Author Report for: Chen HNo contact information in database for Chen H
Yan X, Chen K, Jia H, Zhao Q, Du G, Guo Q, Chen H, Yuan Y, Yue T Ref: Food Chem, 431:137172, 2024 : PubMed ESTHER: Yan_2024_Food.Chem_431_137172 PubMedSearch: Yan 2024 Food.Chem 431 137172 PubMedID: 37603997 Abstract Patulin (PAT) is a mycotoxin known to globally contaminate fruits. The economic losses and health hazards caused by PAT desires a safe and efficient strategy for detoxifying PAT. Here, a magnetic core-shell hierarchical mesoporous metal-organic framework (Fe(3)O(4)@HMUiO-66-NH(2)) was synthesized via a salt-assisted nanoemulsion guided assembly method. This mesoporous structure (centered at 4.25 nm) allowed porcine pancreatic lipase (PPL) to infiltrate into the MOF shell at an immobilized amount of 255 mg/g, providing protection for PPL and enabling rapid separation and recovery. Compared with free PPL, PPL/Fe(3)O(4)@HMUiO-66-NH(2) at 70 degreesC possessed 4.7 folds improved thermal stability in terms of half-life. The detoxification rates of immobilized enzyme for PAT in neutral water, acidic water, and apple juice were 99.6%, 60.9%, and 52.6%, respectively. Moreover, the so designed PPL/Fe(3)O(4)@HMUiO-66-NH(2) showed extraordinary storage stability, reusability, and biocompatibility. Crucially, the quality of apple juice did not change significantly after PPL/Fe(3)O(4)@HMUiO-66-NH(2) treatment, which facilitated its application in apple juice. The magnetic core-shell mesoporous structure along with the revealed mechanism of immobilized enzyme detoxification of PAT provide tremendous opportunity for designing a safe and efficient PAT detoxification method. Title: Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y and Sang Z <1 more author(s)> Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y, Dong W, Sang Z (- 1) Ref: J Enzyme Inhib Med Chem, 38:2169682, 2023 : PubMed ESTHER: Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682 PubMedSearch: Chen 2023 J.Enzyme.Inhib.Med.Chem 38 2169682 PubMedID: 36688444 Abstract A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The insvitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC(50) values of 1.3 microM and 0.81 microM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1beta and NO. In addition, compound 3f presented significant neuroprotective effect on Abeta(25-35)-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes insvitro and plasma. Furthermore, compound 3f could improve AlCl(3)-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD. Title: Lactobacillus plantarum HF02 alleviates lipid accumulation and intestinal microbiota dysbiosis in high-fat diet-induced obese mice Chen H, Zhao H, Qi X, Sun Y, Li Q, Ma Y Ref: J Sci Food Agric, :, 2023 : PubMed ESTHER: Chen_2023_J.Sci.Food.Agric__ PubMedSearch: Chen 2023 J.Sci.Food.Agric PubMedID: 36866521 Abstract BACKGROUND: Obesity is closely associated with lipid accumulation and intestinal microbiota dysbiosis. It has been proved that probiotics supplement contributes to alleviate obesity. The objective of this study was to investigate the mechanism by which Lactobacillus plantarum HF02 (LP-HF02) alleviated lipid accumulation and intestinal microbiota dysbiosis in high-fat diet (HFD)-induced obese mice. RESULTS: Our results showed that LP-HF02 ameliorated body weight, dyslipidemia, liver lipid accumulation, and liver injury in obese mice. As expected, LP-HF02 inhibited pancreatic lipase activity in small intestinal contents and increased fecal triglyceride levels, thereby reducing dietary fat hydrolysis and absorption. Moreover, LP-HF02 ameliorated the intestinal microbiota composition, as evidenced by enhanced the ratio of Bacteroides to Firmicutes, decreased the abundance of pathogenic bacteria (including Bacteroides, Alistipes, Blautia, and Colidextribacter) and increased the abundance of beneficial bacteria (including Muribaculaceae, Akkermansia, Faecalibaculum, and Rikenellaceae_RC9_gut_group). LP-HF02 also increased fecal short-chain fatty acids (SCFAs) levels and colonic mucosal thickness, and subsequently decreased serum lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) levels in obese mice. Additionally, RT-qPCR and western blot results demonstrated that LP-HF02 ameliorated hepatic lipid accumulation via activating the AMP-activated protein kinase (AMPK) pathway. CONCLUSION: Therefore, our results indicated that LP-HF02 could be considered as a probiotic preparation for preventing obesity. This article is protected by copyright. All rights reserved. Title: Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent alpha-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-gamma Agonistic Activities Chen H, Zhang WJ, Kong JB, Liu Y, Zhi YL, Cao YG, Du K, Xue GM, Li M and Xie ZS <3 more author(s)> Chen H, Zhang WJ, Kong JB, Liu Y, Zhi YL, Cao YG, Du K, Xue GM, Li M, Zhao ZZ, Sun YJ, Feng WS, Xie ZS (- 3) Ref: Journal of Agricultural and Food Chemistry, 71:11080, 2023 : PubMed ESTHER: Chen_2023_J.Agric.Food.Chem_71_11080 PubMedSearch: Chen 2023 J.Agric.Food.Chem 71 11080 PubMedID: 37462007 Abstract A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against alpha-glucosidase with IC(50) of 1.11-33.53 microM, 5-150 times stronger than acarbose (IC(50) = 169.78 microM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-gamma), with EC(50) values of 10.09-44.26 microM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC(50) value of 47.13 microM. Furthermore, the banding manner of compounds 14 and 17 with the active site of alpha-glucosidase, DPPIV, and PPAR-gamma was explored by employing molecular docking analysis. Title: Design of a near-infrared fluoro-photoacoustic probe for rapid imaging of carboxylesterase in liver injury Chen H, Li K, Yuan L, Zhang XB Ref: Chem Commun (Camb), 59:10520, 2023 : PubMed ESTHER: Chen_2023_Chem.Commun.(Camb)_59_10520 PubMedSearch: Chen 2023 Chem.Commun.(Camb) 59 10520 PubMedID: 37644758 Abstract Carboxylesterase (CE) is crucial in metabolizing ester-containing biomolecules and is particularly significant in liver metabolic diseases. Herein, we present the first activatable NIRF/PA dual-mode imaging probe QHD-CE for detection of CE in vitro and in vivo. QHD-CE displays excellent sensitivity and selectivity for CE with a high reaction efficiency (-90 min). By utilizing QHD-CE, the dynamic changes of CE in drug-induced liver injury and diabetic mice models were monitored. Title: Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients Liu J, Shao T, Chen H, Ma C, Lu X, Yang X, Song K, Wang L, Lei S, Wang D Ref: Front Med (Lausanne), 10:1175089, 2023 : PubMed ESTHER: Liu_2023_Front.Med.(Lausanne)_10_1175089 PubMedSearch: Liu 2023 Front.Med.(Lausanne) 10 1175089 PubMedID: 37502364 Abstract AIM: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. METHOD: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. RESULTS: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p<0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p<0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO(2) before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO(2) (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p=0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p<0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p<0.01). CONCLUSION: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO(2) were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients. Title: Comparing Longitudinal Measures of Cholinesterase as Biomarkers for Insecticide Exposure Among Latinx Children in Rural Farmworker and Urban Non-Farmworker Communities in North Carolina Quandt SA, Smith SA, Arcury TA, Chen H, Hester K, Pope CN, Anderson KA, Laurienti PJ Ref: J Occup Environ Med, :, 2023 : PubMed ESTHER: Quandt_2023_J.Occup.Environ.Med__ PubMedSearch: Quandt 2023 J.Occup.Environ.Med PubMedID: 37696813 Abstract OBJECTIVE: In a two-group prospective design, this study compares seasonal cholinesterase levels of Latinx children in rural farmworker families and comparable urban children, to assess the impact of environmental exposure to cholinesterase-inhibiting insecticides. METHODS: Quarterly blood samples and passive dosimeter wristbands were collected over 2 years in 8 year old children (74 rural, 62 urban). Laboratory analysis assessed total cholinesterase (total ChE), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) from blood samples, and insecticides from wristbands. RESULTS: In spring and summer, total ChE and AChE levels were depressed in rural children compared to winter and fall. BChE was depressed in rural children in fall, compared to spring and summer. Adjustment for insecticide exposure did not affect these associations. CONCLUSIONS: Environmental exposures to cholinesterase-inhibiting insecticides have measurable biochemical effects on blood cholinesterases in rural children from farmworker families. Title: Ultrathin C(3)N(4) nanosheets-based oxidase-like 2D fluorescence nanozyme for dual-mode detection of organophosphorus pesticides Shen Y, Gao X, Chen H, Wei Y, Yang H, Gu Y Ref: J Hazard Mater, 451:131171, 2023 : PubMed ESTHER: Shen_2023_J.Hazard.Mater_451_131171 PubMedSearch: Shen 2023 J.Hazard.Mater 451 131171 PubMedID: 36913745 Abstract Engineering efficient dual-mode portable sensor with built-in cross reference correction is of great significance for onsite reliable and precise detection of organophosphorus pesticides (OPs) and evading the false-positive outputs, especially in emergency case. Currently, most nanozyme-based sensors for OPs monitoring primarily replied on the peroxidase-like activity, which involved unstable and toxic H(2)O(2). In this scenario, a hybrid oxidase-like 2D fluorescence nanozyme (PtPdNPs@g-C(3)N(4)) was yielded by in situ growing PtPdNPs in the ultrathin two-dimensional (2D) graphitic carbon nitride (g-C(3)N(4)) nanosheet. When acetylcholinesterase (AChE) hydrolyzed acetylthiocholine (ATCh) to thiocholine (TCh), it ablated O(2)(-) from the dissolved O(2) catalyzed by PtPdNPs@g-C(3)N(4)'s oxidase-like activity, hampering the oxidation of o-phenylenediamine (OPD) into 2,3-diaminophenothiazine (DAP). Consequently, with the increasing concentration of OPs which inhibited the blocking effect by inactivating AChE, the produced DAP caused an apparent color change and a dual-color ratiometric fluorescence change in the response system. Through integrating into a smartphone, a H(2)O(2)-free 2D nanozyme-based onsite colorimetric and fluorescence dual-mode visual imaging sensor for OPs was proposed with acceptable results in real samples, which holds vast promise for further development of commercial point-of-care testing platform in early warning and controlling of OPs pollution for safeguarding environmental health and food safety. Title: OsLDDT1, encoding a transmembrane structural DUF726 family protein, is essential for tapetum degradation and pollen formation in rice Sun Z, Liu K, Chen C, Chen D, Peng Z, Zhou R, Liu L, He D, Duan W and Sun L <7 more author(s)> Sun Z, Liu K, Chen C, Chen D, Peng Z, Zhou R, Liu L, He D, Duan W, Chen H, Huang C, Ruan Z, Zhang Y, Cao L, Zhan X, Cheng S, Sun L (- 7) Ref: Plant Sci, :111596, 2023 : PubMed ESTHER: Sun_2023_Plant.Sci__111596 PubMedSearch: Sun 2023 Plant.Sci 111596 PubMedID: 36657664 Gene_locus related to this paper: orysj-q10ss2 Abstract Formation of the pollen wall, which is mainly composed of lipid substances secreted by tapetal cells, is important to ensure pollen development in rice. Although several regulatory factors related to lipid biosynthesis during pollen wall formation have been identified in rice, the molecular mechanisms controlling lipid biosynthesis are unclear. We isolated the male-sterile rice mutant oslddt1 (leaked and delayed degraded tapetum 1). oslddt1 plants show complete pollen abortion resulting from delayed degradation of the tapetum and blocked formation of Ubisch bodies and pollen walls. OsLDDT1 (LOC_Os03g02170) encodes a DUF726 containing protein of unknown functionwith highly conserved transmembrane and alpha/beta Hydrolase domains. OsLDDT1 localizes to the endoplasmic reticulum and the gene is highly expressed in rice panicles. Genes involved in regulating fatty acid synthesis and formation of sporopollenin and pollen exine during anther developmentshowed significantly different expression patterns in oslddt1 plants. Interestingly, the wax and cutin contents in mature oslddt1-1 anthers were decreased by 74.07% and 72.22% compared to WT, indicating that OsLDDT1 is involved in fatty acid synthesis and affects formation of the anther epidermis. Our results provide as deeper understanding of the role of OsLDDT1 in regulating male sterility and also provide materials for hybrid rice breeding. Title: Near-infrared-excitable acetylcholinesterase-activated fluorescent probe for sensitive and anti-interference detection of pesticides in colored food Wu Z, Hao Z, Chai Y, Li A, Wang C, Zhang X, Chen H, Lu C Ref: Biosensors & Bioelectronics, 233:115341, 2023 : PubMed ESTHER: Wu_2023_Biosens.Bioelectron_233_115341 PubMedSearch: Wu 2023 Biosens.Bioelectron 233 115341 PubMedID: 37099980 Abstract The development of a common and anti-interference acetylcholinesterase (AChE) inhibition assay for plant-originated food samples has been of great challenge because of the prevalent and strong signal interferences from natural pigments. Plant pigments normally exhibit non-negligible absorbance in the UV-visible region. As a result, the signals of a typical near-infrared (NIR) fluorescent probe could be disturbed through primary inner filter effect if it is excited by UV-visible light during plant sample analysis. In this work, an NIR-excitable AChE-activated fluorescent probe was biomimetically designed and synthesized. And the NIR-excitation strategy was utilized for the anti-interference detection of organophosphate and carbamate pesticides in colored samples with this probe. Sensitive and rapid response to AChE and pesticides was achieved due to the high affinity of the biomimetic recognition unit in the probe. The limits of detection for four representative pesticides including dichlorvos, carbofuran, chlorpyrifos and methamidophos reached 0.0186 microg/L, 2.20 microg/L, 12.3 microg/L and 13.6 microg/L, respectively. Most importantly, fluorescent response to pesticide contents could be accurately measured in the coexistence of different plant pigments by this probe, and the measured results showed completely irrelevance to the plant pigments and their colors. Taking advantage of such probe, the new developed AChE inhibition assay showed good sensitivity and anti-interference ability in the detection of organophosphate and carbamate pesticides in real samples. Title: Omics techniques reveal the toxicity mechanisms of three antiepileptic drugs to juvenile zebrafish (Danio rerio) brain and liver Yang H, Gu X, Chen H, Zeng Q, Mao Z, Ge Y Ref: Aquat Toxicol, 262:106668, 2023 : PubMed ESTHER: Yang_2023_Aquat.Toxicol_262_106668 PubMedSearch: Yang 2023 Aquat.Toxicol 262 106668 PubMedID: 37659109 Abstract Epilepsy, a neurological disorder, is characterized by seizures that are an appearance of excessive brain activity and is symptomatically treated with antiepileptic drugs (AEDs). Oxcarbazepine (OCBZ), lamotrigine (LTG), and carbamazepine (CBZ) are widely used AEDs in clinics and are very often detected in aquatic environments. However, neither the sub-lethal effects nor the specific mechanisms of these AEDs' action on the fish are well understood. In this study, juvenile zebrafish were exposed to a sub-lethal concentration (100 microg/L) of OCBZ, LTG, and CBZ for 28 d, after which indicators of oxidative stress (i.e. superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) level) and neurotoxicity (i.e. acetylcholinesterase (AChE) activity, gamma-aminobutyric acid (GABA) level, and glutamic acid (Glu) level) were measured. Brain SOD activity was significantly increased by three AEDs, while brain CAT activity was significantly inhibited by LTG and CBZ. Liver SOD activity was significantly enhanced by CBZ, and liver CAT activity was significantly induced by OCBZ and LTG. Liver MDA level was significantly increased by three AEDs. Brain AChE activity was significantly increased by LTG and CBZ, and brain GABA level was significantly enhanced by three AEDs. However, there were no significant alterations in the levels of MDA and Glu in zebrafish brain. To ascertain mechanisms of AEDs-induced toxicity, brain transcriptomics and liver metabolomics were conducted in zebrafish. The brain transcriptomics results showed that lots of differentially expressed genes (DEGs) were enriched in the sensory system, the immune system, the digestive system, the metabolic processes, and others in three AEDs treated groups. The metabolomics data indicated dysregulation of glycerophospholipid signaling and lipid homeostasis in zebrafish liver after three AEDs exposure. The overall results of this study improve understanding of the sub-lethal effects and potential molecular mechanisms of action of AEDs in fish. Title: Biotransformation, metabolic response, and toxicity of UV-234 and UV-326 in larval zebrafish (Danio rerio) Zhang J, Huang Y, Pei Y, Wang Y, Li M, Chen H, Liang X, Martyniuk CJ Ref: Environ Int, 174:107896, 2023 : PubMed ESTHER: Zhang_2023_Environ.Int_174_107896 PubMedSearch: Zhang 2023 Environ.Int 174 107896 PubMedID: 36966637 Abstract Benzotriazole ultraviolet stabilizers (BUVSs) are emerging pollutants that are widely detected in aquatic ecosystems. While structure-dependent effects of BUVSs are reported, the relationship between biotransformation and toxicity outcomes remains unclear. In this study, zebrafish embryos were exposed to two common BUVSs (UV-234 and UV-326) at 1, 10, and 100 microg/L for up to 7 days. Comparison of their uptake and biotransformation revealed that the bioaccumulation capacity of UV-234 was higher than that of UV-326, while UV-326 was more extensively biotransformed with additional conjugation reactions. However, UV-326 showed low metabolism due to inhibited phase II enzymes, which may result in the comparable internal concentrations of both BUVSs in larval zebrafish. Both BUVSs induced oxidative stress while decreased MDA, suggesting the disturbance of lipid metabolism. The subsequent metabolomic profiling revealed that UV-234 and UV-326 exerted different effects on arachidonic acid, lipid, and energy metabolism. However, both BUVSs negatively impacted the cyclic guanosine monophosphate / protein kinase G pathway. This converged metabolic change resulted in comparable toxicity of UV-234 and UV-326, which was confirmed by the induction of downstream apoptosis, neuroinflammation, and abnormal locomotion behavior. These data have important implications for understanding the metabolism, disposition, and toxicology of BUVSs in aquatic organisms. Title: A Multifunctional (-)-Meptazinol-Serotonin Hybrid Ameliorates Oxidative Stress-Associated Apoptotic Neuronal Death and Memory Deficits via Activating the Nrf2/Antioxidant Enzyme Pathway Zhao F, Zhao L, Zhou Y, Tan X, Yang Y, Ni W, Zheng W, Chen H, Qiu Y, Li J Ref: Oxid Med Cell Longev, 2023:6935947, 2023 : PubMed ESTHER: Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947 PubMedSearch: Zhao 2023 Oxid.Med.Cell.Longev 2023 6935947 PubMedID: 36819782 Abstract The pathogenesis of Alzheimer's disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H(2)O(2)-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H(2)O(2) through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H(2)O(2)-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and gamma-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms. Title: Systems pharmacology-based mechanism exploration of Acanthopanax senticosusin for Alzheimer's disease using UPLC-Q-TOF-MS, network analysis, and experimental validation Zhuo Y, Fu X, Jiang Q, Lai Y, Gu Y, Fang S, Chen H, Liu C, Pan H and Fang J <1 more author(s)> Zhuo Y, Fu X, Jiang Q, Lai Y, Gu Y, Fang S, Chen H, Liu C, Pan H, Wu Q, Fang J (- 1) Ref: European Journal of Pharmacology, :175895, 2023 : PubMed ESTHER: Zhuo_2023_Eur.J.Pharmacol__175895 PubMedSearch: Zhuo 2023 Eur.J.Pharmacol 175895 PubMedID: 37422122 Abstract BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease, characterized by progressive cognitive dysfunction and memory loss. However, the disease-modifying treatments for AD are still lacking. Traditional Chinese herbs, have shown their potentials as novel treatments for complex diseases, such as AD. PURPOSE: This study was aimed at investigating the mechanism of action (MOA) of Acanthopanax senticosusin (AS) for treatment of AD. METHODS: In this study, we firstly identified the chemical constituents in Acanthopanax senticosusin (AS) utilizing ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS), and next built the drug-target network of these compounds. We next performed the systems pharmacology-based analysis to preliminary explore the MOA of AS against AD. Moreover, we applied the network proximity approach to identify the potential anti-AD components in AS. Finally, experimental validations, including animal behavior test, ELISA and TUNEL staining, were conducted to verify our systems pharmacology-based analysis. RESULTS: 60 chemical constituents in AS were identified via the UPLC-Q-TOF-MS approach. The systems pharmacology-based analysis indicated that AS might exert its therapeutic effects on AD via acetylcholinesterase and apoptosis signaling pathway. To explore the material basis of AS against AD, we further identified 15 potential anti-AD components in AS. Consistently, in vivo experiments demonstrated that AS could protect cholinergic nervous system damage and decrease neuronal apoptosis caused by scopolamine. CONCLUSION: Overall, this study applied systems pharmacology approach, via UPLC-Q-TOF-MS, network analysis, and experimental validation to decipher the potential molecular mechanism of AS against AD. Title: Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population Bai X, Sun Y, Li Y, Li M, Cao Z, Huang Z, Zhang F, Yan P, Wang L and Zuo T <9 more author(s)> Bai X, Sun Y, Li Y, Li M, Cao Z, Huang Z, Zhang F, Yan P, Wang L, Luo J, Wu J, Fan D, Chen H, Zhi M, Lan P, Zeng Z, Wu X, Miao Y, Zuo T (- 9) Ref: Microbiome, 10:147, 2022 : PubMed ESTHER: Bai_2022_Microbiome_10_147 PubMedSearch: Bai 2022 Microbiome 10 147 PubMedID: 36100953 Abstract BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract. Title: Reduced Fitness and Elevated Oxidative Stress in the Marine Copepod Tigriopus japonicus Exposed to the Toxic Dinoflagellate Karenia mikimotoi Chen H, Wang J, Zhuang Y, Yu W, Liu G Ref: Antioxidants (Basel), 11:2299, 2022 : PubMed ESTHER: Chen_2022_Antioxidants.(Basel)_11_2299 PubMedSearch: Chen 2022 Antioxidants.(Basel) 11 2299 PubMedID: 36421485 Abstract Blooms of the toxic dinoflagellate Karenia mikimotoi cause devastation to marine life, including declines of fitness and population recruitment. However, little is known about the effects of them on benthic copepods. Here, we assessed the acute and chronic effects of K. mikimotoi on the marine benthic copepod Tigriopus japonicus. Results showed that adult females maintained high survival (>85%) throughout 14-d incubation, but time-dependent reduction of survival was detected in the highest K. mikimotoi concentration, and nauplii and copepodites were more vulnerable compared to adults. Ingestion of K. mikimotoi depressed the grazing of copepods but significantly induced the generation of reactive oxygen species (ROS), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and acetylcholinesterase. Under sublethal concentrations for two generations, K. mikimotoi reduced the fitness of copepods by prolonging development time and decreasing successful development rate, egg production, and the number of clutches. Our findings suggest that the bloom of K. mikimotoi may threaten copepod population recruitment, and its adverse effects are associated with oxidative stress. Title: Major biotransformation of phthalic acid esters in Eisenia fetida: Mechanistic insights and association with catalytic enzymes and intestinal symbionts Fan X, Gu C, Jin Z, Cai J, Bian Y, Wang F, Chen H, Jiang X Ref: Environ Int, 171:107712, 2022 : PubMed ESTHER: Fan_2022_Environ.Int_171_107712 PubMedSearch: Fan 2022 Environ.Int 171 107712 PubMedID: 36577298 Abstract Phthalic acid esters (PAEs) are an important group of organic pollutants that are widely used as plasticizers in the environment. The PAEs in soil organisms are likely to be biotransformed into a variety of metabolites, and the combined toxicity of PAEs and their metabolites might be more serious than PAEs alone. However, there are only a few studies on PAE biotransformation by terrestrial animals, e.g. earthworms. Herein, the key biotransformation pathways of PAEs and their association with catalytic enzymes and intestinal symbionts in earthworms were studied using in vivo and in vitro incubation approaches. The widely distributed PAE in soil, dibutyl phthalate (DBP), was proven to be biotransformed rapidly together with apparent bioaccumulation in earthworms. The biotransformation of PAE congeners with medium or long side chains appeared to be faster compared with those with short side chains. DBP was biotransformed into butyl methyl phthalate (BMP), monobutyl phthalate (MBP), and phthalic acid (PA) through esterolysis and transesterification. Besides, the generation of small quantities of low-molecular weight metabolites via beta-oxidation, decarboxylation or ring-cleavage, was also observed, especially when the appropriate proportion of NADPH coenzyme was applied to transfer electrons for oxidases. Interestingly, the esterolysis of PAEs was mainly regulated by the cytoplasmic carboxylesterase (CarE) in earthworms, with a Michaelis constant (K(m)) of 0.416smM in the catalysis of DBP. The stronger esterolysis in non-intestinal tissues indicated that the CarE was primarily secreted by non-intestinal tissues of earthworms. Additionally, the intestinal symbiotic bacteria of earthworms could respond to PAE stress, leading to the changes in their diversity and composition. The enrichment of some genera e.g. Bacillus and Paracoccus, and the enhancement of metabolism function, e.g. amino acids, energy, lipids biosynthesis and oxidase secretion, indicated their important role in the degradation of PAEs. Title: Cymbopogon citratus (DC.) Stapf aqueous extract ameliorates loperamide-induced constipation in mice by promoting gastrointestinal motility and regulating the gut microbiota Gao X, Hu Y, Tao Y, Liu S, Chen H, Li J, Zhao Y, Sheng J, Tian Y, Fan Y Ref: Front Microbiol, 13:1017804, 2022 : PubMed ESTHER: Gao_2022_Front.Microbiol_13_1017804 PubMedSearch: Gao 2022 Front.Microbiol 13 1017804 PubMedID: 36267178 Abstract Slow transit constipation (STC) is the most common type of functional constipation. Drugs with good effects and few side effects are urgently needed form the treatment of STC. Cymbopogon citratus (DC.) Stapf (CC) is an important medicinal and edible spice plant. The wide range of biological activities suggested that CC may have laxative effects, but thus far, it has not been reported. In this study, the loperamide-induced STC mouse model was used to evaluate the laxative effect of the aqueous extract of CC (CCAE), and the laxative mechanism was systematically explored from the perspectives of the enteric nervous system (ENS), neurotransmitter secretion, gastrointestinal motility factors, intestinal inflammation, gut barrier and gut microbiota. The results showed that CCAE not only decreased the serum vasoactive intestinal polypeptide (VIP), induced nitric oxide synthases (iNOS), and acetylcholinesterase (AchE) in STC mice but also increased the expression of gastrointestinal motility factors in colonic interstitial cells of Cajal (ICCs) and smooth muscle cells (SMCs), thereby significantly shortening the defecation time and improving the gastrointestinal transit rate. The significantly affected gastrointestinal motility factors included stem cell factor receptor (c-Kit), stem cell factor (SCF), anoctamin 1 (Ano1), ryanodine receptor 3 (RyR3), smooth muscle myosin light chain kinase (smMLCK) and Connexin 43 (Cx43). Meanwhile, CCAE could repair loperamide-induced intestinal inflammation and intestinal barrier damage by reducing the expression of the pro-inflammatory factor IL-1beta and increasing the expression of the anti-inflammatory factor IL-10, chemical barrier (Muc-2) and mechanical barrier (Cldn4, Cldn12, Occludin, ZO-1, and ZO-2). Interestingly, CCAE could also partially restore loperamide-induced gut microbial dysbiosis in various aspects, such as microbial diversity, community structure and species composition. Importantly, we established a complex but clear network between gut microbiota and host parameters. Muribaculaceae, Lachnospiraceae and UCG-010 showed the most interesting associations with the laxative phenotypes; several other specific taxa showed significant associations with serum neurotransmitters, gastrointestinal motility factors, intestinal inflammation, and the gut barrier. These findings suggested that CCAE might promote intestinal motility by modulating the ENS-ICCs-SMCs network, intestinal inflammation, intestinal barrier and gut microbiota. CC may be an effective and safe therapeutic choice for STC. Title: Immobilization for Lipase: Enhanced Activity and Stability by Flexible Combination and Solid Support Hu R, Niu Z, Lu Y, Zhu H, Mao Z, Yan K, Hu X, Chen H Ref: Appl Biochem Biotechnol, :, 2022 : PubMed ESTHER: Hu_2022_Appl.Biochem.Biotechnol__ PubMedSearch: Hu 2022 Appl.Biochem.Biotechnol PubMedID: 35852759 Abstract In this study, an enhanced activity and stability method for immobilizing porcine pancreatic lipase (PPL) was developed based on ZIF-8 encapsulated supramolecular-modified gold nanoparticle complexes (pSC(4)-AuNPs@ZIF-8). Supramolecular calix[4]arene (pSC(4)) can recognize the amino group of PPL through non-covalent force, and this flexible binding method protected the structure of PPL during the immobilization process. Due to the hydrophilic of pSC(4)-AuNPs and hydrophobic of ZIF-8, PPL can maintain a "lid open" conformation, which can enhance the stability of PPL structure and reduce PPL activity loss. ZIF-8 was used to immobilize PPL to avoid the difficult recovery of free PPL. Compared with the native form of PPL, it exhibited 70.6% maintained activity with terrific pH and temperature stability, and had good performance in thermal stability, time stability, and reusability. In addition, three immobilized PPL methods were designed to further clarify the influence of synthetic methods and additives on the activity and stability of PPL. Importantly, the loading rate of pSC(4)-AuNPs@ZIF-8@PPL was up to 51.2% among these immobilized PPL systems. Therefore, pSC(4)-AuNPs@ZIF-8 may serve as a versatile and promising immobilization system for enzymes. Title: Synergistic Associations of PNPLA3 I148M Variant, Alcohol Intake, and Obesity With Risk of Cirrhosis, Hepatocellular Carcinoma, and Mortality Kim HS, Xiao X, Byun J, Jun G, DeSantis SM, Chen H, Thrift AP, El-Serag HB, Kanwal F, Amos CI Ref: JAMA Netw Open, 5:e2234221, 2022 : PubMed ESTHER: Kim_2022_JAMA.Netw.Open_5_e2234221 PubMedSearch: Kim 2022 JAMA.Netw.Open 5 e2234221 PubMedID: 36190732 Abstract IMPORTANCE: Alcohol drinking and obesity are associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), but the risk is not uniform among people with these risk factors. Genetic variants, such as I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, may play an important role in modulating cirrhosis and HCC risk. OBJECTIVE: To investigate the joint associations of the PNPLA3 I148M variant, alcohol intake, and obesity with the risk of cirrhosis, HCC, and liver disease-related mortality. