Author Report for: Chen JNo contact information in database for Chen J
Cao X, Yuan R, Sun D, Ji X, Wei Y, Li L, Guo S, Li B, Chen J Ref: Aquat Toxicol, 258:106508, 2023 : PubMed ESTHER: Cao_2023_Aquat.Toxicol_258_106508 PubMedSearch: Cao 2023 Aquat.Toxicol 258 106508 PubMedID: 37001197 Abstract Carbon quantum dots (CQDs) have received increasing attention in recent years for their potential toxicity. However, little is known about their neurobehavioral toxicity. This study aimed to investigate the potential mechanisms by which probiotics reduce CQDs neurotoxicity from a brain-gut axis perspective by exposing carp to CQDs and/or probiotics for five weeks. The results showed that CQDs accumulation in the brain reduces the expression of blood-brain-barrier (BBB) related genes in carp, leading to brain damage. In addition, CQDs impaired motor behavior and inhibited acetylcholinesterase activity. These abnormalities were alleviated by probiotic supplementation. Microbiomic analysis showed that probiotics improved the imbalance of intestinal flora caused by CQDs and increased the abundance of Firmicutes. Serum metabolomic analysis showed that probiotic supplementation restored the abnormal metabolic levels associated with neurological, inflammatory, and apoptotic cell death caused by CQDs. Overall, probiotic supplementation improved the CQDs-induced changes in brain damage, gut microbiology, and systemic metabolism. These results suggests that CQDs may cause neurotoxicity via the brain-gut microbial axis. Title: Acalculous cholecystitis is a common extrahepatic manifestation of hepatitis E and suggests a more serious condition Cao X, Jiang W, Shi L, Wang Y, Chen J, Huang W, Zhang S Ref: Virol J, 20:77, 2023 : PubMed ESTHER: Cao_2023_Virol.J_20_77 PubMedSearch: Cao 2023 Virol.J 20 77 PubMedID: 37095526 Abstract BACKGROUND: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE). PATIENTS AND METHODS: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded. RESULTS: Acalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 +/- 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 +/- 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE. CONCLUSION: Acalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay. Title: Aptamer recognition-promoted hybridization chain reaction for amplified label-free and enzyme-free fluorescence analysis of pesticide Chen J, Yang C, Nie H, Li H Ref: Spectrochim Acta A Mol Biomol Spectrosc, 293:122451, 2023 : PubMed ESTHER: Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451 PubMedSearch: Chen 2023 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 293 122451 PubMedID: 36801730 Abstract Development of high-performance fluorescence sensors for pesticide is highly urgent but remains a grand challenge. It is due to that most of known fluorescence sensors detect pesticides based on enzyme-inhibited strategy, which requires high-price cholinesterase, suffers from serious interference of reductive materials, and can't difference pesticides with each other; the known aptamer-based fluorescence ones entail tool enzymes or nanomaterials to transducer/amplify the signal and demand signalers to be tagged in nucleic acid, which are expensive and intricate. Herein, we develop a novel aptamer-based fluorescence system for label-free, enzyme-free and highly sensitive detection of pesticide (profenofos) based on target-initiated hybridization chain reaction (HCR)-assisted signal amplification and specific intercalation of N-methylmesoporphyrin IX (NMM) in G-quadruplex DNA. Hairpin probe ON1 recognizes profenofos to generate profenofos@ON1 complex, which switches the HCR to yield multiple G-quadruplex DNA, consequently making large numbers of NMM be locked. In comparison with profenofos absence, a sharply improved fluorescence signal was recorded and it was dependent on profenofos dose. Hence, label-free, enzyme-free and highly sensitive detection of profenofos is achieved with limit of detection of 0.085 nM, which compared favorably with or superior to those of known fluorescence methods. Furthermore, the present method was applied to determine the profenofos residue in rice with agreeable result, and will provide more valuable information for guaranteeing the pesticide-related food safety. Title: Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate Chen J, Cazenave-Gassiot A, Xu Y, Piroli P, Hwang R, Jr., DeFreitas L, Chan RB, Di Paolo G, Nandakumar R and Marquer C <1 more author(s)> Chen J, Cazenave-Gassiot A, Xu Y, Piroli P, Hwang R, Jr., DeFreitas L, Chan RB, Di Paolo G, Nandakumar R, Wenk MR, Marquer C (- 1) Ref: Commun Biol, 6:210, 2023 : PubMed ESTHER: Chen_2023_Commun.Biol_6_210 PubMedSearch: Chen 2023 Commun.Biol 6 210 PubMedID: 36823305 Gene_locus related to this paper: human-PLA2G15 Abstract The late endosome/lysosome (LE/Lys) lipid bis(monoacylglycero)phosphate (BMP) plays major roles in cargo sorting and degradation, regulation of cholesterol and intercellular communication and has been linked to viral infection and neurodegeneration. Although BMP was initially described over fifty years ago, the enzymes regulating its synthesis remain unknown. The first step in the BMP biosynthetic pathway is the conversion of phosphatidylglycerol (PG) into lysophosphatidylglycerol (LPG) by a phospholipase A2 (PLA2) enzyme. Here we report that this enzyme is lysosomal PLA2 (LPLA2). We show that LPLA2 is sufficient to convert PG into LPG in vitro. We show that modulating LPLA2 levels regulates BMP levels in HeLa cells, and affects downstream pathways such as LE/Lys morphology and cholesterol levels. Finally, we show that in a model of Niemann-Pick disease type C, overexpressing LPLA2 alleviates the LE/Lys cholesterol accumulation phenotype. Altogether, we shed new light on BMP biosynthesis and contribute tools to regulate BMP-dependent pathways. Title: Effect of Histidine Covalent Modification on Strigolactone Receptor Activation and Selectivity Chen J, Shukla D Ref: Biophysical Journal, :, 2023 : PubMed ESTHER: Chen_2023_Biophys.J__ PubMedSearch: Chen 2023 Biophys.J PubMedID: 36798027 Abstract The parasitic weed Striga has led to billions of dollars' worth of agricultural productivity loss worldwide. Striga detects host plants using compounds of the strigolactone class of phytohormones. Early steps in the strigolactone signaling pathway involve substrate binding and hydrolysis followed by a conformational change to an "active" or "closed" state, after which it associates with a MAX2-family downstream signaling partner. The structures of the inactive and active states of strigolactone receptors are known through X-ray crystallography, and the transition pathway of from the inactive to active state in apo receptors has previously been characterized using molecular dynamics simulations. However, it also has been suggested that a covalent butenolide modification of the receptor on the catalytic histidine through substrate hydrolysis promotes formation of the active state. Using molecular dynamics simulations, we show that the presence of the covalent butenolide enhances activation in both AtD14, a receptor found in Arabidopsis, and ShHTL7, a receptor found in Striga, but the enhancement is -50 times greater in ShHTL7. We also show that several conserved interactions with the covalent butenolide modification promote transition to the active state in both AtD14 (non-parasite) and ShHTL7 (parasite). Finally, we demonstrate that the enhanced activation of ShHTL7 likely results from disruption of ShHTL7-specific histidine interactions that inhibited activation in the apo case. These results provide a possible explanation for difference in strigolactone sensitivity seen between different strigolactone-sensitive proteins and can be used to aid the design of selective modulators to control Striga parasites. Title: Label free impedance based acetylcholinesterase enzymatic biosensors for the detection of acetylcholine Chen J, Lin KC, Prasad S, Schmidtke DW Ref: Biosensors & Bioelectronics, 235:115340, 2023 : PubMed ESTHER: Chen_2023_Biosens.Bioelectron_235_115340 PubMedSearch: Chen 2023 Biosens.Bioelectron 235 115340 PubMedID: 37216844 Abstract Realtime monitoring of neurotransmitters is of great interest for understanding their fundamental role in a wide range of biological processes in the central and peripheral nervous system, as well as their role, in several degenerative brain diseases. The measurement of acetylcholine in the brain is particularly challenging due to the complex environment of the brain and the low concentration and short lifetime of acetylcholine. In this paper, we demonstrated a novel, label-free biosensor for the detection of Ach using a single enzyme, acetylcholinesterase (ACHE), and electrochemical impedance spectroscopy (EIS). Acetylcholinesterase was covalently immobilized onto the surface of gold microelectrodes through an amine-reactive crosslinker dithiobis(succinimidyl propionate) (DSP). Passivation of the gold electrode with SuperBlock eliminated or reduced any non-specific response to other major interfering neurotransmitter molecules such as dopamine (DA), norepinephrine (NE) and epinephrine (EH). The sensors were able to detect acetylcholine over a wide concentration range (5.5-550 microM) in sample volumes as small as 300 microL by applying a 10 mV AC voltage at a frequency of 500 Hz. The sensors showed a linear relationship between Ach concentration and deltaZmod(R2 = 0.99) in PBS. The sensor responded to acetylcholine not only when evaluated in a simple buffer (PBS buffer) but in several more complex environments such as rat brain slurry and rat whole blood. The sensor remained responsive to acetylcholine after being implanted ex vivo in rat brain tissue. These results bode well for the future application of these novel sensors for real time in vivo monitoring of acetylcholine. Title: Degradation of poly(butylene adipate-co-terephthalate) films by Thermobifida fusca FXJ-1 isolated from compost Jia X, Zhao K, Zhao J, Lin C, Zhang H, Chen L, Chen J, Fang Y Ref: J Hazard Mater, 441:129958, 2023 : PubMed ESTHER: Jia_2023_J.Hazard.Mater_441_129958 PubMedSearch: Jia 2023 J.Hazard.Mater 441 129958 PubMedID: 36122523 Abstract In recent years, Poly(butylene adipate-co-terephthalate) (PBAT) films were wildly used due to its biodegradable properties. However, there are few reports of strains that can high efficiently degrade PBAT. Thermobifida fusca FXJ-1, a thermophilic actinomycete, was screened and identified from compost. FXJ-1 can efficiently degrade PBAT at 55C in MSM medium. The degradation rates of the pure PBAT film (PF), PBAT film used for mulching on agricultural fields (PAF), and PBAT-PLA-ST film (PPSF) were 82.871.01%, 87.832.00% and 52.530.54%, respectively, after nine days of incubation in MSM medium. Cracking areas were monitored uniformly distributed on the surfaces of three kinds of PBAT-based films after treatment with FXJ-1 using scanning electron microscopy. The LC-MS results showed that PBAT might be degraded into adipic acid, terephthalic acid, butylene adipate, butylene terephthalate and butylene adipate-co-terephthalate, and these products are involved in the cleavage of ester bonds. We also found that amylase produced by FXJ-1 played an important role in the degradation of PPSF. FXJ-1 also showed an efficient PBAT-based films degradation ability in simulating compost environment, which implied its potential application in PBAT and starch-based film degradation by industrial composting. Title: Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers Li J, Wen Z, Lou Y, Chen J, Gao L, Li X, Wang F Ref: Clinics (Sao Paulo), 78:100208, 2023 : PubMed ESTHER: Li_2023_Clinics.(Sao.Paulo)_78_100208 PubMedSearch: Li 2023 Clinics.(Sao.Paulo) 78 100208 PubMedID: 37148830 Abstract OBJECTIVE: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. METHODS: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. RESULTS: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. CONCLUSIONS: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase. Title: Effects of monitoring exercise rehabilitation with target intensity on the patient with twice PCI: A case report Liu X, Chen Y, Chen J, Li A, Zhong M, Zhou W, Tang L Ref: Medicine (Baltimore), 102:e33583, 2023 : PubMed ESTHER: Liu_2023_Medicine.(Baltimore)_102_e33583 PubMedSearch: Liu 2023 Medicine.(Baltimore) 102 e33583 PubMedID: 37083775 Abstract RATIONALE: As the core of cardiac rehabilitation (CR), early exercise rehabilitation is beneficial for patients with coronary heart disease (CHD), and center-based CR with target intensity is superior to home-based CR. However, there was no research to observe the effects of exercise rehabilitation on cardiopulmonary exercise capacity, oxygen uptake efficiency slope, endothelial function evaluated as flow-mediated vasodilation (FMD), and blood plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) in CHD patients undergone percutaneous coronary intervention (PCI) for 3 months. PATIENT CONCERNS: A 57-year-old woman had been identified with triple vessel disease and undergone twice PCI for complete revascularization, however, there was no improvement in Lp-PLA2, FMD, and related indicators of cardiopulmonary exercise testing. DIAGNOSIS: Coronary angiography showed an 85% stenosis in the middle left anterior descending artery, an 85% stenosis in the proximity of a thick first-diagonal branch, a long 75 to 85% stenosis in the middle left circumflex artery, and a 90 to 95% stenosis in the proximal. The case was diagnosed as CHD. INTERVENTIONS: The patient obtained optimal medical therapy comprising therapeutic lifestyle changes, and began monitoring exercise rehabilitation with target intensity 3 months after the second PCI in the CR center. OUTCOMES: There were changes in cardiopulmonary exercise capacity, oxygen uptake efficiency slope, FMD, and Lp-PLA2 in the patient with 3 apparent stenotic coronary arteries who was done PCI twice, without or with postoperative exercise rehabilitation, respectively. LESSONS: We proved that monitoring exercise rehabilitation training with target intensity could improve the prognosis of chronic coronary syndrome patients, and it was never too late to do regular exercise rehabilitation. Title: Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease Luo K, Chen J, Li H, Wu D, Du Y, Zhao S, Liu T, Li L, Dai Z and Fu X <3 more author(s)> Luo K, Chen J, Li H, Wu D, Du Y, Zhao S, Liu T, Li L, Dai Z, Li Y, Zhao Y, Tang L, Fu X (- 3) Ref: Bioorg Chem, 138:106596, 2023 : PubMed ESTHER: Luo_2023_Bioorg.Chem_138_106596 PubMedSearch: Luo 2023 Bioorg.Chem 138 106596 PubMedID: 37186997 Abstract Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies. Title: Mechanistic Basis for Enhanced Strigolactone Sensitivity in KAI2 Triple Mutant Sobecks BL, Chen J, Shukla D Ref: Biorxiv, :, 2023 : PubMed ESTHER: Sobecks_2023_bioRxiv__ PubMedSearch: Sobecks 2023 bioRxiv PubMedID: 36712135 Abstract Striga hermonthica is a parasitic weed that destroys billions of dollars' worth of staple crops every year. Its rapid proliferation stems from an enhanced ability to metabolize strigolactones (SLs), plant hormones that direct root branching and shoot growth. Striga ' s SL receptor, Sh HTL7, bears more similarity to the staple crop karrikin receptor KAI2 than to SL receptor D14, though KAI2 variants in plants like Arabidopsis thaliana show minimal SL sensitivity. Recently, studies have indicated that a small number of point mutations to HTL7 residues can confer SL sensitivity to At KAI2. Here, we analyze both wild-type At KAI2 and SL-sensitive mutant Var64 through all-atom, long-timescale molecular dynamics simulations to determine the effects of these mutations on receptor function at a molecular level. We demonstrate that the mutations stabilize SL binding by about 2 kcal/mol. They also result in a doubling of the average pocket volume, and eliminate the dependence of binding on certain pocket conformational arrangements. While the probability of certain non-binding SL-receptor interactions increases in the mutant compared with the wild-type, the rate of binding also increases by a factor of ten. All these changes account for the increased SL sensitivity in mutant KAI2, and suggest mechanisms for increasing functionality of host crop SL receptors. Title: Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta-analysis Wei N, Liu H, Ye W, Xu S, Lu C, Dai A, Hou T, Zeng X, Wu J, Chen J Ref: CNS Neurosci Ther, :, 2023 : PubMed ESTHER: Wei_2023_CNS.Neurosci.Ther__ PubMedSearch: Wei 2023 CNS.Neurosci.Ther PubMedID: 37088953 Abstract BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized. METHODS: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Abeta), and some new targeted therapeutic drugs. RESULTS: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%). CONCLUSION: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic. Title: Developmental Neurotoxicity of Difenoconazole in Zebrafish Embryos Yang Q, Deng P, Xing D, Liu H, Shi F, Hu L, Zou X, Nie H, Zuo J and Li G <3 more author(s)> Yang Q, Deng P, Xing D, Liu H, Shi F, Hu L, Zou X, Nie H, Zuo J, Zhuang Z, Pan M, Chen J, Li G (- 3) Ref: Toxics, 11:, 2023 : PubMed ESTHER: Yang_2023_Toxics_11_ PubMedSearch: Yang 2023 Toxics 11 PubMedID: 37112580 Abstract Difenoconazole is a type of triazole fungicide that is widely used in the treatment of plant diseases. Triazole fungicides have been shown in several studies to impair the development of the nervous system in zebrafish embryos. There is still little known about difenoconazole-induced neurotoxicity in fish. In this study, zebrafish embryos were exposed to 0.25, 0.5, and 1 mg/L of difenoconazole solution until 120 h post-fertilization (hpf). The difenoconazole-exposed groups showed concentration-dependent inhibitory tendencies in heart rate and body length. Malformation rate and spontaneous movement of zebrafish embryos increased, and the locomotor activity decreased in the highest exposure group. The content of dopamine and acetylcholine was reduced significantly in difenoconazole treatment groups. The activity of acetylcholinesterase (AChE) was also increased after treatment with difenoconazole. Furthermore, the expression of genes involved in neurodevelopment was remarkably altered, which corresponded with the alterations of neurotransmitter content and AChE activity. These results indicated that difenoconazole might affect the development of the nervous system through influencing neurotransmitter levels, enzyme activity, and the expression of neural-related genes, ultimately leading to abnormal locomotor activity in the early stages of zebrafish. Title: CES1-Triggered Liver-Specific Cargo Release of CRISPR/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration Zhao Y, Li Y, Wang F, Gan X, Zheng T, Chen M, Wei L, Chen J, Yu C Ref: Adv Sci (Weinh), :e2300502, 2023 : PubMed ESTHER: Zhao_2023_Adv.Sci.