLP-1/HSA fusion protein was successfully purified from the supernatant of the broth using immunomagnetic cellulose microspheres. HPLC showed that the purified GLP-1/HSA had an overall purity of 93.9%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the fusion protein exhibited the expected molecular mass of 70 kDa. Furthermore, that analysis of in vivo activity indicated that GLP-1/HSA reduced the blood glucose level after intraperitoneal administration to Chinese Kunming mice in a dose-dependent manner, and the effects held significantly 4 h after administration. Overall, this study illustrates the development of a long-acting GLP-1/HSA fusion protein expressed in Pichia pastoris. Title: Pancreatic lipase-inhibiting triterpenoid saponins from fruits of Acanthopanax senticosus Li F, Li W, Fu H, Zhang Q, Koike K Ref: Chem Pharm Bull (Tokyo), 55:1087, 2007 : PubMed ESTHER: Li_2007_Chem.Pharm.Bull.(Tokyo)_55_1087 PubMedSearch: Li 2007 Chem.Pharm.Bull.(Tokyo) 55 1087 PubMedID: 17603209 Abstract Sixteen triterpenoid saponins were isolated from the fruits of Acanthopanax senticosus, including a new compound, acanthopanaxoside E (1), which was established as 3-O-beta-D-glucuronopyranosyl echinocystic acid 28-O-beta-D-glucopyranoside on the basis of various spectroscopic analyses and chemical degradation. By using a pancreatic lipase-inhibiting assay system, the crude saponin fraction showed inhibitory activity on pancreatic lipase, which is a key enzyme in lipid digestion. Among the isolated compounds, silphioside F (2), copteroside B (3), hederagenin 3-O-beta-D-glucuronopyranoside 6'-O-methyl ester (4) and gypsogenin 3-O-beta-D-glucuronopyranoside (5) showed inhibitory activity toward pancreatic lipase with IC(50) values of 0.22, 0.25, 0.26 and 0.29 mM, respectively, and the free carboxylic acid groups in position 28 within their chemical structures were required for enhancement of pancreatic lipase inhibition. Title: Response to pioglitazone treatment is associated with the lipoprotein lipase S447X variant in subjects with type 2 diabetes mellitus Wang G, Wang X, Zhang Q, Ma Z Ref: Int J Clin Pract, 61:552, 2007 : PubMed ESTHER: Wang_2007_Int.J.Clin.Pract_61_552 PubMedSearch: Wang 2007 Int.J.Clin.Pract 61 552 PubMedID: 17394430 Abstract To investigate the influence of the S447X variant in lipoprotein lipase (LPL) gene on the response rate to therapy with the thiazolidinedione pioglitazone. A total of 113 diabetic patients were treated with pioglitazone 30 mg for 10 weeks. Response to the pioglitazone treatment was defined by either a >10% relative reduction in fasting blood glucose (FBG) or a more than 1% decrease in glycosylated haemoglobin (HbA1c) values after 10 weeks of pioglitazone treatment. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method. Using the criteria >10% relative reduction in FBG after 10 weeks of pioglitaone treatment, responder frequency to pioglitazone treatment in S447S genotype group is significantly higher than S447X genotype group. Meanwhile, the S447X genotype conferred a statistically significant 0.538-fold reduction in response rate to pioglitazone treatment relative to the S447S genotype. Moreover, pioglitazone treatment has significantly beneficial effects on serum lipid profile and blood pressure in S447S genotype carriers. The S447X variant in LPL gene may be a cause for therapy modification by pioglitazone. Title: Effect of surface hydrophobicity/hydrophilicity of mesoporous supports on the activity of immobilized lipase He J, Xu Y, Ma H, Zhang Q, Evans DG, Duan X Ref: J Colloid Interface Sci, 298:780, 2006 : PubMed ESTHER: He_2006_J.Colloid.Interface.Sci_298_780 PubMedSearch: He 2006 J.Colloid.Interface.Sci 298 780 PubMedID: 16430912 Abstract Taking advantage of the virtue of hydrophilic surface, lipase was firstly immobilized on SBA-15 as a support. Then the surface of the SBA-15 with enzyme