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 414 209 participants enrolled in the UK Biobank study from March 2006 to December 2010. Participants had no previous diagnosis of cirrhosis and HCC and were followed up through March 2021. EXPOSURES: Self-reported alcohol intake (nonexcessive vs excessive), obesity (body mass index <=30 [calculated as weight in kilograms divided by height in meters squared]), and PNPLA3 I148M variant status (noncarrier, heterozygous carrier, or homozygous carrier) from initial assessment. MAIN OUTCOMES AND MEASURES: The primary outcomes were incident cirrhosis and HCC cases and liver disease-related death ascertained from inpatient hospitalization records and death registry. The risks were calculated by Cox proportional hazards regression models. RESULTS: A total of 414 209 participants (mean [SD] age, 56.3 [8.09] years; 218 567 women [52.8%]; 389 452 White race and ethnicity [94.0%]) were included. Of these participants, 2398 participants (0.6%) developed cirrhosis (5.07 [95% CI, 4.87-5.28] cases per 100 person-years), 323 (0.1%) developed HCC (0.68 [95% CI, 0.61-0.76] cases per 100 person-years), and 878 (0.2%) died from a liver disease-related cause (1.76 [95% CI, 1.64-1.88] cases per 100 person-years) during a median follow-up of 10.9 years. Synergistic interactions between the PNPLA3 I148M variant, obesity, and alcohol intake were associated with the risk of cirrhosis, HCC, and liver disease-related mortality. The risk of cirrhosis increased supramultiplicatively (adjusted hazard ratio [aHR], 17.52; 95% CI, 12.84-23.90) in individuals with obesity, with excessive drinking, and who were homozygous carriers compared with those with no obesity, with nonexcessive drinking, and who were noncarriers. Supramultiplicative associations between the 3 factors and risks of HCC were found in individuals with 3 risk factors (aHR, 30.13; 95% CI, 16.51-54.98) and liver disease-related mortality (aHR, 21.82; 95% CI, 13.78-34.56). The PNPLA3 I148M variant status significantly differentiated the risk of cirrhosis, HCC, and liver disease-related mortality in persons with excessive drinking and obesity. CONCLUSIONS AND RELEVANCE: This study found synergistic associations of the PNPLA3 I148M variant, excessive alcohol intake, and obesity with increased risk of cirrhosis, HCC, and liver disease-related death in the general population. The PNPLA3 I148M variant status may help refine the risk stratification for liver disease in persons with excessive drinking and obesity who may need early preventive measures. Title: Narciclasine inhibits phospholipase A2 and regulates phospholipid metabolism to ameliorate psoriasis-like dermatitis Kong Y, Jiang J, Huang Y, Liu X, Jin Z, Li L, Wei F, Yin J, Zhang Y and Chen H <1 more author(s)> Kong Y, Jiang J, Huang Y, Liu X, Jin Z, Li L, Wei F, Yin J, Zhang Y, Tong Q, Chen H (- 1) Ref: Front Immunol, 13:1094375, 2022 : PubMed ESTHER: Kong_2022_Front.Immunol_13_1094375 PubMedSearch: Kong 2022 Front.Immunol 13 1094375 PubMedID: 36700214 Abstract INTRODUCTION: Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling disease." The fact that metabolic syndrome (MetS) is the most common and important comorbidities of psoriasis suggests an important role of lipid metabolism in the pathogenesis of psoriasis. Narciclasine (Ncs) is an alkaloid isolated from the Amaryllidaceae plants. Its biological activities include antitumor, antibacterial, antiinflammatory, anti-angiogenic and promoting energy expenditure to improve dietinduced obesity. Here, we report that Ncs may be a potential candidate for psoriasis, acting at both the organismal and cellular levels. METHODS: The therapeutic effect of Ncs was assessed in IMQ-induced psoriasis-like mouse model. Then, through in vitro experiments, we explored the inhibitory effect of Ncs on HaCaT cell proliferation and Th17 cell polarization; Transcriptomics and lipidomics were used to analyze the major targets of Ncs; Single-cell sequencing data was used to identify the target cells of Ncs action. RESULTS: Ncs can inhibit keratinocyte proliferation and reduce the recruitment of immune cells in the skin by inhibiting psoriasis-associated inflammatory mediators. In addition, it showed a direct repression effect on Th17 cell polarization. Transcriptomic and lipidomic data further revealed that Ncs extensively regulated lipid metabolismrelated genes, especially the Phospholipase A2 (PLA2) family, and increased antiinflammatory lipid molecules. Combined with single-cell data analysis, we confirmed that keratinocytes are the main cells in which Ncs functions. DISCUSSION: Taken together, our findings indicate that Ncs alleviates psoriasiform skin inflammation in mice, which is associated with inhibition of PLA2 in keratinocytes and improved phospholipid metabolism. Ncs has the potential for further development as a novel anti-psoriasis drug. Title: The Influence of Tyrosol-Enriched Rhodiola sachalinensis Extracts Bioconverted by the Mycelium of Bovista plumbe on Scopolamine-Induced Cognitive, Behavioral, and Physiological Responses in Mice Kwon MJ, Lee JW, Kim KS, Chen H, Cui CB, Lee GW, Cho YH Ref: Molecules, 27:, 2022 : PubMed ESTHER: Kwon_2022_Molecules_27_ PubMedSearch: Kwon 2022 Molecules 27 PubMedID: 35889329 Abstract Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, which are accompanied by memory loss and cognitive disruption. Rhodiola sachalinensis (RSE) is a medicinal plant that has been used in northeastern Asia for various pharmacological activities. We attempted to carry out the bioconversion of RSE (Bio-RSE) using the mycelium of Bovista plumbe to obtain tyrosol-enriched Bio-RSE. The objective of this study was to investigate the effects of Bio-RSE on the activation of the cholinergic system and the inhibition of oxidative stress in mice with scopolamine (Sco)-induced memory impairment. Sco (1 mg/kg body weight, i.p.) impaired the mice's performance on the Y-maze test, passive avoidance test, and water maze test. However, the number of abnormal behaviors was reduced in the groups supplemented with Bio-RSE. Bio-RSE treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. Bio-RSE dramatically improved the cholinergic system by decreasing acetylcholinesterase activity and regulated oxidative stress by increasing antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)). The reduction in nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in the brain tissue due to scopolamine was restored by the administration of Bio-RSE. Bio-RSE also significantly decreased amyloid-beta 1-42 (Abeta1-42) and amyloid precursor protein (APP) expression. Moreover, the increased malondialdehyde (MDA) level and low total antioxidant capacity in Sco-treated mouse brains were reversed by Bio-RSE, and an increase in Nrf2 and HO-1 was also observed. In conclusion, Bio-RSE protected against Sco-induced cognitive impairment by activating Nrf2/HO-1 signaling and may be developed as a potential beneficial material for AD. 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: The strigolactone receptor SlDWARF14 plays a role in photosynthetic pigment accumulation and photosynthesis in tomato Li Z, Pi Y, Zhai C, Xu D, Ma W, Chen H, Li Y, Wu H Ref: Plant Cell Rep, 41:2089, 2022 : PubMed ESTHER: Li_2022_Plant.Cell.Rep_41_2089 PubMedSearch: Li 2022 Plant.Cell.Rep 41 2089 PubMedID: 35907035 Abstract Tomato DWARF14 regulates the development of roots, shoot branches and leaves, and also plays a role in photosynthetic pigment accumulation and photosynthetic capacity. Strigolactones (SLs) are a novel class of plant hormones. DWARF14 (D14) is the only SL receptor identified to date, but it is not functionally analyzed in tomato (Solanum lycopersicum). In the present study, we identified the potential SL receptor in tomato by bioinformatic analysis, which was designated as SlD14. SlD14 was expressed in roots, stems, flowers and developing fruits, with the highest expression level in leaves. sld14 mutant plants produced by the CRISPR/Cas9 system displayed reduced plant height and root biomass, increased shoot branching and altered leaf shape comparing with WT plants. The cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE 3 (SlIPT3), auxin biosynthetic genes FLOOZY (SlFZY) and TRYPTOPHAN AMINOTRANSFERASE RELATED 1 (SlTAR1) and several auxin transport genes SlPINs, which are involved in branch formation, showed higher expression levels in the sld14 plant stem. In addition, sld14 plants exhibited light-green leaves, reduced chlorophyll and carotenoid contents, abnormal chloroplast structure and reduced photosynthetic capacity. Transcriptomic analysis showed that the transcript levels of six chlorophyll biosynthetic genes, three carotenoid biosynthetic genes and numerous chlorophyll a/b-binding protein genes were decreased in sld14 plants. These results suggest that tomato SL receptor gene SlD14 not only regulates the development of roots, shoot branches and leaves, but also plays a role in regulating photosynthetic pigment accumulation and photosynthetic capacity. Title: Design, synthesis and biological evaluation of novel coumarin derivatives as multifunctional ligands for the treatment of Alzheimer's disease Liu W, Wu L, Tian L, Chen H, Wu Z, Wang N, Liu X, Qiu J, Feng X and Zhao Q <2 more author(s)> Liu W, Wu L, Tian L, Chen H, Wu Z, Wang N, Liu X, Qiu J, Feng X, Xu Z, Jiang X, Zhao Q (- 2) Ref: Eur Journal of Medicinal Chemistry, 242:114689, 2022 : PubMed ESTHER: Liu_2022_Eur.J.Med.Chem_242_114689 PubMedSearch: Liu 2022 Eur.J.Med.Chem 242 114689 PubMedID: 36007469 Abstract Multi-targeted directed ligands (MTDLs) are emerging as promising Alzheimer's disease (AD) therapeutic possibilities. Coumarin is a multifunctional backbone with extensive bioactivity that has been utilized to develop innovative anti-neurodegenerative properties and is a desirable starting point for the construction of MTDLs. Herein, we explored and synthesized a series of novel coumarin derivatives and assessed their inhibitory effects on cholinesterase (AChE, BuChE), GSK-3beta, and BACE1. Among these compounds, compound 30 displayed the multifunctional profile of targeting the AChE (IC(50) = 1.313 +/- 0.099 microM) with a good selectivity over BuChE (SI = 24.623), GSK-3beta (19.30% inhibition at 20 microM), BACE1 (IC(50) = 1.227 +/- 0.112 microM), along with moderate HepG2 cytotoxicity, SH-SY5Y cytotoxicity, low HL-7702 cytotoxicity, as well as good blood-brain barrier (BBB) permeability. Kinetic and docking studies indicated that compound 30 was a competitive AChE inhibitor. Furthermore, acute toxicity experiments revealed that it was non-toxic at a dosage of 1000 mg/kg. The ADME prediction results indicate that 30 has acceptable physicochemical properties. Collectively, these findings demonstrated that compound 30 would be a potential multifunctional candidate for AD therapy. Title: Discovery of novel beta-carboline-1,2,3-triazole hybrids as AChE/GSK-3beta dual inhibitors for Alzheimer's disease treatment Liu W, Tian L, Wu L, Chen H, Wang N, Liu X, Zhao C, Wu Z, Jiang X and Zhao Q <2 more author(s)> Liu W, Tian L, Wu L, Chen H, Wang N, Liu X, Zhao C, Wu Z, Jiang X, Wu Q, Xu Z, Zhao Q (- 2) Ref: Bioorg Chem, 129:106168, 2022 : PubMed ESTHER: Liu_2022_Bioorg.Chem_129_106168 PubMedSearch: Liu 2022 Bioorg.Chem 129 106168 PubMedID: 36191431 Inhibitor(s) related to this paper: ZTL-11 Abstract Alzheimer's disease (AD) is characterized by progressive cognitive impairment and mental behavior. The combination inhibition of two essential AD targets, acetylcholinesterase (AChE) and glycogen synthase kinase-3beta (GSK-3beta), might be a breakthrough in the discovery of therapeutic success. Herein, 17 beta-carboline-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their AChE and GSK-3beta inhibitory potential. The results indicated that compound 21 has the most potent inhibition against eeAChE (IC(50) = 0.20 +/- 0.02 microM), hAChE (IC(50) = 0.34 +/- 0.01 microM) and GSK-3beta (IC(50) = 1.14 +/- 0.05 microM) among these compounds. In addition, it inhibited hAChE in a mixed type manner and could occupy the binding pocket forming diverse interactions with the target of AChE and GSK-3beta. Moreover, compound 21 showed low cytotoxicity against SH-SY5Y and HepG2 cell lines and good BBB permeability. Compound 21 also attenuated the tau hyperphosphorylation in the Tau (P301L) 293T cell model. The ADME projection exhibited that compound 21 has acceptable physicochemical characteristics. This study provides new leads for the assessment of AChE and GSK-3beta dual inhibition as a promising strategy for AD treatment. Title: An artificial self-assembling peptide with carboxylesterase activity and substrate specificity restricted to short-chain acid p-nitrophenyl esters Liu Y, Gan L, Feng P, Huang L, Chen L, Li S, Chen H Ref: Front Chem, 10:996641, 2022 : PubMed ESTHER: Liu_2022_Front.Chem_10_996641 PubMedSearch: Liu 2022 Front.Chem 10 996641 PubMedID: 36199662 Abstract Natural enzymes possess remarkable catalytic activity and high substrate specificity. Many efforts have been dedicated to construct artificial enzymes with high catalytic activity. However, how to mimic the exquisite substrate specificity of a natural enzyme remains challenging because of the complexity of the enzyme structure. Here, we report artificial carboxylesterases that are specific for short chain fatty acids and were constructed via peptide self-assembly. These artificial systems have esterase-like activity rather than lipase-like activity towards p-nitrophenyl esters. The designer peptides self-assembled into nanofibers with strong beta-sheet character. The extending histidine units and the hydrophobic edge of the fibrillar structure collectively form the active center of the artificial esterase. These artificial esterases show substrate specificity for short-chain acids esters. Moreover, 1-isopropoxy-4-nitrobenzene could function as a competitive inhibitor of hydrolysis of p-nitrophenyl acetate for an artificial esterase. Title: The Chemical Composition Characteristics and Health Risk Assessment of Cooking Fume Condensates from Residential Kitchens in Different Regions of China Liu Q, Zhang X, Yang Y, Tang Q, Zheng L, Lou H, Chen H, Yang Q Ref: Foods, 12:, 2022 : PubMed ESTHER: Liu_2022_Foods_12_ PubMedSearch: Liu 2022 Foods 12 PubMedID: 36613322 Abstract The aim of this study was to explore the similarities and differences of volatile organic pollutants (VOCs) in cooking fumes (COF) of residential buildings in different regions of China, as well as to evaluate their potential health risks. COF condensates were collected from 10 representative cities in China and analyzed by a GC-MS method. Their effects on alpha-glucosidase, acetylcholinesterase (AchE), and lactate dehydrogenase (LDH) activities were then detected to evaluate potential health risks. A total of 174 kinds of VOCs, including aldehydes, esters, hydrocarbons, alcohols, and carboxylic acid, were identified. There were 59 identical compounds in the northern and southern regions, and 56 common compounds in spicy and non-spicy regions. Health risk assessment results showed that COF condensate could inhibit the activity of alpha-glucosidase to varying degrees (61.73-129.25%), suggesting that it had a potential risk of causing hypoglycemia. Daily and 3 and 6 month intakes of COF in minors, adults, and the elderly had both activated and inhibited effects on AchE. The activated effect in the southern and spicy areas was higher than that in northern and non-spicy areas, revealing that different regions and dietary habits had different effects on the risk of neurological diseases caused by changes in AchE activity. For minors, adults, and the elderly, COF had different degrees of activation of LDH at different exposure times and regions. Activation in the northern and non-spicy areas was higher than that in southern and spicy areas, suggesting that the health risks caused by changes in LDH activity levels were significantly increased. Title: The optimized biocatalytic synthesis of (S)-methyl 2-chlorobutanoate by Acinetobacter sp. lipase Lu Y, Zhan R, Song B, Zhou Y, Zhu L, Chen H, Chen X Ref: Chirality, :, 2022 : PubMed ESTHER: Lu_2022_Chirality__ PubMedSearch: Lu 2022 Chirality PubMedID: 35713364 Abstract Epilepsy is a chronic disease caused by sudden abnormal discharge of brain neurons, leading to transient brain dysfunction. Levetiracetam, developed by the UCB company in Belgium, is an effective drug for the treatment of epilepsy. (S)-Methyl 2-chlorobutanoate is an important chiral building block of levetiracetam, which has attracted a great deal of attention. In this study, a strain of lipase-produced Acinetobacter sp. zjutfet-1 was screened from soil samples. At optimized conditions for fermentation and biocatalysis, the bacterial lipase exhibited high catalytic activity for hydrolysis and stereoselectivity toward racemic methyl 2-chlorobutanoate. When the enzymatic reaction was carried out in 6% of racemic substrate, the enantiomeric excess (e.e.(s) ) reached more than 95%, with a yield of over 86%. Therefore, this lipase can efficiently resolve racemic methyl 2-chlorobutanoate and obtain (S)-methyl 2-chlorobutanoate, which presents great potential in the industrial production of levetiracetam. Title: Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study Masurkar PP, Chatterjee S, Sherer JT, Chen H, Johnson ML, Aparasu RR Ref: Drugs & Aging, :, 2022 : PubMed ESTHER: Masurkar_2022_Drugs.Aging__ PubMedSearch: Masurkar 2022 Drugs.Aging PubMedID: 35666463 Abstract BACKGROUND AND OBJECTIVE: Cholinesterase inhibitors (ChEIs) are used as first-line pharmacotherapy to manage dementia. However, there are limited data regarding their relative safety. This study evaluated the risk of serious adverse events (SAEs) associated with individual ChEIs in older adults with dementia and also examined sex-based and dose-based effects on this risk. METHODS: This was a retrospective cohort study using 2013-2015 US Medicare claims data involving Parts A, B, and D. Patients aged <= 65 years with a dementia diagnosis and incident use of the ChEIs, namely donepezil, galantamine, or rivastigmine, were included. The primary outcome of interest was SAEs defined as emergency department visits, inpatient hospitalizations, or death within 6 months of ChEI initiation. Multivariable Cox proportional hazards regression with propensity score (PS) as a covariate and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of SAEs across individual ChEIs. RESULTS: The study included 767,684 older adults with dementia who were incident new users of ChEIs (donepezil 79.42%, rivastigmine 17.67%, galantamine 2.91%). SAEs were observed in 15.5% of the cohort within 6 months of ChEI prescription. Cox regression model with PS as covariate found that patients prescribed rivastigmine (adjusted hazard ratio [aHR] 1.12; 95% CI 1.03-1.33) and galantamine (aHR 1.51; 95% CI 1.24-1.84) were at increased risk of SAEs compared with patients on donepezil. Stratified analyses revealed that rivastigmine was associated with an 18% increased risk for SAEs in females (aHR 1.18; 95% CI 1.06-1.31), and galantamine was associated with a 71% increased risk in males (aHR 1.71; 95% CI 1.17-2.51) compared with donepezil. High and recommended index doses of rivastigmine and galantamine were associated with an increased risk of SAEs compared with donepezil. The findings were consistent in sensitivity analyses. CONCLUSION: The study found that the risk of SAEs varied across individual ChEIs, with sex and dose moderating these effects. Therefore, these moderating effects should be carefully considered in personalizing dementia care. Title: Correlation of lipoprotein lipase gene polymorphism and mRNA expression with intramuscular fat content in Baicheng-Oil chicken Wang Y, Chen H, Hang C, Chen Y, Gao J, Qiu D Ref: J Anim Physiol Anim Nutr (Berl), :, 2022 : PubMed ESTHER: Wang_2022_J.Anim.Physiol.Anim.Nutr.(Berl)__ PubMedSearch: Wang 2022 J.Anim.Physiol.Anim.Nutr.(Berl) PubMedID: 35267203 Abstract Lipoprotein lipase (LPL) was often taken as a candidate gene for investigating fat metabolism. However, there are few studies on the effect of LPL on intramuscular fat (IMF) deposition in Baicheng oil chicken (BOC) and Three-yellow Chicken (TYC). In this study, we studied the relationship between polymorphism and messenger RNA (mRNA) expression of LPL with IMF deposition in the chest muscle (CM) and leg muscle (LM) of TYC and BOC. Sixty TYCs and 60 BOCs were raised from 1 d and slaughtered by avascularization at their slaughtering age. IMF contents of the CM and LM in the BOC were markedly higher than those in the TYC. Three genotypes following AA, AB and BB were found by the method of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). The synonymous mutation C12315T was detected. The content of IMF with the AA genotype was significantly higher than the AB genotype in the LM of TYC. The mRNA expression both of CM and LM in BOC was prominently higher than those in TYC, and there was a positive significant correlation between LM and CM in both BOC and TYC. These results suggested that the SNPs polymorphism and mRNA expression of the LPL gene might be helpful for selective breeding in IMF of the chicken. Title: The Composition and Anti-Aging Activities of Polyphenol Extract from Phyllanthus emblica L. Fruit Wu M, Cai J, Fang Z, Li S, Huang Z, Tang Z, Luo Q, Chen H Ref: Nutrients, 14:, 2022 : PubMed ESTHER: Wu_2022_Nutrients_14_ PubMedSearch: Wu 2022 Nutrients 14 PubMedID: 35215512 Abstract Phyllanthus emblica L. (PE) is commonly known as a medicine and food homologous plant, which is abundant in natural products polyphenols. In the present study, polyphenols were extracted from PE fruit by response surface method, and the anti-aging ability was determined. PE fruit polyphenols exhibited strong antioxidant capacities in scavenging free radicals, and anti-cholinesterase ability by inhibition of AChE (IC(50) 0.2186 +/- 0.0416 mg/mL) and BuChE (IC(50) 0.0542 +/- 0.0054 mg/mL) in vitro. Moreover, PE fruit polyphenols showed strong protective effect against the aging process in Caenorhabditis elegans model, including increased thermal resistance, extended lifespan by 18.53% (p < 0.05), reduced activity of AChE by 34.71% and BuChE by 45.38% (p < 0.01). This was accompanied by the enhancement in antioxidant enzymes activity of SOD by 30.74% (p < 0.05) and CAT by 8.42% (p > 0.05), while decrease in MDA level by 36.25% (p < 0.05). These properties might be interrelated with the presence of abundant flavonols and phenolic acids identified by UPLC-ESI-QTOF-MS, such as quercetin, myricetin, ellagic, gallic, and chlorogenic acids, together with their glycosides. The remarkable antioxidant and anti-aging potential of PE fruit polyphenols could be implemented in the food and pharmaceutical industry. Title: The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study Wu M, Liu M, Wang F, Cai J, Luo Q, Li S, Zhu J, Tang Z, Fang Z and Chen H <1 more author(s)> Wu M, Liu M, Wang F, Cai J, Luo Q, Li S, Zhu J, Tang Z, Fang Z, Wang C, Chen H (- 1) Ref: Food Res Int, 158:111497, 2022 : PubMed ESTHER: Wu_2022_Food.Res.Int_158_111497 PubMedSearch: Wu 2022 Food.Res.Int 158 111497 PubMedID: 35840206 Abstract The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC(50) values of 0.1974 +/- 0.0047, 0.2589 +/- 0.0131, 1.0905 +/- 0.0598 and 1.503 +/- 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of alpha-helix and reducing beta-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors. Title: From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders Wu J, Zhang H, Wang Y, Yin G, Li Q, Zhuo L, Chen H, Wang Z Ref: Front Pharmacol, 13:1036030, 2022 : PubMed ESTHER: Wu_2022_Front.Pharmacol_13_1036030 PubMedSearch: Wu 2022 Front.Pharmacol 13 1036030 PubMedID: 36518670 Abstract A novel class of benzyl-free and benzyl-substituted carbamylated tryptamine derivatives (CDTs) was designed and synthesized to serve as effective building blocks for the development of novel multi-target directed ligands (MTDLs) for the treatment of neurological disorders linked to cholinesterase (ChE) activity. The majority of them endowed butyrylcholinesterase (BuChE) with more substantial inhibition potency than acetylcholinesterase (AChE), according to the full study of ChE inhibition. Particularly, hybrids with dibenzyl groups (2b-2f, 2j, 2o, and 2q) showed weak or no neuronal toxicity and hepatotoxicity and single-digit nanomolar inhibitory effects against BuChE. Through molecular docking and kinetic analyses, the potential mechanism of action on BuChE was first investigated. In vitro H(2)O(2)-induced HT-22 cells assay demonstrated the favorable neuroprotective potency of 2g, 2h, 2j, 2m, 2o, and 2p. Besides, 2g, 2h, 2j, 2m, 2o, and 2p endowed good antioxidant activities and COX-2 inhibitory effects. This study suggested that this series of hybrids can be applied to treat various ChE-associated neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as promising building blocks for further structure modification to develop efficient MTDLs. Title: Enhancement of DPP-IV inhibitory activity and the capacity for enabling GLP-1 secretion through RADA16-assisted molecular designed rapeseed peptide nanogels Xu F, Xu B, Chen H, Ju X, Gonzalez de Mejia E Ref: Food Funct, :, 2022 : PubMed ESTHER: Xu_2022_Food.Funct__ PubMedSearch: Xu 2022 Food.Funct PubMedID: 35438092 Abstract The potential of pentapeptide IPQVS (RAP1) and octapeptide ELHQEEPL (RAP2) derived from rapeseed napin as natural dipeptidyl-peptidase IV (DPP-IV) inhibitors is promising. The objective was to develop a nanogel strategy to resist the hydrolysis of digestive and intestinal enzymes to enhance the DPP-IV inhibitory activity of RAP1 and RAP2, and stimulate glucagon-like peptide 1 (GLP-1) secretion of RAP2 by a RADA16-assisted molecular design. The linker of double Gly was used in the connection of RADA16 and the functional oligopeptide region (RAP1 and RAP2). Compared to the original oligopeptides, DPP-IV IC(50) of the nanogels RADA16-RAP1 and RADA16-RAP2 decreased by 26.43% and 17.46% in Caco-2 cell monolayers, respectively. The results showed that the two nanogel peptides with no toxicity to cells had higher contents of stable beta-sheet structures (increased by 5.6-fold and 5.2-fold, respectively) than the original oligopeptides, and a self-assembled fibrous morphology. Rheological results suggested that the nanogels RADA16-RAP1 and RADA16-RAP2 exhibit good rheological properties for potential injectable applications; the storage modulus (G') was 10 times higher than the low modulus (G''). Furthermore, the RAP2 and its RADA16-assisted nanogel peptide at the concentration of 250 microM significantly (P < 0.05) increased the release of GLP-1 by 35.46% through the calcium-sensing receptor pathway in the enteroendocrine STC-1 cells. Hence, the innovative and harmless nanogels with the sequence of RADA16-GG-X(n) have the potential for use by oral and injection administration for treating or relieving type 2 diabetes. Title: The Effect of Guilingji Capsules on Vascular Mild Cognitive Impairment: A Randomized, Double-Blind, Controlled Trial Zhang H, Chen H, Pei H, Wang H, Ma L, Li H Ref: Evid Based Complement Alternat Med, 2022:4778163, 2022 : PubMed ESTHER: Zhang_2022_Evid.Based.Complement.Alternat.Med_2022_4778163 PubMedSearch: Zhang 2022 Evid.Based.Complement.Alternat.Med 2022 4778163 PubMedID: 35116067 Abstract Guilingji capsules (GLJC) have been shown to have antiaging effects and improve cognitive function. The aim of this study was to evaluate the clinical efficacy and safety of GLJC for the treatment of vascular mild cognitive impairment (VaMCI). A total of 96 patients with VaMCI (aged 60-85 years) were enrolled in this 24-week, randomized, double-blind, controlled clinical trial. The patients were randomly assigned to a GLJC group (n = 48) or a Ginkgo group (n = 48). Patients in the GLJC group were treated using GLJC, whereas those in the Ginkgo group received Ginkgo extract tablets. We evaluated the participants at baseline and after a 12- and 24-week treatment period using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Chinese Medicine Symptom Scale (CM-SS). The serum acetylcholine (Ach), acetylcholinesterase (AchE), homocysteine (Hcy), and high-sensitivity C-reactive protein (hs-CRP) serum levels of the patients were measured before and after 24-week treatment. Analysis of the results of both groups showed that both interventions significantly increased the MoCA and MMSE scores of the patients and decreased their ADAS-Cog and CM-SS scores (P < 0.05). The GLJC group showed greater improvement in MoCA, MMSE, and CM-SS scores than the Ginkgo group (P < 0.05). However, both groups showed a significant increase in serum Ach and a decrease in serum AchE, Hcy, and hs-CRP levels (P < 0.05). Furthermore, serum Ach increased and Hcy decreased more significantly in the GLJC group than in the Ginkgo group (P < 0.05). These findings indicate that GLJC can improve the cognitive function, cholinergic system, and inflammatory cytokine levels of patients with VaMCI. Furthermore, this treatment can improve symptoms of syndromes diagnosed according to traditional Chinese medicine practice in patients with VaMCI. Title: Essential Oils from Spices Inhibit Cholinesterase Activity and Improve Behavioral Disorder in AlCl(3) Induced Dementia Chen SX, Xiang JY, Han JX, Yang F, Li HZ, Chen H, Xu M Ref: Chem Biodivers, :e2100443, 2021 : PubMed ESTHER: Chen_2021_Chem.Biodivers__e2100443 PubMedSearch: Chen 2021 Chem.Biodivers e2100443 PubMedID: 34855291 Abstract The chemical compositions of essential oils (EOs) prepared from six spices including cinnamon, amomum tsao-ko, cardamom, amomum, black pepper and white pepper were analyzed by gas chromatography-mass spectrometry (GC/MS), which led to identify almost 200 volatile compounds. All EOs of spices showed cholinesterase inhibitory activity. Among them, pepper EO showed most potent acetylcholinesterase (AChE) inhibitory activity with IC(50) values of 8.54microg/mL (black pepper EO) and 5.02microg/mL (white pepper EO). Molecular docking and invitro validation suggested that 3-carene, alpha-pinene and beta-pinene with IC(50) value of 1.73, 2.66, and 14.75microg/mL, respectively, might be active constituents of spices oil in inhibiting AChE. Furthermore, amomum tsao-ko EO and amomum EO can improve behavioral disorder in dementia zebrafish induced by aluminum trichloride (AlCl(3) ). Title: Expression Levels of Detoxification Enzyme Genes from Dendroctonus armandi (Coleoptera: Curculionidae) Fed on a Solid Diet Containing Pine Phloem and Terpenoids Dai L, Gao H, Chen H Ref: Insects, 12:, 2021 : PubMed ESTHER: Dai_2021_Insects_12_ PubMedSearch: Dai 2021 Insects 12 PubMedID: 34680695 Abstract Bark beetles overcome the toxic terpenoids produced by pine trees by both detoxifying and converting them into a pheromone system. Detoxification enzymes such as cytochrome P450s, glutathione S-transferases, and carboxylesterases are involved in the ability of Dendroctonus armandi to adapt to its chemical environment. Ten genes from these three major classes of detoxification enzymes were selected to study how these enzymes help D. armandi to respond to the host defenses. The expression profile of these detoxification enzyme genes was observed in adult beetles after feeding on different types of diet. Significant differences were observed between two types of seminatural diet containing the phloem of pines, and a purely artificial diet containing five monoterpenes ((-)-alpha-pinene, (-)-beta-pinene, (+)-3-carene, (+/-)-limonene, and turpentine oil) also caused differential transcript levels in the detoxification enzyme genes. The results suggest that monoterpenes enter the beetles through different routes (i.e., respiratory and digestive systems) and cause the expression of different genes in response, which might be involved in pheromone metabolism. In addition, the xenobiotic metabolism in bark beetles should be considered as a system comprising multiple detoxifying enzymes. Title: A novel method of subxiphoid video-assisted thoracic surgery for thymectomy Gao L, Lu J, Shen Z, Chen H, Kang M Ref: Ann Transl Med, 9:1339, 2021 : PubMed ESTHER: Gao_2021_Ann.Transl.Med_9_1339 PubMedSearch: Gao 2021 Ann.Transl.Med 9 1339 PubMedID: 34532476 Abstract BACKGROUND: With advances in thoracoscopic surgical instruments and techniques, subxiphoid video-assisted thoracic surgery (S-VATS) has become the main approach for anterior mediastinal tumor resection under thoracoscopy. However, the drawbacks of S-VATS, including it being a relatively unfixed surgical procedure, make it complicated and difficult for unexperienced surgeons to master. METHODS: This study retrospectively reviewed and analyzed consecutive patients with anterior mediastinal tumor or myasthenia gravis (MG) who underwent S-VATS at the Fujian Medical University Union Hospital, China, between March 2015 and April 2019.Patients were divided into the conventional group and the "four-zone one-way" group. Intraoperative and postoperative variables were compared between the groups. Cumulative