(Weinh)__e2300502 PubMedSearch: Zhao 2023 Adv.Sci.(Weinh) e2300502 PubMedID: 37083231 Abstract The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9-mRNA/ single-guide RNA (Cas9-mRNA/sgRNA) in vitro and vivo, using carboxylesterase-responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG-b-P(Met/n-PMA). The copolymer can self-assemble with Cas9-mRNA/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG-b-P(Met/n-PMA)/Cas9 mRNA/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low-density lipoprotein cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed-point release, which expand the application of CRISPR delivery systems. Title: Knockdown of hepatocyte Perilipin-3 mitigates hepatic steatosis and steatohepatitis caused by hepatocyte CGI-58 deletion in mice Bao X, Ma X, Huang R, Chen J, Xin H, Zhou M, Li L, Tong S, Zhang Q and Zhang Z <4 more author(s)> Bao X, Ma X, Huang R, Chen J, Xin H, Zhou M, Li L, Tong S, Zhang Q, Shui G, Deng F, Yu L, Li MD, Zhang Z (- 4) Ref: J Molecular & Cellular Biology, :, 2022 : PubMed ESTHER: Bao_2022_J.Mol.Cell.Biol__ PubMedSearch: Bao 2022 J.Mol.Cell.Biol PubMedID: 36107452 Abstract Comparative gene identification-58 (CGI-58), also known as alpha/beta hydrolase domain containing 5 (ABHD5), is the co-activator of adipose triglyceride lipase that hydrolyzes triglycerides stored in the cytosolic lipid droplets. Mutations in CGI-58 gene cause Chanarin-Dorfman syndrome (CDS), an autosomal recessive neutral lipid storage disease with ichthyosis. The liver pathology of CDS manifests as steatosis and steatohepatitis, which currently has no effective treatments. Perilipin-3 (Plin3) is a member of the Perilipin-ADRP-TIP47 (PAT) protein family that is essential for lipid droplet biogenesis. The objective of this study was to test a hypothesis that deletion of a major lipid droplet protein alleviates fatty liver pathogenesis caused by CGI-58 deficiency in hepatocytes. Adult CGI-58-floxed mice were injected with adeno-associated vectors simultaneously expressing the Cre recombinase and microRNA against Plin3 under the control of a hepatocyte-specific promoter, followed by high-fat diet (HFD) feeding for 6 weeks. Liver and blood samples were then collected from these animals for histological and biochemical analysis. Plin3 knockdown in hepatocytes prevented steatosis, steatohepatitis, and necroptosis caused by hepatocyte CGI-58 deficiency. Our work is the first to show that inhibiting Plin3 in hepatocytes is sufficient to mitigate hepatocyte CGI-58 deficiency-induced hepatic steatosis and steatohepatitis in mice. Title: Toxic effects of glyphosate on the intestine, liver, brain of carp and on epithelioma papulosum cyprinid cells: Evidence from in vivo and in vitro research Cao X, Rao C, Cui H, Sun D, Li L, Guo S, Zhou J, Yuan R, Yang S, Chen J Ref: Chemosphere, :134691, 2022 : PubMed ESTHER: Cao_2022_Chemosphere__134691 PubMedSearch: Cao 2022 Chemosphere 134691 PubMedID: 35489457 Abstract Glyphosate (GLY) is the most widely used organophosphorus herbicide in agriculture. The present study aimed to analyze the comprehensive toxicological effects of GLY on juvenile common carp and an epithelioma papulosum cyprinid (EPC) cell line. In the in vivo experiments, exposure to GLY (5 and 15 mg/L) for 30 days induced liver inflammation and oxidative damage in common carp and changed the physical barrier of the intestine. Histopathological analysis of the intestine, liver, brain, and changes in oxidative stress biomarkers provided evidence of damage and immune system responses to GLY. Moreover, an inhibitory effect of 15 mg/L GLY on acetylcholinesterase (AChE) activity was found in the brain, which may be an important reason for the significant decrease in both swimming distance and average acceleration of common carp. Cell experiments showed that 0.65 and 3.25 mg/L GLY inhibited the viability of EPCs. Furthermore, oxidative DNA damage, mitochondrial dysfunction, and reactive oxygen species (ROS) production were observed in EPC cells following GLY exposure. Taken together, this study not only highlights the negative effects of GLY on common carp but also enriches the knowledge of the cytotoxicity mechanism to further clarify the comprehensive toxicity of GLY in common carp. Title: Activation Mechanism of Strigolactone Receptors and Its Impact on Ligand Selectivity between Host and Parasitic Plants Chen J, Nelson DC, Shukla D Ref: J Chem Inf Model, :, 2022 : PubMed ESTHER: Chen_2022_J.Chem.Inf.Model__ PubMedSearch: Chen 2022 J.Chem.Inf.Model PubMedID: 35192364 Abstract Parasitic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate hydrolysis followed by a conformational change of the receptor to a "closed" or "active" state that associates with a signaling partner, MAX2/D3. Crystal structures of active and inactive AtD14 receptors have helped elucidate the structural changes involved in activation. However, the mechanism by which the receptor activates remains unknown. The ligand dependence of AtD14 activation has been disputed by mutagenesis studies showing that enzymatically inactive receptors are able to associate with MAX2 proteins. Furthermore, activation differences between strigolactone receptor in Striga, ShHTL7, and AtD14 could contribute to the high sensitivity to strigolactones exhibited by parasitic plants. Using molecular dynamics simulations, we demonstrate that both AtD14 and ShHTL7 could adopt an active conformation in the absence of ligand. However, ShHTL7 exhibits a higher population in the inactive apo state as compared to the AtD14 receptor. We demonstrate that this difference in inactive state population is caused by sequence differences between their D-loops and interactions with the catalytic histidine that prevent full binding pocket closure in ShHTL7. These results indicate that ligand hydrolysis would enhance the active state population by destabilizing the inactive state in ShHTL7 as compared to AtD14. We also show that the mechanism of activation is more concerted in AtD14 than in ShHTL7 and that the main barrier to activation in ShHTL7 is closing of the binding pocket. Title: Effects of Lipase and Xylanase Pretreatment on the Structure and Pulping Properties of Wheat Straw Jia Q, Chen J, Yang G, Liu K, Wang Y, Zhang K Ref: Polymers (Basel), 14:, 2022 : PubMed ESTHER: Jia_2022_Polymers.(Basel)_14_ PubMedSearch: Jia 2022 Polymers.(Basel) 14 PubMedID: 36501524 Abstract Based on the reduction of environmental pollution, a biological enzyme assisted alkali-oxygen pulping method was explored to improve the delignification efficiency and fiber accessibility of wheat straw and improve the properties of wheat straw pulp. In this paper, lipase and xylanase were used to pretreat wheat straw and the effects of different enzyme types and enzyme dosage on the microstructure and pulp properties of wheat straw were investigated and experimented. The results showed that the lipase can remove fat and wax on the surface of wheat straw, while xylanase degraded the hemicellulose components, such as xylan, of wheat straw fiber, destroyed the structure of the lignin-carbohydrate complex, increasing lignin removal as a result and enhancing the impregnating, diffusion and penetration of alkali. Compared with wheat straw without enzyme pretreatment, the skeleton of wheat straw pretreated by enzyme became looser, the internal cavity appeared and the wall cavity became thin and transparent. The fines decreased obviously and the length of fibers increased. After combined pretreatment with lipase (15 U.g(-1)) and xylanase (15 U.g(-1)), the pulping performance of wheat straw was improved and the tensile index (97.37 N.m.g(-1)), brightness (40.9% ISO) and yield (58.10%) of the pulp increased by 12.9%, 19.9% and 9.9%, respectively. It can be seen that enzyme pretreatment is a green and effective approach to improving the alkali-oxygen pulping performance of wheat straw. Title: Metal-Organic Frameworks-Based Immobilized Enzyme Microreactors Integrated with Capillary Electrochromatography for High-Efficiency Enzyme Assay Liu M, Yang J, Wang J, Liu Z, Hu C, Liu Y, Wei X, Chen J, Yu YL and Fu Q <8 more author(s)> Liu M, Yang J, Wang J, Liu Z, Hu C, Liu Y, Wei X, Chen J, Yu YL, Wang JH, Qiu H, Liu R, Yi G, Ji B, Liu X, Gui Y, Xia Z, Fu Q (- 8) Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Liu_2022_Anal.Chem__ PubMedSearch: Liu 2022 Anal.Chem PubMedID: 34978797 35385268 35465669 Abstract Enzyme assays are important for studying enzyme-mediated biochemical reactions and for clinical diagnosis and drug development. The technique of an immobilized enzyme microreactor (IMER) integrated with capillary electrophoresis (CE) has been frequently utilized in online enzyme assays. However, the traditional approaches for IMER-CE enzyme analysis have some defects such as low loading capacity and poor stability. Herein, metal-organic frameworks (MOFs), which have enormous potential in the fields of enzyme immobilization and capillary electrochromatographic (CEC) separation, were first explored as novel support materials with good enzyme immobilization performance and stationary phases with excellent separation abilities to construct an integrated MOFs-IMER-CEC microanalysis system for a high-efficiency online enzyme assay. As a proof-of-concept demonstration, acetylcholinesterase (AChE) was immobilized on a densely packed UiO-66-NH(2) nanocrystal coating on a capillary inner surface with abundant intercrystalline mesoporosity and was employed as a highly effective and robust IMER for CEC-integrated online enzyme analysis. The excellent separation performance of the UiO-66-NH(2)-modified capillary was verified by high-efficiency separation of three types of neutral, acidic, and basic compounds. The Michaelis-Menten constant and enzyme inhibition kinetics of UiO-66-NH(2)-IMER were systematically assessed, exhibiting distinct advantages such as remarkably increased enzyme loadability, superior affinity for substrates, and greatly improved stability and repeatability compared to CE-integrated IMERs prepared by the traditional covalent bonding method. Furthermore, the developed method was successfully utilized for detecting organophosphorus pesticides in leguminous vegetable samples, demonstrating its strong practicality. The study not only proposed a novel support material and construction strategy for a high-performance microchannel-based IMER but also can be widely used in bioanalysis and biosensing research. Title: Graphitic-phase C(3)N(4) nanosheets combined with MnO(2) nanosheets for sensitive fluorescence quenching detection of organophosphorus pesticides Liu B, Chen J, Peng Y, Xiao W, Peng Z, Qiu P Ref: J Environ Sci Health B, :1, 2022 : PubMed ESTHER: Liu_2022_J.Environ.Sci.Health.B__1 PubMedSearch: Liu 2022 J.Environ.Sci.Health.B 1 PubMedID: 35414329 Abstract In this study, we have developed a sensitive approach to measure organophosphorus pesticides (OPs) using graphitic-phase C(3)N(4) nanosheets (g-C(3)N(4)) combined with a nanomaterial-based quencher, MnO(2) nanosheets (MnO(2) NS). Since MnO(2) NS can quench the fluorescence of g-C(3)N(4) via the inner-filter effect (IFE), enzymatic hydrolysate (thiocholine, TCh) can efficiently trigger the decomposition of MnO(2) nanosheets in the presence of acetylcholinesterase (AChE) and acetylthiocholine (ATCh), resulting in the fluorescence recovery of g-C(3)N(4). OPs, as inhibitors to AChE activity, can prevent the generation of TCh and decomposition of MnO(2) nanosheets while exhibiting fluorescence quenching. Therefore, the AChE-ATCh-MnO(2)-g-C(3)N(4) system can be utilized to quantitatively detect OPs based on g-C(3)N(4) fluorescence. Under optimal conditions, the linear ranges for the determination of parathion-methyl (PM) and 2,2-dichlorovinyl dimethyl phosphate (DDVP) were found to be 0.1-2.1 ng/mL and 0.5-16 ng/mL, respectively, with limits of detection of 0.069 ng/mL and 0.20 ng/mL, respectively. The advantages of this assay are user-friendliness, ease of use, and cost effectiveness compared to other more sophisticated analytical instruments. Title: Characterization of a Novel Esterase Est33 From an Antarctic Bacterium: A Representative of a New Esterase Family Liu X, Zhou M, Sun R, Xing S, Wu T, He H, Chen J, Bielicki JK Ref: Front Microbiol, 13:855658, 2022 : PubMed ESTHER: Liu_2022_Front.Microbiol_13_855658 PubMedSearch: Liu 2022 Front.Microbiol 13 855658 PubMedID: 35655995 Gene_locus related to this paper: psesp-Est33 Abstract Studies of microorganisms from extreme environments can sometimes reveal novel proteins with unique properties. Here, we identified a novel esterase gene (Est33) from an Antarctic bacterium. The protein was expressed and purified for biochemical characterizations. Site-mutation variants including S94A, D205A, and H233A were constructed to explore the structure-function relationship of the catalytic triad of Est33, and we found mutating Ser(94), Asp(205), and His(233) residues lead to a complete loss of enzyme activity. In addition, the catalytic Ser(94) located in a conserved pentapeptide motif GVSWG. Phylogenetic analysis showed that Est33 and its closely related homologs belonged to an independent group apart from other known family members, indicating that Est33 represented a new family of esterase. The Est33 enzyme was found to be a cold-active esterase retaining 25%-100% activity from 10 degreesC to 30 degreesC and to have optimal catalytic activity toward p-nitrophenol acetate (30 degreesC and pH7.5). The serine modifying reagent phenylmethylsulfonyl fluoride inhibited the activity of Est33 by 77.34%, while thiol reagents such as dithiol threitol (DTT) activated the enzyme by 3-fold. Metal chelating reagents EDTA had no effects, indicating that Est33 is not a metalloenzyme. Collectively, these results indicate that Est33 constitutes the first member of a novel esterase family XXI that has been identified. Title: Ternary heterostructures of 1D/2D/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene: Boosted amperometric sensing for chlorpyrifos Mi Y, Zhao Y, Chen J, Li X, Yang Y, Gao F Ref: J Hazard Mater, 438:129419, 2022 : PubMed ESTHER: Mi_2022_J.Hazard.Mater_438_129419 PubMedSearch: Mi 2022 J.Hazard.Mater 438 129419 PubMedID: 35780734 Abstract Multicomponent heterogeneous Ti(3)C(2) transition metal carbide (MXene)-based materials are receiving extensive research attention due to their interesting synergistic interactions and catalytic properties. However, the morphology-controllable synthesis of heterostructures as structural stabilizers for Ti(3)C(2) MXene remains a challenge owing the complicated synthesis procedure. In this work, a kind of ternary heterogeneous nanomaterials CuCo(2)S(4)/CuS/Ti(3)C(2) MXene with a nanorod/nanoplate/nanosheet hybrid architecture is constructed through a one-step low-temperature solvothermal method. The well-designed ternary one-dimensional (1D)/two-dimensional (2D)/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene heteromaterials exhibit synergistic improvements in substrate-catalyzed reactions for electrochemical acetylcholinesterase (AChE) biosensor. The Michaelis-Menten constant for the Nafion/AChE/CuCo(2)S(4)/CuS/Ti(3)C(2) MXene/GCE biosensor is 228 microM, which is smaller than ones reported in previous literatures, indicating a higher affinity of the fabricated enzyme biosensor to acetylthiocholine chloride. The biosensor exhibits a well linear relationship with chlorpyrifos concentration ranging from 2.852 x 10(-12) M to 2.852 x 10(-6) M. The multicomponent 1D/2D/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene heteromaterial may shine a light in more electrochemical applications. Title: Glutathione-modified graphene quantum dots as fluorescent probes for detecting organophosphorus pesticide residues in Radix Angelica Sinensis Mu XQ, Wang D, Meng LY, Wang YQ, Chen J Ref: Spectrochim Acta A Mol Biomol Spectrosc, 286:122021, 2022 : PubMed ESTHER: Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021 PubMedSearch: Mu 2022 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 286 122021 PubMedID: 36283209 Abstract A novel fluorescent sensor was developed in this study based on glutathione-functionalized graphene quantum dots (GQDs@GSH) to detect organophosphorus pesticide residues in Radix Angelica Sinensis. GQDs@GSH was synthesized by a one-step pyrolysis method with a fluorescence quantum yield as high as 33.9% and its structure was characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. GQDs@GSH exhibited excellent fluorescence property showing strong blue fluorescence under UV irradiation. The fluorescence of GQDs@GSH could be quenched by Fe(3+) by electron transfer and the quenched fluorescence could be recovered due to the strong chelating and reducing ability of phytic acid (PA). Under the catalyzation of acetylcholinesterase (AChE) and choline oxidase (ChOx), acetylcholine (ACh) could be decomposed to H(2)O(2), which could further oxidize Fe(2+) to Fe(3+) thus quenching the fluorescence of GQDs@GSH once again. Coumaphos, a kind of organophosphorus pesticide, could inhibit AChE activity, thus making the quenched fluorescence turn on again. Several parameters influencing the fluorescence response such as Fe(3+), PA, ACh and coumaphos concentration, pH value and reaction time were optimized. Based on such a fluorescence "off-on-off-on" ngkmechanism, GQDs@GSH was successfully applied to the detection of coumaphos in Radix Angelica Sinensis. A good linear relationship between the fluorescence intensity and coumaphos concentration was obtained in the range of 0.1-10.0 micromol.L(-1). By a