entrapped inside the channels was modified by grafting with organic moieties. It has been found that the silylation with n-decyltrimethoxysilane (DE) and 3-(trimethoxysilyl)propyl methacrylate (MA) following the lipase immobilization increases the surface hydrophobicity. But the surface modified by MA shows more hydrophilicity than that modified by DE. The activity assay indicates that the hydrolytic activity for the hydrolysis of insoluble or partly soluble substrates increases with enhanced surface hydrophobicity. Title: Design, synthesis, and biological evaluation of new territrem B analogues Jiang X, Ao L, Zhou C, Yang L, Zhang Q, Li H, Sun L, Wu X, Bai H, Zhao Y Ref: Chem Biodivers, 2:557, 2005 : PubMed ESTHER: Jiang_2005_Chem.Biodivers_2_557 PubMedSearch: Jiang 2005 Chem.Biodivers 2 557 PubMedID: 17192004 Abstract Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined. Title: The complete genome sequence of Mycobacterium avium subspecies paratuberculosis Li L, Bannantine JP, Zhang Q, Amonsin A, May BJ, Alt D, Banerji N, Kanjilal S, Kapur V Ref: Proc Natl Acad Sci U S A, 102:12344, 2005 : PubMed ESTHER: Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_12344 PubMedSearch: Li 2005 Proc.Natl.Acad.Sci.U.S.A 102 12344 PubMedID: 16116077 Gene_locus related to this paper: mycpa-q73tc9, mycpa-q73vt9, mycpa-q73xs5, mycpa-q741s1 Abstract We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease. Title: [Impact of aldicarb and its complex pollution on DNA of zebrafish embryo] Li Y, Zhang Q, Dai S Ref: Ying Yong Sheng Tai Xue Bao, 14:982, 2003 : PubMed ESTHER: Li_2003_Ying.Yong.Sheng.Tai.Xue.Bao_14_982 PubMedSearch: Li 2003 Ying.Yong.Sheng.Tai.Xue.Bao 14 982 PubMedID: 12974010 Abstract This paper deals with the impact of a complex pollution system composed of a very toxic carbamate pesticide, aldicarb and the widely used anionic surfactant, sodium dodecylbenzenesulfonate(SDBS), on DNA of zebrafish (Brachydanio rerio) embryo. The results indicated that DNA damage caused by aldicarb became more serious with its increasing concentration, but single-strand break caused by aldicarb in low concentration and short time could be repaired, and high concentration led to double-strand break which was difficult to repaire. SDBS in certain concentration (20 mg.L-1) could reduce the toxicity of aldicarb in the complex pollution system. Title: The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis Salnikow K, Davidson T, Zhang Q, Chen LC, Su W, Costa M Ref: Cancer Research, 63:3524, 2003 : PubMed ESTHER: Salnikow_2003_Cancer.Res_63_3524 PubMedSearch: Salnikow 2003 Cancer.Res 63 3524 PubMedID: 12839937 Abstract Nickel is a potent environmental pollutant in industrial countries. Because nickel compounds are carcinogenic, exposure to nickel represents a serious hazard to human health. The understanding of how nickel exerts its toxic and carcinogenic effects at a molecular level may be important in risk assessment, as well as in the treatment and prevention of occupational diseases. Previously, using human and rodent cells in vitro, we showed that hypoxia-inducible signaling pathway was activated by carcinogenic nickel compounds. Acute exposure to nickel resulted in the accumulation of hypoxia-inducible transcription factor (HIF)-1, which strongly activated hypoxia-inducible genes, including the recently discovered tumor marker NDRG1 (Cap43). To further identify HIF-1-dependent nickel-inducible genes and to understand the role of the HIF-dependent signaling pathway in nickel-induced transformation, we used the Affymetrix GeneChip to compare the gene expression profiles in wild-type cells or in cells from HIF-1 alpha knockout mouse embryos exposed to nickel chloride. As expected, when we examined 12,000 genes for expression changes, we found that genes coding for glycolytic enzymes and glucose transporters, known to be regulated by HIF-1 