sum (CUSUM) analysis was applied to determine the operation time (OT)-learning curve of the S-VATS "four-zone one-way" method. RESULTS: A total of 82 patients were included in this analysis, of which, 40 patients underwent the conventional method of S-VATS and 42 patients underwent the "four-zone one-way" method. Patients in the "four-zone one-way" group had significantly shorter OT (138.50+/-29.43 and 118.00+/-28.18 minutes, respectively; P=0.002) and significantly less blood loss (36.00+/-20.16 and 23.92+/-14.96 mL, respectively; P=0.003) compared with patients in the conventional group. Our data indicated that there was no difference of the efficacy of MG treatment between the 2 groups. The difference in the preoperative and postoperative quantitative MG scoring system score (QMG-score) and the dose reduction of cholinesterase inhibitors was comparable between patients in the 2 groups. According to the CUSUM analysis curve, after a steady improvement over phase I (cases 1-12 for the traditional method and cases 1-5 for the "four-zone one-way" method), the surgical procedure could be mastered. Phase III occurred after case 26 in the traditional group and case 28 in the "four-zone one-way" group, and is characterized by rapid improvements. CONCLUSIONS: Compared with the conventional method of S-VATS, the "four-zone one-way" method significantly decreased OT and estimated blood loss. These results demonstrated the feasibility and safety of the "four-zone one-way" method of S-VATS. Title: Repressed OsMESL expression triggers reactive oxygen species mediated broad-spectrum disease resistance in rice Hu B, Zhou Y, Zhou Z, Sun B, Zhou F, Yin C, Ma W, Chen H, Lin Y Ref: Plant Biotechnol J, :, 2021 : PubMed ESTHER: Hu_2021_Plant.Biotechnol.J__ PubMedSearch: Hu 2021 Plant.Biotechnol.J PubMedID: 33567155 Gene_locus related to this paper: orysj-q0d4u5 Abstract A few reports have indicated that a single gene confer resistance to bacterial blight, sheath blight, and rice blast. In this study, we identified a novel disease resistance mutant gene, methyl esterase-like (osmesl) in rice. Mutant rice with T-DNA insertion displayed significant resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo), sheath blight caused by Rhizoctonia solani and rice blast caused by Magnaporthe oryzae. Additionally, CRISPR-Cas9 knockout mutants and RNAi lines displayed resistance to these pathogens. Complementary T-DNA mutants demonstrated a phenotype similar to the wild type (WT), thereby indicating that osmesl confers resistance to pathogens. Protein interaction experiments revealed that OsMESL affects reactive oxygen species (ROS) accumulation by interacting with thioredoxin OsTrxm in rice. Moreover, qRT-PCR results showed significantly reduced mRNA levels of multiple ROS scavenging-related genes in osmesl mutants. Nitroblue tetrazolium staining showed that the pathogens cause ROS accumulation, and quantitative detection revealed significantly increased levels of H(2) O(2) in the leaves of osmesl mutants and RNAi lines after infection. The abundance of JA, a hormone associated with disease resistance, was significantly more in osmesl mutants than in WT plants. Overall, these results suggested that osmesl enhances disease resistance to Xoo, R. solani and M. oryzae by modulating the ROS balance. Title: A Highly Efficient Three-Liquid-Phase-Based Enzymatic One-Pot Multistep Reaction System with Recoverable Enzymes for the Synthesis of Biodiesel Li Z, Chen H, Fang Y, Ma Y, Yang B, Wang Y Ref: Journal of Agricultural and Food Chemistry, 69:5481, 2021 : PubMed ESTHER: Li_2021_J.Agric.Food.Chem_69_5481 PubMedSearch: Li 2021 J.Agric.Food.Chem 69 5481 PubMedID: 33955745 Abstract A three-liquid-phase system (TLPS) was developed and used as a novel enzymatic one-pot multistep reaction (EOMR) system. In this system, lipase and phospholipase were enriched in a single liquid phase with a high recovery (ca. 98%) and then used for the simultaneous catalysis of mutually inhibiting and interfering reactions (hydrolysis of phospholipids and glyceride in crude oil). A novel emulsion containing the two dispersed droplets (W(2)/O/W(2) and W(1)/W(2) emulsion structures) could be the key reason for this phenomenon because the emulsion system not only provided a new catalytic interface but also relieved the product inhibition. As a result, the content of free fatty acid (main hydrolysate of the glyceride) and the removal of phospholipid from the crude oil could be increased to 96 and 95%, respectively, within 1 h. The product obtained from the EOMR was directly used in the production of biodiesel via enzymatic esterification, and the content of fatty acid methanol ester could be increased to 93% within 2 h. Furthermore, the enzymes in the middle phase could also be reused, at least for eight rounds without significant loss in catalytic efficiency. Therefore, the TLPS could be considered as an ideal catalytic platform for the EOMR. Title: Prognostic Significance of Hematopoietic-cell Serglycin for the Survival of Hepatocellular Carcinoma: A Single-center Retrospective Study Li Y, Chen H, Lu H, Zou Z Ref: Comb Chem High Throughput Screen, 24:986, 2021 : PubMed ESTHER: Li_2021_Comb.Chem.High.Throughput.Screen_24_986 PubMedSearch: Li 2021 Comb.Chem.High.Throughput.Screen 24 986 PubMedID: 33081679 Abstract AIM AND OBJECTIVE: Inflammation-related changes in peripheral blood cells and blood proteins are prognostic factors for survival in hepatocellular carcinoma (HCC), but their usefulness is limited by an active bacterial infection. This study investigated whether infection interfered with the predictive value of serglycin, a proteoglycan found in hematopoietic cells, on survival in HCC. MATERIALS AND METHODS: Patients with hepatitis B virus (HBV)-induced HCC, 100 without and 30 with a bacterial infection, and 30 healthy adult controls were enrolled retrospectively. Baseline clinical data collected before treatment with transarterial chemoembolization (TACE) was evaluated, and serglycin expression was assayed by flow cytometry. Receiver operating characteristic (ROC) curve analysis identified serglycin cutoff values for patient stratification. Cox regression and Kaplan-Meier analyses were performed to identify predictors of overall survival (OS). RESULTS: Serglycin levels in peripheral blood cells were higher in both groups of HCC patients than in the control group. Cholinesterase, lung metastasis, average neutrophil serglycin fluorescence intensity, and aspartate aminotransferase levels were associated with survival risk. Barcelona Clinic Liver Cancer stage A was associated with a good prognosis of OS. CONCLUSION: The intensity of serglycin fluorescence in peripheral neutrophils was independently predictive of survival in HCC, and its value was not limited by a bacterial infection. The method presented here is a simple and feasible way to predict prognosis in HCC patients with TACE. Title: Discovery of novel beta-carboline derivatives as selective AChE inhibitors with GSK-3beta inhibitory property for the treatment of Alzheimer's disease Liu W, Liu X, Gao Y, Wu L, Huang Y, Chen H, Li D, Zhou L, Wang N and Zhao Q <2 more author(s)> Liu W, Liu X, Gao Y, Wu L, Huang Y, Chen H, Li D, Zhou L, Wang N, Xu Z, Jiang X, Zhao Q (- 2) Ref: Eur Journal of Medicinal Chemistry, 229:114095, 2021 : PubMed ESTHER: Liu_2021_Eur.J.Med.Chem_229_114095 PubMedSearch: Liu 2021 Eur.J.Med.Chem 229 114095 PubMedID: 34995924 Inhibitor(s) related to this paper: ZLWH-23 Abstract The natural product harmine, a representative beta-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biological activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer's disease (AD). The results showed that all the derivatives possessed significant anti-acetylcholinesterase (AChE) activity and good selectivity over butyrylcholinesterase (BChE). In particular, compound ZLWH-23 exhibited potent anti-AChE activity (IC(50) = 0.27 microM) and selective BChE inhibition (IC(50) = 20.82 microM), as well as acceptable glycogen synthase kinase-3 (GSK-3beta) inhibition (IC(50) = 6.78 microM). Molecular docking studies and molecular dynamics simulations indicated that ZLWH-23 could form stable interaction with AChE and GSK-3beta. Gratifyingly, ZLWH-23 exhibited good selectivity for GSK-3beta over multi-kinases and very low cytotoxicity towards SH-SY5Y, HEK-293T, HL-7702, and HepG2 cell lines. Importantly, ZLWH-23 displayed efficient reduction against tau hyperphosphorylation on Ser-396 site in Tau (P301L) 293T cell model. Collectively, harmine-based derivatives could be considered as possible drug leads for the development of AD therapies. Title: Discovery, biological evaluation and molecular dynamic simulations of butyrylcholinesterase inhibitors through structure-based pharmacophore virtual screening Lu T, Liu Y, Chen H, Han C, Feng X, Zhou H, Li Y Ref: Future Med Chem, 13:769, 2021 : PubMed ESTHER: Lu_2021_Future.Med.Chem_13_769 PubMedSearch: Lu 2021 Future.Med.Chem 13 769 PubMedID: 33759552 Abstract Aim: Butyrylcholinesterase (BChE) is a crucial therapeutic target because it is associated with multiple pathological elements of Alzheimer's disease (AD). An integrated computational strategy was employed to exploit effective BChE inhibitors. Methods & results: Ten compounds derived from the Enamine database by structure-based pharmacophore virtual screening were further evaluated for biological activity; out of the ten, only five had an IC(50) of less than 100 microM. Among these five compounds, a new molecule, 970180, presented the most potency against BChE, with an IC(50) of 4.24 +/- 0.16 microM, and acted as a mixed-type inhibitor. Molecular dynamic simulations and absorption, distribution, metabolism and excretion prediction further confirmed its high potential as a good candidate of BChE inhibitor. Furthermore, cytotoxicity of molecule 970180 was not observed at concentrations up to 50 microM, and the molecule also showed a prominent neuroprotective effect compared with tacrine at 25 and 50 microM. Conclusion: This study provides an effective structure-based pharmacophore virtual screening method to discover BChE inhibitors and provide new choices for the development of BChE inhibitors, which may be beneficial for AD patients. Title: Risk of overactive bladder associated with cholinesterase inhibitors in dementia Masurkar PP, Chatterjee S, Sherer JT, Chen H, Johnson ML, Aparasu RR Ref: J Am Geriatr Soc, :, 2021 : PubMed ESTHER: Masurkar_2021_J.Am.Geriatr.Soc__ PubMedSearch: Masurkar 2021 J.Am.Geriatr.Soc PubMedID: 34854475 Abstract BACKGROUND: Although cholinesterase inhibitors (ChEIs) are the primary treatment for dementia, they are associated with overactive bladder (OAB), necessitating antimuscarinic use. Limited data exist regarding the risk of OAB across individual ChEIs in dementia. This study evaluated the risk of OAB associated with individual ChEIs in older adults with dementia. METHODS: This was a new user retrospective cohort study using Medicare claims data involving Parts A, B, and D claims dataset from 2013 to 2015. The study included older adults (aged 65 and older) with a diagnosis of dementia using donepezil, galantamine, or rivastigmine. New ChEI claims were identified with a 6-month baseline washout period. Patients with OAB diagnosis or any antimuscarinic or mirabegron use in the baseline period were excluded. The primary outcome of interest was OAB diagnosis or prescription of antimuscarinics or mirabegron within 6 months of ChEI initiation. Multivariable cox proportional hazards regression with propensity scores (PS) as covariates and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of OAB among donepezil, galantamine, and rivastigmine users. RESULTS: The study included 524,975 older adults with dementia who were incident users of ChEIs (donepezil 80.72%, rivastigmine 16.41%, galantamine 2.87%). Overall, OAB diagnosis/antimuscarinic/mirabegron prescription was observed in 5.07% of the cohort within 6 months of ChEIs prescription. The Cox regression model with PS as covariate approach found that donepezil use increased the risk of OAB compared to rivastigmine (aHR, 1.13; 95% CI, 1.08-1.28; p < 0.0001). However, there was no differential risk of OAB between galantamine and rivastigmine. The findings were consistent with the generalized boosted models. CONCLUSIONS: The study found that the risk of OAB varies across individual ChEIs with an increased risk of OAB with donepezil compared to rivastigmine. The study findings suggest the need to understand and manage medication-related morbidity in older adults with dementia. Title: Red ginseng has stronger anti-aging effects compared to ginseng possibly due to its regulation of oxidative stress and the gut microbiota Peng X, Hao M, Zhao Y, Cai Y, Chen X, Chen H, Zhang Y, Dong L, Liu X and Luo Y <3 more author(s)> Peng X, Hao M, Zhao Y, Cai Y, Chen X, Chen H, Zhang Y, Dong L, Liu X, Ding C, Liu W, Yang M, Luo Y (- 3) Ref: Phytomedicine, 93:153772, 2021 : PubMed ESTHER: Peng_2021_Phytomedicine_93_153772 PubMedSearch: Peng 2021 Phytomedicine 93 153772 PubMedID: 34753028 Abstract BACKGROUND: Panax ginseng (PG) and red ginseng (RG) are considered to be effective anti-aging treatments. However, evidence of their therapeutic mechanisms and difference in anti-aging effects is lacking. PURPOSE: To explore the potential therapeutic mechanisms of RG and PG in brain damage in D-Gal-induced aging mice, and evaluate the difference in anti-aging effects caused by their compositional differences. METHODS: We first tested the chemical components in PG and RG. In D-Gal aging mouse model, RG and PG (800 mg/kg) were orally administered for 9 weeks. The mice performed the Radial Arm Maze (RAM) behavior test. We collected blood, brain tissue, and fecal samples and performed biochemical analysis, histological examination, western blot, and Illumina MiSeq sequencing analysis. RESULTS: The results of component analysis showed that the total polyphenols and rare ginsenosides were present in RG in 3.2, and 2.2 fold greater concentrations, respectively, compared to PG, while the proportion of non-starch polysaccharides in the crude polysaccharides of RG was 1.94 fold greater than that of PG. In D-Gal-induced aging mice, both PG and RG could prevent the increase in acetylcholinesterase (AChE), and malondialdehyde (MDA) levels, and improved the expression of superoxide dismutase (SOD), and catalase (CAT) in the serum. Meanwhile, both PG and RG could ameliorate brain tissue architecture and behavioral trial. In addition, the D-Gal-induced translocation of nuclear factor-kappaB (NF-kappaB), as well as activation of the pro-apoptotic factors Caspase-3 and the PI3K/Akt pathways were inhibited by PG and RG. Overall, both PG and RG exerted anti-aging effects, with RG stronger than PG. Finally, although both PG and RG regulated the diversity of gut microbes, RG appeared to aggravate the increase in probiotics, such as Bifidobacterium and Akkermania, and the decrease in inflammatory bacteria to a greater extent compared to PG. CONCLUSION: Our results suggest that RG is more conducive to delay the D-Gal-induced aging process than PG, with possible mechanisms including beneficial changes in brain structure, cognitive functions, oxidative stress inhibition, and gut microbiome structure and diversity than PG, These mechanisms may rely on the presence of more total polyphenols, rare ginsenosides and non-starch polysaccharides in RG. Title: Antipsychotic Initiation Among Older Dementia Patients Using Cholinesterase Inhibitors: A National Retrospective Cohort Study Rege S, Carnahan RM, Johnson ML, Chen H, Holmes HM, Aparasu RR Ref: Drugs & Aging, :, 2021 : PubMed ESTHER: Rege_2021_Drugs.Aging__ PubMedSearch: Rege 2021 Drugs.Aging PubMedID: 33763822 Abstract BACKGROUND: Evidence regarding the initiation of antipsychotic medications across individual cholinesterase inhibitors (ChEIs) to manage the behavioral symptoms of dementia is lacking. OBJECTIVES: This study compared the risk of initiation of antipsychotic medications among older adults with dementia treated with the ChEIs donepezil, rivastigmine, or galantamine. METHODS: This retrospective cohort study used multiyear (2013-2015) Medicare claims data involving Parts A, B, and D. The study sample included community-dwelling older adults (aged <= 65 years) with a diagnosis of dementia. The study identified new users of ChEIs and followed them for up to 180 days for antipsychotic initiation. The ChEIs included donepezil, rivastigmine, and galantamine, whereas antipsychotics included typical and atypical agents. Donepezil was used as the reference category as it is the most commonly used ChEI and only acts on acetylcholinesterase, whereas both rivastigmine and galantamine have dual mechanisms of action. Multivariable Cox proportional hazards regression compared the risk of and time to antipsychotic initiation among the three ChEIs, adjusting for other risk factors. RESULTS: The study cohort consisted of 178,441 older adults with dementia who were new users of ChEIs. A total of 23,433 (15.14%) donepezil users, 4114 (19.04%) rivastigmine users, and 324 (15.77%) galantamine users initiated antipsychotics. The mean time to antipsychotic initiation among patients who received antipsychotics was 109.29 +/- 69.72 days for donepezil users, 96.70 +/- 71.60 days for rivastigmine users, and 104.15 +/- 72.53 days for galantamine users. The Cox regression analysis showed that rivastigmine (adjusted hazard ratio [aHR] = 1.27; 95% confidence interval [CI], 1.20-1.34) was significantly associated with antipsychotic initiation compared with donepezil, whereas no significant difference was observed between galantamine and donepezil (aHR = 0.98; 95% CI, 0.81-1.20). CONCLUSION: The study found a 27% increased risk of antipsychotic initiation among users of rivastigmine compared with donepezil users. There was no difference between galantamine and donepezil for antipsychotic initiation. Although the limitations of the study should be considered, the results suggest that donepezil or galantamine may be more appropriate treatments for older patients with dementia, to minimize antipsychotic use. Title: Experimental and theoretical evidence of enhanced catalytic performance of lipase B from Candida antarctica acquired by the chemical modification with amino acid ionic liquids Xu C, Suo H, Xue Y, Qin J, Chen H, Hu Y Ref: Molecular Catalysis, 501:111355, 2021 : PubMed ESTHER: Xu_2021_Mol.Catal_501_111355 PubMedSearch: Xu 2021 Mol.Catal 501 111355 Abstract Four types of amino acid ionic liquids (AAILs) with chiral structure were used to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity at different temperatures and pH, thermostability, and tolerance to organic solvents of all modified lipases were improved. The composition and configuration of modifiers have great influence on the catalytic performance of the modified lipases. AAILs composed of l-proline exhibited better modification effect than those containing d-proline. The use of [N-AC-l-Pro] [Cl] led to the highest modification degree (47.92 %) of the lipase, which exhibited the highest hydrolytic activity (430.67 U/g), as well as enhanced thermal stability and tolerance to organic solvents. The structure of CALB was characterized by circular dichroism (CD) and fluorescence spectroscopy. It was found that the introduction of a modifier changes the secondary structure of CALB to a certain extent, and the microenvironment around the fluorescent group changed slightly. The structural stability of CALB modified with [N-AC-l-Pro] [Cl] and the mechanism of reaction were studied by molecular dynamics simulations. The molecular dynamics simulations of the native and modified CALB were performed for 20 ns at 300 and 328 K. The simulation results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating a more stable structure for the modified CALB. The root mean square fluctuation (RMSF) calculations showed that the rigidity of the modified CALB and the flexibility of the active center region were both enhanced. The solvent accessibility area (SASA) calculations showed that both hydrophilicity and hydrophobicity of the modified enzyme-protein were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites was also increased. Thus, the modified CALB has enhanced structural stability and higher hydrolytic activity towards the triglyceride substrates. Title: Molecular and behavioral responses of zebrafish embryos/larvae after sertraline exposure Yang H, Liang X, Zhao Y, Gu X, Mao Z, Zeng Q, Chen H, Martyniuk CJ Ref: Ecotoxicology & Environmental Safety, 208:111700, 2021 : PubMed ESTHER: Yang_2021_Ecotoxicol.Environ.Saf_208_111700 PubMedSearch: Yang 2021 Ecotoxicol.Environ.Saf 208 111700 PubMedID: 33396031 Abstract Sertraline (SER) is one of the most frequently detected antidepressant drugs in aquatic environments. However, knowledge regarding SER-induced behavioral alterations in fish is insufficient, as well as the mechanisms underlying SER-induced toxicity. The present study aimed to determine behavioral and molecular responses in larval fish following SER exposure with a focus on its mode of action. Zebrafish embryos (~6 h-post-fertilization, hpf) were exposed to one of three concentrations of SER (1, 10, 100 microg/L) for 6 days, respectively. Evaluated parameters included development, behavior, transcripts related to serotonin signaling, serotonin levels, and acetylcholinesterase activity. Accelerated hatching of zebrafish embryos was observed for those fish exposed to 100 microg/L SER at 54 hpf. Locomotor activity (e.g. distance moved and mobile cumulative duration) was significantly reduced in larval zebrafish following exposure to 10 and 100 microg/L SER. Conversely, larval fish showed increased dark-avoidance after exposure to 1-100 microg/L SER. Of the measured transcripts related to serotonin signaling, only serotonin transporter (serta) and serotonin receptor 2c (5-ht2c) mRNA levels were increased in fish in response to 10 microg/L SER treatment. However, serotonin levels were unaltered in larvae exposed to SER. There were no differences among groups in acetylcholinesterase activity at any concentration tested. Taking together, the results evidenced that exposure to SER alters behavioral responses in early-staged zebrafish, which may be related to the abnormal expression of 5-ht2c. This study elucidates molecular responses to SER and characterizes targets that may be sensitive to antidepressant pharmaceuticals in larval fish. Title: A highly sensitive acetylcholinesterase electrochemical biosensor based on Au-Tb alloy nanospheres for determining organophosphate pesticides Yang Y, Zhao Y, Liu Q, You T, Gao Y, Chen H, Yin P Ref: Nanotechnology, :, 2021 : PubMed ESTHER: Yang_2021_Nanotechnology__ PubMedSearch: Yang 2021 Nanotechnology PubMedID: 34256363 Abstract Accurately detect the residues of organophosphate pesticides(OPs) in food and environment is critical to our daily lives. In this study, we developed a novel acetylcholinesterase (AChE) biosensor based on Au-Tb alloy nanospheres (NSs) for rapid and sensitive detection of OPs for the first time. Au-Tb alloy nanospheres that with good conductivity and biocompatibility were produced with a mild hydrothermal. Under optimal conditions, the AChE biosensor was obtained by a simple assembly process, with a big linear range (10-13 M - 10-7 M) and the limit of detection was 2.51 x 10-14 M for the determination of methyl parathion. Moreover, the determination of methyl parathion with the prepared biosensor presented a high sensitivity, outstanding repeatability and superior stability compared with other reported biosensors. Through the determination of tap water and Yanming lake samples, it was proved that the modified biosensor with satisfactory recoveries (96.76 %-108.6 %), and are realizable in the determination of OPs in real samples. Title: Identification and validation of EPHX2 as a prognostic biomarker in hepatocellular carcinoma Zhan K, Bai Y, Liao S, Chen H, Kuang L, Luo Q, Lv L, Qiu L, Mei Z Ref: Mol Med Rep, 24:, 2021 : PubMed ESTHER: Zhan_2021_Mol.Med.Rep_24_ PubMedSearch: Zhan 2021 Mol.Med.Rep 24 PubMedID: 34278494 Abstract Hepatocellular carcinoma (HCC) is one of the most common types of cancer, which is associated with a poor prognosis. It is necessary to identify novel prognostic biomarkers and therapeutic targets to improve the survival of patients with HCC. In the present study, a sevengene signature associated with HCC progression was identified using weighted gene coexpression network analysis and least absolute shrinkage and selection operator, and its prognostic prediction value was confirmed in The Cancer Genome Atlasliver HCC and International Cancer Genome Consortium liver cancerRIKEN, Japan cohorts. Subsequently, a rarely reported gene, epoxide hydrolase 2 (EPHX2), was selected for further validation. Downregulation of EPHX2 in HCC was revealed using multiple expression datasets. Furthermore, reduced expression of EPHX2 was confirmed in HCC tissue samples and cell lines using reverse transcriptionquantitative polymerase chain reaction and western blotting. Additionally, KaplanMeier survival curves indicated that patients with higher EPHX2 expression exhibited better prognosis, and clinicopathological analysis also revealed elevated EPHX2 levels in patients with earlystage HCC. Notably, EPHX2 was identified as an independent prognostic biomarker for overall survival of patients with HCC. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis were performed to elucidate the functions of EPHX2. The results suggested that EPHX2 expression was closely associated with metabolic reprogramming. Finally, the prognostic value of EPHX2 was evaluated using HCC tissue microarrays. In conclusion, downregulation of EPHX2 was significantly associated with the development of HCC; therefore, EPHX2 may be considered a putative therapeutic candidate for the targeted treatment of HCC. Title: Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio) Chen H, Yang H, Zhao Y, Gu X, Martyniuk CJ Ref: Int J Environ Research Public Health, 17:, 2020 : PubMed ESTHER: Chen_2020_Int.J.Environ.Res.Public.Health_17_ PubMedSearch: Chen 2020 Int.J.Environ.Res.Public.Health 17 PubMedID: 33260372 Abstract Concerns regarding environmental exposures and the impacts of pharmaceuticals on non-target aquatic organisms continue to increase. The antiepileptic drug carbamazepine (CBZ) is often detected as an aquatic contaminant and can disrupt various behaviors of fishes. However, there are few reports which investigate the mechanism of CBZ action in fish. The aim of the current study was to evaluate the effects of CBZ on embryonic development (i.e., hatching rate, heart rate, and body length) and early spontaneous movement. Moreover, we sought to investigate potential mechanisms by focusing on the gamma-aminobutyric acid (GABA) neurotransmitter system in zebrafish 6 days after of exposure. The results show that CBZ exposure did not cause significant effects on embryo development (hatching rate, heart rate, nor body length) at the test concentrations. However, the early spontaneous movement of embryos was inhibited following 10 g/L CBZ exposure at 28-29 h post-fertilization (hpf). In addition, acetylcholinesterase (AChE) activity and GABA concentrations were increased with exposure, whereas glutamate (Glu) concentrations were decreased in larval zebrafish. Gene expression analysis revealed that GABA and glutamate metabolic pathways in zebrafish larvae were altered following exposure to CBZ. GABA transaminase (abat) and glutamic acid decarboxylase (gad1b) decreased to 100 microg/L, and glutamate receptor, ionotropic, N-methyl D-aspartate 1b (grin1b) as well as the glutamate receptor, ionotropic, alpha-amino-3hydroxy-5methylisoxazole-4propionic 2b (gria2b) were down-regulated with exposure to 1 microg/L CBZ. Our study suggests that CBZ, which can act as an agonist of the GABA(A) receptor in humans, can also induce alterations in the GABAergic system in fish. Overall, this study improves understanding of the neurotoxicity and behavioral toxicity of zebrafish exposed to CBZ and generates data to be used to understand mechanisms of action that may underlie antiepileptic drug exposures. Title: Environmentally relevant concentrations of sertraline disrupts behavior and the brain and liver transcriptome of juvenile yellow catfish (Tachysurus fulvidraco): Implications for the feeding and growth axis Chen H, Liang X, Gu X, Zeng Q, Mao Z, Martyniuk CJ Ref: J Hazard Mater, 409:124974, 2020 : PubMed ESTHER: Chen_2020_J.Hazard.Mater_409_124974 PubMedSearch: Chen 2020 J.Hazard.Mater 409 124974 PubMedID: 33450510 Abstract Sertraline (SER) is one of the most prevalent antidepressants detected in aquatic environments, but its impact on fish behavior and growth remain poorly understood. As such, behavior and growth were assessed in yellow catfish (Tachysurus fulvidraco) following SER exposure. SER induced shoaling, reduced food consumption and growth, and increased cannibalism at environmentally relevant concentrations. To ascertain toxicity mechanisms, acetylcholinesterase (AChE) activity and transcripts related to growth and feeding were measured. AChE activity was increased in fish exposed to 10 and 100 microg/L SER. Transcript levels of neuropeptide Y, somatostatin, growth hormone, and insulin growth factor 1 were reduced in the brain following SER exposure. RNA-seq conducted in brain and liver revealed that gene networks associated with feeding and growth (i.e. leptin expression networks in the brain and insulin signaling pathways in the liver) were altered, proposed to be associated with the decreased food intake and growth. The brain also accumulated SER, which may relate to neurobehavioral responses. Lastly, the main metabolite of SER, norsertraline, was detected in the liver, and may also relate to toxicity. This study uncovers mechanisms and key events proposed to lead to impaired behavior and growth after exposure to some antidepressants. 