standard addition method, the recoveries were measured to be 101.44-117.90% with RSDs lower than 1.98%. The biosensor system is simple, sensitive and accurate. It has a good application prospect in the detection of organophosphorus pesticide residues in traditional Chinese medicine and agricultural products, and also expanded the application scope for glutathione as a highly selective biological molecule. Title: Bisphenol AF induces multiple behavioral and biochemical changes in zebrafish (Danio rerio) at different life stages Rao C, Cao X, Li L, Zhou J, Sun D, Li B, Guo S, Yuan R, Cui H, Chen J Ref: Aquat Toxicol, 253:106345, 2022 : PubMed ESTHER: Rao_2022_Aquat.Toxicol_253_106345 PubMedSearch: Rao 2022 Aquat.Toxicol 253 106345 PubMedID: 36351319 Abstract As common environmental endocrine-disrupting chemicals (EDCs), bisphenol AF (BPAF) raises potential concerns for aquatic organisms due to its widespread presence and continued release in the aquatic environment. This research aimed to use zebrafish embryos and adult fish to explore the effects of environmentally relevant concentrations (5 g/L), 50 g/L and 500 g/L of BPAF on zebrafish embryonic development, behavioral alterations, and the potential mechanisms driving these effects. The results showed that 500 g/L of BPAF severely affected the growth and development of embryos. In behavioral experiments, all concentrations of BPAF significantly inhibited the locomotor activity of larvae, 50 and 500 g/L BPAF significantly altered the anxiety-like and aggressive behavior of adult zebrafish. Furthermore, environmentally relevant concentrations and higher concentrations of BPAF induced varying degrees of oxidative stress in both embryonic and adult fish. The most significant histopathological changes and decreased acetylcholinesterase (AChE) activity were observed in the brain at 50 and 500 g/L of BPAF. We hypothesized that oxidative stress is an important cause of behavioral disturbances in larvae and adult fish. To our best knowledge, the present experiment is a pioneer in studying the effects of BPAF on a variety of complex behaviors (swimming performance, anxiety-like, social behavior, aggression) in zebrafish, which emphasizes the potential health risk of higher concentrations of BPAF in terms of induced neurotoxicity. Title: [(18)F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models Shao T, Chen Z, Rong J, Belov V, Chen J, Jeyarajan A, Deng X, Fu H, Yu Q and Liang SH <5 more author(s)> Shao T, Chen Z, Rong J, Belov V, Chen J, Jeyarajan A, Deng X, Fu H, Yu Q, Rwema SH, Lin W, Papisov M, Josephson L, Chung RT, Liang SH (- 5) Ref: Acta Pharm Sin B, 12:308, 2022 : PubMed ESTHER: Shao_2022_Acta.Pharm.Sin.B_12_308 PubMedSearch: Shao 2022 Acta.Pharm.Sin.B 12 308 PubMedID: 35127387 Abstract Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an (18)F-labeled MAGL inhibitor ([(18)F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [(18)F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl(4)) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [(18)F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [(18)F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [(18)F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [(18)F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues. Title: Dual Role of Strigolactone Receptor Signaling Partner in Inhibiting Substrate Hydrolysis Sobecks BL, Chen J, Shukla D Ref: J Phys Chem B, 126:2188, 2022 : PubMed ESTHER: Sobecks_2022_J.Phys.Chem.B_126_2188 PubMedSearch: Sobecks 2022 J.Phys.Chem.B 126 2188 PubMedID: 35275626 Abstract Plant branch and root growth relies on metabolism of the strigolactone (SL) hormone. The interaction between the SL molecule, Oryza sativa DWARF14 (D14) SL receptor, and D3 F-box protein has been shown to play a critical role in SL perception. Previously, it was believed that D3 only interacts with the closed form of D14 to induce downstream signaling, but recent experiments indicate that D3, as well as its C-terminal helix (CTH), can interact with the open form as well to inhibit strigolactone signaling. Two hypotheses for the CTH induced inhibition are that either the CTH affects the conformational ensemble of D14 by stabilizing catalytically inactive states or the CTH interacts with SLs in a way that prevents them from entering the binding pocket. In this study, we have performed molecular dynamics (MD) simulations to assess the validity of these hypotheses. We used an apo system with only D14 and the CTH to test the active site conformational stability and a holo system with D14, the CTH, and an SL molecule to test the interaction between the SL and CTH. Our simulations show that the CTH affects both active site conformation and the ability of SLs to move into the binding pocket. In the apo system, the CTH allosterically stabilized catalytic residues into their inactive conformation. In the holo system, significant interactions between SLs and the CTH hindered the ability of SLs to enter the D14 binding pocket. These two mechanisms account for the observed decrease in SL binding to D14 and subsequent ligand hydrolysis in the presence of the CTH. Title: Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination Wang D, Zhao T, Zhao S, Chen J, Dou T, Ge G, Wang C, Sun H, Liu K and Wu J <1 more author(s)> Wang D, Zhao T, Zhao S, Chen J, Dou T, Ge G, Wang C, Sun H, Liu K, Meng Q, Wu J (- 1) Ref: Curr Drug Metab, :, 2022 : PubMed ESTHER: Wang_2022_Curr.Drug.Metab__ PubMedSearch: Wang 2022 Curr.Drug.Metab PubMedID: 35114918 Abstract BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2. Title: Lipase induced highly hydrophobic nanofibrillated cellulose film for strain sensor application Wang Y, Wang Q, Liu S, Ji X, Yang G, Chen J Ref: Carbohydr Polym, 284:119193, 2022 : PubMed ESTHER: Wang_2022_Carbohydr.Polym_284_119193 PubMedSearch: Wang 2022 Carbohydr.Polym 284 119193 PubMedID: 35287910 Abstract An environmental-friendly lipase induced highly hydrophobic NFC film was fabricated through lipase induced dimethyl adipate (DA) esterification followed by silver nanowires (AgNWs) coating for strain sensor application. Due to the lipase activation, the substitution degree (DS(NMR)) of 0.18 was achieved, which was three times higher than that of the control sample (without lipase treatment of NFC-DA). As a result, the water contact angle (WCA) of lipase induced adipated-NFC film was reached to 105 +/- 3 degrees from 50 +/- 2.3 degrees of NFC-DA. In addition, the cellulose structure and performance were well maintained after lipase induced esterification, confirmed by AFM, SEM, TG/DTG, and XRD analysis. After AgNWs coating and annealing, the hydrophobic NFC film-based strain sensor exhibited excellent sensitivity towards human motion, such as finger/wrist movement in real-time, even under wet conditions. Overall, a highly hydrophobic NFC film-based strain sensor was fabricated, which has promising application in wearable devices for human motion monitoring. Title: Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease Wu D, Chen J, Luo K, Li H, Liu T, Li L, Dai Z, Li Y, Zhao Y, Fu X Ref: Bioorg Chem, 122:105760, 2022 : PubMed ESTHER: Wu_2022_Bioorg.Chem_122_105760 PubMedSearch: Wu 2022 Bioorg.Chem 122 105760 PubMedID: 35349945 Abstract In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD. Title: Improved liver lipid catabolism and utilization in growth hormone transgenic common carp (Cyprinus carpio L.) through enhanced lipolytic and fatty acid beta-oxidation pathways Wu Y, Li R, Wu X, Guo W, Li Y, Song Y, Tao B, Chen J, Han D and Hu W <3 more author(s)> Wu Y, Li R, Wu X, Guo W, Li Y, Song Y, Tao B, Chen J, Han D, Xie S, Wang Y, Zhu Z, Hu W (- 3) Ref: Front Endocrinol (Lausanne), 13:982488, 2022 : PubMed ESTHER: Wu_2022_Front.Endocrinol.(Lausanne)_13_982488 PubMedSearch: Wu 2022 Front.Endocrinol.(Lausanne) 13 982488 PubMedID: 36171901 Abstract Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid beta-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 +/- 0.32 g) and WT (initial weight 3.30 +/- 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 +/- 0.33 g) and WT (initial weight 3.27 +/- 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid beta-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species. Title: A novel approach for on-site screening of organophosphorus nerve agents based on DTNB modified AgNPs using surface-enhanced Raman spectrometry Wu J, Zhu Y, Liu Y, Chen J, Guo L, Xie J Ref: Anal Methods, :, 2022 : PubMed ESTHER: Wu_2022_Anal.Methods__ PubMedSearch: Wu 2022 Anal.Methods PubMedID: 36285727 Abstract Organophosphorus nerve agents (OPNAs), such as Sarin (GB), Tabun (GA), Soman (GD) and VX, would cause tremendous harm in military and terrorist attacks, and thus the development of simple methods for the rapid and efficient detection of these hazardous substances is of great necessity. Herein, we present a novel approach for the facile, rapid and sensitive detection of real OPNAs. The detection substrate is fabricated using functionalized silver nanoparticles (AgNPs) immobilized with acetylcholinesterase (AChE) and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In the absence of OPs, AChE catalyzes the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which continues to interact quickly with DTNB to produce a very sensitive Raman probing molecule, TNB. The inhibition of the activity of AChE by OPs could induce an obvious decrease of characteristic Raman peaks of 5-thio-2-nitrobenzoic acid (TNB) at 1335 cm(-1). The introduction of DTNB as an enzyme activity indicator significantly improves the detection sensitivity with distinct characteristic Raman peaks. The LOD of GD, which is one of the most easily aged OPNAs, could reach 0.1 nM due to its strongest inhibition of AChE. Moreover, various OPNAs exhibit different SERS intensities due to their different inhibition capacities of AChE. Hence, the new strategy has great potential in public security early warning and environmental analysis. Title: SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J and Huang Z <13 more author(s)> Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J, Zhou S, Jiang H, Du S, Zhou Y, Dong H, Fan Y, Miao S, Lu Q, Chang L, Wang H, Lu Y, Xu X, Wang W, Huang Z (- 13) Ref: Cell Death Dis, 13:638, 2022 : PubMed ESTHER: Xiang_2022_Cell.Death.Dis_13_638 PubMedSearch: Xiang 2022 Cell.Death.Dis 13 638 PubMedID: 35869039 Abstract Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD. Title: Gelsemine relieves the neuropathic pain by down-regulating DPP4 level in rats Yang L, Zhou G, Chen J, Zhang S Ref: Neuroscience Letters, 792:136961, 2022 : PubMed ESTHER: Yang_2022_Neurosci.Lett_792_136961 PubMedSearch: Yang 2022 Neurosci.Lett 792 136961 PubMedID: 36370955 Abstract BACKGROUND: Based on the previous findings on the relieving role of gelsemine in neuropathic pain, this research aims to further investigate the relevant regulatory mechanism. METHODS: Targets of gelsemine were predicted using SwissTargetPrediction. The peripheral neuropathic pain rat model was established by ligating spinal nerves, and then gelsemine (10 g for one day) or dipeptidyl peptidase 4 (DPP4) oligonucleotides (5 g/day, for 7 days) was injected into intrathecal bolus of rats. The mechanical threshold (0, 1, 2, 4 h after the last injection) was examined to evaluate the mechanical allodynia of rats. After the mechanical threshold measurement, the rats were anesthetized with isoflurane and then sacrificed by cervical dislocation. IBA1- and DPP4-positive cells in the spinal dorsal horn of rats were determined using immunohistochemistry and immunofluorescence assays. The expressions of DPP4, IL-1 and TNF- in the spinal dorsal horn of rats were measured by Western blot and quantitative real-time PCR. RESULTS: DPP4 was one of the targets of gelsemine. Gelsemine could elevate the down-regulated mechanical threshold, and lessen the up-regulated IBA1- and DPP4-positive cells and expressions of DPP4, IL-1 and TNF- in the spinal dorsal horn of rats with neuropathic pain. DPP4 overexpression reversed the role of gelsemine in neuropathic pain. CONCLUSION: Gelsemine relieves neuropathic pain by down-regulating DPP4 level in rats, providing a novel drug candidate and biomarker for neuropathic pain treatment. Title: The adverse effects of fluxapyroxad on the neurodevelopment of zebrafish embryos Yu H, Zhang J, Chen Y, Chen J, Qiu Y, Zhao Y, Li H, Xia S, Chen S, Zhu J Ref: Chemosphere, 307:135751, 2022 : PubMed ESTHER: Yu_2022_Chemosphere_307_135751 PubMedSearch: Yu 2022 Chemosphere 307 135751 PubMedID: 35863420 Abstract Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu. Title: Toxicity, Horizontal Transfer, Physiological and Behavioral Effects of Cycloxaprid against Solenopsis invicta (Hymenoptera: Formicidae) Zhang L, Wang L, Chen J, Zhang J, He Y, Lu Y, Cai J, Chen X, Wen X and Wang C <1 more author(s)> Zhang L, Wang L, Chen J, Zhang J, He Y, Lu Y, Cai J, Chen X, Wen X, Xu Z, Wang C (- 1) Ref: Pest Manag Sci, :, 2022 : PubMed ESTHER: Zhang_2022_Pest.Manag.Sci__ PubMedSearch: Zhang 2022 Pest.Manag.Sci PubMedID: 35192738 Abstract BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly-discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and non-repellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. This article is protected by copyright. All rights reserved. Title: Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor Zhang C, Li W, Li X, Wan D, Mack S, Zhang J, Wagner K, Wang C, Tan B and Yang J <7 more author(s)> Zhang C, Li W, Li X, Wan D, Mack S, Zhang J, Wagner K, Wang C, Tan B, Chen J, Wu CW, Tsuji K, Takeuchi M, Chen Z, Hammock BD, Pinkerton KE, Yang J (- 7) Ref: PLoS ONE, 17:e0266608, 2022 : PubMed ESTHER: Zhang_2022_PLoS.One_17_e0266608 PubMedSearch: Zhang 2022 PLoS.One 17 e0266608 PubMedID: 35443010 Inhibitor(s) related to this paper: TPPU Abstract Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment. Title: FAM135B sustains the reservoir of Tip60-ATM assembly to promote DNA damage response Zhang K, Wu Q, Liu W, Wang Y, Zhao L, Chen J, Liu H, Liu S, Li J and Zhan Q <1 more author(s)> Zhang K, Wu Q, Liu W, Wang Y, Zhao L, Chen J, Liu H, Liu S, Li J, Zhang W, Zhan Q (- 1) Ref: Clin Transl Med, 12:e945, 2022 : PubMed ESTHER: Zhang_2022_Clin.Transl.Med_12_e945 PubMedSearch: Zhang 2022 Clin.Transl.Med 12 e945 PubMedID: 35979619 Gene_locus related to this paper: human-FAM135B Abstract BACKGROUND: Recently, the mechanism by which cells adapt to intrinsic and extrinsic stresses has received considerable attention. Tat-interactive protein 60-kDa/ataxia-telangiectasia-mutated (TIP60/ATM) axis-mediated DNA damage response (DDR) is vital for maintaining genomic integrity. METHODS: Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co-immunoprecipitation, proximity ligation assay and GST pull-down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations. RESULTS: We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of gammaH2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non-homologous end-joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre-existing TIP60-ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre-assembled TIP60-ATM complex participates in DDR. CONCLUSIONS: We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60-ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment. Title: Screening of acetylcholinesterase inhibitory and antioxidant active compounds from Terminalia chebula fruits by spectrum-effect relationship and liquid chromatography-mass spectrometry analysis Zhao HH, Li YJ, Guo ZH, Chen J Ref: J Sep Sci, :, 2022 : PubMed Title: Characterization of a carboxylesterase with hyper-thermostability and alkali-stability from Streptomyces lividans TK24 Chang X, Wu S, Chen J, Xiong S, Wang P, Shi X, Wang A, Wang B Ref: Extremophiles, :, 2021 : PubMed ESTHER: Chang_2021_Extremophiles__ PubMedSearch: Chang 2021 Extremophiles PubMedID: 33515353 Gene_locus related to this paper: strco-SCO2123 Abstract A gene (estA', 804 bp) from Streptomyces lividans TK24 was artificially synthesized and successfully overexpressed as a 6His-tagged fusion protein in Escherichia coli. It encoded a carboxylesterase (EstA) that composed of 267 amino acids with a predicted molecular weight of 28.56 kDa. Multiple sequence alignment indicated that EstA has typical characteristics of esterases, including a catalytic triad (Ser93-Asp194-His224) and a conserved pentapeptide motif (Gly91-Leu92-Ser93-Met94-Gly95). Simultaneously, phylogenetic analysis indicated that EstA belongs to family VI. Biochemical characterization displayed its optimum enzyme activity was at 55 and pH 8.5. Additionally, EstA exhibited higher activity towards short carbon substrates and showed the outstanding catalytic efficiency for pNPA2 with k(cat)/K(m) of 2296.14 +/- 10.35 s(-1) mM(-1). Notably, EstA has hyper-thermostability and good alkali stability. The activity of EstA did not change obviously when incubated at 50 and 100 for 337 and 1 h, independently. Besides, by incubating at 100 for 6 h, EstA remained about half of its initial activity. Moreover, EstA showed stability at pH ranging from 8.0 to 11.0, and about 90% residual enzyme activity was reserved by being treated at pH 8.0 or 9.0 for 80 h, especially. Such multiple features prepare EstA for a potential candidate in the field of biological catalysis of some industrial applications under harsh conditions. Title: Aggregation-induced emission luminogen@manganese dioxide core-shell nanomaterial-based paper analytical device for equipment-free and visual detection of organophosphorus pesticide Chen J, Chen X, Wang P, Liu S, Chi Z Ref: J Hazard Mater, 413:125306, 2021 : PubMed ESTHER: Chen_2021_J.Hazard.Mater_413_125306 PubMedSearch: Chen 2021 J.Hazard.Mater 413 125306 PubMedID: 33588332 Abstract Organophosphorus pesticide (OP) residues have gathered considerable attention because of their significant threat to society development and healthy life. Developing a sensitive and practical OPs sensor is highly urgent, whereas remains a huge challenge. To this end, we fabricated a high-performance fluorescence paper analytical device (PAD) for apparatus-free and visual sensing of OPs based on aggregation-induced emission (AIE) luminogen's bright emission in aggregated state, unique