transcription factor, were induced by nickel only in HIF-1 alpha-proficient cells. In addition, we found a number of other hypoxia-inducible genes up-regulated by nickel in a HIF-dependent manner including BCL-2-binding protein Nip3, EGLN1, hypoxia-inducible gene 1 (HIG1), and prolyl 4-hydroxylase. Additionally, we found a number of genes induced by nickel in a HIF-independent manner, suggesting that Ni activated other signaling pathways besides HIF-1. Finally, we found that in HIF-1 alpha knockout cells, nickel strongly induced the expression of the whole group of genes that were not expressed in the presence of HIF-1. Because the majority of modulated genes were induced or suppressed by nickel in a HIF-1-dependent manner, we elucidated the role of HIF-1 transcription factor in cell transformation. In HIF-1 alpha-proficient cells, nickel exposure increased soft agar growth, whereas it decreased soft agar growth in HIF-1 alpha-deficient cells. We hypothesize that the induction of HIF-1 transcription factor by nickel may be important during the nickel-induced carcinogenic process. Title: Schizosaccharomyces pombe cells deficient in triacylglycerols synthesis undergo apoptosis upon entry into the stationary phase. Zhang Q, Chieu HK, Low CP, Zhang S, Heng CK, Yang H Ref: Journal of Biological Chemistry, 278:47145", 2003 : PubMed ESTHER: Zhang_2003_J.Biol.Chem_278_47145 PubMedSearch: Zhang 2003 J.Biol.Chem 278 47145 PubMedID: 12963726 Gene_locus related to this paper: schpo-pdat Abstract Triacylglycerols (TAG) are important energy storage molecules for nearly all eukaryotic organisms. In this study, we found that two gene products (Plh1p and Dga1p) are responsible for the terminal step of TAG synthesis in the fission yeast Schizosaccharomyces pombe through two different mechanisms: Plh1p is a phospholipid diacylglycerol acyltransferase, whereas Dga1p is an acyl-CoA:diacylglycerol acyltransferase. Cells with both dga1+ and plh1+ deleted (DKO cells) lost viability upon entry into the stationary phase and demonstrated prominent apoptotic markers. Exponentially growing DKO cells also underwent dramatic apoptosis when briefly treated with diacylglycerols (DAGs) or free fatty acids. We provide strong evidence suggesting that DAG, not sphingolipids, mediates fatty acids-induced lipoapoptosis in yeast. Lastly, we show that generation of reactive oxygen species is essential to lipoapoptosis. Title: A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG and Stephenson LD <169 more author(s)> Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R, Halpern A, Li PW, Sutton GG, Nadeau J, Salzberg SL, Holt RA, Kodira CD, Lu F, Chen L, Deng Z, Evangelista CC, Gan W, Heiman TJ, Li J, Li Z, Merkulov GV, Milshina NV, Naik AK, Qi R, Shue BC, Wang A, Wang J, Wang X, Yan X, Ye J, Yooseph S, Zhao Q, Zheng L, Zhu SC, Biddick K, Bolanos R, Delcher AL, Dew IM, Fasulo D, Flanigan MJ, Huson DH, Kravitz SA, Miller JR, Mobarry CM, Reinert K, Remington KA, Zhang Q, Zheng XH, Nusskern DR, Lai Z, Lei Y, Zhong W, Yao A, Guan P, Ji RR, Gu Z, Wang ZY, Zhong F, Xiao C, Chiang CC, Yandell M, Wortman JR, Amanatides PG, Hladun SL, Pratts EC, Johnson JE, Dodson KL, Woodford KJ, Evans CA, Gropman B, Rusch DB, Venter E, Wang M, Smith TJ, Houck JT, Tompkins DE, Haynes C, Jacob D, Chin SH, Allen DR, Dahlke CE, Sanders R, Li K, Liu X, Levitsky AA, Majoros WH, Chen Q, Xia AC, Lopez JR, Donnelly MT, Newman MH, Glodek A, Kraft CL, Nodell M, Ali F, An HJ, Baldwin-Pitts D, Beeson KY, Cai S, Carnes M, Carver A, Caulk PM, Center A, Chen YH, Cheng ML, Coyne MD, Crowder M, Danaher S, Davenport LB, Desilets R, Dietz SM, Doup L, Dullaghan P, Ferriera S, Fosler CR, Gire HC, Gluecksmann A, Gocayne JD, Gray J, Hart B, Haynes J, Hoover J, Howland T, Ibegwam C, Jalali M, Johns D, Kline L, Ma DS, MacCawley S, Magoon A, Mann F, May D, McIntosh TC, Mehta S, Moy L, Moy MC, Murphy BJ, Murphy SD, Nelson