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: IRREGULAR POLLEN EXINE2 Encodes a GDSL Lipase Essential for Male Fertility in Maize Huo Y, Pei Y, Tian Y, Zhang Z, Li K, Liu J, Xiao S, Chen H Ref: Plant Physiol, 184:1438, 2020 : PubMed ESTHER: Huo_2020_Plant.Physiol_184_1438 PubMedSearch: Huo 2020 Plant.Physiol 184 1438 PubMedID: 32913046 Abstract Anther cuticle and pollen exine are two physical barriers protecting plant reproductive cells against environmental stresses; defects in either often cause male sterility. Here, we report the characterization of a male-sterile mutant irregular pollen exine2 (ipe2) of maize (Zea mays), which displays shrunken anthers and no starch accumulation in mature pollen grains. We cloned the causal gene IPE2 and confirmed its role in male fertility in maize with a set of complementary experiments. IPE2 is specifically expressed in maize developing anthers during stages 8 to 9 and encodes an endoplasmic-reticulum-localized GDSL lipase. Dysfunction of IPE2 resulted in delayed degeneration of tapetum and middle layer, leading to defective formation of anther cuticle and pollen exine, and complete male sterility. Aliphatic metabolism was greatly altered, with the contents of lipid constituents, especially C16/C18 fatty acids and their derivatives, significantly reduced in ipe2 developing anthers. Our study elucidates GDSL function in anther and pollen development and provides a promising genetic resource for breeding hybrid maize. Title: A facile microfluidic paper-based analytical device for acetylcholinesterase inhibition assay utilizing organic solvent extraction in rapid detection of pesticide residues in food Jin L, Hao Z, Zheng Q, Chen H, Zhu L, Wang C, Liu X, Lu C Ref: Anal Chim Acta, 1100:215, 2020 : PubMed ESTHER: Jin_2020_Anal.Chim.Acta_1100_215 PubMedSearch: Jin 2020 Anal.Chim.Acta 1100 215 PubMedID: 31987143 Abstract The incompatibility of most organic solvents with acetylcholinesterase (AChE) inhibition assay normally limits pesticide extraction efficiency in sample pretreatment, which might cause false negatives in real world sample assessment. Herein, a novel method has been developed for an improved AChE inhibition assay via organic solvent extraction combined spontaneous in situ solvent evaporation on microfluidic paper-based analytical devices. Enzyme pre-immobilization procedure was spared and AChE was added to the system after sampling step until a complete in-situ solvent evaporation process was performed on chip. IC50 levels of the six investigated organophosphate and carbamate pesticides indicated a completely eliminated influence of solvents on AChE behavior with the new method. Most importantly, analytical performances were significantly improved in food sample measurements. Reduction in matrix effect was observed when acetonitrile was adopted for lettuce sample pretreatment instead of water. Studies on different pesticides suggested a remarkably decreased discrimination effect on recoveries from sample pretreatment with the new developed method. The recovery level for phoxim spiked head lettuce samples reached (107.5 +/- 14.2) %, in comparison with that of (18.6 +/- 1.4) % from water-based extraction. Spiked water and apple juice samples with carbaryl concentration of as low as 0.02 mg L(-1) were also successfully recognized with the present method by visual detection. This is the first report on direct sampling of organic extracts for AChE inhibition assay on-chip and it might provide a new perspective for real world sample assessments involving bio-reagents. Title: Learning and memory retention deficits in prepubertal guinea pigs prenatally exposed to low levels of the organophosphorus insecticide malathion Lumsden EW, McCowan L, Pescrille JD, Fawcett WP, Chen H, Albuquerque EX, Mamczarz J, Pereira EFR Ref: Neurotoxicology & Teratology, :106914, 2020 : PubMed ESTHER: Lumsden_2020_Neurotoxicol.Teratol__106914 PubMedSearch: Lumsden 2020 Neurotoxicol.Teratol 106914 PubMedID: 32652103 Abstract High doses of malathion, an organophosphorus (OP) insecticide ubiquitously used in agriculture, residential settings, and public health programs worldwide, induce a well-defined toxidrome that results from the inhibition of acetylcholinesterase (AChE). However, prenatal exposures to malathion levels that are below the threshold for AChE inhibition have been associated with increased risks of neurodevelopmental disorders, including autism spectrum disorder with intellectual disability comorbidity. The present study tested the hypothesis that prenatal exposures to a non-AChE-inhibiting dose of malathion are causally related to male-biased cognitive deficits later in life in a precocial species. To this end, pregnant guinea pigs were injected subcutaneously with malathion (20mg/kg) or vehicle (peanut oil, 0.5ml/kg) once daily between approximate gestational days 53 and 63. This malathion dose regimen caused no significant AChE inhibition in the brain or blood of dams and offspring and had no significant effect on the postnatal growth of the offspring. Around postnatal day 30, locomotor activity and habituation, a form of non-associative learning, were comparable between malathion- and peanut oil-exposed offspring. However, in the Morris water maze, malathion-exposed offspring presented significant sex-dependent spatial learning deficits in addition to memory impairments. These results are far reaching as they indicate that: (i) malathion is a developmental neurotoxicant and (ii) AChE inhibition is not an adequate biomarker to derive safety limits of malathion exposures during gestation. Continued studies are necessary to identify the time and dose dependence of the developmental neurotoxicity of malathion and the mechanisms underlying the detrimental effects of this insecticide in the developing brain. Title: Adipogenic activity of 2-ethylhexyl diphenyl phosphate via peroxisome proliferator-activated receptor gamma pathway Sun W, Duan X, Chen H, Zhang L, Sun H Ref: Sci Total Environ, 711:134810, 2020 : PubMed ESTHER: Sun_2020_Sci.Total.Environ_711_134810 PubMedSearch: Sun 2020 Sci.Total.Environ 711 134810 PubMedID: 31812418 Inhibitor(s) related to this paper: TPHP, Diphenyl-phosphate, EHDPP Abstract Recent studies have shown that exposure to some organophosphates, such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), can affect adipogenesis in preadipocytes. 2-Ethylhexyl diphenyl phosphate (EHDPP), an organophosphate, is frequently detected in various environmental media. However, there is less information about the toxicity effects and the mechanism by which EHDPP affects preadipocytes. In the present study, we investigated whether EHDPP could induce differentiation in 3T3-L1 preadipocytes through the peroxisome proliferator-activated receptor gamma (PPARgamma) signaling pathway. The fluorescence competitive binding assay and the dual-luciferase reporter gene assay were used to assess the binding affinity and activation of PPARgamma, and the results showed that EHDPP can bind to the ligand binding domain of PPARgamma (PPARgamma-LBD) and activate PPARgamma in vitro. Exposure to EHDPP for 10 days extensively induced adipogenesis in 3T3-L1 preadipocytes as assessed by lipid accumulation and gene expression of adipogenic markers of fatty acid binding protein 4 (FABP4), lipoprotein lipase (Lpl), adiponectin (Adip), and fatty acid synthase (Fasn). Furthermore, the preadipocytes differentiation was blocked by the PPARgamma-specific antagonist GW9662, indicating that the PPARgamma signaling pathway plays an important part in 3T3-L1 cell differentiation induced by EHDPP. Taken together, EHDPP can bind to PPARgamma-LBD, activate PPARgamma receptor, and induce cell differentiation via the PPARgamma signaling pathway in 3T3-L1 preadipocytes. Title: Preparative separation of the flavonoid fractions from Periploca forrestii Schltr. ethanol extracts using macroporous resin combined with HPLC analysis and evaluation of their biological activities Chen H, Liang Q, Zhou X, Wang X Ref: J Sep Sci, 42:650, 2019 : PubMed ESTHER: Chen_2019_J.Sep.Sci_42_650 PubMedSearch: Chen 2019 J.Sep.Sci 42 650 PubMedID: 30461196 Abstract A preparative separation method using macroporous absorptive resin coupled with high-performance liquid chromatography was developed for the separation of six fractions of the 80% ethanol extract of Periploca forrestii Schltr. The six ethanol fractions (5-95; A, B, C, D, E, and F) obtained were carefully analyzed to locate the corresponding peaks in the high-performance liquid chromatography chromatogram of the total extract, which was established in a previous study. Furthermore, the biological activities, including antioxidant activities, acetyl cholinesterase inhibitory capacities, antihyaluronidase activities, and anti-inflammatory effects, were evaluated in MH7A cells. The results demonstrated that fraction E could significantly prevent oxidation and inhibit hyaluronidase and acetyl cholinesterase. Finally, the main flavonoids in fractions A and E from P. forrestii Schltr. were purified, and the compounds were identified as chlorogenic acid, quercetin-3-O-alpha-L-arabinopyranoside, and quercetin-7-O-beta-D-glucopyranoside. The chemical structures were confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy. Furthermore, the inhibitory effects of these compounds against complete Freund's adjuvant-induced secondary immune arthritis in rats were evaluated. Title: Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus Chen H, Li J, Yan L, Cao J, Li D, Huang GY, Shi WJ, Dong W, Zha J and Xie L <5 more author(s)> Chen H, Li J, Yan L, Cao J, Li D, Huang GY, Shi WJ, Dong W, Zha J, Ying GG, Zhong H, Wang Z, Huang Y, Luo Y, Xie L (- 5) Ref: Fish Shellfish Immunol, 97:283, 2019 : PubMed ESTHER: Chen_2019_Fish.Shellfish.Immunol_97_283 PubMedSearch: Chen 2019 Fish.Shellfish.Immunol 97 283 PubMedID: 31863904 Abstract Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 mug/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 mug/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1beta, IFN-gamma and TNF-alpha) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 mug/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme alpha-glucosidase (alpha-Glu) in the intestine at 12 mug/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus. Title: A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review Li T, Feng Y, Liu Y, He C, Liu J, Chen H, Deng Y, Li M, Li W and Ling J <8 more author(s)> Li T, Feng Y, Liu Y, He C, Liu J, Chen H, Deng Y, Li M, Li W, Song J, Niu Z, Sang S, Wen J, Men M, Chen X, Li J, Liu X, Ling J (- 8) Ref: Gene, 704:113, 2019 : PubMed ESTHER: Li_2019_Gene_704_113 PubMedSearch: Li 2019 Gene 704 113 PubMedID: 30974196 Gene_locus related to this paper: human-ABHD12 Abstract Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12. Title: Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of beta-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer's Disease Wang Y, Xia J, Shen M, Zhou Y, Wu Z, Shi Y, Xu J, Hou L, Zhang R and Wang H <4 more author(s)> Wang Y, Xia J, Shen M, Zhou Y, Wu Z, Shi Y, Xu J, Hou L, Zhang R, Qiu Z, Xie Q, Chen H, Zhang Y, Wang H (- 4) Ref: Front Aging Neurosci, 11:3, 2019 : PubMed ESTHER: Wang_2019_Front.Aging.Neurosci_11_3 PubMedSearch: Wang 2019 Front.Aging.Neurosci 11 3 PubMedID: 30723404 Inhibitor(s) related to this paper: bis9-(-)-nor-meptazinol Abstract Alzheimer's disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the beta-amyloid (Abeta) aggregation process. In this study, we bilaterally injected Abeta oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Abeta plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFalpha and IL-6) induced by Abeta were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Abeta intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Abeta deposition and the inflammatory response in the brain. Title: Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection Zhang H, Liu J, Zhu X, Li X, Jin W, Chen H, Wu M, Li C, Liu C and Ding Y <1 more author(s)> Zhang H, Liu J, Zhu X, Li X, Jin W, Chen H, Wu M, Li C, Liu C, JunqiNiu, Ding Y (- 1) Ref: Antiviral Res, :104693, 2019 : PubMed ESTHER: Zhang_2019_Antiviral.Res__104693 PubMedSearch: Zhang 2019 Antiviral.Res 104693 PubMedID: 31838002 Abstract BACKGROUND & AIMS: Pradefovir is a liver targeted novel prodrug of adefovir (PMEA) developed to provide higher antiviral activity with reduced systemic toxicities. This study evaluated the tolerability, pharmacokinetics, and antiviral activity of pradefovir in patients with chronic hepatitis B (CHB) virus infection. METHODS: Non-cirrhotic, treatment-naive subjects with CHB were divided into five groups (10 patients each) and randomized within each group in a ratio of 6:2:2 to receive an ascending dose of 30, 60, 75, 90, or 120mg pradefovir, 10mg adefovir dipivoxil (ADV), or 300mg tenofovir disoproxil fumarate (TDF) once a day for 28 days. RESULTS: A total of 51 subjects were randomized and 49 subjects completed the study. The groups were well matched and included 39 males, of whom 71% were hepatitis B e-antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.4-7.16 log10 IU/mL. No subject experienced a serious adverse event or nephrotoxicity. The most frequently reported adverse event was asymptomatic reduction in blood cholinesterase levels in the pradefovir group which recovered without any treatment about 13+/-7 days after drug discontinuation. This adverse event was not observed in the ADV and TDF groups. The mean changes in serum HBV DNA were -2.78, -2.77, -3.08, -3.18, -3.44, -2.34, and -3.07 log10 IU/mL at 30, 60, 75, 90, and 120mg pradefovir, 10mg ADV and 300mg TDF, respectively, with plateau levels reached with 60mg pradefovir. Pradefovir and its metabolite PMEA showed linear pharmacokinetics proportional to the dose. The half-life of PMEA in the pradefovir group was 11.47-17.63h. CONCLUSIONS: Short-term use of pradefovir was well tolerated. A decline in HBV DNA levels was superior to TDF at higher doses of pradefovir. 30-60mg pradefovir is recommended for CHB treatment. CLINICAL TRIAL NUMBER: CTR20150224. Title: Graphene oxide disrupts the protein-protein interaction between Neuroligin/NLG-1 and DLG-1 or MAGI-1 in nematode Caenorhabditis elegans Zhao Y, Chen H, Yang Y, Wu Q, Wang D Ref: Sci Total Environ, 700:134492, 2019 : PubMed ESTHER: Zhao_2019_Sci.Total.Environ_700_134492 PubMedSearch: Zhao 2019 Sci.Total.Environ 700 134492 PubMedID: 31627046 Gene_locus related to this paper: caeel-NLGN1, human-NLGN1 Abstract Graphene oxide (GO) is a carbon-based engineered nanomaterial (ENM). Using Caenorhabditis elegans as an animal model, we investigated the effect of GO exposure on protein-protein interactions. In nematodes, NLG-1/Neuroligin, a postsynaptic protein, acted only in the neurons to regulate the GO toxicity. In the neurons, DLG-1, a PSD-95 protein, and MAGI-1, a S-SCAM protein, were identified as the downstream targets of NLG-1 in the regulation of GO toxicity. PKC-1, a serine/threonine protein kinase C, further acted downstream of neuronal DLG-1 and MAGI-1 to regulate the GO toxicity. Co-immunoprecipitation analysis demonstrated the protein-protein interaction between NLG-1 and DLG-1 or MAGI-1. After GO expression, this protein-protein interaction between NLG-1 and DLG-1 or MAGI-1 was significantly inhibited. Therefore, our data raised the evidence to suggest the potential of GO exposure in disrupting protein-protein interactions in organisms. Title: The molecular basis for lipase stereoselectivity Chen H, Meng X, Xu X, Liu W, Li S Ref: Applied Microbiology & Biotechnology, 102:3487, 2018 : PubMed ESTHER: Chen_2018_Appl.Microbiol.Biotechnol_102_3487 PubMedSearch: Chen 2018 Appl.Microbiol.Biotechnol 102 3487 PubMedID: 29500755 Abstract Lipases are among the most applied biocatalysts in organic synthesis to catalyze the kinetic resolution of a wide range of racemic substrates to yield optically pure compounds. Due to the rapidly increased demands for optically pure compounds, deep understanding of the molecular basis for lipase stereoselectivity and how to obtain lipases with excellent asymmetric selectivity have become one of primary research goals in this field. This review is focused on the molecular factors that have impacts on the stereoselectivity of lipases including the steric complementarity between the lipase topological structure and its substrate, the regional structural flexibility, the hydrogen bonds between the residues around the catalytic site and the tetrahedral intermediates, and the electrostatic interactions between surface residues. Moreover, the synergistic effects of these structural factors on the catalytic properties including stereoselectivity, activity, and stability are also discussed. 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: Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice Chen H, Wu X, Gu X, Zhou Y, Ye L, Zhang K, Pan H, Wang J, Wei H and Han YF <5 more author(s)> Chen H, Wu X, Gu X, Zhou Y, Ye L, Zhang K, Pan H, Wang J, Wei H, Zhu B, Naman CB, Mak SH, Carlier PR, Cui W, Han YF (- 5) Ref: Front Cell Neurosci, 12:396, 2018 : PubMed ESTHER: Chen_2018_Front.Cell.Neurosci_12_396 PubMedSearch: Chen 2018 Front.Cell.Neurosci 12 396 PubMedID: 30483056 Inhibitor(s) related to this paper: Hupyridone Abstract Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD. Title: Tacrine(10)-hupyridone, a dual-binding acetylcholinesterase inhibitor, potently attenuates scopolamine-induced impairments of cognition in mice Chen H, Xiang S, Huang L, Lin J, Hu S, Mak SH, Wang C, Wang Q, Cui W, Han Y Ref: Metabolic Brain Disease, 33:1131, 2018 : PubMed ESTHER: Chen_2018_Metab.Brain.Dis_33_1131 PubMedSearch: Chen 2018 Metab.Brain.Dis 33 1131 PubMedID: 29564727 Inhibitor(s) related to this paper: Hupyridone Abstract Tacrine(10)-hupyridone (A10E) was designed as a dual-binding acetylcholinesterase (AChE) inhibitor from the modification of tacrine and a fragment of huperzine A. We have found that A10E effectively inhibited AChE in a mixed competitive manner, with an IC50 of 26.4 nM, which is more potent than those of tacrine and huperzine A. Most importantly, we have shown, for the first time that A10E attenuated scopolamine-induced cognitive impairments without affecting motor function in mice. A10E effectively attenuated impairments of learning and memory to a similar extent as donepezil, an inhibitor of AChE used for treating Alzheimer's disease (AD). In addition, A10E significantly decreased AChE activity in the brain of mice, suggesting that A10E might cross the brain blood-barrier. Taken together, our results demonstrated that A10E, a designed dual-binding AChE inhibitor, could effectively reverse cognitive impairments, indicating that A10E might provide therapeutic efficacy for AD treatment. Title: Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY and Woo PCY <11 more author(s)> Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY, Wong ACP, Ahmed SS, Cai JP, Chan JFW, Sun Y, Jin D, Chen H, Lau TCK, Kok RKH, Li W, Yuen KY, Woo PCY (- 11) Ref: J Infect Dis, 218:197, 2018 : PubMed ESTHER: Lau_2018_J.Infect.Dis_218_197 PubMedSearch: Lau 2018 J.Infect.Dis 218 197 PubMedID: 29346682 Abstract Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4. Title: The Herb-Drug Interaction of Clopidogrel and Xuesaitong Dispersible Tablet by Modulation of the Pharmacodynamics and Liver Carboxylesterase 1A Metabolism Ma S, Dai G, Bi X, Gong M, Miao C, Chen H, Gao L, Zhao W, Liu T, Zhang N Ref: Evid Based Complement Alternat Med, 2018:5651989, 2018 : PubMed ESTHER: Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989 PubMedSearch: Ma 2018 Evid.Based.Complement.Alternat.Med 2018 5651989 PubMedID: 30498515 Abstract Objective: Clopidogrel and Xuesaitong dispersible tablet (XST) have been clinically proven to be effective for treating cardiocerebrovascular disease. The present study was to investigate the herb-drug interaction of Clopidogrel and XST by modulation of the pharmacodynamics and liver Carboxylesterase 1A(CES1A) metabolism. Methods: 30 male SD rats were randomly divided into a control group (equal volumes of saline, 6 rats for mRNA analysis), a clopidogrel group (clopidogrel with dose 30 mg/kg), and a combination group (clopidogrel and XST, with dose 30 and 50 mg/kg respectively, each group continuous administration once daily for 30 days). The clopidogrel and combination group comprised 12 rats, with 6 designated for mRNA analysis and 6 for the pharmacokinetic study. The 2-bromo-3'-methoxyacetophenone- (MPB-) derivatized clopidogrel active thiol metabolite (CAMD) was measured by UHPLC-MS/MS for pharmacokinetics (n=6). The expression of CES1A mRNA was examined with real-time RT-PCR (n=6). Molecular simulation was used to investigate the inhibition effect of XST on the CES1A protein. The CAMD pharmacodynamics and CES1A metabolism were investigated to evaluated the herb-drug interaction. Results: Clopidogrel and XST coadministration appreciably increased the Cmax, AUC, and MRT of CAMD. However, the expression of CES1A mRNA was decreased accordingly. It also indicated that the bioactive components in XST had good interaction with the CES1A metabolism target by molecular simulation. The animal study indicated that clopidogrel and XST coadministration produced significant herb-drug interactions at active CAMD pharmacokinetic and CES1A metabolic enzyme aspect. Conclusion: 30-days dose of coadministration altered hepatic CES1A protein and resulted in reduced plasma levels of active CAMD. both the decreased CES1A mRNA expression and the inhibition on the protein were due to the combination of XST, which accordingly upregulated the pharmacokinetics of plasma active CAMD. Title: Bis(9)-(-)-Meptazinol, a novel dual-binding AChE inhibitor, rescues cognitive deficits and pathological changes in APP/PS1 transgenic mice Shi Y, Huang W, Wang Y, Zhang R, Hou L, Xu J, Qiu Z, Xie Q, Chen H and Wang H <1 more author(s)> Shi Y, Huang W, Wang Y, Zhang R, Hou L, Xu J, Qiu Z, Xie Q, Chen H, Zhang Y, Wang H (- 1) Ref: Transl Neurodegener, 7:21, 2018 : PubMed ESTHER: Shi_2018_Transl.Neurodegener_7_21 PubMedSearch: Shi 2018 Transl.Neurodegener 7 21 PubMedID: 30237878 Abstract Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder, which is the most common form of dementia. Intensive efforts have been made to find effective and safe treatment against AD. Acetylcholinesterase inhibitors (AChEIs) have been widely used for the treatment of mild to moderate AD. In this study, we investigated the effect of Bis(9)-(-)-Meptazinol (B9M), a novel potential dual-binding acetylcholinesterase (AChE) inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Methods: B9M (0.1 mug/kg, 0.3 mug/kg, and 1 mug/kg) was administered by subcutaneous injection into eight-month-old APP/PS1 transgenic mice for four weeks. Morris water maze, nest-building and novel object recognition were used to examine learning and memory ability. Abeta levels and Abeta plaque were evaluated by ELISA and immunochemistry. Results: Our results showed that chronic treatment with B9M significantly improved the cognitive function of APP/PS1 transgenic mice in the Morris water maze test, nest-building test and novel object recognition test. Moreover, B9M improved cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of the AChE activity, Abeta plaque burden, levels of Abeta and the consequent activation of astrocytes and microglia in the brain of APP/PS1 transgenic mice. Most of important, the most effective dose of B9M in the present study is 1 mug/kg, which is one thousand of the dosage of Donepezil acted as the control treatment. Furthermore, B9M reduced Abeta plaque burden better than Donepezil. Conclusion: These results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties. Title: Lychee seed extract protects against neuronal injury and improves cognitive function in rats with type II diabetes mellitus with cognitive impairment Tang Y, Yu C, Wu J, Chen H, Zeng Y, Wang X, Yang L, Mei Q, Cao S, Qin D Ref: Int J Mol Med, 41:251, 2018 : PubMed ESTHER: Tang_2018_Int.J.Mol.Med_41_251 PubMedSearch: Tang 2018 Int.J.Mol.Med 41 251 PubMedID: 29138799 Abstract Lychee seed is a traditional Chinese medicine and has many beneficial effects such as modulation of blood sugar and lipids, antioxidation, antivirus and antitumor. Studies have indicated that type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) share common biological mechanisms including insulin resistance, impaired glucose metabolism, betaamyloid (Abeta) formation, oxidative stress and presence of advanced glycation end products (AGEs). The present study investigated the effects of lychee seed extract (LSE) on neuroprotection, cognitive function improvement and possible underlying mechanisms in a rat model of T2DM with cognitive impairment. We analyzed the chemical profile of LSE using a UHPLCSPD chromatogram and evaluated its effect on the improvement of spatial learning and memory of rats by a Morris water maze. The levels of glucose, insulin, Abeta, AGEs, Tau protein and acetylcholinesterase in the blood and/or hippocampus of rats were determined by bloodglucose meter, radioimmunoassay, chemical chromatometry, enzymelinked immunosorbent assay (ELISA) and immunohistochemical analysis, respectively. Results demonstrated that LSE consists of eight major and around 20 minor ingredients, and it remarkably prevents neuronal injury and improves cognitive functions in T2DM rats. The levels of glucose, insulin, Abeta, AGEs and Tau protein were significantly increased in the blood and/or hippocampus of T2DM rats, while LSE remarkably decreased their levels compared to vehicle treatment (P<0.01). The possible mechanisms may be associated with IR improvement and decreased formations of Abeta, AGEs and Tau protein in the hippocampus of T2DM rats. LSE may be developed as the agent for the treatment of T2DM and/or AD clinically. Title: Identification of interneurons required for the aversive response of Caenorhabditis elegans to graphene oxide Xiao G, Chen H, Krasteva N, Liu Q, Wang D Ref: J Nanobiotechnology, 16:45, 2018 : PubMed ESTHER: Xiao_2018_J.Nanobiotechnology_16_45 PubMedSearch: Xiao 2018 J.Nanobiotechnology 16 45 PubMedID: 29703212 Abstract BACKGROUND: So far, how the animals evade the environmental nanomaterials is still largely unclear. In this study, we employed in vivo assay system of Caenorhabditis elegans to investigate the aversive behavior of nematodes to graphene oxide (GO) and the underlying neuronal basis. RESULTS: In this assay model, we detected the significant aversive behavior of nematodes to GO at concentrations more than 50 mg/L. Loss-of-function mutation of nlg-1 encoding a neuroligin with the function in connecting pre- and post-synaptic neurons suppressed the aversive behavior of nematodes to GO. Moreover, based on the neuron-specific activity assay, we found that the NLG-1 activity in AIY or AIB interneurons was required for the regulation of aversive behavior to GO. The neuron-specific activities of NLG-1 in AIY or AIB interneurons were also required for the regulation of GO toxicity. CONCLUSIONS: Using nlg-1 mutant as a genetic tool, we identified the AIY and AIB interneurons required for the regulation of aversive behavior to GO. Our results provide an important neuronal basis for the aversive response of animals to environmental nanomaterials. Title: The impacts of pesticide and nicotine exposures on functional brain networks in Latino immigrant workers Bahrami M, Laurienti PJ, Quandt SA, Talton J, Pope CN, Summers P, Burdette JH, Chen H, Liu J and Simpson SL <2 more author(s)> Bahrami M, Laurienti PJ, Quandt SA, Talton J, Pope CN, Summers P, Burdette JH, Chen H, Liu J, Howard TD, Arcury TA, Simpson SL (- 2) Ref: Neurotoxicology, 62:138, 2017 : PubMed ESTHER: Bahrami_2017_Neurotoxicol_62_138 PubMedSearch: Bahrami 2017 Neurotoxicol 62 138 PubMedID: 28583619 Abstract Latino immigrants that work on farms experience chronic exposures to potential neurotoxicants, such as pesticides, as part of their work. For tobacco farmworkers there is the additional risk of exposure to moderate to high doses of nicotine. Pesticide and nicotine exposures have been associated with neurological changes in the brain. Long-term exposure to cholinesterase-inhibiting pesticides, such as organophosphates and carbamates, and nicotine place this vulnerable population at risk for developing neurological dysfunction. In this study we examined whole-brain connectivity patterns and brain network properties of Latino immigrant workers. Comparisons were made between farmworkers and non-farmworkers using resting-state functional magnetic resonance imaging data and a mixed-effects modeling framework. We also evaluated how measures of pesticide and nicotine exposures contributed to the findings. Our results indicate that despite having the same functional connectivity density and strength, brain networks in farmworkers had more clustered and modular structures when compared to non-farmworkers. Our findings suggest increased functional specificity and decreased functional integration in farmworkers when compared to non-farmworkers. Cholinesterase activity was associated with population differences in community structure and the strength of brain network functional connections. Urinary cotinine, a marker of nicotine exposure, was associated with the differences in network community structure. Brain network differences between farmworkers and non-farmworkers, as well as pesticide and nicotine exposure effects on brain functional connections in this study, may illuminate underlying mechanisms that cause neurological implications in later life. Title: Graphene Oxide Dysregulates Neuroligin/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans Chen H, Li H, Wang D Ref: Sci Rep, 7:41655, 2017 : PubMed ESTHER: Chen_2017_Sci.Rep_7_41655 PubMedSearch: Chen 2017 Sci.Rep 7 41655 PubMedID: 28128356 Abstract Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure. Title: Novel Double-Potential Electrochemiluminescence Ratiometric Strategy in Enzyme-Based Inhibition Biosensing for Sensitive Detection of Organophosphorus Pesticides Chen H, Zhang H, Yuan R, Chen S Ref: Analytical Chemistry, 89:2823, 2017 : PubMed ESTHER: Chen_2017_Anal.Chem_89_2823 PubMedSearch: Chen 2017 Anal.Chem 89 2823 PubMedID: 28192982 Abstract Generally, electrochemiluminescence (ECL) ratiometric assays were based on the energy transfer (ET) between an emitter and a metal nanomaterial or between two different emitters. The choice of suitable energy donor-acceptor pair and the distance dependence of ET would greatly limit the practical application of ratiometric assays. This work explored a novel double-potential ECL ratiometry without the ET for organophosphorus pesticides (OPs) analysis, in which, reduced graphene oxide-CdTe quantum dots (RGO-CdTe QDs) and carboxyl-conjugated polymer dots (PFO dots) were chosen as cathodic and anodic ECL emitters, and the reactant (dissolved O2) and the product (H2O2) in enzymatic reactions served as their coreactants, respectively. With the occurrence of the enzymatic reactions induced by the acetylcholinesterase (AChE) and choline oxidase (ChOx), the cathodic ECL signal from RGO-CdTe QDs was at "signal off" state due to the consumption of dissolved O2. Meanwhile, the anodic ECL signal from PFO dots was at "signal on" state due to the in situ generation of H2O2. In the presence of OPs, the cathodic ECL signal would increase while the anodic ECL signal would decline correspondingly due to the inhibition of OPs on the activity of AChE. Using the reactant and the product in enzymatic reactions as the coreactants of two different ECL emitters, we conveniently achieved the opposite change trend in two ECL signals for the ratiometric detection of OPs, which exhibited a greatly improved accuracy, reliability and sensitivity, thus, showing a great attraction for developing ECL ratiometric systems for the bioanalysis. Title: Effect of Linker Length and Flexibility on the Clostridium thermocellum Esterase Displayed on Bacillus subtilis Spores Chen H, Wu B, Zhang T, Jia J, Lu J, Chen Z, Ni Z, Tan T Ref: Appl Biochem Biotechnol, 182:168, 2017 : PubMed ESTHER: Chen_2017_Appl.Biochem.Biotechnol_182_168 PubMedSearch: Chen 2017 Appl.Biochem.Biotechnol 182 168 PubMedID: 27933482 Abstract In fusion protein design strategies, the flexibility and length of linkers are important parameters affecting the bioactivity of multifunctional proteins. A series of fusion proteins with different linkers were constructed. The effect of temperature, pH, and organic solvents was investigated on the enzymatic activity. Fusion proteins with P1(PTPTPT) and P2((PTPTPT)2) linkers remained highly active with wide temperature range. At pH 9.6, the relative activity of fusion proteins with (PTPTPT)2 and S2(EGKSSGSGSESKST) linkers was 70 and 62 % (1.75 and 1.5 times of that of non-linker ones). Fusion proteins with S3((GGGGS)4) linker retained 55 % activity after 5 h of incubation at 80 degrees C (1.2-fold of that of non-linker fusion proteins and 1.9-fold of GGGGS-linker fusion proteins). Finally, the relative activity of fusion proteins having different linkers was increased with 20 % dimethyl sulfoxide (DMSO) and methanol; relative activity of fusion proteins with EGKSSGSGSESKST linkers was enhanced 1.5- and 2.2-fold, respectively. These results suggest that longer flexible linker can enhance the activity and stability of displayed esterase than shorter flexible linker. Optimizing peptide linkers with length, flexibility, and amino acid composition could improve the thermostability and activity of the displayed enzyme. Title: Orlistat response to missense mutations in lipoprotein lipase Chen H, Jia J, Ni Z, Vastermark A, Wu B, Le Y, Jawad U Ref: Biotechnol Appl Biochem, 64:464, 2017 : PubMed ESTHER: Chen_2017_Biotechnol.Appl.Biochem_64_464 PubMedSearch: Chen 2017 Biotechnol.Appl.Biochem 64 464 PubMedID: 27097985 Abstract The human lipoprotein lipase (LPL) is a therapeutic target for obesity, and inhibition of LPL with the approved small molecule agent orlistat has been widely used in clinic to treat obesity-related health problems such as diabetes and cardiovascular diseases. However, a variety of missense mutations in LPL protein have been observed, which may cause resistance or sensitization for orlistat, largely limiting the clinical applications of orlistat in obesity therapy. Here, we integrated molecular dynamics simulations and enzyme inhibition to investigate orlistat response to 16 disorder-associated missense mutations in LPL catalytic domain. It was found that most mutations have a modest effect on orlistat binding, and only few can exert strong impact to the binding. Three unfavorable (Trp86Arg, Ile194Thr, and Glu242Lys) and two favorable (His136Arg and Gly188Glu) mutations were identified, which can alter the binding affinity and