response of MnO(2) to thiol compounds, and difference of MnO(2) and Mn(2+) in quenching fluorescence. AIE nanoparticles PTDNPs-0.10 and MnO(2) respectively acted as core and shell to prepare PTDNPs@MnO(2), which possessed high stability and were dripped on cellulose paper's surface to fabricate AIE-PAD. The sensing mechanism is that OPs-treated acetylcholinesterase (AChE) prevents the formation of thiocholine, thereby minimizing the reduction of MnO(2) into Mn(2+) and changing the output signal. As a result, equipment-free and visual sensing of OPs was acquired with limit of detection of 1.60 ng/mL. This work justifies the feasibility of applying core-shell material to develop high-performance sensor and substituting complex/expensive solution-phase sensor with PAD, providing a new avenue to bring OPs analysis out of the lab and into the world. Title: Synergistic enhancement of the emergency treatment effect of organophosphate poisoning by a supramolecular strategy Chen J, Zhang Y, Chai Y, Meng Z, Chen L, Quan D, Wang Y, Meng Q, Li C Ref: Chem Sci, 12:5202, 2021 : PubMed ESTHER: Chen_2021_Chem.Sci_12_5202 PubMedSearch: Chen 2021 Chem.Sci 12 5202 PubMedID: 34163757 Abstract Poisoning by organophosphorus agents (OPs) is a serious public health issue across the world. These compounds irreversibly inhibit acetylcholinesterase (AChE), resulting in the accumulation of acetylcholine (ACh) and overstimulation of ACh receptors. A supramolecular detoxification system (SDS) has been designed with a view to deliver pyridine-2-aldoxime methochloride (PAM) with a synergistic inhibition effect on the ACh-induced hyperstimulation through host-guest encapsulation. NMR and fluorescence titration served to confirm the complexation between carboxylatopillar[6]arene (CP6A) and PAM as well as ACh with robust affinities. Patch-clamp studies proved that CP6A could exert an inhibition effect on the ACh-induced hyperstimulation of ACh receptors. Support for the feasibility of this strategy came from fluorescence imaging results. In vivo studies revealed that complexation by CP6A serves to increase the AChE reactivation efficiency of PAM. The formation of the PAM/CP6A complex contributed to enhance in a statistically significant way the ability of PAM not only to relieve symptoms of seizures but also to improve the survival ratio in paraoxon-poisoned model rats. These favorable findings are attributed to synergistic effects that PAM reactivates AChE to hydrolyze ACh and excess ACh is encapsulated in the cavity of CP6A to relieve cholinergic crisis symptoms. Title: Development of a highly-specific (18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping Chen Z, Mori W, Rong J, Schafroth MA, Shao T, Van RS, Ogasawara D, Yamasaki T, Hiraishi A and Liang SH <12 more author(s)> Chen Z, Mori W, Rong J, Schafroth MA, Shao T, Van RS, Ogasawara D, Yamasaki T, Hiraishi A, Hatori A, Chen J, Zhang Y, Hu K, Fujinaga M, Sun J, Yu Q, Collier TL, Shao Y, Cravatt BF, Josephson L, Zhang MR, Liang SH (- 12) Ref: Acta Pharm Sin B, 11:1686, 2021 : PubMed ESTHER: Chen_2021_Acta.Pharm.Sin.B_11_1686 PubMedSearch: Chen 2021 Acta.Pharm.Sin.B 11 1686 PubMedID: 34221877 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: PF-06795071 Abstract As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S(N)Ar reaction to form 2-[(18)F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [(18)F]14 (also named as [(18)F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent (18)F-labeled MAGL PET tracers. Title: Long-term exposure to polyethylene microplastics and glyphosate interferes with the behavior, intestinal microbial homeostasis, and metabolites of the common carp (Cyprinus carpio L.) Chen J, Rao C, Yuan R, Sun D, Guo S, Li L, Yang S, Qian D, Lu R, Cao X Ref: Sci Total Environ, :152681, 2021 : PubMed ESTHER: Chen_2021_Sci.Total.Environ__152681 PubMedSearch: Chen 2021 Sci.Total.Environ 152681 PubMedID: 34973326 Abstract Polyethylene microplastics (PE-MPs) and glyphosate (GLY) occur widely and have toxic characteristics, resulting in increased research interest. In this study, common carp were used to assess the individual and combined toxicity of PE-MPs (0, 1.5, or 4.5 mg/L) and GLY (0, 5, or 15 mg/L) on the brain-gut axis. After 60 days of exposure, the developmental toxicity, blood-brain barrier (BBB), locomotor behavior, intestinal barrier (physical barrier, chemical barrier, microbial barrier), and intestinal content metabolism of common carp were evaluated. Results showed that 15 mg/L of GLY exposure significantly reduced the mRNA expression of tight-junction genes (occludin, claudin-2, and ZO-1) in the brain, and acetylcholinesterase (AChE) activity was clearly inhibited by high concentrations of GLY. However, different concentrations of PE-MPs had no significant effect on the activity of AChE. Furthermore, the free-swimming behavior of common carp was distinctly inhibited by treatment with a combination of 15 mg/L GLY and 4.5 mg/L PE-MPs. Histological studies indicated that PE-MPs alone and in combination with GLY could disrupt the physical and chemical intestinal barriers of common carp. Additionally, the abundance and diversity of gut microbiota in common carp were significantly changed when exposed to a combination of PE-MPs and GLY. Metabolomics further revealed that PE-MPs combined with GLY triggered metabolic changes and that differential metabolites were related to amino acid and lipid metabolism. These findings illustrate that exposure to PE-MPs or GLY alone is toxic to fish and results in physiological changes to the brain-gut axis. This work offers a robust analysis to understand the mechanisms underlying GLY and MP-induced aquatic toxicity. Title: High-efficiency degradation of phthalic acid esters (PAEs) by Pseudarthrobacter defluvii E5: Performance, degradative pathway, and key genes Chen F, Chen Y, Chen C, Feng L, Dong Y, Chen J, Lan J, Hou H Ref: Sci Total Environ, 794:148719, 2021 : PubMed ESTHER: Chen_2021_Sci.Total.Environ_794_148719 PubMedSearch: Chen 2021 Sci.Total.Environ 794 148719 PubMedID: 34214821 Abstract Phthalic acid esters (PAEs) are a class of biologically accumulated carcinogenic and teratogenic toxic chemicals that exist widely in the environment. This study, Pseudarthrobacter defluvii E5 was isolated from agricultural soils and showed efficient PAEs-degradation and -mineralization abilities for five PAEs, and encouraging PAEs tolerance and bioavailable range for dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) (0.25-1200 mg/L). The complete catalytic system in E5 genome enables PAEs to be degraded into monoester, phthalate (PA) and Protocatechuic acid (PCA), which eventually enter the tricarboxylic acid cycle (TCA cycle). The preferred PAEs-metabolic pathway in soil by E5 is the metabolism induced by enzymes encoded by pehA, mehpH, pht Operon and pca Operon. For the first time, two para-homologous pht gene clusters were found to coexist on the plasmid and contribute to PAEs degradation. Further study showed that P. defluvii E5 has a broad application prospect in microplastics-contaminated environments. Title: A GRN Autocrine-Dependent FAM135B/AKT/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression Dong D, Zhang W, Xiao W, Wu Q, Cao Y, Gao X, Huang L, Wang Y, Chen J and Zhan Q <1 more author(s)> Dong D, Zhang W, Xiao W, Wu Q, Cao Y, Gao X, Huang L, Wang Y, Chen J, Wang W, Zhan Q (- 1) Ref: Cancer Research, 81:910, 2021 : PubMed ESTHER: Dong_2021_Cancer.Res_81_910 PubMedSearch: Dong 2021 Cancer.Res 81 910 PubMedID: 33323378 Gene_locus related to this paper: human-FAM135B Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomics study, we found that family with sequence similarity 135 member B (FAM135B) was a novel cancer-related gene, yet its biological functions and molecular mechanisms remain unclear. In this study, we demonstrate that the protein levels of FAM135B are significantly higher in ESCC tissues than in precancerous tissues, and high expression of FAM135B correlates with poorer clinical prognosis. Ectopic expression of FAM135B promoted ESCC cell proliferation in vitro and in vivo, likely through its direct interaction with growth factor GRN, thus forming a feedforward loop with AKT/mTOR signaling. Patients with ESCC with overexpression of both FAM135B and GRN had worse prognosis; multivariate Cox model analysis indicated that high expression of both FAM135B and GRN was an independent prognostic factor for patients with ESCC. FAM135B transgenic mice bore heavier tumor burden than wild-type mice and survived a relatively shorter lifespan after 4-nitroquinoline 1-oxide treatment. In addition, serum level of GRN in transgenic mice was higher than in wild-type mice, suggesting that serum GRN levels might provide diagnostic discrimination for patients with ESCC. These findings suggest that the interaction between FAM135B and GRN plays critical roles in the regulation of ESCC progression and both FAM135B and GRN might be potential therapeutic targets and prognostic factors in ESCC. SIGNIFICANCE: These findings investigate the mechanisms of FAM135B in promoting ESCC progression and suggest new potential prognostic biomarkers and therapeutic targets in patients with ESCC. Title: The Role of Clt1-Regulated Xylan Metabolism in Melanin and Toxin Formation for the Pathogenicity of Curvularia lunata in Maize Gao J, Chen J Ref: Mol Plant Microbe Interact, :MPMI08200235R, 2021 : PubMed ESTHER: Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R PubMedSearch: Gao 2021 Mol.Plant.Microbe.Interact MPMI08200235R PubMedID: 33417477 Abstract We previously reported that the BTB (brica-brac, tramtrack, and broad) domain-containing protein Clt1 regulates melanin and toxin synthesis, conidiation, and pathogenicity in Curvularia lunata, but the interacting proteins and regulative mechanism of Clt1 are unclear. In this research, we identified two proteins, which respectively correspond to xylanase (Clxyn24) and acetyl xylan esterase (Claxe43) from C. lunata, that were regulated by Clt1. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation assays were conducted to verify the interaction of Clt1 with full-length Clxyn24 and Claxe43. Furthermore, the Y2H assay revealed that Clt1 physically interacted with Clxyn24 and Claxe43 through its BTB domain to degrade xylan, which was used as a carbon source for C. lunata growth. The utilization of xylan provides acetyl-CoA for the synthesis of melanin and toxin as well as energy and other intermediate metabolites for conidiation. Furthermore, transcriptome analysis revealed that PKS18 and its 13 flanking genes found clustered in a region spanning 57.89 kb on scaffold 9 of the C. lunata CX-3 genome were down-regulated in toxin production-deficient mutant T806, and this cluster is possibly responsible for toxin biosynthesis of C. lunata. [Formula: see text] Copyright 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license. Title: Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression He W, Huang J, Liu Y, Xie C, Zhang K, Zhu X, Chen J, Huang H Ref: Cell Death Dis, 12:992, 2021 : PubMed ESTHER: He_2021_Cell.Death.Dis_12_992 PubMedSearch: He 2021 Cell.Death.Dis 12 992 PubMedID: 34689162 Abstract Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention. Title: Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure Kang L, Chen J, Wang J, Zhao T, Wei Y, Wu Y, Han L, Zheng X, Shen L and Wu S <2 more author(s)> Kang L, Chen J, Wang J, Zhao T, Wei Y, Wu Y, Han L, Zheng X, Shen L, Long C, Wei G, Wu S (- 2) Ref: Environ Sci Pollut Res Int, :, 2021 : PubMed ESTHER: Kang_2021_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Kang 2021 Environ.Sci.Pollut.Res.Int PubMedID: 34595713 Abstract The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP. Title: PubChem in 2021: new data content and improved web interfaces Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA and Bolton EE <3 more author(s)> Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE (- 3) Ref: Nucleic Acids Research, 49:D1388, 2021 : PubMed ESTHER: Kim_2021_Nucleic.Acids.Res_49_D1388 PubMedSearch: Kim 2021 Nucleic.Acids.Res 49 D1388 PubMedID: 33151290 Abstract PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Title: Screening and identification of acetylcholinesterase inhibitors from Terminalia chebula fruits by immobilized enzyme on cellulose filter paper coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and molecular docking Li YJ, He FQ, Zhao HH, Li Y, Chen J Ref: Journal of Chromatography A, 1663:462784, 2021 : PubMed ESTHER: Li_2021_J.Chromatogr.A_1663_462784 PubMedSearch: Li 2021 J.Chromatogr.A 1663 462784 PubMedID: 34974370 Abstract With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-beta-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC(50) values of 0.43 +/- 0.03, 0.46 +/- 0.02, 0.50 +/- 0.03 and 0.51 +/- 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs. Title: Reproductive stimulation and energy allocation variation of BDE-47 and its derivatives on Daphnia magna Liu Y, Chen M, Ma Y, Guo R, Yan Z, Chen J Ref: Chemosphere, 288:132492, 2021 : PubMed ESTHER: Liu_2021_Chemosphere_288_132492 PubMedSearch: Liu 2021 Chemosphere 288 132492 PubMedID: 34626654 Abstract As endocrine disrupting chemical, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is widely distributed in water environment with a high detection rate. 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE-47) are two main derivatives of BDE-47. To explore the aquatic risk of BDE-47 and its derivatives, the effects of them and their ternary mixture on the reproduction, growth, energy allocation, and neurological and antioxidant responses of Daphnia magna were monitoring during different exposure periods, i.e., daphnids exposed to compounds for 21 days or pre-exposed to compounds for 14 days and then recovered 7 days in clean water. In general, in 21-day test, reproductive parameters of exposed daphnids were significantly stimulated, and the growth and enzymatic activities of super oxidase dimutase (SOD), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) were significantly depressed by the single- or mixture compounds. In (14 + 7)-day test, the levels of body length, number of living offspring per female and the enzyme activities recovered to some degree. However, after 7 days of recovery in pollution free medium, the reproductive parameters and enzymatic activities of D. magna were unable to restore control values. These results showed that D. magna has a tendency that the energy allocated to reproduction was greater than that to grow after exposure. The energy distribution of D. magna occurred autonomously after being exposed, which can make it better adapt to environmental changes. Moreover, based on the behavioral and enzymology indicators of D. magna, the spider chart's application in the characteristic analysis of function indicators of D. magna implied that SOD, GPx and AChE could become sensitive biomarkers for different exposure periods. Those findings enable us to better understand BDE-47 and metabolites, and are conducive to better take measures to solve the pressure it brings. Title: Trelagliptin ameliorates IL-1beta-impaired chondrocyte function via the AMPK/SOX-9 pathway Liu J, Zuo Q, Li Z, Chen J, Liu F Ref: Mol Immunol, 140:70, 2021 : PubMed ESTHER: Liu_2021_Mol.Immunol_140_70 PubMedSearch: Liu 2021 Mol.Immunol 140 70 PubMedID: 34666245 Inhibitor(s) related to this paper: Trelagliptin Abstract Chondrocyte dysregulation plays a critical role in the development of osteoarthritis (OA). The pro-inflammatory cytokine interleukin-1beta (IL-1beta) activates chondrocytes and degrades the structural extracellular matrix (ECM). These events are the important mechanism of OA. Trelagliptin, a selective inhibitor of dipeptidyl Peptidase 4 (DPP-4) used for the treatment of type 2 diabetes mellitus (T2DM), has displayed a wide range of anti-inflammatory capacities. The effects of Trelagliptin in OA and chondrocytes have not been tested before. Here, we show that Trelagliptin mitigates IL-1beta-induced production of inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in human chondrocytes. Trelagliptin ameliorates IL-1beta-induced oxidative stress by reducing the generation of reactive oxygen species (ROS). Particularly, the presence of Trelagliptin prevents IL-1beta-induced reduction of Acan genes and the protein Aggrecan. Moreover, we show that Trelagliptin restores IL-1beta-induced reduction of SOX-9 and that the knockdown of SOX-9 abolishes the protective effects of Trelagliptin. Mechanistically, we demonstrate that AMPK is required for the amelioration of Trelagliptin on SOX-9- reduction by IL-1beta. Collectively, our study demonstrates that the DPP-4 inhibitor Trelagliptin has a protective effect on chondrocyte function. Trelagliptin may have the potential role to antagonize chondrocyte-derived inflammation in OA. Title: Identification and Biochemical Characterization of a Novel Hormone-Sensitive Lipase Family Esterase Est19 from the Antarctic Bacterium Pseudomonas sp. E2-15 Liu X, Zhou M, Xing S, Wu T, He H, Bielicki JK, Chen J Ref: Biomolecules, 11:1552, 2021 : PubMed ESTHER: Liu_2021_Biomolecules_11_1552 PubMedSearch: Liu 2021 Biomolecules 11 1552 Gene_locus related to this paper: psesp-MT761613 Abstract Esterases represent an important class of enzymes with a wide variety of industrial applications. A novel hormone-sensitive lipase (HSL) family esterase, Est19, from the Antarctic bacterium Pseudomonas sp. E2-15 is identified, cloned, and expressed. The enzyme possesses a GESAG motif containing an active serine (S) located within a highly conserved catalytic triad of Ser155, Asp253, and His282 residues. The catalytic efficiency (kcat/Km) of Est19 for the pNPC6 substrate is 148.68 s-1 mM-1 at 40 C. Replacing Glu154 juxtaposed to the critical catalytic serine with Asp (E154->D substitution) reduced the -activity and catalytic efficiency of the enzyme two-fold, with little change in the substrate affinity. The wild-type enzyme retained near complete activity over a temperature range of 10-60 C, while ~50% of its activity was retained at 0 C. A phylogenetic analysis suggested that Est19 and its homologs may represent a new subfamily of HSL. The thermal stability and stereo-specificity