KA, Nuri Z, Parker KA, Prudhomme AC, Puri VN, Qureshi H, Raley JC, Reardon MS, Regier MA, Rogers YH, Romblad DL, Schutz J, Scott JL, Scott R, Sitter CD, Smallwood M, Sprague AC, Stewart E, Strong RV, Suh E, Sylvester K, Thomas R, Tint NN, Tsonis C, Wang G, Williams MS, Williams SM, Windsor SM, Wolfe K, Wu MM, Zaveri J, Chaturvedi K, Gabrielian AE, Ke Z, Sun J, Subramanian G, Venter JC, Pfannkoch CM, Barnstead M, Stephenson LD (- 169) Ref: Science, 296:1661, 2002 : PubMed ESTHER: Mural_2002_Science_296_1661 PubMedSearch: Mural 2002 Science 296 1661 PubMedID: 12040188 Gene_locus related to this paper: mouse-ABH15, mouse-Ces3b, mouse-Ces4a, mouse-dpp4, mouse-FAP, mouse-Lipg, mouse-Q8C1A9, mouse-rbbp9, mouse-SERHL, mouse-SPG21, mouse-w4vsp6 Abstract The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart. Title: Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks Smoot JC, Barbian KD, Van Gompel JJ, Smoot LM, Chaussee MS, Sylva GL, Sturdevant DE, Ricklefs SM, Porcella SF and Musser JM <8 more author(s)> Smoot JC, Barbian KD, Van Gompel JJ, Smoot LM, Chaussee MS, Sylva GL, Sturdevant DE, Ricklefs SM, Porcella SF, Parkins LD, Beres SB, Campbell DS, Smith TM, Zhang Q, Kapur V, Daly JA, Veasy LG, Musser JM (- 8) Ref: Proc Natl Acad Sci U S A, 99:4668, 2002 : PubMed ESTHER: Smoot_2002_Proc.Natl.Acad.Sci.U.S.A_99_4668 PubMedSearch: Smoot 2002 Proc.Natl.Acad.Sci.U.S.A 99 4668 PubMedID: 11917108 Gene_locus related to this paper: strpy-ESTA, strpy-PEPXP, strpy-SPY1308, strpy-SPYM18.1727, strpy-SPYM18.1957 Abstract Acute rheumatic fever (ARF), a sequelae of group A Streptococcus (GAS) infection, is the most common cause of preventable childhood heart disease worldwide. The molecular basis of ARF and the subsequent rheumatic heart disease are poorly understood. Serotype M18 GAS strains have been associated for decades with ARF outbreaks in the U.S. As a first step toward gaining new insight into ARF pathogenesis, we sequenced the genome of strain MGAS8232, a serotype M18 organism isolated from a patient with ARF. The genome is a circular chromosome of 1,895,017 bp, and it shares 1.7 Mb of closely related genetic material with strain SF370 (a sequenced serotype M1 strain). Strain MGAS8232 has 178 ORFs absent in SF370. Phages, phage-like elements, and insertion sequences are the major sources of variation between the genomes. The genomes of strain MGAS8232 and SF370 encode many of the same proven or putative virulence factors. Importantly, strain MGAS8232 has genes encoding many additional secreted proteins involved in human-GAS interactions, including streptococcal pyrogenic exotoxin A (scarlet fever toxin) and two uncharacterized pyrogenic exotoxin homologues, all phage-associated. DNA microarray analysis of 36 serotype M18 strains from diverse localities showed that most regions of variation were phages or phage-like elements. Two epidemics of ARF occurring 12 years apart in Salt Lake City, UT, were caused by serotype M18 strains that were genetically identical, or nearly so. Our analysis provides a critical foundation for accelerated research into ARF pathogenesis and a molecular framework to study the plasticity of GAS genomes. Title: Complete genomic sequence of Pasteurella multocida, Pm70 May BJ, Zhang Q, Li LL, Paustian ML, Whittam TS, Kapur V Ref: Proc Natl Acad Sci U S A, 98:3460, 2001 : PubMed ESTHER: May_2001_Proc.Natl.Acad.Sci.U.S.A_98_3460 PubMedSearch: May 2001 Proc.Natl.Acad.Sci.U.S.A 98 3460 PubMedID: 11248100 Gene_locus related to this paper: pasmu-KMT1, pasmu-metx, pasmu-PLDB, pasmu-PM0055, pasmu-PM0355, pasmu-PM1358, pasmu-q9cjt9, pasmu-XYNC, pasmu-y825 Abstract We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise comparisons of 1,197 orthologous sequences between P. multocida, Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H. influenzae diverged approximately 270 million years ago and the gamma subdivision