inhibitory activity of orlistat considerably. Structural and energetic analysis revealed that these potent mutations induce orlistat resistance and sensitization by directly influencing the intermolecular interaction between LPL and orlistat or by indirectly addressing allosteric effect on LPL structure. Title: Online Monitoring of Enzymatic Reactions Using Time-Resolved Desorption Electrospray Ionization Mass Spectrometry Cheng S, Wu Q, Xiao H, Chen H Ref: Analytical Chemistry, 89:2338, 2017 : PubMed ESTHER: Cheng_2017_Anal.Chem_89_2338 PubMedSearch: Cheng 2017 Anal.Chem 89 2338 PubMedID: 28192910 Abstract Electrospray ionization mass spectrometry (ESI-MS) is powerful for determining enzymatic reaction kinetics because of its soft ionization nature. However, it is limited to use ESI-favored solvents containing volatile buffers (e.g., ammonium acetate). In addition, lack of a quenching step for online ESI-MS reaction monitoring might introduce inaccuracy, due to the possible acceleration of reaction in the sprayed microdroplets. To overcome these issues, this study presents a new approach for online measuring enzymatic reaction kinetics using desorption electrospray ionization mass spectrometry (DESI-MS). By using DESI-MS, enzymatic reaction products in a buffered aqueous media (e.g., a solution containing Tris buffer or high concentration of inorganic salts) could be directly detected. Furthermore, by adjusting the pH and solvent composition of the DESI spray, reaction can be online quenched to avoid the postionization reaction event, leading to fast and accurate measurement of kinetic constants. Reaction time control can be obtained simply by adjusting the injection flow rates of enzyme and substrate solutions. Enzymatic reactions examined in this study include hydrolysis of 2-nitrophenyl-beta-D-galactopyranoside by beta-galactosidase and hydrolysis of acetylcholine by acetylcholinesterase. Derived Michaelis-Menten constants Km for these two reactions were determined to be 214 muM and 172 muM, respectively, which are in good agreement with the values of 300 muM and 230 muM reported in literature, validating the DESI-MS approach. Furthermore, this time-resolved DESI-MS also allowed us to determine Km and turnover number kcat for trypsin digestion of angiotensin II (Km and kcat are determined to be 6.4 mM and 1.3 s-1, respectively). Title: Molecular Mechanism of MDGA1: Regulation of Neuroligin 2:Neurexin Trans-synaptic Bridges Gangwar SP, Zhong X, Seshadrinathan S, Chen H, Machius M, Rudenko G Ref: Neuron, 94:1132, 2017 : PubMed ESTHER: Gangwar_2017_Neuron_94_1132 PubMedSearch: Gangwar 2017 Neuron 94 1132 PubMedID: 28641112 Gene_locus related to this paper: ratno-2neur Abstract Neuroligins and neurexins promote synapse development and validation by forming trans-synaptic bridges spanning the synaptic cleft. Select pairs promote excitatory and inhibitory synapses, with neuroligin 2 (NLGN2) limited to inhibitory synapses and neuroligin 1 (NLGN1) dominating at excitatory synapses. The cell-surface molecules, MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) and 2 (MDGA2), regulate trans-synaptic adhesion between neurexins and neuroligins, impacting NLGN2 and NLGN1, respectively. We have determined the molecular mechanism of MDGA action. MDGA1 Ig1-Ig2 is sufficient to bind NLGN2 with nanomolar affinity; its crystal structure reveals an unusual locked rod-shaped array. In the crystal structure of the complex, two MDGA1 Ig1-Ig2 molecules each span the entire NLGN2 dimer. Site-directed mutagenesis confirms the observed interaction interface. Strikingly, Ig1 from MDGA1 binds to the same region on NLGN2 as neurexins do. Thus, MDGAs regulate the formation of neuroligin-neurexin trans-synaptic bridges by sterically blocking access of neurexins to neuroligins. Title: Colorimetric biosensor for the assay of paraoxon in environmental water samples based on the iodine-starch color reaction Guo L, Li Z, Chen H, Wu Y, Chen L, Song Z, Lin T Ref: Anal Chim Acta, 967:59, 2017 : PubMed ESTHER: Guo_2017_Anal.Chim.Acta_967_59 PubMedSearch: Guo 2017 Anal.Chim.Acta 967 59 PubMedID: 28390486 Abstract In this work, a new colorimetric biosensor for the assay of paraoxon was developed via the conventional iodine-starch color reaction and multi-enzyme cascade catalytic reactions. In the presence of acetylcholine chloride, acetylcholinesterase (AChE) and choline oxidase (ChO) catalyzed the formation of H2O2, which then activated horseradish peroxidase (HRP) to catalyze the oxidation of KI to produce an iodine-starch color reaction. Upon exposure to paraoxon, the catalytic activity of AChE was inhibited and less H2O2 generated, resulting in a decrease in the production of I2 and a drop in the intensity of solution color. This colorimetric biosensor showed high sensitivity for the assay of paraoxon with a limit of detection 4.7 ppb and was applied for the assay of paraoxon in spiked real samples. By employing the conventional iodine-starch color reaction, this biosensor has the potential of on-site assay of OPs residues in environmental samples. Title: The asparagus genome sheds light on the origin and evolution of a young Y chromosome Harkess A, Zhou J, Xu C, Bowers JE, Van der Hulst R, Ayyampalayam S, Mercati F, Riccardi P, McKain MR and Chen G <31 more author(s)> Harkess A, Zhou J, Xu C, Bowers JE, Van der Hulst R, Ayyampalayam S, Mercati F, Riccardi P, McKain MR, Kakrana A, Tang H, Ray J, Groenendijk J, Arikit S, Mathioni SM, Nakano M, Shan H, Telgmann-Rauber A, Kanno A, Yue Z, Chen H, Li W, Chen Y, Xu X, Zhang Y, Luo S, Gao J, Mao Z, Pires JC, Luo M, Kudrna D, Wing RA, Meyers BC, Yi K, Kong H, Lavrijsen P, Sunseri F, Falavigna A, Ye Y, Leebens-Mack JH, Chen G (- 31) Ref: Nat Commun, 8:1279, 2017 : PubMed ESTHER: Harkess_2017_Nat.Commun_8_1279 PubMedSearch: Harkess 2017 Nat.Commun 8 1279 PubMedID: 29093472 Gene_locus related to this paper: aspof-a0a5p1ew48 Abstract Sex chromosomes evolved from autosomes many times across the eukaryote phylogeny. Several models have been proposed to explain this transition, some involving male and female sterility mutations linked in a region of suppressed recombination between X and Y (or Z/W, U/V) chromosomes. Comparative and experimental analysis of a reference genome assembly for a double haploid YY male garden asparagus (Asparagus officinalis L.) individual implicates separate but linked genes as responsible for sex determination. Dioecy has evolved recently within Asparagus and sex chromosomes are cytogenetically identical with the Y, harboring a megabase segment that is missing from the X. We show that deletion of this entire region results in a male-to-female conversion, whereas loss of a single suppressor of female development drives male-to-hermaphrodite conversion. A single copy anther-specific gene with a male sterile Arabidopsis knockout phenotype is also in the Y-specific region, supporting a two-gene model for sex chromosome evolution. Title: Individual and binary mixture effects of bisphenol A and lignin-derived bisphenol in Daphnia magna under chronic exposure Li D, Chen H, Bi R, Xie H, Zhou Y, Luo Y, Xie L Ref: Chemosphere, 191:779, 2017 : PubMed ESTHER: Li_2017_Chemosphere_191_779 PubMedSearch: Li 2017 Chemosphere 191 779 PubMedID: 29080539 Abstract In recent years, many new chemicals have been synthesized from biomass with an aim for sustainable development by replacing the existing toxic chemicals with those having similar properties and applications. However, the effects of these new chemicals on aquatic organisms remain relatively unknown. In this study, the effects of bisphenol A (BPA) and lignin-derived bisphenol (LD-BP, a BPA analogue) on Daphnia magna were evaluated. The animals were exposed to BPA, LD-BP, and their binary mixture at concentrations (2-2000 mug L-1) for 21 days. The expression of various biochemical markers and the effects on growth, molting, and reproduction parameters were examined. The results showed that the weight of daphnids significantly increased after exposure to BPA, LD-BP, and the binary mixture relative to that of the control animals. The activity of superoxide dismutase was significantly inhibited by LD-BP and the binary mixture. At the highest exposure concentration of the binary mixture, the activities of acetylcholinesterase and alpha-glucosidase, fecundity, and the number of neonates per brood were significantly altered. Our results showed that the effects of BPA and LD-BP on D. magna were generally comparable, except for the effect on the weight at their environmentally relevant concentrations (e.g., <20 mug L-1). The effects on the reproduction of D. magna could be mainly due to the shift in energy redistribution under BPA and LD-BP exposures. Our results implied that exposures to both BPA and LD-BP could potentially cause deleterious effects at the population level in D. magna. Title: A novel assay to determine acetylcholinesterase activity: The application potential for screening of drugs against Alzheimer's disease Peng L, Rong Z, Wang H, Shao B, Kang L, Qi H, Chen H Ref: Biomedical Chromatography, 31:, 2017 : PubMed ESTHER: Peng_2017_Biomed.Chromatogr_31_ PubMedSearch: Peng 2017 Biomed.Chromatogr 31 PubMedID: 28295437 Abstract Acetycholinesterase (AChE) that regulates hydrolysis of acetylcholine (ACh) in the brain, is an important target for treatment of Alzheimer's disease (AD), a feature of which is ACh deficiency. However, the methods to precisely determine AChE activity are still under development. We developed a new method to exploit acetylcholine-d4 as a surrogate substrate of ACh and measure product choline-d4 via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay detected activity of AChE present in the normal mouse brain, which is consistent with the standard Ellman assay that determines products spectrophotometrically. In AD mouse models, the result of LC-MS/MS assay showed significant higher AChE activity than that seen in control normal mice, while treatment of AD mice with an AChE inhibitor, huperzine A, led to partial decreases in AChE activity. Our results suggest that this surrogate-based LC-MS/MS method is a new, sensitive and convenient assay for the determination of AChE activity, providing a useful means for screening active compounds that target AChE. Title: Prunella vulgaris L., an Edible and Medicinal Plant, Attenuates Scopolamine-Induced Memory Impairment in Rats Qu Z, Zhang J, Yang H, Gao J, Chen H, Liu C, Gao W Ref: Journal of Agricultural and Food Chemistry, 65:291, 2017 : PubMed ESTHER: Qu_2017_J.Agric.Food.Chem_65_291 PubMedSearch: Qu 2017 J.Agric.Food.Chem 65 291 PubMedID: 28001065 Abstract Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-kappaB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement. Title: Impact of orientation and flexibility of peptide linkers on T. maritima lipase Tm1350 displayed on Bacillus subtilis spores surface using CotB as fusion partner Ullah J, Chen H, Vastermark A, Jia J, Wu B, Ni Z, Le Y, Wang H Ref: World J Microbiol Biotechnol, 33:166, 2017 : PubMed ESTHER: Ullah_2017_World.J.Microbiol.Biotechnol_33_166 PubMedSearch: Ullah 2017 World.J.Microbiol.Biotechnol 33 166 PubMedID: 28822027 Abstract Fusion protein construction often requires peptide linkers for prolonged conformation, extended stability and enzyme activity. In this study a series of fusion between Thermotoga maritima lipase Tm1350 and Bacillus subtillis coat protein CotB, comprising of several peptide linkers, with different length, flexibility and orientations were constructed. Effects of temperature, pH and chemicals were examined, on the activity of displayed enzyme. The fusion protein with longer flexible linkers L9 [(GGGGS)4] and L7 (GGGGS-GGGGS-EAAAK-EAAAK-GGGGS-GGGGS) possess 1.29 and 1.16-fold higher activity than the original, under optimum temperature and pH respectively. Moreover, spore surface displaying Tm1350 with L3 (EAAAK-GGGGS) and L9 ((GGGGS)4) showed extended thermostably, maintaining 1.40 and 1.35-fold higher activity than the original respectively, at 80 degrees C after 5 h of incubation. The enzyme activity of linkers with different orientation, including L5, L6 and L7 was determined, where L7 maintained 1.05 and 1.27-fold higher activity than L5 and L6. Effect of 0.1% proteinase K, bromelain, 20% ethanol and 30% methanol was investigated. Linkers with appropriate Glycine residues (flexible) showed higher activity than Alanine residues (rigid). The activity of the displayed enzyme can be improved by maintaining orientation and flexibility of peptide linkers, to evaluate high activity and stability in industrial processes. Title: In vivo metabolism of organophosphate flame retardants and distribution of their main metabolites in adult zebrafish Wang G, Chen H, Du Z, Li J, Wang Z, Gao S Ref: Sci Total Environ, 590-591:50, 2017 : PubMed ESTHER: Wang_2017_Sci.Total.Environ_590-591_50 PubMedSearch: Wang 2017 Sci.Total.Environ 590-591 50 PubMedID: 28292737 Abstract Understanding the metabolism of chemicals as well as the distribution and depuration of their main metabolites in tissues are essential for evaluating their fate and potential toxicity in vivo. Herein, we investigated the metabolism of six typical organophosphate (OP) flame retardants (tripropyl phosphate (TPRP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tri-p-cresyl phosphate (p-TCP)) in adult zebrafish in laboratory at three levels (0, 1/150 LC50 (environmentally relevant level), and 1/30 LC50 per OP analog). Twenty main metabolites were detected in the liver of OPs-exposed zebrafish using high resolution mass spectrometry (Q-TOF). The reaction pathways involving scission of the ester bond (hydrolysis), cleavage of the ether bond, oxidative hydroxylation, dechlorination, and coupling with glucuronic acid were proposed, and were further confirmed by the frontier electron density and point charge calculations. Tissue distribution of the twenty metabolites revealed that liver and intestine with the highest levels of metabolites were the most active organs for OPs biotransformation among the studied tissues of intestine, liver, roe, brain, muscle, and gill, which showed the importance of hepatobiliary system (liver-bile-intestine) in the metabolism and excretion of OPs in zebrafish. Fast depuration of metabolites from tissues indicated that the formed metabolites might be not persistent in fish, and easily released into water. This study provides comprehensive information on the metabolism of OPs in the tissue of zebrafish, which might give some hints for the exploration of their toxic mechanism in aquatic life. Title: Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors Wang L, Wang Y, Tian Y, Shang J, Sun X, Chen H, Wang H, Tan W Ref: Bioorganic & Medicinal Chemistry, 25:360, 2017 : PubMed ESTHER: Wang_2017_Bioorg.Med.Chem_25_360 PubMedSearch: Wang 2017 Bioorg.Med.Chem 25 360 PubMedID: 27856236 Abstract A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- and submicromolar ranges. The most potent compound 3 exhibited comparable IC50 to the commercially available drug (rivastigmine). To better understand their structure activity relationships (SAR) and mechanisms of enzyme-inhibitor interactions, kinetic and molecular modeling studies including molecular docking and molecular dynamics (MD) simulations were carried out. Furthermore, compound 3 blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells and shows the required druggability and low cytotoxicity, suggesting this hybrid is a promising multifunctional drug candidate for Alzheimer's disease (AD) treatment. Title: Colorimetric assay of butyrylcholinesterase activity based on para-sulfonatocalix[4]arene-modified gold nanoparticles Wang X, Koh K, Chen H Ref: Sensors and Actuators B: Chemical, 251:869, 2017 : PubMed ESTHER: Wang_2017_Sens.Actuators.B.Chem_251_869 PubMedSearch: Wang 2017 Sens.Actuators.B.Chem 251 869 Abstract A novel colorimetric method has been developed for butyrylcholinesterase (BChE) assay and screening of its inhibitors based on para-sulfonatocalix[4]arene-modified gold nanoparticles (pSC4-AuNPs). The host-guest interaction between succinylcholine (SuCh, substrate of BChE) and two pSC4-AuNPs result in pSC4-AuNPs tending to aggregate. However, the hydrolyzed product of choline (Ch) has no coordination reactivity with pSC4. Therefore, owing to the hydrolysis of BChE, the aggregation of pSC4-AuNPs will be influenced by BChE activity. A simple colorimetric method for the assay of BChE activity can be developed. Under the optimized experimental conditions, the ratios of absorbance at a wavelength of 700 nm to that at 528 nm vary linearly with the BChE activity in the range from 0.05 to 0.25 U mL-1 with the lowest detection limit of 0.0068 U mL-1, providing a new tool for the direct measurement of BChE. Moreover, using this proposed method, the inhibition effect of Tacrine on BChE activity can be tested with IC50 values of 220 uM. This method has great potential not only for the detection of BChE activity but also for the screening of the inhibitors. Title: Bioaccumulation mechanism of organophosphate esters in adult zebrafish (Danio rerio) Wang G, Shi H, Du Z, Chen H, Peng J, Gao S Ref: Environ Pollut, 229:177, 2017 : PubMed ESTHER: Wang_2017_Environ.Pollut_229_177 PubMedSearch: Wang 2017 Environ.Pollut 229 177 PubMedID: 28599202 Abstract Although organophosphate esters (OPEs) have been detected with growing frequency in water ecosystems, the underlying accumulation mechanisms of these compounds in fish are still unknown. Here, we investigated the tissue-specific accumulation and depuration of seven OPEs in adult zebrafish at three levels (0, 1/150 LC50 (environmentally relevant level), and 1/30 LC50 per OPE congener) in laboratory after 19 days exposure and 3 days depuration. The bioaccumulation of OPEs varied among tissues. Muscle contained the lowest level of OPEs and liver had the highest level of two (TPP and TCEP) of the seven OPEs at steady state. The high levels and slow depuration rates of TDCIPP, TPHP, and TCP observed in roe indicated that the accumulated OPEs were potentially stored in roe and transferred to the next generation. After examination of the major metabolites (organophosphate diesters) in selected tissues, a physiologically based toxicokinetic (PBTK) model used in fish was adopted to explore the key factors affecting the bioaccumulation of OPEs in zebrafish. Biotransformation of OPEs with polychlorinated alkyl moieties (i.e. TDCIPP) and aryl moieties (i.e. TPHP and TCP) has more significant impacts on the accumulation than those of OPEs with alkyl or short chain chlorinated alkyl moieties. Furthermore, the partition process between tissues and blood was also investigated, and was demonstrated to be the dominant process for OPEs accumulation in zebrafish. This study provides critical information on the bioaccumulation, tissue distribution, and metabolization of OPEs in relation with OPE structures in fish, as well as the underlying bioaccumulation mechanisms/pathways of OPEs in aquatic life. Title: Four new bi-phenylethylchromones from artificial agarwood Xiang P, Mei W, Chen H, Kong F, Wang H, Liao G, Zhou L, Dai H Ref: Fitoterapia, 120:61, 2017 : PubMed ESTHER: Xiang_2017_Fitoterapia_120_61 PubMedSearch: Xiang 2017 Fitoterapia 120 61 PubMedID: 28576723 Abstract Four new bi-phenylethylchromones (1-4) were isolated from the EtOAc extract of artificial agarwood induced by holing method originating from Aquilaria sinensis (Lour.) Gilg. The structures of new compounds were unambiguously elucidated by one- and two-dimensional NMR and HRESIMS measurements, and the absolute configuration was determined by analysis of circular dichroism (CD) spectra. All compounds were tested for acetylcholinesterase (AChE) inhibitory activity using modified Ellman's colorimetric method and alpha-glucosidase inhibitory activity using PNPG method. Compounds 2-4 exhibited different levels of inhibitory activity against AChE with the inhibition ratios in the range of 10-45%. However, none of the compounds was active against the alpha-glucosidase. 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: Accumulation and effects of Cr(VI) in Japanese medaka (Oryzias latipes) during chronic dissolved and dietary exposures Chen H, Mu L, Cao J, Mu J, Klerks PL, Luo Y, Guo Z, Xie L Ref: Aquat Toxicol, 176:208, 2016 : PubMed ESTHER: Chen_2016_Aquat.Toxicol_176_208 PubMedSearch: Chen 2016 Aquat.Toxicol 176 208 PubMedID: 27162070 Abstract Chromium (Cr) is an essential metal and a nutritional supplement for both human and agricultural uses. It is also a pollutant from a variety of industrial uses. These uses can lead to elevated Cr levels in aquatic environments, where it can enter and affect aquatic organisms. Its accumulation and subsequent effects in fish have received relatively little attention, especially for chronic exposure. In the present study, Japanese medaka were chronically exposed to dissolved or dietary Cr(VI) for 3 months. Cr accumulation in liver, gills, intestine, and brain was evaluated. Effects on the antioxidant system, nervous system (acetylcholinesterase, AChE), digestive system (alpha-glucosidase, alpha-Glu), and tissue histology (liver and gills) were also assessed. Cr accumulation was observed in the intestine and liver of fish exposed to Cr-contaminated brine shrimp. However, chronic dissolved Cr exposure led to significant Cr accumulation in all organs tested. Analysis of the subcellular distribution of Cr in medaka livers revealed that 37% of the Cr was present in the heat stable protein fraction. The dissolved Cr exposure had pronounced effects on the antioxidant system in the liver, with an elevated ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) and decreases in GSH and glutathione S-transferase (GST). The alpha-Glu activity in the intestine was significantly inhibited. In addition, Cr exposure caused histopathological alterations in the gills and liver. In general, the effects of dietary Cr were relatively minor, possible due to the much lower accumulation in the fish. Our results imply that Japanese medaka accumulate Cr mainly via uptake of dissolved Cr(VI). Title: Quantitative trait locus mapping and functional genomics of an organophosphate resistance trait in the western corn rootworm, Diabrotica virgifera virgifera Coates BS, Alves AP, Wang H, Zhou X, Nowatzki T, Chen H, Rangasamy M, Robertson HM, Whitfield CW and Miller NJ <8 more author(s)> Coates BS, Alves AP, Wang H, Zhou X, Nowatzki T, Chen H, Rangasamy M, Robertson HM, Whitfield CW, Walden KK, Kachman SD, French BW, Meinke LJ, Hawthorne D, Abel CA, Sappington TW, Siegfried BD, Miller NJ (- 8) Ref: Insect Molecular Biology, 25:1, 2016 : PubMed ESTHER: Coates_2016_Insect.Mol.Biol_25_1 PubMedSearch: Coates 2016 Insect.Mol.Biol 25 1 PubMedID: 26566705 Gene_locus related to this paper: diavi-a0a0s2sw77, diavi-a0a0s2swc2 Abstract The western corn rootworm, Diabrotica virgifera virgifera, is an insect pest of corn and population suppression with chemical insecticides is an important management tool. Traits conferring organophosphate insecticide resistance have increased in frequency amongst D. v. virgifera populations, resulting in the reduced efficacy in many corn-growing regions of the USA. We used comparative functional genomic and quantitative trait locus (QTL) mapping approaches to investigate the genetic basis of D. v. virgifera resistance to the organophosphate methyl-parathion. RNA from adult methyl-parathion resistant and susceptible adults was hybridized to 8331 microarray probes. The results predicted that 11 transcripts were significantly up-regulated in resistant phenotypes, with the most significant (fold increases >/= 2.43) being an alpha-esterase-like transcript. Differential expression was validated only for the alpha-esterase (ST020027A20C03), with 11- to 13-fold greater expression in methyl-parathion resistant adults (P < 0.05). Progeny with a segregating methyl-parathion resistance trait were obtained from a reciprocal backcross design. QTL analyses of high-throughput single nucleotide polymorphism genotype data predicted involvement of a single genome interval. These data suggest that a specific carboyxesterase may function in field-evolved corn rootworm resistance to organophosphates, even though direct linkage between the QTL and this locus could not be established. Title: Glutathione regulation-based dual-functional upconversion sensing-platform for acetylcholinesterase activity and cadmium ions Fang A, Chen H, Li H, Liu M, Zhang Y, Yao S Ref: Biosensors & Bioelectronics, 87:545, 2016 : PubMed ESTHER: Fang_2016_Biosens.Bioelectron_87_545 PubMedSearch: Fang 2016 Biosens.Bioelectron 87 545 PubMedID: 27611473 Abstract A dual-functional platform for the sensing of acetylcholinesterase (AChE) activity and cadmium ions (Cd2+) was developed based on the fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) via glutathione regulation. The detection mechanism is based on the fact that AuNPs can quench the fluorescence of UCNPs. AChE catalyzes the hydrolysis of acetylthiocholine (ATC) into thiocholine which reacts with AuNPs by S-Au conjunction and results the aggregation of AuNPs and change in fluorescence of UCNPs. Therefore, the AChE activity can be detected through the changes of the color of solution and fluorescence recovery of UCNPs. However, the presence of glutathione (GSH) can protect AuNPs from aggregation and enlarge the inter-particle distance between AuNPs and UCNPs. When Cd2+ is added into the stable mixture of AuNPs, GSH and AChE/ATC, Cd2+ could interact with GSH to form a spherical shaped (GSH)4Cd complex, which decreases the free GSH on the surface of AuNPs to weaken the stability of AuNPs and lead to the easily aggregation of them in the system. The aggregated-AuNPs are released from the surface of UCNPs, which results in the fluorescence of UCNPs gradually recovered. Under the optimized conditions, the detection limits of AChE activity and Cd2+ are estimated to be 0.015mU/mL and 0.2microM, respectively. The small molecules regulated dual-functional platform based on UCNPs/AuNPs is a simple, label-free method and can be applied for the turn-on fluorescence detection of AChE activity in human serum and Cd2+ in real water samples. The present work demonstrates a general strategy for the design of small molecules regulated multifunctional platform and will be expanded for different areas in the future. Title: Brain Anatomy in Latino Farmworkers Exposed to Pesticides and Nicotine Laurienti PJ, Burdette JH, Talton J, Pope CN, Summers P, Walker FO, Quandt SA, Lyday RG, Chen H and Arcury TA <1 more author(s)> Laurienti PJ, Burdette JH, Talton J, Pope CN, Summers P, Walker FO, Quandt SA, Lyday RG, Chen H, Howard TD, Arcury TA (- 1) Ref: J Occup Environ Med, 58:436, 2016 : PubMed ESTHER: Laurienti_2016_J.Occup.Environ.Med_58_436 PubMedSearch: Laurienti 2016 J.Occup.Environ.Med 58 436 PubMedID: 27158949 Abstract OBJECTIVE: Migrant tobacco farmworkers experience regular occupational exposure to pesticides and nicotine. The present study was designed to determine whether there are differences in brain anatomy between Latino farmworkers and non-farmworkers. Title: Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications Mamczarz J, Pescrille JD, Gavrushenko L, Burke RD, Fawcett WP, DeTolla LJ, Jr., Chen H, Pereira EF, Albuquerque EX Ref: Neurotoxicology, 56:17, 2016 : PubMed ESTHER: Mamczarz_2016_Neurotoxicol_56_17 PubMedSearch: Mamczarz 2016 Neurotoxicol 56 17 PubMedID: 27296654 Abstract Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25mg/kg,s.c.) or vehicle (peanut oil) for 10days starting on presumed gestation day (GD) 53-55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. Title: Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat Qu Z, Zhang J, Yang H, Huo L, Gao J, Chen H, Gao W Ref: Physiol Behav, 154:114, 2016 : PubMed ESTHER: Qu_2016_Physiol.Behav_154_114 PubMedSearch: Qu 2016 Physiol.Behav 154 114 PubMedID: 26592138 Inhibitor(s) related to this paper: Palmatine Abstract Aging is associated with Alzheimer's disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. d-galactose (d-gal), a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. To understand the ability of tetrahydropalmatine (THP) to ameliorate memory impairment caused by aging, we investigated the effect of THP on d-gal induced memory impairment in rats. Subcutaneous injection of d-gal (100mg/kg/d) for 8weeks caused memory loss as detected by the Morris water maze and morphologic abnormalities of neurons in the hippocampus regions and cortex of rat brain. THP treatment ameliorated d-gal induced memory impairment associated with the decrease of malondialdehyde (MDA) and nitric oxide (NO) contents, as well as the increase of glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. THP treatment was also found to reverse the abnormality of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activities. In addition, treatment with THP could decrease the expression of nuclear factor kappa (NF-kappaB) and glial fibrillary acidic protein (GFAP) which prevented the neuroinflammation and memory impairment in the d-gal treated rats. Taken together, these results clearly demonstrated that subcutaneous injection of d-gal produced memory deficits, meanwhile THP could protect neuron from d-gal insults and improve cognition. This study provided an experimental basis for clinical application of THP in AD therapy. Title: Developmental exposure of zebrafish larvae to organophosphate flame retardants causes neurotoxicity Sun L, Xu W, Peng T, Chen H, Ren L, Tan H, Xiao D, Qian H, Fu Z Ref: Neurotoxicology & Teratology, 55:16, 2016 : PubMed ESTHER: Sun_2016_Neurotoxicol.Teratol_55_16 PubMedSearch: Sun 2016 Neurotoxicol.Teratol 55 16 PubMedID: 27018022 Inhibitor(s) related to this paper: Tris(2-chloroethyl)-phosphate Abstract With the gradual ban on brominated flame retardants (FRs), the application of organophosphate flame retardants (OPFRs) has increased remarkably. Considering the structural similarity between OPFRs and organophosphate pesticides, hypotheses that OPFRs may interfere with neurodevelopment as organophosphate pesticides are reasonable. In this study, the neurotoxicity of three OPFRs, including tri-n-butyl phosphate (TNBP), tris (2-butoxyethyl) phosphate (TBOEP) and tris (2-chloroethyl) phosphate (TCEP), was evaluated in zebrafish larvae and then compared with the neurotoxicity of organophosphate pesticide chlorpyrifos (CPF). The results showed that similar to CPF, exposure to OPFRs for 5days resulted in significant changes in locomotor behavior, either in free swimming or in photomotor response. However, given the transcriptional changes that occur in nervous system genes in response to OPFRs and CPF, as well as the altered enzyme activity of AChE and its mRNA level, the underlying mechanisms for neurotoxicity among these organophosphate chemicals might be varied. In summary, the results confirm the potential neurodevelopmental toxicity of OPFRs and underscore the importance of identifying the mechanistic targets of the OPFRs with specific moieties. Furthermore, as the neurobehavioral responses are well conserved among vertebrates and the exposure of children to OPFRs is significant, a thorough assessment of the risk of OPFRs exposure during early development should be highly emphasized in future studies. Title: Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARx03B3; Signaling Yang D, Chen H, Zeng X, Xie P, Wang X, Liu C Ref: Cell Physiol Biochem, 38:696, 2016 : PubMed ESTHER: Yang_2016_Cell.Physiol.Biochem_38_696 PubMedSearch: Yang 2016 Cell.Physiol.Biochem 38 696 PubMedID: 26872126 Abstract BACKGROUND/AIMS: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Title: Lipase genes in Mucor circinelloides: identification, sub-cellular location, phylogenetic analysis and expression profiling during growth and lipid accumulation Zan X, Tang X, Chu L, Zhao L, Chen H, Chen YQ, Chen W, Song Y Ref: J Ind Microbiol Biotechnol, 43:1467, 2016 : PubMed ESTHER: Zan_2016_J.Ind.Microbiol.Biotechnol_43_1467 PubMedSearch: Zan 2016 J.Ind.Microbiol.Biotechnol 43 1467 PubMedID: 27535142 Gene_locus related to this paper: muccl-a0a162riy7, muccl-a0a168kyh0, muccl-a0a168h480, muccl-a0a168lmw6, muccl-a0a168ia30, muccl-a0a168mc90, muccl-a0a162rng6, muccl-a0a168hm46, muccl-a0a168i578, muccl-a0a162r071, muccl-a0a168jxt4, muccl-a0a168nw20, muccl-a0a168n679, muccl-a0a168i244, muccl-a0a168nm44, muccl-a0a162mt71, muccl-a0a168npk8, muccl-a0a162mvq2 