suggest that the Est19 esterase may be useful for cold and chiral catalyses. Title: Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study Mu L, Chen J, Li J, Sobotka S, Nyirenda T Ref: Neurol Res Int, 2021:6009342, 2021 : PubMed ESTHER: Mu_2021_Neurol.Res.Int_2021_6009342 PubMedSearch: Mu 2021 Neurol.Res.Int 2021 6009342 PubMedID: 34925918 Abstract BACKGROUND: Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause "foot drop," a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). METHODS: As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler's stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. RESULTS: The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. CONCLUSION: NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l. Title: Nitrogen-Doped Graphdiyne as a Robust Electrochemical Biosensing Platform for Ultrasensitive Detection of Environmental Pollutants Niu K, Gao J, Wu L, Lu X, Chen J Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Niu_2021_Anal.Chem__ PubMedSearch: Niu 2021 Anal.Chem PubMedID: 34110153 Abstract Owing to its unique chemical structure, natural pores, high structure defects, good surface hydrophilicity and biocompatibility, and favorable electrical conductivity, nitrogen-doped graphdiyne (NGDY) has been attracting attention in the application of electrochemical sensing. Taking advantage of these fascinating electrochemical properties, for the first time, two types of electrochemical enzymatic biosensors were fabricated for the respective detection of organophosphorus pesticides (OPs) and phenols based on the immobilization of acetylcholinesterase or tyrosinase with NGDY. Results revealed that the sensitivities of the NGDY-based enzymatic biosensors were almost twice higher than that of the matching biosensor in the absence of NGDY, proving that NGDY plays a vital role in immobilizing the enzymes and improving the performance of the fabricated biosensors. The effects of nitrogen doping on improving the biosensing performance were studied in depth. Graphitic N atoms can enhance the electrical conductivity, while imine N and pyridinic N can help to adsorb and accumulate the substance molecules to the electrode surface, all of which contribute to the significantly improved performance. Furthermore, these two types of biosensors also demonstrated excellent reproducibility, high stability, and good recovery rate in real environmental samples, which showed a valuable way for the rapid detection of OPs and phenols in the environment. With these excellent performances, it is strongly anticipated that NGDY has tremendous potential to be applied to many other biomedical and environmental fields. Title: Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold Rong J, Mori W, Xia X, Schafroth MA, Zhao C, Van RS, Yamasaki T, Chen J, Xiao Z and Liang SH <23 more author(s)> Rong J, Mori W, Xia X, Schafroth MA, Zhao C, Van RS, Yamasaki T, Chen J, Xiao Z, Haider A, Ogasawara D, Hiraishi A, Shao T, Zhang Y, Chen Z, Pang F, Hu K, Xie L, Fujinaga M, Kumata K, Gou Y, Fang Y, Gu S, Wei H, Bao L, Xu H, Collier TL, Shao Y, Carson RE, Cravatt BF, Wang L, Zhang MR, Liang SH (- 23) Ref: Journal of Medicinal Chemistry, :, 2021 : PubMed ESTHER: Rong_2021_J.Med.Chem__ PubMedSearch: Rong 2021 J.Med.Chem PubMedID: 34569803 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: ZYH-deriv-F Abstract Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [(18)F]10 and [(18)F]15 ([(18)F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [(18)F]15 demonstrated a better performance. In conclusion, [(18)F]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans. Title: Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays Song YQ, Guan XQ, Weng ZM, Liu JL, Chen J, Wang L, Cui LT, Fang SQ, Hou J, Ge GB Ref: Food Funct, 12:162, 2021 : PubMed ESTHER: Song_2021_Food.Funct_12_162 PubMedSearch: Song 2021 Food.Funct 12 162 PubMedID: 33291124 Abstract Human carboxylesterase 2 (hCES2A) is a key target to ameliorate the intestinal toxicity triggered by irinotecan that causes severe diarrhea in 50%-80% of patients receiving this anticancer agent. Herbal medicines are frequently used for the prevention and treatment of the intestinal toxicity of irinotecan, but it is very hard to find strong hCES2A inhibitors from herbal medicines in an efficient way. Herein, an integrated strategy via combination of chemical profiling, docking-based virtual screening and fluorescence-based high-throughput inhibitor screening assays was utilized. Following the screening of a total of 73 herbal products, licorice (the dried root of Glycyrrhiza species) was found with the most potent hCES2A inhibition activity. Further investigation revealed that the chalcones and several flavonols in licorice displayed strong hCES2A inhibition activities, while isoliquiritigenin, echinatin, naringenin, gancaonin I and glycycoumarin exhibited moderate inhibition of hCES2A. Inhibition kinetic analysis demonstrated that licochalcone A, licochalcone C, licochalcone D and isolicoflavonol potently inhibited hCES2A-mediated fluorescein diacetate hydrolysis in a reversible and mixed inhibition manner, with K(i) values less than 1.0 microM. Further investigations demonstrated that licochalcone C, the most potent hCES2A inhibitor identified from licorice, dose-dependently inhibited intracellular hCES2A in living HepG2 cells. In summary, this study proposed an integrated strategy to find hCES2A inhibitors from herbal medicines, and our findings suggested that the chalcones and isolicoflavonol in licorice were the key ingredients responsible for hCES2A inhibition, which would be very helpful to develop new herbal remedies or drugs for ameliorating hCES2A-associated drug toxicity. Title: The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L and Wang A <3 more author(s)> Wang S, Zhao Q, Li G, Wang M, Liu H, Yu X, Chen J, Li P, Dong L, Zhou G, Cui Y, Liu L, Wang A (- 3) Ref: Ecotoxicology & Environmental Safety, 228:112959, 2021 : PubMed ESTHER: Wang_2021_Ecotoxicol.Environ.Saf_228_112959 PubMedSearch: Wang 2021 Ecotoxicol.Environ.Saf 228 112959 PubMedID: 34808511 Abstract Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence. Title: Novel amide derivatives containing an imidazo[1,2-a]pyridine moiety: Design, synthesis as potential nematicidal and antibacterial agents Wei C, Huang J, Luo Y, Wang S, Wu S, Xing Z, Chen J Ref: Pestic Biochem Physiol, 175:104857, 2021 : PubMed ESTHER: Wei_2021_Pestic.Biochem.Physiol_175_104857 PubMedSearch: Wei 2021 Pestic.Biochem.Physiol 175 104857 PubMedID: 33993975 Abstract To discover new nematicides, a series of novel amide derivatives containing an imidazo[1,2-a]pyridine moeity were designed and synthesized. Among the title compounds, compounds 3 and 27 exhibited good nematicidal activities against Aphelenchoides besseyi (rice white-tip nematode), with LC(50) values against of 27.3 and 35.9 mg/L, respectively, which were superior to that of fosthiazate (45.4 mg/L). Meanwhile, the LC(50) value of compound 27 against Caenorhabditis elegans was 5.7 mg/L, which was superior to that of fosthiazate (77.2 mg/L). Compound 27 not only binds well to acetylcholinesterase (AChE) of nematodes, but also has a good inhibitory activity against AChE. Thus, AChE may be a potential target of compound 27 against nematodes. Unexpectedly, compound 28 exhibited excellent antibacterial activities with EC(50) values of 1.2 and 3.1 mg/L against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively, which were superior to those of bismerthiazol (68.6 and 77.1 mg/L) and thiodiazole copper (80.8 and 96.6 mg/L). The curative and protective activities of compound 28 against bacterial leaf blight were 37.0% and 36.8% at 50 mg/L, respectively, which were higher than those of thiodiazole copper (16.1% and 15.5%). In addition, compound 28 may inhibit the growth of Xoo by affecting the production of cell membranes and extracellular polysaccharides. Amide derivatives containing an imidazo[1,2-a]pyridine moeity can be used as good lead-structures to discover new nematicidal and antibacterial agents in the future. Title: A methyl esterase 1 (PvMES1) promotes the salicylic acid pathway and enhances Fusarium wilt resistance in common beans Xue R, Feng M, Chen J, Ge W, Blair MW Ref: Theor Appl Genet, :, 2021 : PubMed ESTHER: Xue_2021_Theor.Appl.Genet__ PubMedSearch: Xue 2021 Theor.Appl.Genet PubMedID: 34128089 Gene_locus related to this paper: phavu-v7cf29 Abstract Methyl esterase (MES), PvMES1, contributes to the defense response toward Fusarium wilt in common beans by regulating the salicylic acid (SA) mediated signaling pathway from phenylpropanoid synthesis and sugar metabolism as well as others. Common bean (Phaseolus vulgaris L.) is an important food legume. Fusarium wilt caused by Fusarium oxysporum f. sp. phaseoli is one of the most serious soil-borne diseases of common bean found throughout the world and affects the yield and quality of the crop. Few sources of Fusarium wilt resistance exist in legumes and most are of quantitative inheritance. In this study, we have identified a methyl esterase (MES), PvMES1, that contributes to plant defense response by regulating the salicylic acid (SA) mediated signaling pathway in response to Fusarium wilt in common beans. The result showed the role of PvMES1 in regulating SA levels in common bean and thus the SA signaling pathway and defense response mechanism in the plant. Overexpression of the PvMES1 gene enhanced Fusarium wilt resistance; while silencing of the gene caused susceptibility to the diseases. RNA-seq analysis with these transiently modified plants showed that genes related to SA level changes included the following gene ontologies: (a) phenylpropanoid synthesis; (b) sugar metabolism; and (c) interaction between host and pathogen as well as others. These key signal elements activated the defense response pathway in common bean to Fusarium wilt. Collectively, our findings indicate that PvMES1 plays a pivotal role in regulating SA biosynthesis and signaling, and increasing Fusarium wilt resistance in common bean, thus providing novel insight into the practical applications of both SA and MES genes and pathways they contribute to for developing elite crop varieties with enhanced broad-spectrum resistance to this critical disease. Title: Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice Yang Y, Xu X, Wu H, Yang J, Chen J, Morisseau C, Hammock BD, Bettaieb A, Zhao L Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Yang_2021_Int.J.Mol.Sci_22_ PubMedSearch: Yang 2021 Int.J.Mol.Sci 22 PubMedID: 34361032 Inhibitor(s) related to this paper: t-TUCB Abstract 17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1alpha expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFkappaB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT. Title: Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2 Zhao T, Wang D, Shan Z, Chen J, Dou T, Ge G, Wang C, Meng Q, Sun H and Wu J <1 more author(s)> Zhao T, Wang D, Shan Z, Chen J, Dou T, Ge G, Wang C, Meng Q, Sun H, Liu K, Wu J (- 1) Ref: Curr Drug Metab, :, 2021 : PubMed ESTHER: Zhao_2021_Curr.Drug.Metab__ PubMedSearch: Zhao 2021 Curr.Drug.Metab PubMedID: 33568030 Abstract BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 microM, 8.63 microM and 29.0 microM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects. Title: Re-pigmentation of hair after prolonged cholinesterase inhibitor therapy in a Chinese population Chan LKM, Braidy N, Ng W, Xu YH, Chen J, McDonald R, Chan DKY Ref: Australas J Dermatol, 61:e417, 2020 : PubMed ESTHER: Chan_2020_Australas.J.Dermatol_61_e417 PubMedSearch: Chan 2020 Australas.J.Dermatol 61 e417 PubMedID: 32597493 Abstract Eighty consecutive Chinese patients diagnosed with Alzheimer disease were assessed for darkening of grey hair. Of the 62 eligible patients (mean age = 79.3 +/- 7.9 years; male: female = 1:1.48), 24/62 (38.7%, 95%CI: 26.6 - 51.9) reported hair darkening after prolonged usage of cholinesterase inhibitor for at least 6 months. Of the 24 patients with hair darkening, 17 (70.9%) experienced hair darkening in the occipital region, 3 (12.5%) in the parietal region, 2 (8.3%) patients in the frontal region and 2 (8.3%) patients experienced hair darkening in multiple regions. Analysis of melanin concentration showed no significant difference between darkened hair of patients after prolonged drug use and the dark hair of controls (P = 0.381). Title: Aberrant mPFC GABAergic Synaptic Transmission and Fear Behavior in Neuroligin-2 R215H Knock-in Mice Chen J, Dong B, Feng X, Jiang D, Chen G, Long C, Yang L Ref: Brain Research, :146671, 2020 : PubMed ESTHER: Chen_2020_Brain.Res__146671 PubMedSearch: Chen 2020 Brain.Res 146671 PubMedID: 31953212 Abstract Aberrant medial prefrontal cortex (mPFC) activity is associated with neuropsychiatric disorders such as schizophrenia, but the precise role of mPFC GABAergic neurotransmission in the pathogenesis of schizophrenia remains not well understood. Neuroligin-2 (Nlgn 2) is a postsynaptic cell-adhesion protein playing an important role in inhibitory synapse formation and function. Mutations of Nlgn 2 have been reported to be associated with schizophrenia. Using a Nlgn 2 Arg(215)-->His(215) mutation knock-in (NL2 R215H KI) mouse model of schizophrenia, we show here that inhibitory synaptic transmission, such as miniature and evoked inhibitory postsynaptic currents (mIPSCs, eIPSCs), is significantly reduced in the mPFC of NL2 R215H KI mice. The levels of inhibition-related proteins, including parvalbumin (PV), the gamma2 subunit of the GABAA receptor, and a vesicular GABA transporter vGAT, are also reduced significantly in NL2 R215H KI mPFC. The reduction of GABAergic inhibition disrupts the excitation/inhibition (E/I) ratio in mPFC, and results in the subsequent abnormal gamma oscillation in the mPFC of R215H KI mice. Behavioral evaluation suggests that GABAergic deficits contribute, at least in part, to alterations in fear response, which requires balanced E/I ratio of mPFC neurons. These results suggest a pivotal role of Nlgn 2 in maintaining E/I balance in the mPFC and in the maintenance of normal behaviors governed by the mPFC. Title: Instrument-free and visual detection of organophosphorus pesticide using a smartphone by coupling aggregation-induced emission nanoparticle and two-dimension MnO(2) nanoflake Chen J, Chen X, Zhao J, Liu S, Chi Z Ref: Biosensors & Bioelectronics, 170:112668, 2020 : PubMed ESTHER: Chen_2020_Biosens.Bioelectron_170_112668 PubMedSearch: Chen 2020 Biosens.Bioelectron 170 112668 PubMedID: 33032200 Abstract Given the importance of food safety, it is highly desirable to develop a convenient, low-cost, and practical sensor for organophosphorus pesticides (OPs) detection. Here, a fluorescent paper analytical device (FPAD) based on aggregation-induced emission (AIE) nanoparticles (PTDNPs-0.10) and two-dimension MnO(2) nanoflakes (2D-MnNFs) was developed for instrument-free and naked-eye analysis of OPs. PTDNP-MnNFs composites were obtained through 2D-MnNFs and PTDNPs-0.10 by electrostatic interaction and the fluorescence emission of PTDNPs-0.10 was quenched through fluorescence resonance energy transfer (FRET). When acetylcholinesterase (AChE) was present, acetylthiocholine (ATCh) was catalytically hydrolyzed into thiocholine, which reduced MnO(2) of PTDNP-MnNFs into Mn(2+), subsequently blocking the FRET and enhancing the fluorescence. Upon the addition of OP, AChE activity was depressed and thus the FRET between 2D-MnNFs and PTDNPs-0.10 was not affected, resulting in a slight change in fluorescence. On the basis of the variation in fluorescence intensity, highly sensitive detection of OP was readily achieved with a detection limit of 0.027 ng/mL; on the basis of the variation in brightness of FPAD, instrument-free and visual detection of OP was realized using a smartphone with a detection limit of 0.73 ng/mL. The application of FPAD has significantly simplified the detection procedure and decreased the test cost, supplying a new approach for on-site detection of OPs. Title: Insecticidal and Enzyme Inhibitory Activities of Isothiocyanates against Red Imported Fire Ants, Solenopsis invicta Du Y, Grodowitz MJ, Chen J Ref: Biomolecules, 10:, 2020 : PubMed ESTHER: Du_2020_Biomolecules_10_ PubMedSearch: Du 2020 Biomolecules 10 PubMedID: 32380698 Abstract Contact and fumigation toxicity of four isothiocyanates (ITCs), including allyl isothiocyanate (AITC), 3-butenyl isothiocyanate (3BITC), 3-(methylthio) propyl isothiocyanate (3MPITC) and 2-phenylethyl isothiocyanate (2PEITC), were evaluated against the red imported fire ant worker, Solenopsis invicta Buren. 