of the proteobacteria radiated about 680 million years ago. Two previously undescribed open reading frames, accounting for approximately 1% of the genome, encode large proteins with homology to the virulence-associated filamentous hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron in the survival of many microbial pathogens, in silico and whole-genome microarray analyses identified more than 50 Pm70 genes with a potential role in iron acquisition and metabolism. Overall, the complete genomic sequence and preliminary functional analyses provide a foundation for future research into the mechanisms of pathogenesis and host specificity of this important multispecies pathogen. 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: The genome sequence of Drosophila melanogaster Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA and Venter JC <185 more author(s)> Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, George RA, Lewis SE, Richards S, Ashburner M, Henderson SN, Sutton GG, Wortman JR, Yandell MD, Zhang Q, Chen LX, Brandon RC, Rogers YH, Blazej RG, Champe M, Pfeiffer BD, Wan KH, Doyle C, Baxter EG, Helt G, Nelson CR, Gabor GL, Abril JF, Agbayani A, An HJ, Andrews-Pfannkoch C, Baldwin D, Ballew RM, Basu A, Baxendale J, Bayraktaroglu L, Beasley EM, Beeson KY, Benos PV, Berman BP, Bhandari D, Bolshakov S, Borkova D, Botchan MR, Bouck J, Brokstein P, Brottier P, Burtis KC, Busam DA, Butler H, Cadieu E, Center A, Chandra I, Cherry JM, Cawley S, Dahlke C, Davenport LB, Davies P, de Pablos B, Delcher A, Deng Z, Mays AD, Dew I, Dietz SM, Dodson K, Doup LE, Downes M, Dugan-Rocha S, Dunkov BC, Dunn P, Durbin KJ, Evangelista CC, Ferraz C, Ferriera S, Fleischmann W, Fosler C, Gabrielian AE, Garg NS, Gelbart WM, Glasser K, Glodek A, Gong F, Gorrell JH, Gu Z, Guan P, Harris M, Harris NL, Harvey D, Heiman TJ, Hernandez JR, Houck J, Hostin D, Houston KA, Howland TJ, Wei MH, Ibegwam C, Jalali M, Kalush F, Karpen GH, Ke Z, Kennison JA, Ketchum KA, Kimmel BE, Kodira CD, Kraft C, Kravitz S, Kulp D, Lai Z, Lasko P, Lei Y, Levitsky AA, Li J, Li Z, Liang Y, Lin X, Liu X, Mattei B, McIntosh TC, McLeod MP, McPherson D, Merkulov G, Milshina NV, Mobarry C, Morris J, Moshrefi A, Mount SM, Moy M, Murphy B, Murphy L, Muzny DM, Nelson DL, Nelson DR, Nelson KA, Nixon K, Nusskern DR, Pacleb JM, Palazzolo M, Pittman GS, Pan S, Pollard J, Puri V, Reese MG, Reinert K, Remington K, Saunders RD, Scheeler F, Shen H, Shue BC, Siden-Kiamos I, Simpson M, Skupski MP, Smith T, Spier E, Spradling AC, Stapleton M, Strong R, Sun E, Svirskas R, Tector C, Turner R, Venter E, Wang AH, Wang X, Wang ZY, Wassarman DA, Weinstock GM, Weissenbach J, Williams SM, WoodageT, Worley KC, Wu D, Yang S, Yao QA, Ye J, Yeh RF, Zaveri JS, Zhan M, Zhang G, Zhao Q, Zheng L, Zheng XH, Zhong FN, Zhong W, Zhou X, Zhu S, Zhu X, Smith HO, Gibbs RA, Myers EW, Rubin GM, Venter JC (- 185) Ref: Science, 287:2185, 2000 : PubMed ESTHER: Adams_2000_Science_287_2185 PubMedSearch: Adams 2000 Science 287 2185 PubMedID: 10731132 Gene_locus related to this paper: drome-1vite, drome-2vite, drome-3vite, drome-a1z6g9, drome-abhd2, drome-ACHE, drome-b6idz4, drome-BEM46, drome-CG5707, drome-CG5704, drome-CG1309, drome-CG1882, drome-CG1986, drome-CG2059, drome-CG2493, drome-CG2528, drome-CG2772, drome-CG3160, drome-CG3344, drome-CG3523, drome-CG3524, drome-CG3734, drome-CG3739, drome-CG3744, drome-CG3841, drome-CG4267, drome-CG4382, drome-CG4390, drome-CG4572, drome-CG4582, drome-CG4851, drome-CG4979, drome-CG5068, drome-CG5162, drome-CG5355, drome-CG5377, drome-CG5397, drome-CG5412, drome-CG5665, drome-CG5932, drome-CG5966, drome-CG6018, drome-CG6113, drome-CG6271, drome-CG6283, drome-CG6295, drome-CG6296, drome-CG6414, drome-CG6431, drome-CG6472, drome-CG6567, drome-CG6675, drome-CG6753, drome-CG6847, drome-CG7329, drome-CG7367, drome-CG7529, drome-CG7632, drome-CG8058, drome-CG8093, drome-CG8233, drome-