Abstract Lipases or triacylglycerol hydrolases are widely spread in nature and are particularly common in the microbial world. The filamentous fungus Mucor circinelloides is a potential lipase producer, as it grows well in triacylglycerol-contained culture media. So far only one lipase from M. circinelloides has been characterized, while the majority of lipases remain unknown in this fungus. In the present study, 47 potential lipase genes in M. circinelloides WJ11 and 30 potential lipase genes in M. circinelloides CBS 277.49 were identified by extensive bioinformatics analysis. An overview of these lipases is presented, including several characteristics, sub-cellular location, phylogenetic analysis and expression profiling of the lipase genes during growth and lipid accumulation. All of these proteins contained the consensus sequence for a classical lipase (GXSXG motif) and were divided into four types including alpha/beta-hydrolase_1, alpha/beta-hydrolase_3, class_3 and GDSL lipase (GDSL) based on gene annotations. Phylogenetic analyses revealed that class_3 family and alpha/beta-hydrolase_3 family were the conserved lipase family in M. circinelloides. Additionally, some lipases also contained a typical acyltransferase motif of H-(X) 4-D, and these lipases may play a dual role in lipid metabolism, catalyzing both lipid hydrolysis and transacylation reactions. The differential expression of all lipase genes were confirmed by quantitative real-time PCR, and the expression profiling were analyzed to predict the possible biological roles of these lipase genes in lipid metabolism in M. circinelloides. We preliminarily hypothesized that lipases may be involved in triacylglycerol degradation, phospholipid synthesis and beta-oxidation. Moreover, the results of sub-cellular localization, the presence of signal peptide and transcriptional analyses of lipase genes indicated that four lipase in WJ11 most likely belong to extracellular lipases with a signal peptide. These findings provide a platform for the selection of candidate lipase genes for further detailed functional study. Title: Bioinformatical analysis and preliminary study ofthe role of lipase in lipid metabolism in Mucorcircinelloides Zan X, Tang X, Zhao L, Chu L, Chen H, Chen W, Chen YQ, Song Y Ref: , 6:60673, 2016 : PubMed ESTHER: Zan_2016_RSC.Adv_6_60673 PubMedSearch: Zan 2016 RSC.Adv 6 60673 Gene_locus related to this paper: muccl-a0a162riy7, muccl-a0a168kyh0, muccl-a0a168h480, muccl-a0a168lmw6, muccl-a0a168ia30, muccl-a0a168mc90, muccl-a0a162rng6, muccl-a0a168hm46, muccl-a0a168i578, muccl-a0a162r071, muccl-a0a168jxt4, muccl-a0a168nw20, muccl-a0a168n679, muccl-a0a168i244, muccl-a0a168nm44, muccl-a0a162mt71, muccl-a0a168npk8, muccl-a0a162mvq2 no abstract Title: The Toxicity and Detoxifying Mechanism of Cycloxaprid and Buprofezin in Controlling Sogatella furcifera (Homoptera: Delphacidae) Chang X, Yuan Y, Zhang T, Wang D, Du X, Wu X, Chen H, Chen Y, Jiao Y, Teng H Ref: J Insect Sci, 15:, 2015 : PubMed ESTHER: Chang_2015_J.Insect.Sci_15_ PubMedSearch: Chang 2015 J.Insect.Sci 15 PubMedID: 26175461 Abstract The effects of cycloxaprid (a modified neonicotinoid insecticide) and buprofezin (a thiadiazine insecticide) on mortality of the white-backed planthopper (WBPH), Sogatella furcifera, were determined in laboratory assays. Cycloxaprid killed WBPH nymphs and adults but buprofezin killed only nymphs, and cycloxaprid acted faster than buprofezin. One day after infestation, mortality of third-instar nymphs was >65% with cycloxaprid at 125 mg liter(-1) but was <38% with buprofezin at 148 mg liter(-1). By the 4th day after infestation, however, control of nymphs by the two insecticides was similar, and cycloxaprid at 125 mg liter(-1) caused >/=80% mortality of adults but buprofezin at 148 mg liter(-1) (the highest rate tested) caused almost no adult mortality. LC50 values for cycloxaprid were lowest with nymphs, intermediate with adult males, and highest with adult females. Although buprofezin was slower acting than cycloxaprid, its LC50 for nymphs 5 d after infestation was 3.79-fold lower than that of cycloxaprid. Mean carboxylesterase (CarE) specific activity of nymphal WBPH treated with cycloxaprid and buprofezin was higher than that of control, but there was no significant difference between cycloxaprid and control (no insecticide), and it was significantly higher for buprofezin than those of cycloxaprid and control. For glutathione S-transferase and mixed function oxygenase, the specific activity of nymphal WBPH treated with buprofezin was significantly higher than those of cycloxaprid and control, too. Title: Expression and display of a novel thermostable esterase from Clostridium thermocellum on the surface of Bacillus subtilis using the CotB anchor protein Chen H, Zhang T, Jia J, Vastermark A, Tian R, Ni Z, Chen Z, Chen K, Yang S Ref: J Ind Microbiol Biotechnol, 42:1439, 2015 : PubMed ESTHER: Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439 PubMedSearch: Chen 2015 J.Ind.Microbiol.Biotechnol 42 1439 PubMedID: 26318029 Abstract Esterases expressed in microbial hosts are commercially valuable, but their applications are limited due to high costs of production and harsh industrial processes involved. In this study, the esterase-DSM (from Clostridium thermocellum) was expressed and successfully displayed on the spore surface, and the spore-associated esterase was confirmed by western blot analysis and activity measurements. The optimal temperature and pH of spore surface-displayed DSM was 60 and 8.5 degrees C, respectively. It also demonstrates a broad temperature and pH optimum in the range of 50-70, 7-9.5 degrees C. The spore surface-displayed esterase-DSM retained 78, 68 % of its original activity after 5 h incubation at 60 and 70 degrees C, respectively, which was twofold greater activity than that of the purified DSM. The recombinant spores has high activity and stability in DMSO, which was 49 % higher than the retained activity of the purified DSM in DMSO (20 % v/v), and retained 65.2 % of activity after 7 h of incubation in DMSO (20 % v/v). However, the recombinant spores could retain 77 % activity after 3 rounds of recycling. These results suggest that enzyme displayed on the surface of the Bacillus subtilis spore could serve as an effective approach for enzyme immobilization. Title: Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and the Risk of Head and Neck Cancer Chen H, Ge L, Sui Q, Lin M Ref: PLoS ONE, 10:e0123347, 2015 : PubMed ESTHER: Chen_2015_PLoS.One_10_e0123347 PubMedSearch: Chen 2015 PLoS.One 10 e0123347 PubMedID: 25923690 Abstract AIM: To evaluate the association between the EPHX1 Tyr113His and His139Arg polymorphisms in the EPHX1 gene and the risk of head and neck cancer. MATERIALS AND 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: (-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-beta aggregation with high antioxidant potency for Alzheimer's therapy Cheng S, Zheng W, Gong P, Zhou Q, Xie Q, Yu L, Zhang P, Chen L, Li J and Chen H <1 more author(s)> Cheng S, Zheng W, Gong P, Zhou Q, Xie Q, Yu L, Zhang P, Chen L, Li J, Chen J, Chen H (- 1) Ref: Bioorganic & Medicinal Chemistry, 23:3110, 2015 : PubMed ESTHER: Cheng_2015_Bioorg.Med.Chem_23_3110 PubMedSearch: Cheng 2015 Bioorg.Med.Chem 23 3110 PubMedID: 26025073 Abstract The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-beta (Abeta) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Abeta self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. Title: Discovering New Acetylcholinesterase Inhibitors by Mining the Buzhongyiqi Decoction Recipe Data Cui L, Wang Y, Liu Z, Chen H, Wang H, Zhou X, Xu J Ref: J Chem Inf Model, 55:2455, 2015 : PubMed ESTHER: Cui_2015_J.Chem.Inf.Model_55_2455 PubMedSearch: Cui 2015 J.Chem.Inf.Model 55 2455 PubMedID: 26509353 Abstract Myasthenia gravis (MG) is a neuromuscular disease that is conventionally treated with acetylcholinesterase (AChE) inhibitors, which may not fully remove the symptom for many reasons. When AChE inhibitors do not work, Chinese patients turn to Chinese medicine, such as the Buzhongyiqi decoction (BD), to treat MG. By elucidating the relations between the herbs of the Buzhongyiqi decoction recipe and AChE inhibitors with structure-based and ligand-based drug design methods and chemoinformatics approaches, we have found the key active components of BD. Using these key active components as templates, we have discovered five new AChE inhibitors through virtual screening of a commercial compound library. The new AChE inhibitors have been confirmed with Ellman assays. This study demonstrates that lead identification can be inspired by elucidating Chinese medicine. Since BD is a mixture, further studies against other drug targets are needed. Title: Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1 Gazzard L, Williams K, Chen H, Axford L, Blackwood E, Burton B, Chapman K, Crackett P, Drobnick J and Malek S <22 more author(s)> Gazzard L, Williams K, Chen H, Axford L, Blackwood E, Burton B, Chapman K, Crackett P, Drobnick J, Ellwood C, Epler J, Flagella M, Gancia E, Gill M, Goodacre S, Halladay J, Hewitt J, Hunt H, Kintz S, Lyssikatos J, Macleod C, Major S, Medard G, Narukulla R, Ramiscal J, Schmidt S, Seward E, Wiesmann C, Wu P, Yee S, Yen I, Malek S (- 22) Ref: Journal of Medicinal Chemistry, 58:5053, 2015 : PubMed ESTHER: Gazzard_2015_J.Med.Chem_58_5053 PubMedSearch: Gazzard 2015 J.Med.Chem 58 5053 PubMedID: 25988399 Abstract Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analogue synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model. Title: Increased permeability of the blood-brain barrier and Alzheimer's disease-like alterations in slit-2 transgenic mice Li JC, Han L, Wen YX, Yang YX, Li S, Li XS, Zhao CJ, Wang TY, Chen H and Wang LJ <12 more author(s)> Li JC, Han L, Wen YX, Yang YX, Li S, Li XS, Zhao CJ, Wang TY, Chen H, Liu Y, Qi CL, He XD, Gu QL, Ye YX, Zhang Y, Huang R, Wu YE, He RR, Kurihara H, Song XY, Cao L, Wang LJ (- 12) Ref: J Alzheimers Dis, 43:535, 2015 : PubMed ESTHER: Li_2015_J.Alzheimers.Dis_43_535 PubMedSearch: Li 2015 J.Alzheimers.Dis 43 535 PubMedID: 25114073 Abstract Alzheimer's disease (AD) is a progressive neurological disorder that primarily affects memory, and its prevalence is rising. Increasing evidence suggests that dysfunction of the blood-brain barrier (BBB) may be involved in AD and other neurodegenerative diseases. Herein, we report that the permeability of the BBB is increased and that AD-like alterations are present in Slit-2 overexpressing transgenic mice. We found that behavioral change and the corresponding molecular diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-beta (Abeta) protein deposition, and acetylcholinesterase expression, were increased in the Slit-2 transgenic mice. Moreover, the endothelial cells were dysfunctional, the size of the lateral ventricle cavity increased, and the permeability of the BBB increased. Additionally, there was an increased serum level of glutamate indicating that the BBB is related to AD. Finally, histopathological analysis of other organs in the Slit-2 overexpressing mice did not show any marked abnormalities. These findings demonstrate that Slit2 overexpression may be responsible for AD-like alterations and the increased BBB permeability in these mice. Our study provides a potential novel mechanism for the development of AD. Title: Bioaccumulation, subcellular distribution, and acute effects of chromium in Japanese medaka (Oryzias latipes) Li L, Chen H, Bi R, Xie L Ref: Environ Toxicol Chem, 34:2611, 2015 : PubMed ESTHER: Li_2015_Environ.Toxicol.Chem_34_2611 PubMedSearch: Li 2015 Environ.Toxicol.Chem 34 2611 PubMedID: 26096885 Abstract Chromium (Cr) is an essential element but is toxic to aquatic organisms at elevated concentrations. In the present study, adult Japanese medaka (Oryzias latipes) were exposed to a sublethal hexavalent chromium (Cr(VI)) concentration via dissolved and dietary exposures for 6 d. Various measurements of Cr were made: bioaccumulation in different tissues, subcellular distribution in the liver, effects on antioxidants and acetylcholinesterase (AChE), and Cr-induced lipid peroxidation. The results showed that bioaccumulation increased dramatically in all tested tissues from dissolved exposure but only significantly in the intestine from dietary treatment, implying that dissolved exposure may be predominant for Cr accumulation in medaka. Subcellular distribution revealed that Cr accumulated in the liver was mainly (46%) associated with the heat-stable protein fraction. Among the antioxidants examined, catalase (CAT) responded to dissolved Cr exposure in most tissues whereas superoxide dismutase (SOD) was less responsive. Malondialdehyde concentrations were significantly elevated in most tissues examined in the dissolved Cr-exposed fish, but were only elevated in the liver and intestine in the dietary Cr-exposed fish. The AChE activity in the brain was stimulated by 49% in the dissolved Cr-exposed fish. Reductions in condition factor and gonadosomatic index were also observed. These data help in an understanding of Cr tissue distribution and the acute effects of Cr in Japanese medaka. Environ Toxicol Chem 2015;34:2611-2617. (c) 2015 SETAC. Title: The chronic effects of lignin-derived bisphenol and bisphenol A in Japanese medaka Oryzias latipes Li D, Chen Q, Cao J, Chen H, Li L, Cedergreen N, Xie H, Xie L Ref: Aquat Toxicol, 170:199, 2015 : PubMed ESTHER: Li_2015_Aquat.Toxicol_170_199 PubMedSearch: Li 2015 Aquat.Toxicol 170 199 PubMedID: 26674368 Abstract One of the ultimate goals of green chemistry is to produce greener and more environmentally friendly chemicals to replace the existing toxic chemicals. In this study, Japanese medaka were exposed to 1.5mg/L of bisphenol A or lignin-derived bisphenol for 60 days, and the expressions of various biochemical markers, effects on reproduction, and histopathology were evaluated. The results showed that concentrations of liver vitellogenin of LD-BP exposed males were approximately 125% higher compared to the control males. Total number of eggs from the BPA and LD-BP exposed fish was approximately 47% (p<0.001) and 25% (p<0.05) less than the control fish, respectively. Total number of brood was lower from the BPA (46%, p<0.05) and LD-BP (17%, p<0.05) exposed fish than that of the control fish. Relative to the control fish, catalase and glutathione-S-transferase were significantly affected by the two chemicals in all tested tissues. BPA and LD-BP caused lipid peroxidation in all the tested tissues. Furthermore, acetylcholinesterase and alpha-glucosidase activity were significantly inhibited. Histopathological analysis showed that both the testis and ovary were mildly damaged by both chemicals. LD-BP affected medaka slightly more severe than BPA except on the reproduction, which was most likely due to different uptake, translocation, binding to targets and metabolism. Our results demonstrated that chronic exposure to both chemicals caused several adverse effects to medaka. Further research on the toxicity of LD-BP to other aquatic organisms is needed before substitution of traditional BPA with LD-BP can be recommended. Title: Ultrasonic pretreatment in lipase-catalyzed synthesis of structured lipids with high 1,3-dioleoyl-2-palmitoylglycerol content Liu SL, Dong XY, Wei F, Wang X, Lv X, Zhong J, Wu L, Quek SY, Chen H Ref: Ultrason Sonochem, 23:100, 2015 : PubMed ESTHER: Liu_2015_Ultrason.Sonochem_23_100 PubMedSearch: Liu 2015 Ultrason.Sonochem 23 100 PubMedID: 25453210 Abstract Production of structured lipid 1,3-dioleoyl-2-palmitoylglycerol (OPO), from tripalmitin (PPP) and oleic acid (OA) using lipases and ultrasonic pretreatment was conducted. Factors influencing both the ultrasonic conditions and enzymatic reaction were investigated. Optimum conditions could be attained with 6 min pretreatment time, 50% ultrasonic power, 3 s/9 s (work/pause) cycle of ultrasonic pulse, 1:8 PPP/OA molar ratio, 12% enzyme dosage and 50 degreeC temperature of. At the optimum conditions, the OPO yield of 51.8% could be achieved in 4h. Studies showed that the OPO content increased to 35.9% in 1h with ultrasonic pretreatment, in comparison to 4h without ultrasonic pretreatment. Reuse of Lipozyme RM IM for 10 cycles under ultrasonic irradiation did not cause essential damage to its lipase activity. Reaction kinetic model fitted well with the proposed Ping-Pong mechanism. The apparent kinetic constant (Vm'/K) of ultrasound pretreatment reaction was 2.52 times higher than the conventional mechanical stirring, indicating that ultrasound pretreatment enhanced the substrates affinity to the enzyme. This study confirmed that ultrasonic pretreatment was more efficient in OPO production than conventional mechanical agitation. Title: Deciphering the venomic transcriptome of killer-wasp Vespa velutina Liu Z, Chen S, Zhou Y, Xie C, Zhu B, Zhu H, Liu S, Wang W, Chen H, Ji Y Ref: Sci Rep, 5:9454, 2015 : PubMed ESTHER: Liu_2015_Sci.Rep_5_9454 PubMedSearch: Liu 2015 Sci.Rep 5 9454 PubMedID: 25896434 Gene_locus related to this paper: vesve-pa1 Abstract Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world. Title: Longitudinal Assessment of Blood Cholinesterase Activities Over 2 Consecutive Years Among Latino Nonfarmworkers and Pesticide-Exposed Farmworkers in North Carolina Quandt SA, Pope CN, Chen H, Summers P, Arcury TA Ref: J Occup Environ Med, 57:851, 2015 : PubMed ESTHER: Quandt_2015_J.Occup.Environ.Med_57_851 PubMedSearch: Quandt 2015 J.Occup.Environ.Med 57 851 PubMedID: 26247638 Abstract OBJECTIVE: This study (1) describes patterns of whole blood total cholinesterase, acetylcholinesterase, and butyrylcholinesterase activities across the agricultural season, comparing farmworkers and nonfarmworkers; and (2) explores differences between farmworkers' and non-farmworkers' likelihood of cholinesterase depression. 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: Expression and Characterization of a New Thermostable Esterase from Clostridium thermocellum Zhang T, Chen H, Ni Z, Tian R, Jia J, Chen Z, Yang S Ref: Appl Biochem Biotechnol, 177:1437, 2015 : PubMed ESTHER: Zhang_2015_Appl.Biochem.Biotechnol_177_1437 PubMedSearch: Zhang 2015 Appl.Biochem.Biotechnol 177 1437 PubMedID: 26373940 Gene_locus related to this paper: clotm-q4cf59 Abstract The thermostable esterase from the thermophilic bacterium Clostridium thermocellum DSM 1313 was expressed in Escherichia coli and purified by Ni(2+) affinity chromatography. Its molecular weight was approximately 35 kDa according to 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The enzyme exhibited the highest specific activity with p-nitrophenyl butyrate (285 s(-1) mM(-1)). The activity of the esterase was greatest at 65 degrees C, and the esterase maintained residual activity levels of 70 and 50 % after 3 h incubation at 65 and 70 degrees C, respectively. Its activity was optimal at pH 7.0, was enhanced in the presence of Ca(2+) and Mg(2+), and was inhibited by Ni(2+) and Cu(2+). The addition of surfactants, such as Tween-20, Tween-80, Triton X-100, and SDS, at concentrations of 5 % (v/v) significantly inhibited the lipolytic action of the esterase. Enzyme activity was relatively stable in 10 % methanol, and 50 % residual activity was seen in 10 % DMSO, demonstrating its potential in biodiesel production and industrial applications. Title: Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice Chen SR, Chen H, Yuan WX, Wess J, Pan HL Ref: Journal of Biological Chemistry, 289:14321, 2014 : PubMed ESTHER: Chen_2014_J.Biol.Chem_289_14321 PubMedSearch: Chen 2014 J.Biol.Chem 289 14321 PubMedID: 24695732 Abstract Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in approximately 67% of neurons but increased it in approximately 10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons ( approximately 26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs. Title: Conformational transition pathway in the inhibitor binding process of human monoacylglycerol lipase Chen H, Tian R, Ni Z, Zhang Z, Guo Q, Saier MH, Jr. Ref: Protein J, 33:503, 2014 : PubMed ESTHER: Chen_2014_Protein.J_33_503 PubMedSearch: Chen 2014 Protein.J 33 503 PubMedID: 25078047 Abstract Human monoacylglycerol lipase (MGL) catalyzes the hydrolysis of 2-arachidonoylglycerol to arachidonic and glycerol, which plays a pivotal role in the normal biological processes of brain. Co-crystal structure of the MGL in complex with its inhibitor, compound 1, shows that the helix alpha4 undergoes large-scale conformational changes in response to the compound 1 binding compared to the apo MGL. However, the detailed conformational transition pathway of the helix alpha4 in the inhibitor binding process of MGL has remained unclear. Here, conventional molecular dynamics (MD) and nudged elastic band (NEB) simulations were performed to explore the conformational transition pathway of the helix alpha4. Conventional MD simulations unveiled that the compound 1 induced the closed conformation of the active site of MGL, reduced the conformational flexibility of the helix alpha4, and elicited the large-scale conformational rearrangement of the helix alpha4, leading to the complete folding of the helix alpha4. Moreover, NEB simulations revealed that the conformational transition pathway of helix alpha4 underwent an almost 180 degrees counter-clockwise rotation of the helix alpha4. Our computational results advance the structural and mechanistic understanding of the inhibitory mechanism. Title: Characterization and structure basis of Pseudomonas alcaligenes lipase's enantiopreference towards d,l-menthyl propionate Chen H, Wu J, Yang L, Xu G Ref: J Mol Catal B Enzym, 102:81, 2014 : PubMed ESTHER: Chen_2014_J.Mol.Catal.B.Enzym_102_81 PubMedSearch: Chen 2014 J.Mol.Catal.B.Enzym 102 81 Gene_locus related to this paper: stema-s4tny8 Abstract In this work, a lipase from Pseudomonas alcaligenes CGMCC4405 (PaL) was cloned and expressed. It was very attractive that the recombinant PaL exhibited excellent enantioselectivity (E > 200) in the resolution of racemic d,l-menthyl propionate to produce l-menthol. The structure basis of enantiopreference is a fundamental scientific problem which needs to be resolved. In our research, molecular dynamic simulation (MD) research was employed to research the different binding modes of d and l-menthyl propionate. The results showed that when bound with slow-reacting enantiomer (d-menthyl propionate), the steric requirements of the large substituent (isopropyl) of the d-menthyl propionate force a rotation of the imidazole ring of catalytic residue His271 and further pushed the active site His271 away from its proper orientation. Moreover, the average distance between alcohol oxygen (Oalc) and HNe of catalytic His271 increased to 3.7 A, which was too far to form an essential hydrogen bond and further prevented efficient catalysis of slow enantiomer. This correlation of the distance between alcohol oxygen (Oalc) and HNe of catalytic His271 and the enantioselectivity was also confirmed by the result of site-directed mutagenesis. Title: Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1; q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male Li L, Chen H, Yin C, Yang C, Wang B, Zheng S, Zhang J, Fan W Ref: Gene, 547:43, 2014 : PubMed ESTHER: Li_2014_Gene_547_43 PubMedSearch: Li 2014 Gene 547 43 PubMedID: 24937803 Abstract It is widely accepted that the incidence of chromosomal aberration is 10-15.2% in the azoospermic male; however, the exact genetic damages are currently unknown for more than 40% of azoospermia. To elucidate the causative gene defects, we used the next generation sequencing (NGS) to map the breakpoints of a chromosome insertion from an azoospermic male who carries a balanced, maternally inherited karyotype 46, XY, inv ins (18,7) (q22.1; q36.2q21.11). The analysis revealed that the breakage in chromosome 7 disrupts two genes, dipeptidyl aminopeptidase-like protein 6 (DPP6) and contactin-associated protein-like 2 (CACNA2D1), the former participates in regulation of voltage-gated potassium channels, and the latter is one of the components in voltage-gated calcium channels. The deletion and duplication were not identified equal or beyond 100 kb, but 4 homologous DNA elements were verified proximal to the breakpoints. One of the proband's sisters inherited the same aberrant karyotype and experienced recurrent miscarriages and consecutive fetus death, while in contrast, another sister with a normal karyotype experienced normal labor and gave birth to healthy babies. The insertional translocation is confirmed with FISH and the Y-chromosome microdeletions were excluded by genetic testing. This is the first report describing chromosome insertion inv ins (18,7) and attributes DPP6 and CACNA2D1 to azoospermia. Title: A Fluorogenic Probe with Aggregation-Induced Emission Characteristics for Carboxylesterase Assay through Formation of Supramolecular Microfibers Wang X, Liu H, Li J, Ding K, Lv Z, Yang Y, Chen H, Li X Ref: Chem Asian J, 9:784, 2014 : PubMed ESTHER: Wang_2014_Chem.Asian.J_9_784 PubMedSearch: Wang 2014 Chem.Asian.J 9 784 PubMedID: 24403215 Abstract Herein, we report a novel fluorescent "light-up" probe useful for carboxylesterase assay that is based on a tetraphenylethylene derivative containing carboxylic ester groups. The specific cleavage of the carboxylic ester bonds by carboxylesterase results in the generation of a relatively hydrophobic moiety that self-assembles into supramolecular microfibers, thus giving rise to "turn-on" fluorescent signals. A high sensitivity towards carboxylesterase was achieved with a detection limit as low as 29 pM, which is much lower than the corresponding assays based on other fluorescent approaches. Title: Parkinson's disease and cancer: A register-based family study Wirdefeldt K, Weibull CE, Chen H, Kamel F, Lundholm C, Fang F, Ye W Ref: Am J Epidemiol, 179:85, 2014 : PubMed ESTHER: Wirdefeldt_2014_Am.J.Epidemiol_179_85 PubMedSearch: Wirdefeldt 2014 Am.J.Epidemiol 179 85 PubMedID: 24142916 Abstract We wanted to compare cancer incidence rates between Parkinson's disease (PD) patients and persons without PD, as well as between siblings of these groups. We conducted a family-based matched cohort study based on nationwide Swedish health registries and the Swedish Multi-Generation Register. We assessed risk of incident cancer in PD patients (n = 11,786) during 1964-2009 versus a matched cohort of PD-free individuals (n = 58,930) and in siblings of PD patients (n = 16,841) versus siblings of PD-free individuals (n = 84,205). Hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards regression. Cancer occurrence was slightly higher in PD patients than in PD-free individuals (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 1.00, 1.10), largely because of cancers arising within 1 year before or after the index date for PD, but risk of smoking-related cancers was lower (HR = 0.87, 95% CI: 0.79, 0.96). PD patients had a higher risk of melanoma both up to 1 year before the PD index date (HR = 1.53, 95% CI: 1.23, 1.91) and from 1 year after the index date onward (HR = 1.46, 95% CI: 1.01, 2.10). In the sibling comparison, cancer occurrence was largely similar. These results indicate that melanoma risk is higher among PD patients and that mechanisms other than familial ones explain the association. Title: Determination of Meserine, a new candidate for Alzheimer's disease in mice brain by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic and tissue distribution study Zheng Z, Tang Y, Lv H, Xu J, Zhao H, Xie Q, Qiu Z, Chen H, Wang H Ref: Anal Bioanal Chem, 406:3451, 2014 : PubMed ESTHER: Zheng_2014_Anal.Bioanal.Chem_406_3451 PubMedSearch: Zheng 2014 Anal.Bioanal.Chem 406 3451 PubMedID: 24756818 Abstract A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of Meserine ((-)-meptazinol phenylcarbamate), a novel potent inhibitor of acetylcholinesterase (AChE), was developed, validated, and applied to a pharmacokinetic study in mice brain. The lower limit of quantification (LLOQ) was 1 ng mL(-1) and the linear range was 1-1,000 ng mL(-1). The analyte was eluted on a Zorbax SB-Aq column (2.1 x 100 mm, 3.5 mum) with the mobile phase composed of methanol and water (70:30, v/v, aqueous phase contained 10 mM ammonium formate and 0.3% formic acid) using isocratic elution, and monitored by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The flow rate was 0.25 mL min(-1). The injection volume was 5 muL and total run time was 4 min. The relative standard deviation (RSD) of intraday and interday variation was 2.49-7.81 and 3.01-7.67%, respectively. All analytes were stable after 4 h at room temperature and 6 h in autosampler. The extraction recoveries of Meserine in brain homogenate were over 90%. The main brain pharmacokinetic parameters obtained after intranasal administration were T max = 0.05 h, C max = 462.0 +/- 39.7 ng g(-1), T 1/2 = 0.4 h, and AUC(0-infinity) = 283.1 +/- 9.1 ng h g(-1). Moreover, Meserine was distributed rapidly and widely into brain, heart, liver, spleen, lung, and kidney tissue. The method is validated and could be applied to the pharmacokinetic and tissue distribution study of Meserine in mice. Title: A small predatory core genome in the divergent marine Bacteriovorax marinus SJ and the terrestrial Bdellovibrio bacteriovorus Crossman LC, Chen H, Cerdeno-Tarraga AM, Brooks K, Quail MA, Pineiro SA, Hobley L, Sockett RE, Bentley SD and Stine OC <2 more author(s)> Crossman LC, Chen H, Cerdeno-Tarraga AM, Brooks K, Quail MA, Pineiro SA, Hobley L, Sockett RE, Bentley SD, Parkhill J, Williams HN, Stine OC (- 2) Ref: Isme J, 7:148, 2013 : PubMed ESTHER: Crossman_2013_ISME.J_7_148 PubMedSearch: Crossman 2013 ISME.J 7 148 PubMedID: 22955231 Gene_locus related to this paper: bacms-e1x4r0, bacms-e1wxp3 Abstract Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a marine environment. The genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium Bdellovibrio bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were originally designated as members of the genus Bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. B. marinus attaches to gram-negative bacteria, penetrates through the cell wall to form a bdelloplast, in which it replicates, as shown using microscopy. Bacteriovorax is distinct, as it shares only 30% of its gene products with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500 nt in length were completely unique with no significant matches in the databases. As expected, Bacteriovorax shares several characteristic loci with the other delta-proteobacteria. A geneset shared between Bacteriovorax and Bdellovibrio that is not conserved among other delta-proteobacteria such as Myxobacteria (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo-bacteria and Geobacter species was identified. These 291 gene orthologues common to both Bacteriovorax and Bdellovibrio may be the key indicators of host-interaction predatory-specific processes required for prey entry. The locus from Bdellovibrio bacteriovorus is implicated in the switch from predatory to prey/host-independent growth. Although the locus is conserved in B. marinus, the sequence has only limited similarity. The results of this study advance understanding of both the similarities and differences between Bdellovibrio and Bacteriovorax and confirm the distant relationship between the two and their separation into different families. Title: SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties Han K, Holder JL, Jr., Schaaf CP, Lu H, Chen H, Kang H, Tang J, Wu Z, Hao S and Zoghbi HY <6 more author(s)> Han K, Holder JL, Jr., Schaaf CP, Lu H, Chen H, Kang H, Tang J, Wu Z, Hao S, Cheung SW, Yu P, Sun H, Breman AM, Patel A, Lu HC, Zoghbi HY (- 6) Ref: Nature, 503:72, 2013 : PubMed ESTHER: Han_2013_Nature_503_72 PubMedSearch: Han 2013 Nature 503 72 PubMedID: 24153177 Abstract Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, indicating that proper SHANK3 dosage is critical for normal brain function. However, SHANK3 overexpression per se has not been established as a cause of human disorders because 22q13 duplications involve several genes. Here we report that Shank3 transgenic mice modelling a human SHANK3 duplication exhibit manic-like behaviour and seizures consistent with synaptic excitatory/inhibitory imbalance. We also identified two patients with hyperkinetic disorders carrying the smallest SHANK3-spanning duplications reported so far. These findings