2PEITC and 3MPITC exhibited strong contact toxicity. The median lethal dose (LD50)value of AITC, 2PEITC and 3MPITC were 7.99, 2.36 and 2.09 microg/ant respectively. In addition, AITC and 3MPITC also showed strong fumigation toxicity but not 2PEITC. The median lethal concentration (LC50) values of AITC and 3MPITC were 32.49 and 57.6 microg/L, respectively. In contrast, 3BITC did not exhibit any contact and fumigation toxicity even at 100 mug/muL. Esterase (EST), glutathione S-transferase (GST) and acetylcholinesterase (AChE)-inhibiting activities were assessed for three ITCs in S. invicta workers. All three ITCs inhibited both EST and GST activities but not AChE. The in vitro half maximal inhibitory concentration (IC50)values of AITC, 2PEITC and 3MPITC for GST were 3.32, 0.61 and 0.66 microg/microL, respectively. These results suggested that naturally occurring ITCs might be potentially useful for developing fire ants control products. Title: Biodegradation mechanism of polycaprolactone by a novel esterase MGS0156: a QM/MM approach Feng S, Yue Y, Chen J, Zhou J, Li Y, Zhang Q Ref: Environ Sci Process Impacts, 22:2332, 2020 : PubMed ESTHER: Feng_2020_Environ.Sci.Process.Impacts_22_2332 PubMedSearch: Feng 2020 Environ.Sci.Process.Impacts 22 2332 PubMedID: 33146659 Gene_locus related to this paper: 9zzzz-A0A0G3FEJ8 Abstract Nowadays micro-plastic pollution has become one of the most serious global environmental problems. A potential strategy in managing micro-plastic waste is enzyme-catalyzed degradation. MGS0156 is a hydrolase screened from environmental metagenomes, which can efficiently degrade commercial plastics such as polycaprolactone, polylactide, etc. Here a combined molecular dynamics, molecular mechanics Poisson-Boltzmann surface area, and quantum mechanics/molecular mechanism method was used to reveal the enzymatic depolymerization mechanism. By systematically analyzing the binding processes of nine oligomers (from a monomer to tetramer), we found that longer oligomers have relatively stronger binding energy. The degradation process involves two concerted elementary steps: triad-assisted nucleophilic attack and C-O bond cleavage. C-O bond cleavage is the rate determining step with an average barrier of 15.7 kcal mol-1, which is consistent with the experimentally determined kcat (1101 s-1, corresponds to 13.3 kcal mol-1). The electrostatic influence analysis of twenty amino acids highlights His231 and Asp237 as potential mutation targets for designing more efficient MGS0156 mutants. Title: Soluble epoxide hydrolase inhibitors improve angiogenic function of endothelial progenitor cells via ERK/p38-mediated miR-126 upregulation in myocardial infarction mice after exercise Gui Y, Chen J, Hu J, Liao C, Ouyang M, Deng L, Yang J, Xu D Ref: Experimental Cell Research, :112360, 2020 : PubMed ESTHER: Gui_2020_Exp.Cell.Res__112360 PubMedSearch: Gui 2020 Exp.Cell.Res 112360 PubMedID: 33188851 Abstract It is well established that exercise could protect against myocardial infarction (MI). Previously, we found that epoxyeicosatrienoic acids (EETs) could be induced by exercise and has been found to protect against MI via promoting angiogenic function of endothelial progenitor cells (EPCs). However, the underling mechanism of EETs in promoting EPC functions is unclear. C57BL/6 mice were fed with a novel soluble epoxide hydrolase inhibitor (sEHi), TPPU, to increase EET levels, for 1 week before undergoing MI surgery. Mice were then subjected to exercise training for 4 weeks. Bone marrow-derived EPCs were isolated and cultured in vitro. Exercise upregulated miR-126 expression but downregulated the protein levels of its target gene, Spred1, in EPCs from MI mice. TPPU further enhanced the effects of exercise on EPCs. Spred1 overexpression abolished the protective effects of TPPU on EPC functions. Downregulation of miR-126 by antagomiR-126 impaired the inhibitor effects of TPPU on Spred1 mRNA and protein expression. Additionally, TPPU upregulated miR-126 is partially mediated through ERK/p38 MAPK pathway. This study showed that sEHi promoted miR-126 expression, which might be related to the beneficial effect of sEHi on EPC functions in MI mice under exercise conditions, by increasing ERK and p38 MAPK phosphorylation and inhibiting Spred1. Title: Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study Li M, Chen Y, Zhang Y, Liu X, Xie T, Yin J, Wang L, Gang S, Chen J and Geng T <2 more author(s)> Li M, Chen Y, Zhang Y, Liu X, Xie T, Yin J, Wang L, Gang S, Chen J, Liu L, Yang F, Geng T (- 2) Ref: Aging Clin Exp Res, :, 2020 : PubMed ESTHER: Li_2020_Aging.Clin.Exp.Res__ PubMedSearch: Li 2020 Aging.Clin.Exp.Res PubMedID: 32067216 Abstract BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (>/= 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged >/= 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged >/= 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS. Title: Positive correlation between human exposure to organophosphate esters and gastrointestinal cancer in patients from Wuhan, China Li Y, Fu Y, Hu K, Zhang Y, Chen J, Zhang S, Zhang B, Liu Y Ref: Ecotoxicology & Environmental Safety, 196:110548, 2020 : PubMed ESTHER: Li_2020_Ecotoxicol.Environ.Saf_196_110548 PubMedSearch: Li 2020 Ecotoxicol.Environ.Saf 196 110548 PubMedID: 32278140 Abstract As kinds of endocrine disruptors, organophosphate esters (OPEs) pollution in the environment had received increasing attention recently. Food and water intake were two important exposure pathways for OPEs. However, the studies about the potential association between OPEs and gastrointestinal cancer were limited. This study investigated the possible association between OPEs and gastrointestinal cancer. All cancer patients were diagnosed with gastrointestinal cancer from a Grade 3 A hospital in Wuhan, China, while the control group was non-cancer healthy persons. The results showed that 6 OPEs were found in the control samples, while 8 in the samples from patients with gastrointestinal cancer. The detection frequencies of OPEs in gastrointestinal cancer patients were significantly higher than those in the control group (p < 0.05 or p < 0.01), except for triethyl phosphate (TEP) and tris (methylphenyl) phosphate (TMPP) in the gastric cancer group. The concentrations of OPEs in the control group were significantly lower than those in the gastric cancer group and colorectal cancer group (p < 0.01). In the control group and gastrointestinal cancer group, TEP was the dominant pollutant. Correlation analysis found that concentrations of TEP, tris(2-chloroisopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), TMPP, tris(2-ethylhexyl) phosphate (TEHP), and 2-ethylhexyl diphenyl phosphate (EHDPP) were associated with gastric cancer (p < 0.01), and concentrations of TEP, TCIPP, TPHP, TMPP and TEHP were associated with colorectal cancer (p < 0.01). A cluster analysis divided the 34 patients with gastric cancer and 40 patients with colorectal cancer in four groups. The results showed that the elderly male patients with gastric cancer were more sensitive to the exposure of EHDPP, while the TEP exposure was more sensitive to the relatively young gastrointestinal cancer patients. These findings indicated that OPEs might play a role in developing gastrointestinal cancer. Title: Antioxidative enzyme activities in the Rhodeinae sinensis Gunther and Macrobrachium nipponense and multi-endpoint assessment under tonalide exposure Li W, Wang S, Li J, Wang X, Cui L, Chen J, Liu Z Ref: Ecotoxicology & Environmental Safety, 199:110751, 2020 : PubMed ESTHER: Li_2020_Ecotoxicol.Environ.Saf_199_110751 PubMedSearch: Li 2020 Ecotoxicol.Environ.Saf 199 110751 PubMedID: 32446104 Abstract Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 mug/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 mug/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 mug/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 mug/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 mug/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 mug/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 mug/L and 0.000395 mug/L, respectively, which were significantly lower than the PNEC of 2.636 mug/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment. Title: Reduced insecticide sensitivity of the wheat aphid Sitobion miscanthi after infection by the secondary bacterial symbiont Hamiltonella defensa Li Q, Sun J, Qin Y, Fan J, Zhang Y, Tan X, Hou M, Chen J Ref: Pest Manag Sci, 77:1936, 2020 : PubMed ESTHER: Li_2020_Pest.Manag.Sci_77_1936 PubMedSearch: Li 2020 Pest.Manag.Sci 77 1936 PubMedID: 33300163 Abstract BACKGROUND: Bacterial symbionts in insects, especially aphids, have a major influence on host adaptation. The authors previously showed that infection with the secondary symbiont Hamiltonella defensa increases the fitness of the wheat aphid Sitobion miscanthi, yielding increases in fitness parameters such as adult weight and offspring number. However, whether H. defensa affects the sensitivity of host aphids to insecticides remains unknown. RESULTS: We tested the effects of H. defensa on host aphid susceptibility to the insecticides chlorpyrifos methyl, imidacloprid, cyantraniliprole and acetamiprid. Our results showed that compared with Hamiltonella-free aphid clones, Hamiltonella-infected aphid clones exhibited lower sensitivity to most of the tested insecticides at low concentrations. Quantitative PCR showed that the density of H. defensa in the infected clones was slightly decreased at 24 h but then sharply increased until the late stage after treatment with the different insecticides. H. defensa in the host aphids was detected by fluorescence in situ hybridization and was localized to the aphid hindgut. The levels of the detoxification enzymes acetylcholinesterase (AChE), glutathione transferase (GST) and carboxylesterase (CarE) were significantly higher in the Hamiltonella-infected clones than in the Hamiltonella-free clones. CONCLUSIONS: The findings indicated that infection with H. defensa reduced aphid sensitivity to the investigated insecticides at low concentrations, potentially by increasing detoxification enzyme activity in the host. Therefore, symbiont-mediated insecticide resistance should be taken into account when performing resistance-monitoring studies. Studies of symbiont-mediated insecticide resistance may enhance our understanding of the emergence of insecticide resistance in agricultural systems. This article is protected by copyright. All rights reserved. Title: [Predictive value of early detection of hs-cTnI and sST2 for secondary cardiac damage in severe acute organophosphorus pesticide poisoning] Liu XT, Wang L, Chen J, Qi HN, Ma GY Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 38:241, 2020 : PubMed ESTHER: Liu_2020_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_38_241 PubMedSearch: Liu 2020 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 38 241 PubMedID: 32447883 Abstract Objective: To investigate the value of high-sensitivity cardiac troponin I (hs-cTnI) and soluble suppression of tumorigenicity 2 (sST2) in predicting cardiac complications of severe acute organophosphorus pesticide poisoning (SAOPP) . Methods: All 274 SAOPP patients from September 2014 to February 2019 were selected. According to the results of hs-cTnI detection, the patients were divided into non-elevated troponin group (78 cases) and troponin elevation group (196 cases) at 1 hour after admission. 3 days after admission, there were 109 cases of complication and 165 cases of non-complication according to the presence or absence of cardiac complications. The changes of hs-cTnI, sST2, N-terminal B-type brain natriuretic peptide (NT proBNP) , acute physiology and chronic health (APACHE-) , cholinesterase activity, left ventricular ejection fraction (LVEF) , short axis shortening rate (FS) were observed and analyzed. The predictive value of hs-cTnI and sST2 were evaluated by receiver operating characteristic curve (ROC) analysis. Results: The sST2 level in patients with troponin elevation group was significantly higher than that in non-elevated troponin group (P<0.05) . Compared with the non-complication and non-elevated troponin group, the patients with non-complication and troponin elevation group had elevated hs-cTnI, sST2 and decreased cholinesterase (P<0.05) . Compared with other groups, the hs-cTnI, sST2, NT-proBNP, and APACHE- scores in the complication and troponin elevation group were significantly increased, and cholinesterase was significantly reduced (P<0.05) . In the non-complication group, LVEF and FS were in the normal range, and there was no significant difference between the groups (P>0.05) . Compared with other groups, the LVEF and FS of patients with elevated troponin in the complications group were significantly decreased (P<0.05) . Correlation analysis showed that hs-cTnI and sST2 were positively correlated in patients with SAOPP complications (r=0.725, P<0.01) . hs-cTnI, sST2 and APACHE- scores were positively correlated in the complications group (r=0.846, 0.885, P<0.01) . ROC results showed that the areas under the curve for predicting SAOPP secondary heart damage of hs-cTnI (1 hour after admission) and sST2 (3 days after admission) were 0.945 and 0.833, respectively. Conclusion: hs-cTnI and sST2 may have important clinical value in the early diagnosis and prognosis evaluation of patients with SAOPP secondary cardiac damage. Title: Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays Song YQ, Guan XQ, Weng ZM, Liu JL, Chen J, Wang L, Cui LT, Fang SQ, Hou J, Ge GB Ref: Food Funct, :, 2020 : PubMed ESTHER: Song_2020_Food.Funct__ PubMedSearch: Song 2020 Food.Funct PubMedID: 33291124 Abstract Human carboxylesterase 2 (hCES2A) is a key target to ameliorate the intestinal toxicity triggered by irinotecan that causes severe diarrhea in 50%-80% of patients receiving this anticancer agent. Herbal medicines are frequently used for the prevention and treatment of the intestinal toxicity of irinotecan, but it is very hard to find strong hCES2A inhibitors from herbal medicines in an efficient way. Herein, an integrated strategy via combination of chemical profiling, docking-based virtual screening and fluorescence-based high-throughput inhibitor screening assays was utilized. Following the screening of a total of 73 herbal products, licorice (the dried root of Glycyrrhiza species) was found with the most potent hCES2A inhibition activity. Further investigation revealed that the chalcones and several flavonols in licorice displayed strong hCES2A inhibition activities, while isoliquiritigenin, echinatin, naringenin, gancaonin I and glycycoumarin exhibited moderate inhibition of hCES2A. Inhibition kinetic analysis demonstrated that licochalcone A, licochalcone C, licochalcone D and isolicoflavonol potently inhibited hCES2A-mediated fluorescein diacetate hydrolysis in a reversible and mixed inhibition manner, with Ki values less than 1.0 M. Further investigations demonstrated that licochalcone C, the most potent hCES2A inhibitor identified from licorice, dose-dependently inhibited intracellular hCES2A in living HepG2 cells. In summary, this study proposed an integrated strategy to find hCES2A inhibitors from herbal medicines, and our findings suggested that the chalcones and isolicoflavonol in licorice were the key ingredients responsible for hCES2A inhibition, which would be very helpful to develop new herbal remedies or drugs for ameliorating hCES2A-associated drug toxicity. Title: Genome-Wide Identification, Evolution, and Expression of GDSL-Type Esterase/Lipase Gene Family in Soybean Su HG, Zhang XH, Wang TT, Wei WL, Wang YX, Chen J, Zhou YB, Chen M, Ma YZ and Min DH <1 more author(s)> Su HG, Zhang XH, Wang TT, Wei WL, Wang YX, Chen J, Zhou YB, Chen M, Ma YZ, Xu ZS, Min DH (- 1) Ref: Front Plant Sci, 11:726, 2020 : PubMed ESTHER: Su_2020_Front.Plant.Sci_11_726 PubMedSearch: Su 2020 Front.Plant.Sci 11 726 PubMedID: 32670311 Abstract GDSL-type esterase/lipase proteins (GELPs) belong to the SGNH hydrolase superfamily and contain a conserved GDSL motif at their N-terminus. GELPs are widely distributed in nature, from microbes to plants, and play crucial roles in growth and development, stress responses and pathogen defense. However, the identification and functional analysis of GELP genes are hardly explored in soybean. This study describes the identification of 194 GELP genes in the soybean genome and their phylogenetic classification into 11 subfamilies (A-K). GmGELP genes are disproportionally distributed on 20 soybean chromosomes. Large-scale WGD/segmental duplication events contribute greatly to the expansion of the soybean GDSL gene family. The Ka/Ks ratios of more than 70% of duplicated gene pairs ranged from 0.1-0.3, indicating that most GmGELP genes were under purifying selection pressure. Gene structure analysis indicate that more than 74% of GmGELP genes are interrupted by 4 introns and composed of 5 exons in their coding regions, and closer homologous genes in the phylogenetic tree often have similar exon-intron organization. Further statistics revealed that approximately 56% of subfamily K members contain more than 4 introns, and about 28% of subfamily I members consist of less than 4 introns. For this reason, the two subfamilies were used to simulate intron gain and loss events, respectively. Furthermore, a new model of intron position distribution was established in current study to explore whether the evolution of multi-gene families resulted from the diversity of gene structure. Finally, RNA-seq data were used to investigate the expression profiles of GmGELP gene under different tissues and multiple abiotic stress treatments. Subsequently, 7 stress-responsive GmGELP genes were selected to verify their expression levels by RT-qPCR, the results were consistent with RNA-seq data. Among 7 GmGELP genes, GmGELP28 was selected for further study owing to clear responses to drought, salt and ABA treatments. Transgenic Arabidopsis thaliana and soybean plants showed drought and salt tolerant phenotype. Overexpression of GmGELP28 resulted in the changes of several physiological indicators, which allowed plants to adapt adverse conditions. In all, GmGELP28 is a potential candidate gene for improving the salinity and drought tolerance of soybean. Title: Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J and Li F <3 more author(s)> Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J, Shi Z, Zhou Y, Du L, Li F (- 3) Ref: J Virol, 94:, 2020 : PubMed ESTHER: Wan_2020_J.Virol_94_ PubMedSearch: Wan 2020 J.Virol 94 PubMedID: 31826992 Abstract Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy. Title: Characterization of a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC: A representative of the new esterase family XIX Wang B, Wu S, Chang X, Chen J, Ma J, Wang P, Zhu G Ref: Pestic Biochem Physiol, 170:104704, 2020 : PubMed ESTHER: Wang_2020_Pestic.Biochem.Physiol_170_104704 PubMedSearch: Wang 2020 Pestic.Biochem.Physiol 170 104704 PubMedID: 32980065 Gene_locus related to this paper: 9acto-h1qtl0 Abstract Carboxylesterases have widely been used in a series of industrial applications, especially, the detoxification of pesticide residues. In the present study, EstC, a novel carboxylesterase from Streptomyces lividans TK24, was successfully heterogeneously expressed, purified and characterized. Phylogenetic analysis showed that EstC can be assigned as the first member of a novel family XIX. Multiple sequence alignment indicated that EstC has highly conserved structural features, including a catalytic triad formed by Ser155, Asp248 and His278, as well as a canonical Gly-His-Ser-Ala-Gly pentapeptide. Biochemical characterization indicated that EstC exhibited maximal activity at pH 9.0 (Tris-HCl buffer) and 55 degC. It also showed higher activity towards