CG8424, drome-CG8425, drome-CG9059, drome-CG9186, drome-CG9287, drome-CG9289, drome-CG9542, drome-CG9858, drome-CG9953, drome-CG9966, drome-CG10116, drome-CG10163, drome-CG10175, drome-CG10339, drome-CG10357, drome-CG10982, drome-CG11034, drome-CG11055, drome-CG11309, drome-CG11319, drome-CG11406, drome-CG11598, drome-CG11600, drome-CG11608, drome-CG11626, drome-CG11935, drome-CG12108, drome-CG12869, drome-CG13282, drome-CG13562, drome-CG13772, drome-CG14034, drome-nlg3, drome-CG14717, drome-CG15101, drome-CG15102, drome-CG15106, drome-CG15111, drome-CG15820, drome-CG15821, drome-CG15879, drome-CG17097, drome-CG17099, drome-CG17101, drome-CG17191, drome-CG17192, drome-CG17292, drome-CG18258, drome-CG18284, drome-CG18301, drome-CG18302, drome-CG18493, drome-CG18530, drome-CG18641, drome-CG18815, drome-CG31089, drome-CG31091, drome-CG32333, drome-CG32483, drome-CG33174, drome-dnlg1, drome-este4, drome-este6, drome-GH02384, drome-GH02439, drome-glita, drome-KRAKEN, drome-lip1, drome-LIP2, drome-lip3, drome-MESK2, drome-nrtac, drome-OME, drome-q7k274, drome-Q9VJN0, drome-Q8IP31, drome-q9vux3 Abstract The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity. Title: A whole-genome assembly of Drosophila Myers EW, Sutton GG, Delcher AL, Dew IM, Fasulo DP, Flanigan MJ, Kravitz SA, Mobarry CM, Reinert KH and Venter JC <19 more author(s)> Myers EW, Sutton GG, Delcher AL, Dew IM, Fasulo DP, Flanigan MJ, Kravitz SA, Mobarry CM, Reinert KH, Remington KA, Anson EL, Bolanos RA, Chou HH, Jordan CM, Halpern AL, Lonardi S, Beasley EM, Brandon RC, Chen L, Dunn PJ, Lai Z, Liang Y, Nusskern DR, Zhan M, Zhang Q, Zheng X, Rubin GM, Adams MD, Venter JC (- 19) Ref: Science, 287:2196, 2000 : PubMed ESTHER: Myers_2000_Science_287_2196 PubMedSearch: Myers 2000 Science 287 2196 PubMedID: 10731133 Abstract We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community. Title: [Experimental study on effect of bushen yijing recipe in delaying senility of bone and brain of aged male rats] Zhang G, Ma J, Zhang Q Ref: Zhongguo Zhong Xi Yi Jie He Za Zhi, 20:43, 2000 : PubMed ESTHER: Zhang_2000_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_20_43 PubMedSearch: Zhang 2000 Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi 20 43 PubMedID: 11783337 Abstract OBJECTIVE To evaluate the effect of Bushen Yijing recipe BSYJR in delaying senility of bone and brain of aged male rats and infer its mechanism in delaying systemic senility METHODS Forty male SD rats 24 months old were randomly divided into 4 groups the baseline control group the aged control group 30 months old the BSYJR high dose group and the BSYJR low dose group The latter two groups received BSYJR treatment from 24 months old to 30 months old Bone indexes bone density of the proximal middle and distal segments of left femur and break bending load of right femur and brain indexes binding capacity of M receptor and cholinesterase activity of brain were measured after responding treatment RESULTS In bone BSYJR could not only increase the bone mineral density in various segments of femur but also raise the bending break load of femur dose-effect dependently In brain BSYJR could both up-regulate the binding capacity of M receptor and inhibit the activity of cholinesterase CONCLUSION BSYJR could delay the senility of bone and brain in male rats inferring that it might regulate integrally the abnormality of aging in Kidney Asthenia and Essence Deficiency through mediation of nerve-endocrine-immunity network Title: Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects Zhang Q, Liu Y, Liu BW, Fan P, Cavanna J, Galton DJ Ref: Mol Genet Metab, 64:177, 1998 : PubMed ESTHER: Zhang_1998_Mol.Genet.Metab_64_177 PubMedSearch: Zhang 1998 Mol.Genet.Metab 64 177 PubMedID: 9719626 Abstract The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted. | |||||||
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