indicate that SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder. To probe the mechanism underlying the phenotype, we generated a Shank3 in vivo interactome and found that Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice. The mood-stabilizing drug valproate, but not lithium, rescues the manic-like behaviour of Shank3 transgenic mice raising the possibility that this hyperkinetic disorder has a unique pharmacogenetic profile. Title: Visible-light-activated photoelectrochemical biosensor for the study of acetylcholinesterase inhibition induced by endogenous neurotoxins Huang Q, Chen H, Xu L, Lu D, Tang L, Jin L, Xu Z, Zhang W Ref: Biosensors & Bioelectronics, 45C:292, 2013 : PubMed ESTHER: Huang_2013_Biosens.Bioelectron_45C_292 PubMedSearch: Huang 2013 Biosens.Bioelectron 45C 292 PubMedID: 23500378 Abstract In this report, a novel visible-light-activated photoelectrochemical biosensor was fabricated to study the inhibition of acetylcholinesterase (AChE) activity induced by two endogenous neurotoxins, 1(R)-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-Sal] and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline [(R)-NMSal], which have drawn much attention in the study of the pathogenesis of neurodegenerative diseases such as Parkinson's disease. The photoelectrode was prepared by three steps, as follows. At first, nitrogen and fluorine co-doped TiO2 nanotubes (TNs) were obtained by anodic oxidation of a Ti sheet. Secondly, silver nanoparticles (AgNPs) were deposited onto the TNs through a microwave-assisted heating polyol (MAHP) process. At last, AChE was immobilized on the obtained photoelectrode and the biosensor was marked as AChE/Ag/NFTNs. Due to the nitrogen and fluorine co-doping, the photoelectrochemical biosensors can produce high photocurrent under visible light irradiation. Moreover, the presence of AgNPs greatly increased the photocurrent response of the biosensor. AChE/Ag/NFTNs hybrid system was used to study AChE inhibition induced by (R)-Sal and (R)-NMSal. The result proved that both (R)-Sal and (R)-NMSal exhibited mixed and reversible inhibition against AChE. This strategy is of great significance for the development of novel photoelectrochemical biosensors in the future. Title: The duck genome and transcriptome provide insight into an avian influenza virus reservoir species Huang Y, Li Y, Burt DW, Chen H, Zhang Y, Qian W, Kim H, Gan S, Zhao Y and Li N <40 more author(s)> Huang Y, Li Y, Burt DW, Chen H, Zhang Y, Qian W, Kim H, Gan S, Zhao Y, Li J, Yi K, Feng H, Zhu P, Li B, Liu Q, Fairley S, Magor KE, Du Z, Hu X, Goodman L, Tafer H, Vignal A, Lee T, Kim KW, Sheng Z, An Y, Searle S, Herrero J, Groenen MA, Crooijmans RP, Faraut T, Cai Q, Webster RG, Aldridge JR, Warren WC, Bartschat S, Kehr S, Marz M, Stadler PF, Smith J, Kraus RH, Ren L, Fei J, Morisson M, Kaiser P, Griffin DK, Rao M, Pitel F, Wang J, Li N (- 40) Ref: Nat Genet, 45:776, 2013 : PubMed ESTHER: Huang_2013_Nat.Genet_45_776 PubMedSearch: Huang 2013 Nat.Genet 45 776 PubMedID: 23749191 Gene_locus related to this paper: anapl-BCHE, anapl-r0lw36, anapl-r0m5n4, anapl-thioe, anapl-u3iqr9, anapl-r0l4n7, anapl-u3j4v8, anapl-u3icy5, anapl-u3ivv9, anapl-u3j4g1, anapl-u3j4i2, anapl-u3j4v5, anapl-r0kv25, anapl-u3ild2, anapl-u3imh5, anapl-b6dzk9, anapl-u3imp7, anapl-u3i5h5, anapl-u3id17, anapl-r0m1y3, anapl-r0lhc4, anapl-r0ktn0, anapl-r0l8l1, anapl-r0lin6, anapl-r0jhf3 Abstract The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its beta-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses. Title: Comparative analysis of the complete genome of an epidemic hospital sequence type 203 clone of vancomycin-resistant Enterococcus faecium Lam MM, Seemann T, Tobias NJ, Chen H, Haring V, Moore RJ, Ballard S, Grayson LM, Johnson PD and Stinear TP <1 more author(s)> Lam MM, Seemann T, Tobias NJ, Chen H, Haring V, Moore RJ, Ballard S, Grayson LM, Johnson PD, Howden BP, Stinear TP (- 1) Ref: BMC Genomics, 14:595, 2013 : PubMed ESTHER: Lam_2013_BMC.Genomics_14_595 PubMedSearch: Lam 2013 BMC.Genomics 14 595 PubMedID: 24004955 Abstract BACKGROUND: In this report we have explored the genomic and microbiological basis for a sustained increase in bloodstream infections at a major Australian hospital caused by Enterococcus faecium multi-locus sequence type (ST) 203, an outbreak strain that has largely replaced a predecessor ST17 sequence type. Title: Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration Liu Z, Jiang M, Kang T, Miao D, Gu G, Song Q, Yao L, Hu Q, Tu Y and Chen J <4 more author(s)> Liu Z, Jiang M, Kang T, Miao D, Gu G, Song Q, Yao L, Hu Q, Tu Y, Pang Z, Chen H, Jiang X, Gao X, Chen J (- 4) Ref: Biomaterials, 34:3870, 2013 : PubMed ESTHER: Liu_2013_Biomaterials_34_3870 PubMedSearch: Liu 2013 Biomaterials 34 3870 PubMedID: 23453061 Abstract Development of effective non-invasive drug delivery systems is of great importance to the treatment of Alzheimer's diseases and has made great progress in recent years. In this work, lactoferrin (Lf), a natural iron binding protein, whose receptor is highly expressed in both respiratory epithelial cells and neurons is here utilized to facilitate the nose-to-brain drug delivery of neuroprotection peptides. The Lf-conjugated PEG-PCL nanoparticle (Lf-NP) was constructed via a maleimide-thiol reaction with the Lf conjugation confirmed by CBQCA Protein Quantitation and XPS analysis. Other important parameters such as particle size distribution, zeta potential and in vitro release of fluorescent probes were also characterized. Compared with unmodified nanoparticles (NP), Lf-NP exhibited a significantly enhanced cellular accumulation in 16HBE14o-cells through both caveolae-/clathrin-mediated endocytosis and direct translocation. Following intranasal administration, Lf-NP facilitated the brain distribution of the coumarin-6 incorporated with the AUC0-8h in rat cerebrum (with hippocampus removed), cerebellum, olfactory tract, olfactory bulb and hippocampus 1.36, 1.53, 1.70, 1.57 and 1.23 times higher than that of coumarin-6 carried by NP, respectively. Using a neuroprotective peptide - NAPVSIPQ (NAP) as the model drug, the neuroprotective and memory improvement effect of Lf-NP was observed even at lower dose than that of NP in a Morris water maze experiment, which was also confirmed by the evaluation of acetylcholinesterase, choline acetyltransferase activity and neuronal degeneration in the mice hippocampus. In conclusion, Lf-NP may serve as a promising nose-to-brain drug delivery carrier especially for peptides and proteins. Title: Complete genome sequence of the frog pathogen Mycobacterium ulcerans ecovar Liflandii Tobias NJ, Doig KD, Medema MH, Chen H, Haring V, Moore R, Seemann T, Stinear TP Ref: Journal of Bacteriology, 195:556, 2013 : PubMed ESTHER: Tobias_2013_J.Bacteriol_195_556 PubMedSearch: Tobias 2013 J.Bacteriol 195 556 PubMedID: 23204453 Gene_locus related to this paper: mycmm-b2hjb4, mycmm-b2ht49, mycua-a0pqm2, mycmm-b2hqm3 Abstract In 2004, a previously undiscovered mycobacterium resembling Mycobacterium ulcerans (the agent of Buruli ulcer) was reported in an outbreak of a lethal mycobacteriosis in a laboratory colony of the African clawed frog Xenopus tropicalis. This mycobacterium makes mycolactone and is one of several strains of M. ulcerans-like mycolactone-producing mycobacteria recovered from ectotherms around the world. Here, we describe the complete 6,399,543-bp genome of this frog pathogen (previously unofficially named "Mycobacterium liflandii"), and we show that it has undergone an intermediate degree of reductive evolution between the M. ulcerans Agy99 strain and the fish pathogen Mycobacterium marinum M strain. Like M. ulcerans Agy99, it has the pMUM mycolactone plasmid, over 200 chromosomal copies of the insertion sequence IS2404, and a high proportion of pseudogenes. However, M. liflandii has a larger genome that is closer in length, sequence, and architecture to M. marinum M than to M. ulcerans Agy99, suggesting that the M. ulcerans Agy99 strain has undergone accelerated evolution. Scrutiny of the genes specifically lost suggests that M. liflandii is a tryptophan, tyrosine, and phenylalanine auxotroph. A once-extensive M. marinum-like secondary metabolome has also been diminished through reductive evolution. Our analysis shows that M. liflandii, like M. ulcerans Agy99, has the characteristics of a niche-adapted mycobacterium but also has several distinctive features in important metabolic pathways that suggest that it is responding to different environmental pressures, supporting earlier proposals that it could be considered an M. ulcerans ecotype, hence the name M. ulcerans ecovar Liflandii. Title: The Reference Genome of the Halophytic Plant Eutrema salsugineum Yang R, Jarvis DE, Chen H, Beilstein MA, Grimwood J, Jenkins J, Shu S, Prochnik S, Xin M and Wang X <5 more author(s)> Yang R, Jarvis DE, Chen H, Beilstein MA, Grimwood J, Jenkins J, Shu S, Prochnik S, Xin M, Ma C, Schmutz J, Wing RA, Mitchell-Olds T, Schumaker KS, Wang X (- 5) Ref: Front Plant Sci, 4:46, 2013 : PubMed ESTHER: Yang_2013_Front.Plant.Sci_4_46 PubMedSearch: Yang 2013 Front.Plant.Sci 4 46 PubMedID: 23518688 Gene_locus related to this paper: theha-e4mxu0, thesl-v4nk72, eutsa-v4l4z1, eutsa-v4kk46, eutsa-v4mej3, eutsa-v4ns11, eutsa-v4mg02, eutsa-v4mqm9, eutsa-v4k1y6, eutsa-v4lad0, eutsa-v4nr92, eutsa-v4kqc3, eutsa-v4l0s2, eutsa-v4lip3, eutsa-v4kkg2, eutsa-v4kvd3, eutsa-v4m9g4, eutsa-v4lqg2, eutsa-v4lp36, eutsa-v4km66, eutsa-v4nhr8 Abstract Halophytes are plants that can naturally tolerate high concentrations of salt in the soil, and their tolerance to salt stress may occur through various evolutionary and molecular mechanisms. Eutrema salsugineum is a halophytic species in the Brassicaceae that can naturally tolerate multiple types of abiotic stresses that typically limit crop productivity, including extreme salinity and cold. It has been widely used as a laboratorial model for stress biology research in plants. Here, we present the reference genome sequence (241 Mb) of E. salsugineum at 8x coverage sequenced using the traditional Sanger sequencing-based approach with comparison to its close relative Arabidopsis thaliana. The E. salsugineum genome contains 26,531 protein-coding genes and 51.4% of its genome is composed of repetitive sequences that mostly reside in pericentromeric regions. Comparative analyses of the genome structures, protein-coding genes, microRNAs, stress-related pathways, and estimated translation efficiency of proteins between E. salsugineum and A. thaliana suggest that halophyte adaptation to environmental stresses may occur via a global network adjustment of multiple regulatory mechanisms. The E. salsugineum genome provides a resource to identify naturally occurring genetic alterations contributing to the adaptation of halophytic plants to salinity and that might be bioengineered in related crop species. Title: Biosynthesis of ethyl oleate, a primer pheromone, in the honey bee (Apis mellifera L.) Castillo C, Chen H, Graves C, Maisonnasse A, Le Conte Y, Plettner E Ref: Insect Biochemistry & Molecular Biology, 42:404, 2012 : PubMed ESTHER: Castillo_2012_Insect.Biochem.Mol.Biol_42_404 PubMedSearch: Castillo 2012 Insect.Biochem.Mol.Biol 42 404 PubMedID: 22406167 Abstract Honey bees undergo a physiological transition from nursing to foraging approximately 21 days after adult emergence. This transition is delayed by ethyl oleate (EO), a primer pheromone produced by foragers when exposed to ethanol from fermented nectar. We demonstrate here that two secreted alpha/beta-hydrolases (BeeBase ID: GB11403 and GB13365) are responsible for the reversible esterification of ethanol with oleic acid, giving EO. Expression of hydrolase GB11403 was shown to be significantly up-regulated in foragers, relative to nurses. Tissue perfusion experiments with labeled substrates consistently localized the highest level of EO production in the head, whereas in situ imaging revealed expression of relevant EO biosynthetic genes and enzymatic activity along the esophagus, the site of ethanol exposure during nectar intake. Both alpha/beta-hydrolases were expressed in Pichia pastoris, purified and were shown produce EO in vitro. Experiments with live bees fed ethanol demonstrated that EO formed in regurgitate accumulates in the honey crop and exudes to the exoskeleton, from where it exerts its primer effect on younger bees. Title: First genome sequence of a Burkholderia pseudomallei Isolate in China, strain BPC006, obtained from a melioidosis patient in Hainan Fang Y, Huang Y, Li Q, Chen H, Yao Z, Pan J, Gu J, Tang B, Wang HG and Mao XH <3 more author(s)> Fang Y, Huang Y, Li Q, Chen H, Yao Z, Pan J, Gu J, Tang B, Wang HG, Yu B, Tong YG, Zou QM, Mao XH (- 3) Ref: Journal of Bacteriology, 194:6604, 2012 : PubMed ESTHER: Fang_2012_J.Bacteriol_194_6604 PubMedSearch: Fang 2012 J.Bacteriol 194 6604 PubMedID: 23144371 Gene_locus related to this paper: burma-a5tq93, burma-q62mq7 Abstract Melioidosis, caused by Burkholderia pseudomallei, is considered to be endemic to Northern Australia and Southeast Asia, with high mortality and relapse rates, regardless of powerful antibiotic therapy. Here we report the first genome sequence of Burkholderia pseudomallei strain BPC006, obtained from a melioidosis patient in Hainan, China. The genome sizes of the 2 chromosomes were determined to be 4,001,777 bp and 3,153,284 bp. Title: Comparative analysis of the first complete Enterococcus faecium genome Lam MM, Seemann T, Bulach DM, Gladman SL, Chen H, Haring V, Moore RJ, Ballard S, Grayson ML and Stinear TP <2 more author(s)> Lam MM, Seemann T, Bulach DM, Gladman SL, Chen H, Haring V, Moore RJ, Ballard S, Grayson ML, Johnson PD, Howden BP, Stinear TP (- 2) Ref: Journal of Bacteriology, 194:2334, 2012 : PubMed ESTHER: Lam_2012_J.Bacteriol_194_2334 PubMedSearch: Lam 2012 J.Bacteriol 194 2334 PubMedID: 22366422 Abstract Vancomycin-resistant enterococci (VRE) are one of the leading causes of nosocomial infections in health care facilities around the globe. In particular, infections caused by vancomycin-resistant Enterococcus faecium are becoming increasingly common. Comparative and functional genomic studies of E. faecium isolates have so far been limited owing to the lack of a fully assembled E. faecium genome sequence. Here we address this issue and report the complete 3.0-Mb genome sequence of the multilocus sequence type 17 vancomycin-resistant Enterococcus faecium strain Aus0004, isolated from the bloodstream of a patient in Melbourne, Australia, in 1998. The genome comprises a 2.9-Mb circular chromosome and three circular plasmids. The chromosome harbors putative E. faecium virulence factors such as enterococcal surface protein, hemolysin, and collagen-binding adhesin. Aus0004 has a very large accessory genome (38%) that includes three prophage and two genomic islands absent among 22 other E. faecium genomes. One of the prophage was present as inverted 50-kb repeats that appear to have facilitated a 683-kb chromosomal inversion across the replication terminus, resulting in a striking replichore imbalance. Other distinctive features include 76 insertion sequence elements and a single chromosomal copy of Tn1549 containing the vanB vancomycin resistance element. A complete E. faecium genome will be a useful resource to assist our understanding of this emerging nosocomial pathogen. Title: Complete genome sequence of Paenibacillus mucilaginosus 3016, a bacterium functional as microbial fertilizer Ma M, Wang Z, Li L, Jiang X, Guan D, Cao F, Chen H, Wang X, Shen D and Li J <1 more author(s)> Ma M, Wang Z, Li L, Jiang X, Guan D, Cao F, Chen H, Wang X, Shen D, Du B, Li J (- 1) Ref: Journal of Bacteriology, 194:2777, 2012 : PubMed ESTHER: Ma_2012_J.Bacteriol_194_2777 PubMedSearch: Ma 2012 J.Bacteriol 194 2777 PubMedID: 22535950 Gene_locus related to this paper: paemk-f8fjj7, paemk-f8fd43, paemk-f8fl06, 9bacl-h6ntc5 Abstract Paenibacillus mucilaginosus is a ubiquitous functional bacterium in microbial fertilizer. Here we report the complete sequence of P. mucilaginosus 3016. Multiple sets of functional genes have been found in the genome. To the best of our knowledge, this is the first announcement about the complete genome sequence of a P. mucilaginosus strain. Title: Comparative geno-plasticity analysis of Mycoplasma bovis HB0801 (Chinese isolate) Qi J, Guo A, Cui P, Chen Y, Mustafa R, Ba X, Hu C, Bai Z, Chen X and Chen H <1 more author(s)> Qi J, Guo A, Cui P, Chen Y, Mustafa R, Ba X, Hu C, Bai Z, Chen X, Shi L, Chen H (- 1) Ref: PLoS ONE, 7:e38239, 2012 : PubMed ESTHER: Qi_2012_PLoS.One_7_e38239 PubMedSearch: Qi 2012 PLoS.One 7 e38239 PubMedID: 22693604 Abstract Mycoplasma bovis pneumonia in cattle has been epidemic in China since 2008. To investigate M. bovis pathogenesis, we completed genome sequencing of strain HB0801 isolated from a lesioned bovine lung from Hubei, China. The genomic plasticity was determined by comparing HB0801 with M. bovis strain ATCC(R) 25523/PG45 from cow mastitis milk, Chinese strain Hubei-1 from lesioned lung tissue, and 16 other Mycoplasmas species. Compared to PG45, the genome size of HB0801 was reduced by 11.7 kb. Furthermore, a large chromosome inversion (580 kb) was confirmed in all Chinese isolates including HB0801, HB1007, a strain from cow mastitis milk, and Hubei-1. In addition, the variable surface lipoproteins (vsp) gene cluster existed in HB0801, but contained less than half of the genes, and had poor identity to that in PG45, but they had conserved structures. Further inter-strain comparisons revealed other mechanisms of gene acquisition and loss in HB0801 that primarily involved insertion sequence (IS) elements, integrative conjugative element, restriction and modification systems, and some lipoproteins and transmembrane proteins. Subsequently, PG45 and HB0801 virulence in cattle was compared. Results indicated that both strains were pathogenic to cattle. The scores of gross pathological assessment for the control group, and the PG45- and HB0801-infected groups were 3, 13 and 9, respectively. Meanwhile the scores of lung lesion for these three groups were 36, 70, and 69, respectively. In addition, immunohistochemistry detection demonstrated that both strains were similarly distributed in lungs and lymph nodes. Although PG45 showed slightly higher virulence in calves than HB0801, there was no statistical difference between the strains (P>0.05). Compared to Hubei-1, a total of 122 SNP loci were disclosed in HB0801. In conclusion, although genomic plasticity was thought to be an evolutionary advantage, it did not apparently affect virulence of M. bovis strains in cattle. Title: Genome sequence of Mycoplasma iowae strain 695, an unusual pathogen causing deaths in turkeys Wei S, Guo Z, Li T, Zhang T, Li X, Zhou Z, Li Z, Liu M, Luo R and Jin H <3 more author(s)> Wei S, Guo Z, Li T, Zhang T, Li X, Zhou Z, Li Z, Liu M, Luo R, Bi D, Chen H, Zhou R, Jin H (- 3) Ref: Journal of Bacteriology, 194:547, 2012 : PubMed ESTHER: Wei_2012_J.Bacteriol_194_547 PubMedSearch: Wei 2012 J.Bacteriol 194 547 PubMedID: 22207750 Abstract Mycoplasma iowae is associated mainly with reduced hatchability in turkeys and is well known for the unusual ability of phenotypic variation in the Mycoplasma surface components as well as a relative resistance to heat, bile salts, and many antimicrobials. A subset of unique genes and a gene cluster responsible for these characteristics could be identified from the genome. Here, we report the first genome sequence of this species. 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: Novel bis-(-)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property Zheng W, Li J, Qiu Z, Xia Z, Li W, Yu L, Chen H, Chen J, Chen Y and Xie Q <4 more author(s)> Zheng W, Li J, Qiu Z, Xia Z, Li W, Yu L, Chen H, Chen J, Chen Y, Hu Z, Zhou W, Shao B, Cui Y, Xie Q (- 4) Ref: Toxicol Appl Pharmacol, 264:65, 2012 : PubMed ESTHER: Zheng_2012_Toxicol.Appl.Pharmacol_264_65 PubMedSearch: Zheng 2012 Toxicol.Appl.Pharmacol 264 65 PubMedID: 22842334 Inhibitor(s) related to this paper: bis9-(-)-nor-meptazinol Abstract The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(-)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC(50) values of 9.63uM (for ZLA) and 8.64uM (for ZLB), and prevent AChE-induced amyloid-beta (Abeta) aggregation with IC(50) values of 49.1uM (for ZLA) and 55.3uM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Abeta aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. Title: Draft genome sequence of Mesorhizobium alhagi CCNWXJ12-2T, a novel salt-resistant species isolated from the desert of northwestern China Zhou M, Chen W, Chen H, Wei G Ref: Journal of Bacteriology, 194:1261, 2012 : PubMed ESTHER: Zhou_2012_J.Bacteriol_194_1261 PubMedSearch: Zhou 2012 J.Bacteriol 194 1261 PubMedID: 22328758 Gene_locus related to this paper: 9rhiz-h0hm22, 9rhiz-h0hp47, 9rhiz-h0hji9 Abstract Mesorhizobium alhagi strain CCNWXJ12-2(T) is a novel species of soil-dwelling, nitrogen-fixing bacteria that can form symbiotic root nodules with Alhagi sparsifolia. Moreover, the strain has high resistance to salt and alkali. Here we report the draft genome sequence of Mesorhizobium alhagi strain CCNWXJ12-2(T). A large number of osmotic regulation-related genes have been identified. Title: Draft genome sequence of strain HIMB100, a cultured representative of the SAR116 clade of marine Alphaproteobacteria Grote J, Bayindirli C, Bergauer K, Carpintero de Moraes P, Chen H, D'Ambrosio L, Edwards B, Fernandez-Gomez B, Hamisi M and Rappe MS <13 more author(s)> Grote J, Bayindirli C, Bergauer K, Carpintero de Moraes P, Chen H, D'Ambrosio L, Edwards B, Fernandez-Gomez B, Hamisi M, Logares R, Nguyen D, Rii YM, Saeck E, Schutte C, Widner B, Church MJ, Steward GF, Karl DM, DeLong EF, Eppley JM, Schuster SC, Kyrpides NC, Rappe MS (- 13) Ref: Stand Genomic Sci, 5:269, 2011 : PubMed ESTHER: Grote_2011_Stand.Genomic.Sci_5_269 PubMedSearch: Grote 2011 Stand.Genomic.Sci 5 269 PubMedID: 22675578 Gene_locus related to this paper: 9prot-g5zwk9, 9prot-g5zy12 Abstract Strain HIMB100 is a planktonic marine bacterium in the class Alphaproteobacteria. This strain is of interest because it is one of the first known isolates from a globally ubiquitous clade of marine bacteria known as SAR116 within the family Rhodospirillaceae. Here we describe preliminary features of the organism, together with the draft genome sequence and annotation. This is the second genome sequence of a member of the SAR116 clade. The 2,458,945 bp genome contains 2,334 protein-coding and 42 RNA genes. Title: Complete genome sequence of Streptococcus suis serotype 3 strain ST3 Hu P, Yang M, Zhang A, Wu J, Chen B, Hua Y, Yu J, Chen H, Xiao J, Jin M Ref: Journal of Bacteriology, 193:3428, 2011 : PubMed ESTHER: Hu_2011_J.Bacteriol_193_3428 PubMedSearch: Hu 2011 J.Bacteriol 193 3428 PubMedID: 21572001 Gene_locus related to this paper: strsu-b9wvz1 Abstract Streptococcus suis is a zoonotic pathogen causing economic loss in the swine industry and is also a threat to human health. To date, the mechanism of pathogenesis is not fully understood. Here, we report the complete genome sequence of S. suis strain ST3 of serotype 3, which provides opportunities to reveal genetic basis of infection of S. suis non-serotype 2 strains. Title: Complete genome sequence of Mycoplasma hyopneumoniae strain 168 Liu W, Feng Z, Fang L, Zhou Z, Li Q, Li S, Luo R, Wang L, Chen H and Xiao S <1 more author(s)> Liu W, Feng Z, Fang L, Zhou Z, Li Q, Li S, Luo R, Wang L, Chen H, Shao G, Xiao S (- 1) Ref: Journal of Bacteriology, 193:1016, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_1016 PubMedSearch: Liu 2011 J.Bacteriol 193 1016 PubMedID: 21148737 Abstract Mycoplasma hyopneumoniae strain 168, a pathogenic strain prevalent in China, was isolated in 1974. Although this strain has been widespread for a long time, the genome sequence had not been determined. Here, we announce the complete genome sequence of M. hyopneumoniae strain 168. Title: Complete genome sequence of Paenibacillus polymyxa SC2, a strain of plant growth-promoting Rhizobacterium with broad-spectrum antimicrobial activity Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H and Du B <7 more author(s)> Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H, Feng R, Wang X, Ge Y, Yao L, Bing X, Yang X, Li J, Du B (- 7) Ref: Journal of Bacteriology, 193:311, 2011 : PubMed ESTHER: Ma_2011_J.Bacteriol_193_311 PubMedSearch: Ma 2011 J.Bacteriol 193 311 PubMedID: 21037012 Gene_locus related to this paper: paep6-e0rmc7, paeps-e3e5s8, paeps-e3ebx3, paeps-e3e602 Abstract Paenibacillus polymyxa SC2 is an important plant growth-promoting rhizobacterium (PGPR). Here, we report the complete genome sequence of P. polymyxa SC2. Multiple sets of functional genes have been found in the genome. As far as we know, this is the first complete genome sequence of Paenibacillus polymyxa. Title: Surrogate based accurate quantification of endogenous acetylcholine in murine brain by hydrophilic interaction liquid chromatography-tandem mass spectrometry Peng L, Jiang T, Rong Z, Liu T, Wang H, Shao B, Ma J, Yang L, Kang L and Chen H <3 more author(s)> Peng L, Jiang T, Rong Z, Liu T, Wang H, Shao B, Ma J, Yang L, Kang L, Shen Y, Li H, Qi H, Chen H (- 3) Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 879:3927, 2011 : PubMed ESTHER: Peng_2011_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_879_3927 PubMedSearch: Peng 2011 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 879 3927 PubMedID: 22088352 Abstract Cholinergic dysfunction is known as a hallmark feature of Alzheimer's disease (AD). Measurement of endogenous acetylcholine (ACh) in specific brain regions is important in understanding the pathology of AD and in designing and evaluating novel cholinomimetic agents for the treatment of AD. Since ACh is an endogenous neurotransmitter, there is no real blank matrix available to construct standard curves. It has been a challenging task to determine ACh in complex brain matrices. To overcome these difficulties, we employed a surrogate analyte strategy using ACh-d(4) instead of ACh to generate calibration curves and Ch-d(9) as internal standard (IS). The brain samples were deproteinized by acetonitrile with IS. Analytes and IS were separated by a HILIC column with the mobile phase composed of 20 mM ammonium formate in water-acetonitrile (30:70, v/v, adjusted to pH 3.0 with formic acid) and monitored in multiple reaction monitoring (MRM) mode using a positive electrospray source. The concentrations of endogenous ACh were calculated based on the peak area ratio of the analyte to the IS using a regression equation for the corresponding surrogate standard (ACh-d(4)). The lower limit of detection was 0.2 ng/mL and linearity was maintained over the range of 10-1000 ng/mL. Compared to other currently available methods, this approach offers improved accuracy and precision for efficient analysis of ACh. The proposed method was proved successfully by evaluating the action of typical acetylcholinesterase inhibitor huperzine A in senescence accelerated mouse prone 8 (SAMP8). Title: Genome sequence of a porcine extraintestinal pathogenic Escherichia coli strain Tan C, Xu Z, Zheng H, Liu W, Tang X, Shou J, Wu B, Wang S, Zhao GP, Chen H Ref: Journal of Bacteriology, 193:5038, 2011 : PubMed ESTHER: Tan_2011_J.Bacteriol_193_5038 PubMedSearch: Tan 2011 J.Bacteriol 193 5038 PubMedID: 21742868 Gene_locus related to this paper: ecoli-IROD, ecoli-IROE, ecoli-ycfp, ecoli-YFBB, ecoli-ypt1, ecoli-yqia Abstract Extraintestinal pathogenic Escherichia coli (ExPEC) is an important pathogen which can infect humans and animals and cause many diseases outside the intestine. Here, we report the first draft genome sequence of a porcine ExPEC strain, PCN033, isolated from a pig with meningitis. Title: Disposable screen-printed electrode coupled with recombinant Drosophila melanogaster acetylcholinesterase and multiwalled carbon nanotubes for rapid detection of pesticides Tang Z, Chen H, Song S, Fan C, Zhang D, Wu A Ref: Journal of AOAC International, 94:307, 2011 : PubMed ESTHER: Tang_2011_J.AOAC.Int_94_307 PubMedSearch: Tang 2011 J.AOAC.Int 94 307 PubMedID: 21391508 Abstract Recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE), multiwalled carbon nanotubes (MWCNTs), and Prussian blue have been combined for development of a three-electrode biosensor with more rapid responses and higher stability than in our previous study. A new disposable screen-printed electrode (SPE) was developed for rapid detection of organophosphate and carbamate pesticides. After optimization, 10 microg MWCNT and 5 microL enzyme immobilization solution consisting of 0.2% glutaraldehyde, 0.1% Nafion, 0.2% bovine serum albumin, 0.1 g/L MWCNT, and 1.5 mU R-DmAChE were fixed on each of the R-DmAChE/MWCNT SPEs. The LOD of this biosensor was 0.5 microg/L for pesticide standards of dichlorvos (DDV) and carbofuran. The performance of this biosensor was tested for vegetable and water samples at various spiked levels, and good stability and sensitivity were found. The obtained recoveries were from 82.6 to 110.5% for DDV at levels of 0.5-5 microg/L and 73.4 to 118.4% for carbofuran at 1-10 microg/L in lake and sea water samples, demonstrating that the proposed approach is an alternative means for rapid detection of pesticide residues and contaminants in food safety and environmental monitoring. Title: Genomic characterization of Haemophilus parasuis SH0165, a highly virulent strain of serovar 5 prevalent in China Xu Z, Yue M, Zhou R, Jin Q, Fan Y, Bei W, Chen H Ref: PLoS ONE, 6:e19631, 2011 : PubMed ESTHER: Xu_2011_PLoS.ONE_6_E19631 PubMedSearch: Xu 2011 PLoS.ONE 6 E19631 PubMedID: 21611187 Gene_locus related to this paper: haeps-b8f714 Abstract Haemophilus parasuis can be either a commensal bacterium of the porcine respiratory tract or an opportunistic pathogen causing Glasser's disease, a severe systemic disease that has led to significant economical losses in the pig industry worldwide. We determined the complete genomic sequence of H. parasuis SH0165, a highly virulent strain of serovar 5, which was isolated from a hog pen in North China. The single circular chromosome was 2,269,156 base pairs in length and contained 2,031 protein-coding genes. Together with the full spectrum of genes detected by the analysis of metabolic pathways, we confirmed that H. parasuis generates ATP via both fermentation and respiration, and possesses an intact TCA cycle for anabolism. In addition to possessing the complete pathway essential for the biosynthesis of heme, this pathogen was also found to be well-equipped with different iron acquisition systems, such as the TonB system and ABC-type transport complexes, to overcome iron limitation during infection and persistence. We identified a number of genes encoding potential virulence factors, such as type IV fimbriae and surface polysaccharides. Analysis of the genome confirmed that H. parasuis is naturally competent, as genes related to DNA uptake are present. A nine-mer DNA uptake signal sequence (ACAAGCGGT), identical to that found in Actinobacillus pleuropneumoniae and Mannheimia haemolytica, followed by similar downstream motifs, was identified in the SH0165 genome. Genomic and phylogenetic comparisons with other Pasteurellaceae species further indicated that H. parasuis was closely related to another swine pathogenic bacteria A. pleuropneumoniae. The comprehensive genetic analysis presented here provides a foundation for future research on the metabolism, natural competence and virulence of H. parasuis. Title: Comparative genomic analysis of Streptococcus suis reveals significant genomic diversity among different serotypes Zhang A, Yang M, Hu P, Wu J, Chen B, Hua Y, Yu J, Chen H, Xiao J, Jin M Ref: BMC Genomics, 12:523, 2011 : PubMed ESTHER: Zhang_2011_BMC.Genomics_12_523 PubMedSearch: Zhang 2011 BMC.Genomics 12 523 PubMedID: 22026465 Gene_locus related to this paper: strsu-b9wvz1 Abstract BACKGROUND: Streptococcus suis (S. suis) is a major swine pathogen and an emerging zoonotic agent. Serotypes 1, 2, 3, 7, 9, 14 and 1/2 are the most prevalent serotypes of this pathogen. However, almost all studies were carried out on serotype 2 strains. Therefore, characterization of genomic features of other serotypes will be required to better understand their virulence potential and phylogenetic relationships among different serotypes. Title: Smoking duration, intensity, and risk of Parkinson disease Chen H, Huang X, Guo