short-chain substrates, with the highest activity for p-nitrophenyl acetate (pNPA2) (K(m) = 0.31 +/- 0.02 mM, k(cat)/K(m) = 1923.35 +/- 9.62 s(-1) mM(-1)) compared to other pNP esters used in this experiment. Notably, EstC showed hyper-thermostability and good alkali stability. The activity of EstC had no significant changes when it was incubated under 55 degC for 100 h and reached half-life after incubation at 100 degC for 8 h. Beyond that, EstC also showed stability at pH ranging from 6.0 to 11.0 and about 90% residual activity still reserved after treatment at pH 8.0 or 9.0 for 26 h, especially. Furthermore, EstC had outstanding potential for bioremediation of chlorpyrifos-contaminated environment. The recombinant enzyme (0.5 U mL(-1)) could hydrolyze 79.89% chlorpyrifos (5 mg L(-1)) at 37 degC within 80 min. These properties will make EstC have a potential application value in various industrial productions and detoxification of chlorpyrifos residues. Title: Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK/HO-1 pathway Wu J, Zhao Y, Fan Z, Chen Q, Chen J, Sun Y, Jiang X, Xiao Q Ref: Biochemical & Biophysical Research Communications, :, 2020 : PubMed ESTHER: Wu_2020_Biochem.Biophys.Res.Commun__ PubMedSearch: Wu 2020 Biochem.Biophys.Res.Commun PubMedID: 32001002 Abstract Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation. Title: Effects of Malania oleifera Chun Oil on the Improvement of Learning and Memory Function in Mice Wu R, Zhong S, Ni M, Zhu X, Chen Y, Chen X, Zhang L, Chen J Ref: Evid Based Complement Alternat Med, 2020:8617143, 2020 : PubMed ESTHER: Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143 PubMedSearch: Wu 2020 Evid.Based.Complement.Alternat.Med 2020 8617143 PubMedID: 33014116 Abstract BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products. Title: Screening acetylcholinesterase inhibitors from traditional Chinese medicines by paper-immobilized enzyme combined with capillary electrophoresis analysis Zhao HH, Liu YQ, Chen J Ref: J Pharm Biomed Anal, 190:113547, 2020 : PubMed ESTHER: Zhao_2020_J.Pharm.Biomed.Anal_190_113547 PubMedSearch: Zhao 2020 J.Pharm.Biomed.Anal 190 113547 PubMedID: 32866747 Abstract Discovering acetylcholinesterase (AChE) inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease. In this work, a simple strategy was developed for screening AChE inhibitors from traditional Chinese medicines (TCMs) by capillary electrophoresis (CE) analysis combined with enzymatic assay, in which immobilized AChE was employed. For AChE immobilization, cellulose filter paper (CFP) was used as the carrier material and physically coated with chitosan owing to moderate viscosity of chitosan to be introduced into amino groups, and then AChE was covalently bonded to the amino-functionalized CFP through a Schiff base reaction using glutaraldehyde (GA) as a cross-linking agent. The CFP-immobilized AChE exhibited enhanced endurance to pH and temperature, improved storage stability, excellent repeatability and reusability. More remarkably, CFP-immobilized AChE can be instantly separated from enzyme reaction mixture thus greatly simplifying the operational process. For immobilized AChE, the Michaelis-Menten constant, inhibition constant and IC(50) were determined using huperzine A as a model inhibitor. Finally, CFP-immobilized AChE was applied to inhibitor screening from 17 TCMs, among which Chebulae Fructus (ripe fruits of Terminalia chebula) exhibited the strongest inhibitory effect on AChE. The positive results indicated that such a screening strategy may open up a new avenue to discover active components from TCMs. Title: Degradation mechanism for Zearalenone ring-cleavage by Zearalenone hydrolase RmZHD: A QM/MM study Zhou J, Zhu L, Chen J, Wang W, Zhang R, Li Y, Zhang Q Ref: Sci Total Environ, 709:135897, 2020 : PubMed ESTHER: Zhou_2020_Sci.Total.Environ_709_135897 PubMedSearch: Zhou 2020 Sci.Total.Environ 709 135897 PubMedID: 31887512 Gene_locus related to this paper: 9euro-a0a0d2ilk1 Abstract The danger of zearalenone (ZEN) as an endocrine disruptor to humans and the environment has aroused increasing attention. In this study, we implemented the quantum mechanics/molecular mechanics (QM/MM) method to investigate the degradation mechanism of ZEN hydrolase (RmZHD) toward ZEN at the atomic level. The degradation process involves two concerted reaction pathways, where the active site contains a Ser-His-Glu triplet as a proton donor. With the Boltzmann-weighted average potential barriers of 18.1 and 21.5 kcal/mol, the process undergoes proton transfer and nucleophilic-substituted ring opening to form a hydroxyl product. Non-covalent interaction analyses elucidated hydrogen bonding between key amino acids with ZEN. The electrostatic influence analysis of 16 amino acids proposes residues Asp34 and His128 as the possible mutation target for future mutation design of enzyme RmZHD. An in-depth investigation of the protein environment of RmZHD can improve the bioremediation efficiency of endocrine disrupting chemicals. Title: Ester-Producing Mechanism of Ethanol O-acyltransferase EHT1 Gene in Pichia pastoris from Shanxi Aged Vinegar Chen J, Nan R, Wang R, Zhang L, Shi J Ref: Biomed Res Int, 2019:4862647, 2019 : PubMed ESTHER: Chen_2019_Biomed.Res.Int_2019_4862647 PubMedSearch: Chen 2019 Biomed.Res.Int 2019 4862647 PubMedID: 30719444 Gene_locus related to this paper: kompc-f2qms6 Abstract The ethanol O-acyltransferase EHT1 is an important element of key signaling pathways and is widely expressed in yeast strains. In this study, we investigated the expression of EHT1 in the overexpression lines or knockout system of Pichia pastoris using qRT-PCR and western blotting. The amount of total protein was determined using the Bradford method; the esterase activity was determined using p-nitrophenyl acetate as a substrate, and the production of volatile fatty acids in wild-type, knockout, and over-expression systems was detected using SPME GC-MS. The esterase activity of EHT1-knockout P. pastoris was significantly lower than that in wild type (P<0.01), and the activities of esterase in three EHT1-overexpressing strains-OE-1, OE-2, and OE-3-were significantly higher than those in wild type (P<0.01). In the EHT1-knockout strain products, the contents of nine volatile fatty acids were significantly lower than those in wild type (P<0.01), and the relative percentages of three fatty acids, methyl nonanoate, methyl decanoate, and ethyl caprate, were significantly lower than those in the other six species in the wild-type and knockout groups (P<0.05). The nine volatile fatty acids in the fermentation products of the overexpressed EHT1 gene were significantly higher than those in the wild-type group (P<0.01). The relative percentages of the three fatty acid esters, methyl nonanoate, methyl caprate, and ethyl caprate, were significantly higher than those in the other six species (P<0.05). EHT1 plays an important regulatory role in esterase activity and the production of medium-chain volatile fatty acids. Title: Different durations of cognitive stimulation therapy for Alzheimer's disease: a systematic review and meta-analysis Chen J, Duan Y, Li H, Lu L, Liu J, Tang C Ref: Clin Interv Aging, 14:1243, 2019 : PubMed ESTHER: Chen_2019_Clin.Interv.Aging_14_1243 PubMedSearch: Chen 2019 Clin.Interv.Aging 14 1243 PubMedID: 31371930 Abstract Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of cognitive stimulation therapy (CST) of different durations for Alzheimer's disease (AD). Methods: A comprehensive search was carried out in three databases. The primary outcome was Mini-Mental State Examination (MMSE) score. We conducted a meta-analysis with Review Manager, version 5.3 and assessed the methodological quality of the included studies using the Cochrane Collaboration Recommendations assessment tool. Results: Treatment effects from the meta-analysis showed that CST plus acetylcholinesterase inhibitors (ChEIs) was better than the control assessed by MMSE. In addition, the meta-analysis indicated that long-term CST was better than short-term or maintenance CST. Conclusion: Our study confirmed that the combination of CST and drug treatment for AD is effective in AD, regardless of whether short-term CST, maintenance CST, or long-term CST is used. The long-term CST appears to be more effective. Title: Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a Tail Switching Strategy on a Piperazinyl Azetidine Skeleton Chen Z, Mori W, Deng X, Cheng R, Ogasawara D, Zhang G, Schafroth MA, Dahl K, Fu H and Liang SH <24 more author(s)> Chen Z, Mori W, Deng X, Cheng R, Ogasawara D, Zhang G, Schafroth MA, Dahl K, Fu H, Hatori A, Shao T, Zhang Y, Yamasaki T, Zhang X, Rong J, Yu Q, Hu K, Fujinaga M, Xie L, Kumata K, Gou Y, Chen J, Gu S, Bao L, Wang L, Collier TL, Vasdev N, Shao Y, Ma JA, Cravatt BF, Fowler C, Josephson L, Zhang MR, Liang SH (- 24) Ref: Journal of Medicinal Chemistry, 62:3336, 2019 : PubMed ESTHER: Chen_2019_J.Med.Chem_62_3336 PubMedSearch: Chen 2019 J.Med.Chem 62 3336 PubMedID: 30829483 Gene_locus related to this paper: human-MGLL Abstract Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with (11)C or (18)F. [(11)C]8 ([(11)C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [(11)C]17 ([(11)C]PAD) and [(18)F]37 ([(18)F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms. Title: Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin Fu F, Chen J, Zhao P, Lu X, Gao R, Chen D, Liu H, Wang H, Pei C Ref: Toxicology, 430:152346, 2019 : PubMed ESTHER: Fu_2019_Toxicology_430_152346 PubMedSearch: Fu 2019 Toxicology 430 152346 PubMedID: 31857189 Abstract V-type agents are highly toxic organophosphorus nerve agents that inhibit acetylcholinesterase in the nervous system, causing a series of poison symptoms. Trace analytical methods are essential for the specific verification of exposure to these agents, especially for human exposure. This paper investigates the phosphonylated and disulfide adducts between human ceruloplasmin and O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2-(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). After being digested by trypsin, the mixture of peptides was separated by a nano-liquid chromatography (nano-LC) and analyzed using quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS). The sensitive LC-MS/MS-assisted proteomics approach was developed to achieve the identification of human exposure to V-type agents based on these modified sites; results revealed that potential biomarkers could be derived from adducts based on the sulfur- and phosphorus-containing groups of V-type agents. This work offered a novel insight into the mechanism of disulfide-containing adducts resulting from the replacement of disulfide bridges by the thiolate groups from the V-type agents. Moreover, four disulfide adducts on human ceruloplasmin were also discovered during this research, specifically confirming exposure to the V-type agents. Furthermore, molecular simulation testified to the reactivity of the modified sites. Collectively, our findings suggest that the eleven binding sites on human ceruloplasmin have the potential use as a selective marker for prediction the V-type agent exposure in humans. Title: Nox4 and soluble epoxide hydrolase synergistically mediate homocysteine-induced inflammation in vascular smooth muscle cells Liu X, Qin Z, Liu C, Song M, Luo X, Zhao H, Qian D, Chen J, Huang L Ref: Vascul Pharmacol, 120:106544, 2019 : PubMed ESTHER: Liu_2019_Vascul.Pharmacol_120_106544 PubMedSearch: Liu 2019 Vascul.Pharmacol 120 106544 PubMedID: 30610956 Abstract BACKGROUND: Hyperhomocysteinemia leads to a vascular smooth muscle cell (VSMC) inflammatory response. Meanwhile, Nox4 dependent reactive oxygen species (ROS) signaling and soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids (EETs) are both involved in vascular inflammation. Herein, we hypothesized that Nox4 and soluble epoxide hydrolase cross regulated during homocysteine-induced VSMC inflammation. METHODS AND RESULTS: In cultured VSMCs, the expression of the inflammatory factors VCAM1 and ICAM1 was measured by real-time PCR and Western blotting, while supernatant MCP1 was measured by ELISA. Upon VSMC stimulation with 50 muMu homocysteine, we observed the VCAM1 and ICAM1 mRNA levels were increased by 1.15 and 1.0 folds, respectively. The MCP1 levels in the supernatant of cultured VSMCs treated with 100 muMu increased to 1.76 folds. As expected, homocysteine induced Nox4 expression and Nox4-dependent ROS generation. The sEH expression was also upregulated in the presence of homocysteine in a dose-dependent manner. Furthermore, we knocked down Nox4 with siRNA. Knockdown of Nox4 decreased ROS generation and homocysteine-induced sEH expression. Overexpression of Nox4 with an adenovirus stimulated sEH expression. Similarly, knockdown or chemical inhibition of sEH blunted the upregulation of Nox4 by homocysteine. In vivo, in homocysteine-fed mice, concomitant upregulation of Nox4 and sEH was associated with increased VCAM1 and ICAM1 expression in the aortic wall. CONCLUSIONS: The inflammatory response induced by homocysteine in VSMCs was accompanied by Nox4 and sEH upregulation. Nox4 and soluble epoxide hydrolase synergistically contribute to homocysteine-induced inflammation. Title: Structural and functional analyses of the lipase CinB from Enterobacter asburiae Shang F, Lan J, Liu W, Chen Y, Wang L, Zhao J, Chen J, Gao P, Ha NC and Xu Y <2 more author(s)> Shang F, Lan J, Liu W, Chen Y, Wang L, Zhao J, Chen J, Gao P, Ha NC, Quan C, Nam KH, Xu Y (- 2) Ref: Biochemical & Biophysical Research Communications, 519:274, 2019 : PubMed ESTHER: Shang_2019_Biochem.Biophys.Res.Commun_519_274 PubMedSearch: Shang 2019 Biochem.Biophys.Res.Commun 519 274 PubMedID: 31493870 Gene_locus related to this paper: entas-cinB Abstract Lipases are widely present in various plants, animals and microorganisms, constituting a large category of enzymes. They have the ability to catalyze the cleavage of ester bonds. The lipase CinB from Enterobacter asburiae (E. asburiae) is an acetyl esterase. The primary amino acid sequence suggests that the EaCinB protein belongs to the alpha/beta-hydrolase (ABH) superfamily of the esterase/lipase superfamily. However, its molecular functions have not yet been determined. Here, we report the crystal structure of E. asburiae CinB at a 1.45A resolution. EaCinB contains a signal peptide, cap domain and catalytic domain. The active site of EaCinB contains the catalytic triad (Ser180-His307-Asp277) on the catalytic domain. The oxyanion hole is composed of Gly106 and Gly107 within the conserved sequence motif HGGG (amino acid residues 106-109). The substrate is accessible between the alpha1 and alpha2 helices or the alpha1 helix and catalytic domain. Narrow substrate pockets are formed by the alpha2 helix of the cap domain. Site-directed mutagenesis showed that EaCinB-W208H exhibits a higher catalytic ability than EaCinB-WT by approximately nine times. Our results provide insight into the molecular function of EaCinB. Title: Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis Shang S, Ji X, Zhang L, Chen J, Li C, Shi R, Xiang W, Kang X, Zhang D and Miao H <6 more author(s)> Shang S, Ji X, Zhang L, Chen J, Li C, Shi R, Xiang W, Kang X, Zhang D, Yang F, Dai R, Chen P, Chen S, Chen Y, Li Y, Miao H (- 6) Ref: Cancer Research, 79:5513, 2019 : PubMed ESTHER: Shang_2019_Cancer.Res_79_5513 PubMedSearch: Shang 2019 Cancer.Res 79 5513 PubMedID: 31439546 Gene_locus related to this paper: human-ABHD5 Abstract Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg. Title: Discovery of a highly specific and efficacious inhibitor of human carboxylesterase 2 by large-scale screening Song YQ, Guan XQ, Weng ZM, Wang YQ, Chen J, Jin Q, Fang SQ, Fan B, Cao YF and Ge GB <1 more author(s)> Song YQ, Guan XQ, Weng ZM, Wang YQ, Chen J, Jin Q, Fang SQ, Fan B, Cao YF, Hou J, Ge GB (- 1) Ref: Int J Biol Macromol, 137:261, 2019 : PubMed ESTHER: Song_2019_Int.J.Biol.Macromol_137_261 PubMedSearch: Song 2019 Int.J.Biol.Macromol 137 261 PubMedID: 31260759 Abstract Human carboxylesterase 2 (CES2A), one of the most abundant hydrolases distributed in human small intestine and colon, play key roles in the hydrolysis of a wide range of prodrugs and other esters. Recent studies have demonstrated that CES2A inhibitors may ameliorate irinotecan-induced severe diarrhea, but the specific and efficacious inhibitors targeting intracellular CES2A are rarely reported. Herein, a large-scale screening campaign was conducted for discovery of potent and specific CES2A inhibitor(s). Following screening of more than one hundred of natural products, glabridin (a bioactive compound of Glycyrrhiza glabra L.) was found displaying potent inhibition on CES2A and high specificity over CES1A (>500-fold) and other serine hydrolases. Further investigation showed that glabridin was cell permeable and low cytotoxic, as well as capable of inhibiting intracellular CES2A in living cells, with the IC50 value of 0.52muM. Molecular dynamics simulations showed that glabridin formed strong and stable interactions with both the catalytic cavity and Z site of CES2A via hydrophobic interactions. In summary, glabridin was a potent and specific inhibitor targeting intracellular CES2A, which could be used as an ideal lead compound to develop more efficacious CES2A inhibitors for modulating the pharmacokinetic behaviors of CES2A-substrate drugs and alleviating irinotecan-induced diarrhea. Title: Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats Wang K, Chen Q, Wu N, Li Y, Zhang R, Wang J, Gong D, Zou X, Liu C, Chen J Ref: Front Pharmacol, 10:1003, 2019 : PubMed ESTHER: Wang_2019_Front.Pharmacol_10_1003 PubMedSearch: Wang 2019 Front.Pharmacol 10 1003 PubMedID: 31551793 Inhibitor(s) related to this paper: Berberine Abstract Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and beta-Amyloid (Abeta) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Abeta formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Abeta deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats. Title: Synergistic effect of acetyl xylan esterase from Talaromyces leycettanus JCM12802 and xylanase from Neocallimastix patriciarum achieved by introducing carbohydrate-binding module-1 Zhang Y, Yang