X, Mailman RB, Park Y, Kamel F, Umbach DM, Xu Q, Hollenbeck A and Blair A <1 more author(s)> Chen H, Huang X, Guo X, Mailman RB, Park Y, Kamel F, Umbach DM, Xu Q, Hollenbeck A, Schatzkin A, Blair A (- 1) Ref: Neurology, 74:878, 2010 : PubMed ESTHER: Chen_2010_Neurology_74_878 PubMedSearch: Chen 2010 Neurology 74 878 PubMedID: 20220126 Abstract OBJECTIVE: To evaluate the relative importance of smoking duration vs intensity in reducing the risk of Parkinson disease (PD). Title: Complete genome sequence of Staphylococcus aureus strain JKD6159, a unique Australian clone of ST93-IV community methicillin-resistant Staphylococcus aureus Chua K, Seemann T, Harrison PF, Davies JK, Coutts SJ, Chen H, Haring V, Moore R, Howden BP, Stinear TP Ref: Journal of Bacteriology, 192:5556, 2010 : PubMed ESTHER: Chua_2010_J.Bacteriol_192_5556 PubMedSearch: Chua 2010 J.Bacteriol 192 5556 PubMedID: 20729356 Gene_locus related to this paper: staau-c8mfq3, staau-d2feb3, staau-LIP, staau-lipas, staau-MW0741, staau-MW2456, staau-q6gfm6, staau-SA0011, staau-SA0569, staau-SA0572, staau-SA0897, staau-SA1143, staau-SA2240, staau-SA2306, staau-SA2422, staau-SAV0321, staau-SAV0457, staau-SAV0655, staau-SAV1014, staau-SAV1765, staau-SAV1793, staau-SAV2188, staau-SAV2350, staau-SAV2484, staau-SAV2594 Abstract Community methicillin-resistant Staphylococcus aureus (cMRSA) is an emerging issue that has resulted in multiple worldwide epidemics. We report the first complete genome sequence of an ST93-MRSA-IV clinical isolate that caused severe invasive infection and a familial outbreak of skin infection. This isolate is a representative of the most common Australian clone of cMRSA that is more distantly related to the previously sequenced genomes of S. aureus. Title: Depression and the subsequent risk of Parkinson's disease in the NIH-AARP Diet and Health Study Fang F, Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Kamel F, Chen H Ref: Movement Disorders, 25:1157, 2010 : PubMed ESTHER: Fang_2010_Mov.Disord_25_1157 PubMedSearch: Fang 2010 Mov.Disord 25 1157 PubMedID: 20310050 Abstract We conducted a case-control study to examine the association between depression and Parkinson's disease (PD). Participants included 992 PD cases diagnosed after 2,000 and 279,958 individuals without PD from the NIH-AARP Diet and Health Study follow-up survey. Physician-diagnosed depression and PD were self-reported with information on the year of diagnosis in the following categories: before 1985, 1985-1994, 1995-1999, and 2000-present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR = 4.7, 95% CI = 3.9, 5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000 (OR = 2.0, 95% CI = 1.6, 2.4). This association was stronger for depression diagnosed in 1995-1999 (OR = 2.7, 95% CI = 2.0, 3.6), but was also noted for depression diagnosed in 1985-1994 (OR = 1.6, 95% CI = 1.1, 2.3) or even before 1985 (OR = 1.7, 95% CI = 1.3, 2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD. Title: Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE Howard TD, Hsu FC, Grzywacz JG, Chen H, Quandt SA, Vallejos QM, Whalley LE, Cui W, Padilla S, Arcury TA Ref: Environmental Health Perspectives, 118:1395, 2010 : PubMed ESTHER: Howard_2010_Environ.Health.Perspect_118_1395 PubMedSearch: Howard 2010 Environ.Health.Perspect 118 1395 PubMedID: 20529763 Abstract BACKGROUND: Organophosphate pesticides act as cholinesterase inhibitors. For those with agricultural exposure to these chemicals, risk of potential exposure-related health effects may be modified by genetic variability in cholinesterase metabolism. Cholinesterase activity is a useful, indirect measurement of pesticide exposure, especially in high-risk individuals such as farmworkers. To understand fully the links between pesticide exposure and potential human disease, analyses must be able to consider genetic variability in pesticide metabolism. OBJECTIVES: We studied participants in the Community Participatory Approach to Measuring Farmworker Pesticide Exposure (PACE3) study to determine whether cholinesterase levels are associated with single-nucleotide polymorphisms (SNPs) involved in pesticide metabolism. METHODS: Cholinesterase levels were measured from blood samples taken from 287 PACE3 participants at up to four time points during the 2007 growing season. We performed association tests of cholinesterase levels and 256 SNPs in 30 candidate genes potentially involved in pesticide metabolism. A false discovery rate (FDR) p-value was used to account for multiple testing. RESULTS: Thirty-five SNPs were associated (unadjusted p < 0.05) based on at least one of the genetic models tested (general, additive, dominant, and recessive). The strongest evidence of association with cholinesterase levels was observed with two SNPs, rs2668207 and rs2048493, in the butyrylcholinesterase (BCHE) gene (FDR adjusted p = 0.15 for both; unadjusted p = 0.00098 and 0.00068, respectively). In participants with at least one minor allele, cholinesterase levels were lower by 4.3-9.5% at all time points, consistent with an effect that is independent of pesticide exposure. CONCLUSIONS: Common genetic variation in the BCHE gene may contribute to subtle changes in cholinesterase levels. Title: Complete genome sequence of Mycoplasma hyorhinis strain HUB-1 Liu W, Fang L, Li S, Li Q, Zhou Z, Feng Z, Luo R, Shao G, Wang L and Xiao S <1 more author(s)> Liu W, Fang L, Li S, Li Q, Zhou Z, Feng Z, Luo R, Shao G, Wang L, Chen H, Xiao S (- 1) Ref: Journal of Bacteriology, 192:5844, 2010 : PubMed ESTHER: Liu_2010_J.Bacteriol_192_5844 PubMedSearch: Liu 2010 J.Bacteriol 192 5844 PubMedID: 20802032 Abstract Mycoplasma hyorhinis is generally considered a swine pathogen yet is most commonly found infecting laboratory cell lines. An increasing body of evidence suggests that chronic infections with M. hyorhinis may cause oncogenic transformation. Here, we announce the complete genome sequence of M. hyorhinis strain HUB-1. Title: Cholinesterase depression and its association with pesticide exposure across the agricultural season among Latino farmworkers in North Carolina Quandt SA, Chen H, Grzywacz JG, Vallejos QM, Galvan L, Arcury TA Ref: Environmental Health Perspectives, 118:635, 2010 : PubMed ESTHER: Quandt_2010_Environ.Health.Perspect_118_635 PubMedSearch: Quandt 2010 Environ.Health.Perspect 118 635 PubMedID: 20085857 Abstract BACKGROUND: Farmworkers can be exposed to a wide variety of pesticides. Assessing cholinesterase activity over time can be used to monitor exposure to organophosphorus and carbamate pesticides. OBJECTIVES: The goal of this study was to document patterns and variation in cholinesterase levels across the agricultural season (May-August) among field-workers, and to explore the association of cholinesterase depression with pesticide exposure across the agricultural season. METHODS: Dried blood samples collected from 231 migrant farmworkers sampled from camps in eastern North Carolina up to four times across a summer agricultural season were analyzed for cholinesterase activity, and urine samples were analyzed for metabolites of organophosphorus and carbamate pesticides. Reductions of >or= 15% from an individual's highest value were identified and considered evidence of meaningful cholinesterase activity depression. RESULTS: The average cholinesterase activity levels were lowest in June, with significantly higher mean values in July and August. When adjusted for age, sex, minutes waited to shower, and days worked in the fields, the number of organophosphorus and carbamate pesticides detected in urine predicted reductions in cholinesterase activity. CONCLUSIONS: These data demonstrate that workers are experiencing pesticide exposure. Greater enforcement of existing safety regulations or strengthening of these regulations may be warranted. This study demonstrates that serial measurements of cholinesterase activity across an agricultural season can detect exposure to pesticides among field-workers. Title: Pharmacological characterization of [(125)I]CHIBA-1006 binding, a new radioligand for alpha7 nicotinic acetylcholine receptors, to rat brain membranes Wu J, Toyohara J, Tanibuchi Y, Fujita Y, Zhang J, Chen H, Matsuo M, Wang RF, Hashimoto K Ref: Brain Research, 1360:130, 2010 : PubMed ESTHER: Wu_2010_Brain.Res_1360_130 PubMedSearch: Wu 2010 Brain.Res 1360 130 PubMedID: 20816767 Abstract The alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable small molecule radioligands for imaging alpha7 nAChRs in the brain. In this study, we synthesized the novel radioligand [(125)I]4-iodophenyl 1,4-diazaicyclo[3.2.2]nonane-4-carboxylate ([(125)I]CHIBA-1006), a iodine-derivative of the selective alpha7 nAChR agonist SSR180711, and studied the characterization of [(125)I]CHIBA-1006 binding to rat brain membranes. The assays of [(125)I]CHIBA-1006 binding to rat brain membranes were performed at 4 degrees C. The presence of a single saturable high-affinity binding component for [(125)I]CHIBA-1006 in the rat brain was shown. Scatchard analysis revealed an apparent equilibrium dissociation constant (K(d)) of 88.2+/-21.4nM and a maximal number of binding sites (B(max)) of 65.4+/-6.8fmol/mg protein (mean+/-SEM, n=4). The specific binding of [(125)I]CHIBA-1006 was inhibited by a number of alpha7 nAChR-selective ligands (e.g., unlabeled CHIBA-1006, SSR180711, CHIBA-1001, MG624 and A844606), suggesting a similarity among alpha7 nAChR pharmacological profiles. In contrast, alpha-bungarotoxin, MLA, and nicotine showed very weak affinity for [(125)I]CHIBA-1006 binding. The regional distribution of [(125)I]CHIBA-1006 binding to crude membranes from dissected regions of the rat brain was different from that of [(125)I]alpha-bungarotoxin binding, suggesting that [(125)I]CHIBA-1006 binding sites may not be identical to [(125)I]alpha-bungarotoxin binding sites in the rat brain. The present findings suggest that [(125)I]CHIBA-1006 would be a useful new small molecule radioligand for alpha7 nAChRs in the brain. Title: Comparative genomic characterization of Actinobacillus pleuropneumoniae Xu Z, Chen X, Li L, Li T, Wang S, Chen H, Zhou R Ref: Journal of Bacteriology, 192:5625, 2010 : PubMed ESTHER: Xu_2010_J.Bacteriol_192_5625 PubMedSearch: Xu 2010 J.Bacteriol 192 5625 PubMedID: 20802045 Gene_locus related to this paper: actp2-a3mzf9, actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2 Abstract The Gram-negative bacterium Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumoniae, a lethal respiratory infectious disease causing great economic losses in the swine industry worldwide. In order to better interpret the genetic background of serotypic diversity, nine genomes of A. pleuropneumoniae reference strains of serovars 1, 2, 4, 6, 9, 10, 11, 12, and 13 were sequenced by using rapid high-throughput approach. Based on 12 genomes of corresponding serovar reference strains including three publicly available complete genomes (serovars 3, 5b, and 7) of this bacterium, we performed a comprehensive analysis of comparative genomics and first reported a global genomic characterization for this pathogen. Clustering of 26,012 predicted protein-coding genes showed that the pan genome of A. pleuropneumoniae consists of 3,303 gene clusters, which contain 1,709 core genome genes, 822 distributed genes, and 772 strain-specific genes. The genome components involved in the biogenesis of capsular polysaccharide and lipopolysaccharide O antigen relative to serovar diversity were compared, and their genetic diversity was depicted. Our findings shed more light on genomic features associated with serovar diversity of A. pleuropneumoniae and provide broader insight into both pathogenesis research and clinical/epidemiological application against the severe disease caused by this swine pathogen. Title: Meeting report: consensus statement-Parkinson's disease and the environment: collaborative on health and the environment and Parkinson's Action Network (CHE PAN) conference 26-28 June 2007 Bronstein J, Carvey P, Chen H, Cory-Slechta D, DiMonte D, Duda J, English P, Goldman S, Grate S and Weisskopf M <19 more author(s)> Bronstein J, Carvey P, Chen H, Cory-Slechta D, DiMonte D, Duda J, English P, Goldman S, Grate S, Hansen J, Hoppin J, Jewell S, Kamel F, Koroshetz W, Langston JW, Logroscino G, Nelson L, Ravina B, Rocca W, Ross GW, Schettler T, Schwarzschild M, Scott B, Seegal R, Singleton A, Steenland K, Tanner CM, Van Den Eeden S, Weisskopf M (- 19) Ref: Environmental Health Perspectives, 117:117, 2009 : PubMed ESTHER: Bronstein_2009_Environ.Health.Perspect_117_117 PubMedSearch: Bronstein 2009 Environ.Health.Perspect 117 117 PubMedID: 19165397 Abstract BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Title: Protection of PMS777, a new AChE inhibitor with PAF antagonism, against amyloid-beta-induced neuronal apoptosis and neuroinflammation Li J, Hu J, Shao B, Zhou W, Cui Y, Dong C, Ezoulin JM, Zhu X, Ding W and Chen H <1 more author(s)> Li J, Hu J, Shao B, Zhou W, Cui Y, Dong C, Ezoulin JM, Zhu X, Ding W, Heymans F, Chen H (- 1) Ref: Cellular Molecular Neurobiology, 29:589, 2009 : PubMed ESTHER: Li_2009_Cell.Mol.Neurobiol_29_589 PubMedSearch: Li 2009 Cell.Mol.Neurobiol 29 589 PubMedID: 19194797 Abstract Amyloid-beta (Abeta) plays a central role in the neuroinflammation and cholinergic neuronal apoptosis in Alzheimer's disease, and thus has been considered as a main determinant of this disease. In the previous study, we reported that PMS777, a novel bis-interacting ligand for acetylcholinesterase (AChE) inhibition and platelet-activating factor (PAF) receptor antagonism, could significantly attenuate PAF-induced neurotoxicity. Continuing our efforts, we further investigated the protective effect of PMS777 on Abeta-induced neuronal apoptosis in vitro and neuroinflammation in vivo. PMS777 (1-100 microM) was found to inhibit Abeta-induced human neuroblastoma SH-SY5Y cell apoptosis in a concentration-dependent manner. Concurrently, PMS777 increased ratio of bcl-2 to bax mRNA, and inhibited both mRNA expression and activity of caspase-3 in SH-SY5Y cells after the exposure with Abeta. In vivo experimental study demonstrated that PMS777 could attenuate Abeta-induced microglial and astrocytic activation in the rat hippocampus after systemic administration. These results suggest that PMS777 potently protects against Abeta-induced neuronal apoptosis and neuroinflammation, and warrants further investigations in connection with its potential value in the treatment of Alzheimer's disease. Title: Complete genome sequence of Haemophilus parasuis SH0165 Yue M, Yang F, Yang J, Bei W, Cai X, Chen L, Dong J, Zhou R, Jin M and Chen H <1 more author(s)> Yue M, Yang F, Yang J, Bei W, Cai X, Chen L, Dong J, Zhou R, Jin M, Jin Q, Chen H (- 1) Ref: Journal of Bacteriology, 191:1359, 2009 : PubMed ESTHER: Yue_2009_J.Bacteriol_191_1359 PubMedSearch: Yue 2009 J.Bacteriol 191 1359 PubMedID: 19074396 Gene_locus related to this paper: haepr-b0qsi5, haepr-b0qve9, haeps-b8f6u1, haeps-b8f692, haeps-b8f714 Abstract Haemophilus parasuis is the causative agent of Glasser's disease, which produces big losses in swine populations worldwide. H. parasuis SH0165, belonging to the dominant serovar 5 in China, is a clinically isolated strain with high-level virulence. Here, we report the first completed genome sequence of this species. Title: Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists Morytko MJ, Betschmann P, Woller K, Ericsson A, Chen H, Donnelly-Roberts D, Namovic MT, Jarvis MF, Carroll WA, Rafferty P Ref: Bioorganic & Medicinal Chemistry Lett, 18:2093, 2008 : PubMed ESTHER: Morytko_2008_Bioorg.Med.Chem.Lett_18_2093 PubMedSearch: Morytko 2008 Bioorg.Med.Chem.Lett 18 2093 PubMedID: 18272365 Abstract A novel series of cyanoguanidine-piperazine P2X(7) antagonists was designed based upon the structure of A-740003. Structure-activity relationship (SAR) studies focused on the piperazine moiety and the right hand side substitution. Compounds were assayed for activity at human and rat P2X(7) receptors and compound 29 was found to possess potent activity (IC(50)=30-60 nM) at both species. Title: Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-beta aggregation Xie Q, Wang H, Xia Z, Lu M, Zhang W, Wang X, Fu W, Tang Y, Sheng W and Chen H <4 more author(s)> Xie Q, Wang H, Xia Z, Lu M, Zhang W, Wang X, Fu W, Tang Y, Sheng W, Li W, Zhou W, Zhu X, Qiu Z, Chen H (- 4) Ref: Journal of Medicinal Chemistry, 51:2027, 2008 : PubMed ESTHER: Xie_2008_J.Med.Chem_51_2027 PubMedSearch: Xie 2008 J.Med.Chem 51 2027 PubMedID: 18333606 Inhibitor(s) related to this paper: bis9-(-)-nor-meptazinol Abstract Bis-(-)-nor-meptazinols (bis-(-)-nor-MEPs) 5 were designed and synthesized by connecting two (-)-nor-MEP monomers with alkylene linkers of different lengths via the secondary amino groups. Their acetylcholinesterase (AChE) inhibitory activities were more greatly influenced by the length of the alkylene chain than butyrylcholinesterase (BChE) inhibition. The most potent nonamethylene-tethered dimer 5h exhibited low-nanomolar IC 50 values for both ChEs, having a 10 000-fold and 1500-fold increase in inhibition of AChE and BChE compared with (-)-MEP. Molecular docking elucidated that 5h simultaneously bound to the catalytic and peripheral sites in AChE via hydrophobic interactions with Trp86 and Trp286. In comparison, it folded in the large aliphatic cavity of BChE because of the absence of peripheral site and the enlargement of the active site. Furthermore, 5h and 5i markedly prevented the AChE-induced Abeta aggregation with IC 50 values of 16.6 and 5.8 microM, similar to that of propidium (IC 50 = 12.8 microM), which suggests promising disease-modifying agents for the treatment of AD patients. Title: Genome biology of Actinobacillus pleuropneumoniae JL03, an isolate of serotype 3 prevalent in China Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W and Chen H <16 more author(s)> Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W, Jin H, Kang M, Dalai B, Li T, Liu L, Cheng Y, Zhang L, Xu T, Zheng H, Pu S, Wang B, Gu W, Zhang XL, Zhu GF, Wang S, Zhao GP, Chen H (- 16) Ref: PLoS ONE, 3:e1450, 2008 : PubMed ESTHER: Xu_2008_PLoS.ONE_3_E1450 PubMedSearch: Xu 2008 PLoS.ONE 3 E1450 PubMedID: 18197260 Gene_locus related to this paper: actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2, actpj-b0bpm3, actpj-b0bqd8 Abstract Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a cause of considerable world wide economic losses in the swine industry. We sequenced the complete genome of A. pleuropneumoniae, JL03, an isolate of serotype 3 prevalent in China. Its genome is a single chromosome of 2,242,062 base pairs containing 2,097 predicted protein-coding sequences, six ribosomal rRNA operons, and 63 tRNA genes. Preliminary analysis of the genomic sequence and the functions of the encoded proteins not only confirmed the present physiological and pathological knowledge but also offered new insights into the metabolic and virulence characteristics of this important pathogen. We identified a full spectrum of genes related to its characteristic chemoheterotrophic catabolism of fermentation and respiration with an incomplete TCA system for anabolism. In addition to confirming the lack of ApxI toxin, identification of a nonsense mutation in apxIVA and a 5'-proximal truncation of the flp operon deleting both its promoter and the flp1flp2tadV genes have provided convincing scenarios for the low virulence property of JL03. Comparative genomic analysis using the available sequences of other serotypes, probable strain (serotype)-specific genomic islands related to capsular polysaccharides and lipopolysaccharide O-antigen biosyntheses were identified in JL03, which provides a foundation for future research into the mechanisms of serotypic diversity of A. pleuropneumoniae. Title: Construction of the pharmacophore model of acetylcholinesterase inhibitor Zhu Y, Tong XY, Zhao Y, Chen H, Jiang FC Ref: Yao Xue Xue Bao, 43:267, 2008 : PubMed ESTHER: Zhu_2008_Yao.Xue.Xue.Bao_43_267 PubMedSearch: Zhu 2008 Yao.Xue.Xue.Bao 43 267 PubMedID: 18630262 Abstract Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening. Title: Production of a novel recombinant Drosophila melanogaster acetylcholinesterase for detection of organophosphate and carbamate insecticide residues Xu S, Wu A, Chen H, Xie Y, Xu Y, Zhang L, Li J, Zhang D Ref: Biomol Eng, 24:253, 2007 : PubMed ESTHER: Xu_2007_Biomol.Eng_24_253 PubMedSearch: Xu 2007 Biomol.Eng 24 253 PubMedID: 17222583 Abstract A novel recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) produced in Pichia pastoris was first reported in this study. We cloned the DmAChE cDNA by reverse transcription PCR with removal of the signal for glycosylphosphatidylinositol (GPI) anchor attachment and the endogenous signal peptide coding sequence, and inserted it into P. pastoris vector pPIC9K under control of the alcohol oxidase gene AOX1 promoter (5'AOX1). The expression cassette of AChE cDNA was then introduced into methylotrophic yeast GS115 and several recombinant strains expressing R-DmAChE were obtained. The secreted R-DmAChE showed high stability in neutral phosphate buffer at 4 degrees C, and its kinetic parameters were identical to those of the native DmAChE. The bimolecular rate constants of R-DmAChE to dichlorvos, aldicarb and carbaryl were ranging from three to six times higher than of native DmAChE. Within six insecticides, the R-DmAChE was more sensitive than EeAChE, NbAChE and HuAChE. For 10 widely used insecticides, the IC50 values to the R-DmAChE were much lower than those to AChEs commonly used in China. With the R-DmAChE-based assay, samples spiked with three concentrations of pesticides caused enzymatic activity inhibition with R.S.D. of 0-13.7%. These results suggest that the R-DmAChE can be useful for detection of organophosphate and carbamate insecticide residues. Title: d-Conopeptide EVIA isolated from Conus ermineus is a new pharmacological tool for discriminating sodium channel subtypes Barbier J, Lamthanh H, Gall FL, Favreau P, Benoit E, Chen H, Gilles N, Ilan N, Heinemann SH and Molgo J <2 more author(s)> Barbier J, Lamthanh H, Gall FL, Favreau P, Benoit E, Chen H, Gilles N, Ilan N, Heinemann SH, Gordon D, Menez A, Molgo J (- 2) Ref: Journal de Physiologie (Paris), 99:247, 2006 : PubMed Title: The Genomes of Oryza sativa: a history of duplications Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S and Yang H <88 more author(s)> Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Xiao Y, Bu D, Tan J, Yang L, Ye C, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Huang X, Su Z, Tong W, Tong Z, Ye J, Wang L, Lei T, Chen C, Chen H, Huang H, Zhang F, Li N, Zhao C, Huang Y, Li L, Xi Y, Qi Q, Li W, Hu W, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wong GK, Yang H (- 88) Ref: PLoS Biol, 3:e38, 2005 : PubMed ESTHER: Yu_2005_PLoS.Biol_3_e38 PubMedSearch: Yu 2005 PLoS.Biol 3 e38 PubMedID: 15685292 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9S7P1, orysa-Q9FYP7, orysa-Q5ZBH3, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P9, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-Q949C9, orysa-cbp1, orysa-cbp3, orysa-cbpx, orysa-Q33B71, orysa-Q8GSJ3, orysa-LPL1, orysa-Q6YSZ8, orysa-Q8S5X5, orysa-Q8LIG3, orysa-Q6K7F5, orysa-Q7F1B1, orysa-Q8H4S9, orysa-Q69UB1, orysa-Q9FW17, orysa-Q337C3, orysa-Q7F959, orysa-Q84QZ6, orysa-Q84QY7, orysa-Q851E3, orysa-Q6YTH5, orysa-Q0JK71, orysa-Q8S1D9, orysa-Q5N8V4, orysa-Q0JCY4, orysa-Q8GTK2, orysa-B9EWJ8, orysa-Q8H3K6, orysa-Q6ZDG8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q6ZDG4, orysa-Q5NAI4, orysa-Q658B2, orysa-Q5JMQ8, orysa-Q5QMD9, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-Q8W0F0, orysa-pir7a, orysa-pir7b, orysa-q2qlm4, orysa-q2qm78, orysa-q2qm82, orysa-q2qn31, orysa-q2qnj4, orysa-q2qnt9, orysa-q2qur1, orysa-q2qx94, orysa-q2qyi1, orysa-q2qyj1, orysa-q2r051, orysa-q2r077, orysa-q2ram0, orysa-q2rat1, orysa-q2rbb3, orysa-Q4VWY7, orysa-q5na00, orysa-q5nbu1, orysa-Q5QLC0, orysa-q5smv5, orysa-Q5VP27, orysa-q5vrt2, orysa-q5w6c5, orysa-q5z5a3, orysa-q5z9i2, orysa-q5z417, orysa-q5z901, orysa-Q5ZAM8, orysa-Q5ZBI5, orysa-Q5ZCR3, orysa-q6atz0, orysa-q6ave2, orysa-q6f358, orysa-q6h6s1, orysa-q6h7i6, orysa-q6i5q3, orysa-q6i5u7, orysa-q6j657, orysa-q6k3d9, orysa-q6k4q2, orysa-q6k880, orysa-q6l5b6, orysa-Q6L5F5, orysa-q6l556, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zc62, orysa-q6zia4, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xej4, orysa-q7xem8, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q7XVB5, orysa-Q8L562, orysa-Q8LQS5, orysa-Q8RZ40, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8S0V0, orysa-Q8S125, orysa-Q8SAY7, orysa-Q8SAY9, orysa-Q8W3C6, orysa-Q8W3F2, orysa-Q8W3F4, orysa-Q8W3F6, orysa-Q9LHX5, orysa-q33aq0, orysa-q53lh1, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q60ew8, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j07, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q67uz1, orysa-q67v34, orysa-q67wz5, orysa-q69j38, orysa-q69k08, orysa-q69md7, orysa-q69me0, orysa-q69pf3, orysa-q69ti3, orysa-q69xr2, orysa-q69y12, orysa-q69y21, orysa-q75hy2, orysa-q75i01, orysa-Q94JD7, orysa-Q0J0A4, orysa-q651a8, orysa-q651z3, orysa-q652g4, orysa-q688m0, orysa-q688m8, orysa-q688m9, orysa-Q6H8G1, orysi-a2wn01, orysi-a2xc83, orysi-a2yh83, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-a3b9l8, orysj-b9eub8, orysj-b9eya5, orysj-b9fi05, orysj-b9fkb0, orysj-b9fn42, orysj-b9gbb7, orysj-cgep, orysj-PLA7, orysj-q0d4u5, orysj-q0djj0, orysj-q0jaf0, orysj-q5jl22, orysj-q5jlw7, orysj-q5z419, orysj-q6h7q9, orysj-q6yvk6, orysj-q6z6i1, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q338c0, orysi-b8bly4, orysj-b9gbs4, orysi-a2zb88, orysj-b9gbs1, orysi-b8b698, orysj-pla4, orysj-pla1 Abstract We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family. Title: Empirical analysis of transcriptional activity in the Arabidopsis genome Yamada K, Lim J, Dale JM, Chen H, Shinn P, Palm CJ, Southwick AM, Wu HC, Kim C and Ecker JR <60 more author(s)> Yamada K, Lim J, Dale JM, Chen H, Shinn P, Palm CJ, Southwick AM, Wu HC, Kim C, Nguyen M, Pham P, Cheuk R, Karlin-Newmann G, Liu SX, Lam B, Sakano H, Wu T, Yu G, Miranda M, Quach HL, Tripp M, Chang CH, Lee JM, Toriumi M, Chan MM, Tang CC, Onodera CS, Deng JM, Akiyama K, Ansari Y, Arakawa T, Banh J, Banno F, Bowser L, Brooks S, Carninci P, Chao Q, Choy N, Enju A, Goldsmith AD, Gurjal M, Hansen NF, Hayashizaki Y, Johnson-Hopson C, Hsuan VW, Iida K, Karnes M, Khan S, Koesema E, Ishida J, Jiang PX, Jones T, Kawai J, Kamiya A, Meyers C, Nakajima M, Narusaka M, Seki M, Sakurai T, Satou M, Tamse R, Vaysberg M, Wallender EK, Wong C, Yamamura Y, Yuan S, Shinozaki K, Davis RW, Theologis A, Ecker JR (- 60) Ref: Science, 302:842, 2003 : PubMed ESTHER: Yamada_2003_Science_302_842 PubMedSearch: Yamada 2003 Science 302 842 PubMedID: 14593172 Gene_locus related to this paper: arath-AT2G42690, arath-AT4g30610, arath-At5g13640, arath-AT5G20520, arath-AT5G27320, arath-CGEP, arath-clh1, arath-clh2, arath-CXE12, arath-CXE15, arath-SCP25, arath-F14F8.240, arath-MES6, arath-LCAT1, arath-PLA11, arath-PLA15, arath-PLA16, arath-PLA17, arath-SCP8, arath-SCP11, arath-SCP40, arath-MES14, arath-AXR4, arath-SFGH, arath-B9DFR3, arath-pae2 Abstract Functional analysis of a genome requires accurate gene structure information and a complete gene inventory. A dual experimental strategy was used to verify and correct the initial genome sequence annotation of the reference plant Arabidopsis. Sequencing full-length cDNAs and hybridizations using RNA populations from various tissues to a set of high-density oligonucleotide arrays spanning the entire genome allowed the accurate annotation of thousands of gene structures. We identified 5817 novel transcription units, including a substantial amount of antisense gene transcription, and 40 genes within the genetically defined centromeres. This approach resulted in completion of approximately 30% of the Arabidopsis ORFeome as a resource for global functional experimentation of the plant proteome. Title: Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R and Davis RW <79 more author(s)> Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R, Bowman CL, Brooks SY, Buehler E, Chan A, Chao Q, Chen H, Cheuk RF, Chin CW, Chung MK, Conn L, Conway AB, Conway AR, Creasy TH, Dewar K, Dunn P, Etgu P, Feldblyum TV, Feng J, Fong B, Fujii CY, Gill JE, Goldsmith AD, Haas B, Hansen NF, Hughes B, Huizar L, Hunter JL, Jenkins J, Johnson-Hopson C, Khan S, Khaykin E, Kim CJ, Koo HL, Kremenetskaia I, Kurtz DB, Kwan A, Lam B, Langin-Hooper S, Lee A, Lee JM, Lenz CA, Li JH, Li Y, Lin X, Liu SX, Liu ZA, Luros JS, Maiti R, Marziali A, Militscher J, Miranda M, Nguyen M, Nierman WC, Osborne BI, Pai G, Peterson J, Pham PK, Rizzo M, Rooney T, Rowley D, Sakano H, Salzberg SL, Schwartz JR, Shinn P, Southwick AM, Sun H, Tallon LJ, Tambunga G, Toriumi MJ, Town CD, Utterback T, Van Aken S, Vaysberg M, Vysotskaia VS, Walker M, Wu D, Yu G, Fraser CM, Venter JC, Davis RW (- 79) Ref: Nature, 408:816, 2000 : PubMed ESTHER: Theologis_2000_Nature_408_816 PubMedSearch: Theologis 2000 Nature 408 816 PubMedID: 11130712 Gene_locus related to this paper: arath-At1g05790, arath-At1g09280, arath-At1g09980, arath-AT1G29120, arath-AT1G52695, arath-AT1G66900, arath-At1g73750, arath-AT1G73920, arath-AT1G74640, arath-AT1G76140, arath-AT1G78210, arath-clh1, arath-F1O17.3, arath-F1O17.4, arath-F1O17.5, arath-F5I6.3, arath-At1g52700, arath-F6D8.27, arath-F6D8.32, arath-F9L1.44, arath-F9P14.11, arath-F12A4.4, arath-MES11, arath-F14G24.2, arath-F14G24.3, arath-F14I3.4, arath-F14O10.2, arath-F16N3.25, arath-LCAT2, arath-At1g34340, arath-MES15, arath-CXE6, arath-ICML1, arath-At1g72620, arath-LCAT1, arath-PLA12, arath-PLA15, arath-PLA17, arath-Q8L7S1, arath-At1g15070, arath-SCP2, arath-SCP4, arath-SCP5, arath-SCP18, arath-SCP32, arath-SCP44, arath-SCP45, arath-SCPL6, arath-F4IE65, arath-At1g30370, arath-T6L1.8, arath-T6L1.20, arath-T14P4.6, arath-MES14, arath-SCP3, arath-AXR4, arath-At1g10040, arath-ZW18, arath-pae2, arath-pae1, arath-a0a1p8awg3 Abstract The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence. Title: Characterization of an acetyl xylan esterase from the anaerobic fungus Orpinomyces sp. strain PC-2 Blum DL, Li XL, Chen H, Ljungdahl LG Ref: Applied Environmental Microbiology, 65:3990, 1999 : PubMed ESTHER: Blum_1999_Appl.Environ.Microbiol_65_3990 PubMedSearch: Blum 1999 Appl.Environ.Microbiol 65 3990 PubMedID: 10473406 Abstract A 1,067-bp cDNA, designated axeA, coding for an acetyl xylan esterase (AxeA) was cloned from the anaerobic rumen fungus Orpinomyces sp. strain PC-2. The gene had an open reading frame of 939 bp encoding a polypeptide of 313 amino acid residues with a calculated mass of 34,845 Da. An active esterase using the original start codon of the cDNA was synthesized in Escherichia coli. Two active forms of the esterase were purified from recombinant E. coli cultures. The size difference of 8 amino acids was a result of cleavages at two different sites within the signal peptide. The enzyme released acetate from several acetylated substrates, including acetylated xylan. The activity toward acetylated xylan was tripled in the presence of recombinant xylanase A from the same fungus. Using p-nitrophenyl acetate as a substrate, the enzyme had a K(m) of 0.9 mM and a V(max) of 785 micromol min(-1) mg(-1). It had temperature and pH optima of 30 degrees C and 9.0, respectively. AxeA had 56% amino acid identity with BnaA, an acetyl xylan esterase of Neocallimastix patriciarum, but the Orpinomyces AxeA was devoid of a noncatalytic repeated peptide domain (NCRPD) found at the carboxy terminus of the Neocallimastix BnaA. The NCRPD found in many glycosyl hydrolases and esterases of anaerobic fungi has been postulated to function as a docking domain for cellulase-hemicellulase complexes, similar to the dockerin of the cellulosome of Clostridium thermocellum. The difference in domain structures indicated that the two highly similar esterases of Orpinomyces and Neocallimastix may be differently located, the former being a free enzyme and the latter being a component of a cellulase-hemicellulase complex. Sequence data indicate that AxeA and BnaA might represent a new family of hydrolases. Title: Poster: Molecular signaling mechanisms involved in Ach-induced cell proliferation in porcine tracheal smooth muscle cells Mamoon AM, Smith J, Chen H, Baker RC, Farley JM Ref: Life Sciences, 64:581, 1999 : PubMed | |||||||
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