H, Yu X, Kong H, Chen J, Luo H, Bai Y, Yao B Ref: AMB Express, 9:13, 2019 : PubMed ESTHER: Zhang_2019_AMB.Express_9_13 PubMedSearch: Zhang 2019 AMB.Express 9 13 PubMedID: 30694400 Gene_locus related to this paper: 9euro-a0a411dz87 Abstract Wheat bran is an effective raw material for preparation xylooligosaccharides; however, current research mainly focuses on alkali extraction and enzymatic hydrolysis methods. Since ester bonds are destroyed during the alkali extraction process, xylanase and arabinofuranosidase are mainly used to hydrolyze xylooligosaccharides. However, alkali extraction costs are very high, and the method also causes pollution. Therefore, this study focuses on elucidating a method to efficiently and directly degrade destarched wheat bran. First, an acidic acetyl xylan esterase (AXE) containing a carbohydrate-binding module-1 (CBM1) domain was cloned from Talaromyces leycettanus JCM12802 and successfully expressed in Pichia pastoris. Characterization showed that the full-length acetyl xylan esterase AXE + CBM1 was similar toe uncovered AXE with an optimum temperature and pH of 55 degrees C and 6.5, respectively. Testing the acetyl xylan esterase and xylanase derived from Neocallimastix patriciarum in a starch-free wheat bran cooperative experiment revealed that AXE + CBM1 and AXE produced 29% and 16% reducing sugars respectively, compared to when only NPXYN11 was used. In addition, introduced the CBM1 domain into NPXYN11, and the results indicated that the CBM1 domain showed little effect on NPXYN11 properties. Finally, the systematically synergistic effects between acetyl xylan esterase and xylanase with/without the CBM1 domain demonstrated that the combined ratio of AXE + CBM1 coming in first and NPXYN11 + CBM1 s increased reducing sugars by almost 35% with AXE and NPXYN11. Furthermore, each component's proportion remained the same with respect to xylooligosaccharides, with the largest proportion (86%) containing of 49% xylobiose and 37% xylotriose. Title: Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease Chen Y, Zhu J, Mo J, Yang H, Jiang X, Lin H, Gu K, Pei Y, Wu L and Sun H <5 more author(s)> Chen Y, Zhu J, Mo J, Yang H, Jiang X, Lin H, Gu K, Pei Y, Wu L, Tan R, Hou J, Chen J, Lv Y, Bian Y, Sun H (- 5) Ref: J Enzyme Inhib Med Chem, 33:290, 2018 : PubMed ESTHER: Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290 PubMedSearch: Chen 2018 J.Enzyme.Inhib.Med.Chem 33 290 PubMedID: 29278947 Abstract Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid beta-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50 = 10.2 +/- 1.2, 16.5 +/- 1.7, and 15.3 +/- 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD. Title: Psychosocial interventions for Alzheimer's disease cognitive symptoms: a Bayesian network meta-analysis Duan Y, Lu L, Chen J, Wu C, Liang J, Zheng Y, Wu J, Rong P, Tang C Ref: BMC Geriatr, 18:175, 2018 : PubMed ESTHER: Duan_2018_BMC.Geriatr_18_175 PubMedSearch: Duan 2018 BMC.Geriatr 18 175 PubMedID: 30086714 Abstract BACKGROUND: Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. CONCLUSION: Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice. Title: Deciphering the Role of Lipid Droplets in Cardiovascular Disease: A Report From the 2017 National Heart, Lung, and Blood Institute Workshop Goldberg IJ, Reue K, Abumrad NA, Bickel PE, Cohen S, Fisher EA, Galis ZS, Granneman JG, Lewandowski ED and Chen J <6 more author(s)> Goldberg IJ, Reue K, Abumrad NA, Bickel PE, Cohen S, Fisher EA, Galis ZS, Granneman JG, Lewandowski ED, Murphy R, Olive M, Schaffer JE, Schwartz-Longacre L, Shulman GI, Walther TC, Chen J (- 6) Ref: Circulation, 138:305, 2018 : PubMed ESTHER: Goldberg_2018_Circulation_138_305 PubMedSearch: Goldberg 2018 Circulation 138 305 PubMedID: 30012703 Abstract Lipid droplets (LDs) are distinct and dynamic organelles that affect the health of cells and organs. Much progress has been made in understanding how these structures are formed, how they interact with other cellular organelles, how they are used for storage of triacylglycerol in adipose tissue, and how they regulate lipolysis. Our understanding of the biology of LDs in the heart and vascular tissue is relatively primitive in comparison with LDs in adipose tissue and liver. The National Heart, Lung, and Blood Institute convened a working group to discuss how LDs affect cardiovascular diseases. The goal of the working group was to examine the current state of knowledge on the cell biology of LDs, including current methods to study them in cells and organs and reflect on how LDs influence the development and progression of cardiovascular diseases. This review summarizes the working group discussion and recommendations on research areas ripe for future investigation that will likely improve our understanding of atherosclerosis and heart function. Title: Soluble epoxide hydrolase inhibitors, t-AUCB, downregulated miR-133 in a mouse model of myocardial infarction Gui Y, Li D, Chen J, Wang Y, Hu J, Liao C, Deng L, Xiang Q, Yang T and Xu D <2 more author(s)> Gui Y, Li D, Chen J, Wang Y, Hu J, Liao C, Deng L, Xiang Q, Yang T, Du X, Zhang S, Xu D (- 2) Ref: Lipids Health Dis, 17:129, 2018 : PubMed ESTHER: Gui_2018_Lipids.Health.Dis_17_129 PubMedSearch: Gui 2018 Lipids.Health.Dis 17 129 PubMedID: 29843720 Inhibitor(s) related to this paper: t-AUCB Abstract BACKGROUND: It has been demonstrated that soluble epoxide hydrolase inhibitors (sEHIs) are protective against ischemia-induced lethal arrhythmias, but the mechanisms involved are unknown. Previously, we showed that sEHIs might reduce the incidence of ischemic arrhythmias by suppressing microRNA-1 (miR-1) in the myocardium. As miR-1 and miR-133 have the same proarrhythmic effects in the heart, we assumed that the beneficial effects of sEHIs might also relate to the regulation of miR-133. METHODS: A mouse model of myocardial infarction (MI) was established by ligating the coronary artery. The sEHI t-AUCB (trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) was administered daily for 7 days before MI. Myocardial infarct size and cardiac function was assessed at 24 h post-MI. The miRNA expression profiles of sham and MI mice treated with or without t-AUCB were determined by microarray and verified by real-time PCR. The incidence of arrhythmias was assessed by in vivo electrophysiologic studies. The mRNA levels of miR-133, its target genes (KCNQ1 [potassium voltage-gated channel subfamily Q member 1] and KCNH2 [potassium voltage-gated channel subfamily H member 2]), and serum response factor (SRF) were measured by real-time PCR; KCNQ1, KCNH2, and SRF protein levels were assessed by western blotting. RESULTS: We demonstrated that the treatment with sEHIs could reduce infarct size, improve cardia function, and prevent the development of cardiac arrhythmias in MI mice. The expression levels of 14 miRNAs differed between the sham and MI groups. t-AUCB treatment altered the expression of eight miRNAs: two were upregulated and six were downregulated. Of these, the muscle-specific miR-133 was downregulated in the ischemic myocardium. In line with this, up-regulation of miR-133 and down-regulation of KCNQ1 and KCNH2 mRNA/protein were observed in ischemic myocaridum, whereas administration of sEHIs produced an opposite effect. In addition, miR-133 overexpression inhibited expression of the target mRNA, whereas t-AUCB reversed the effects. Furthermore, SRF might participate in the negative regulation of miR-133 by t-AUCB. CONCLUSIONS: In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias. Title: Perfluorododecanoic acid exposure induced developmental neurotoxicity in zebrafish embryos Guo X, Zhang S, Lu S, Zheng B, Xie P, Chen J, Li G, Liu C, Wu Q and Sang N <1 more author(s)> Guo X, Zhang S, Lu S, Zheng B, Xie P, Chen J, Li G, Liu C, Wu Q, Cheng H, Sang N (- 1) Ref: Environ Pollut, 241:1018, 2018 : PubMed ESTHER: Guo_2018_Environ.Pollut_241_1018 PubMedSearch: Guo 2018 Environ.Pollut 241 1018 PubMedID: 30029309 Abstract Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6mg/L PFDoA for 120h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system. Title: Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester Hui A, Yin H, Zhang Z, Zhou A, Chen J, Yang L, Wu Z, Zhang W Ref: Drug Deliv Transl Res, 8:787, 2018 : PubMed ESTHER: Hui_2018_Drug.Deliv.Transl.Res_8_787 PubMedSearch: Hui 2018 Drug.Deliv.Transl.Res 8 787 PubMedID: 29524164 Abstract Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders. Title: Food up-take and reproduction performance of Daphnia magna under the exposure of Bisphenols Liu Y, Yan Z, Zhang L, Deng Z, Yuan J, Zhang S, Chen J, Guo R Ref: Ecotoxicology & Environmental Safety, 170:47, 2018 : PubMed ESTHER: Liu_2018_Ecotoxicol.Environ.Saf_170_47 PubMedSearch: Liu 2018 Ecotoxicol.Environ.Saf 170 47 PubMedID: 30522006 Abstract Because the application of Bisphenol A (BPA) was restricted, many substitutes, such as Bisphenol F (BPF) and Bisphenol S (BPS), were developed as BPA substitutes. Therefore, environmental impacts of BPA and its substitutes on aquatic organisms should be concerned, especially their combined toxicity. In this study, the impacts of BPA, BPF, BPS and their mixture on the feeding behavior, reproduction and physiological function of daphnids were synthetically evaluated, involving the duration and mode of exposure. In short-term exposure tests, feeding rates of D. magna decreased after exposure to BPA, BPF, BPS and their mixture, while the inhibition reversed into stimulation in the recovery period. It may benefit from overcompensation of D. magna. In long-term exposure tests, the inhibition effect on the reproduction and growth of the exposed D. magna was difficult to recover, and only some experimental groups have a certain recovery. In conclusion, environmental risk of BPA, BPF, BPS and their mixture on the behavior of D. magna increased with prolonged exposure time. Moreover, relative activities of trypsin, amylase (AMS), acetylcholinesterase (AChE), carbonic anhydrase (CA), glutathione peroxidase (GPx) and super oxidase dimutase (SOD) of the exposed daphnids decreased in most treatment groups, indicating the disorder of digestive, nervous and antioxidative system of D. magna. Interestingly, inhibition of enzymes activities decreased with the increase of the exposure time, which implied the tolerance may be occurred. Title: Glioblastoma recurrence correlates with NLGN3 levels Liu R, Qin XP, Zhuang Y, Zhang Y, Liao HB, Tang JC, Pan MX, Zeng FF, Lei Y and Wan Q <9 more author(s)> Liu R, Qin XP, Zhuang Y, Zhang Y, Liao HB, Tang JC, Pan MX, Zeng FF, Lei Y, Lei RX, Wang S, Liu AC, Chen J, Zhang ZF, Zhao D, Wu SL, Liu RZ, Wang ZF, Wan Q (- 9) Ref: Cancer Med, 7:2848, 2018 : PubMed ESTHER: Liu_2018_Cancer.Med_7_2848 PubMedSearch: Liu 2018 Cancer.Med 7 2848 PubMedID: 29777576 Abstract Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum. Title: Pezizomycetes genomes reveal the molecular basis of ectomycorrhizal truffle lifestyle Murat C, Payen T, Noel B, Kuo A, Morin E, Chen J, Kohler A, Krizsan K, Balestrini R and Martin FM <40 more author(s)> Murat C, Payen T, Noel B, Kuo A, Morin E, Chen J, Kohler A, Krizsan K, Balestrini R, Da Silva C, Montanini B, Hainaut M, Levati E, Barry KW, Belfiori B, Cichocki N, Clum A, Dockter RB, Fauchery L, Guy J, Iotti M, Le Tacon F, Lindquist EA, Lipzen A, Malagnac F, Mello A, Molinier V, Miyauchi S, Poulain J, Riccioni C, Rubini A, Sitrit Y, Splivallo R, Traeger S, Wang M, Zifcakova L, Wipf D, Zambonelli A, Paolocci F, Nowrousian M, Ottonello S, Baldrian P, Spatafora JW, Henrissat B, Nagy LG, Aury JM, Wincker P, Grigoriev IV, Bonfante P, Martin FM (- 40) Ref: Nat Ecol Evol, 2:1956, 2018 : PubMed ESTHER: Murat_2018_Nat.Ecol.Evol_2_1956 PubMedSearch: Murat 2018 Nat.Ecol.Evol 2 1956 PubMedID: 30420746 Gene_locus related to this paper: 9pezi-a0a3n4l4q5, 9pezi-a0a3n4lpg7 Abstract Tuberaceae is one of the most diverse lineages of symbiotic truffle-forming fungi. To understand the molecular underpinning of the ectomycorrhizal truffle lifestyle, we compared the genomes of Piedmont white truffle (Tuber magnatum), Perigord black truffle (Tuber melanosporum), Burgundy truffle (Tuber aestivum), pig truffle (Choiromyces venosus) and desert truffle (Terfezia boudieri) to saprotrophic Pezizomycetes. Reconstructed gene duplication/loss histories along a time-calibrated phylogeny of Ascomycetes revealed that Tuberaceae-specific traits may be related to a higher gene diversification rate. Genomic features in Tuber species appear to be very similar, with high transposon content, few genes coding lignocellulose-degrading enzymes, a substantial set of lineage-specific fruiting-body-upregulated genes and high expression of genes involved in volatile organic compound metabolism. Developmental and metabolic pathways expressed in ectomycorrhizae and fruiting bodies of T. magnatum and T. melanosporum are unexpectedly very similar, owing to the fact that they diverged ~100 Ma. Volatile organic compounds from pungent truffle odours are not the products of Tuber-specific gene innovations, but rely on the differential expression of an existing gene repertoire. These genomic resources will help to address fundamental questions in the evolution of the truffle lifestyle and the ecology of fungi that have been praised as food delicacies for centuries. Title: Bushen recipe and its disassembled prescriptions inhibit inflammation of liver injury associated with Concanavalin A through Tolllike receptor 3/9 signaling pathway Nie H, Mei Z, Wang R, Zhao B, Gao Y, Chen J, Wang L Ref: Mol Med Rep, 18:1682, 2018 : PubMed ESTHER: Nie_2018_Mol.Med.Rep_18_1682 PubMedSearch: Nie 2018 Mol.Med.Rep 18 1682 PubMedID: 29845244 Abstract The aim of the present study was to explore the effect of Bushen recipe and its disassembled prescriptions on liver injury and chronic hepatitis B. Liver injury was induced in normal and hepatitis B virus (HBV)transgenic mice through injection of Concanavalin A, followed by treatment with Bushen recipe and its disassembled prescriptions including the Bushenyang, the Bushenyin and the QingHua groups as well as the GanYanLing group (positive control). Subsequently, their liver function indexes were investigated by a microplate method and liver sections were blindly evaluated using an optical microscope by a pathologist. Subsequently, the activation state of Tolllike receptor (TLR)3/9 signaling pathway in liver tissues was analyzed by western blotting. Additionally, the inflammatory factors produced following liver injury in peripheral blood were detected via ELISA. Following intervention with the Bushen recipe and its disassembled prescriptions, the liver function indexe alanine aminotransferase had declined, whereas cholinesterase increased. The pathological alterations of liver tissue in HBV transgenic mice were reversed by Bushen recipe and its disassembled prescriptions. In addition, the TLR3/9 signaling pathway in liver tissues of HBV transgenic mice was inhibited and inflammatory factors such as interleukin (IL)6, IL1, tumor necrosis factoralpha and interferongamma were reduced significantly. In conclusion, the present study demonstrated that Bushen recipe and its disassembled prescriptions repaired liver injury induced by Concanavalin A through inhibition of TLR3/9 signaling pathway. Title: Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes Sun S, Zhou Y, Chen J, Shi J, Zhao H, Song W, Zhang M, Cui Y, Dong X and Lai J <16 more author(s)> Sun S, Zhou Y, Chen J, Shi J, Zhao H, Song W, Zhang M, Cui Y, Dong X, Liu H, Ma X, Jiao Y, Wang B, Wei X, Stein JC, Glaubitz JC, Lu F, Yu G, Liang C, Fengler K, Li B, Rafalski A, Schnable PS, Ware DH, Buckler ES, Lai J (- 16) Ref: Nat Genet, 50:1289, 2018 : PubMed ESTHER: Sun_2018_Nat.Genet_50_1289 PubMedSearch: Sun 2018 Nat.Genet 50 1289 PubMedID: 30061735 Gene_locus related to this paper: maize-a0a1d6kqc9, maize-k7v3i9, maize-b6u9v9, maize-a0a3l6e780, maize-b4fv80, maize-a0a3l6d913 Abstract Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution. Title: Clinical diagnostic significance of prealbumin, cholinesterase and retinol binding protein in liver cirrhosis combined with encephalopathy Tan L, Meng Y, Zeng T, Wang Q, Long T, Wu S, Guan X, Fu H, Zheng W and Cao L <5 more author(s)> Tan L, Meng Y, Zeng T, Wang Q, Long T, Wu S, Guan X, Fu H, Zheng W, Tian Y, Chen J, Yu J, Wu Y, Li H, Cao L (- 5) Ref: Br J Biomed Sci, :1, 2018 : PubMed ESTHER: Tan_2018_Br.J.Biomed.Sci__1 PubMedSearch: Tan 2018 Br.J.Biomed.Sci 1 PubMedID: 30392460 Abstract OBJECTIVE: Hepatic encephalopathy is a common consequence of liver cirrhosis, but diagnosis can be difficult as it is based on clinical criteria alone. We hypothesised that serum prealbumin, cholinesterase and retinol binding protein (RBP) can help support the diagnosis of hepatic encephalopathy. METHODS: We enrolled 306 cirrhotic patients (110 with encephalopathy), 100 chronic hepatitis B patients and 50 healthy controls, measuring routine liver function tests (ALT, AST, GGT, ALP, and bilirubin), albumin, prothrombin time, prealbumin, cholinesterase and RBP by routine methods. Logistic regression analysis and areas under the receiver operating characteristic curves (AUCs) were used to find predictive factors for hepatic encephalopathy. RESULTS: There were differences in all laboratory indices between the three groups (all p < 0.001). In univariate analysis, albumin, prothrombin time, prealbumin, cholinesterase and RBP were significantly altered in those with encephalopathy (p < 0.01), but only prealbumin, cholinesterase and RBP levels were significant predictors in multivariate analysis, and each was linked to the severity of liver fibrosis defined by the Child-Pugh score (all p < 0.001). The AUCs (95% CI) of prealbumin, cholinesterase and RBP for diagnosing liver cirrhosis with hepatic encephalopathy were comparable at 0.85 (81-90), 0.81 (0.76-0.85) and 0.81 (0.76-0.86), respectively (all p < 0.01). CONCLUSIONS: Serum prealbumin, cholinesterase and RBP levels are of potential clinical value in diagnosis of liver cirrhosis complicated by encephalopathy. Title: Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells Tang L, Wang G, Jiang L, Chen P, Wang W, Chen J, Wang L Ref: Gene, 667:95, 2018 : PubMed ESTHER: Tang_2018_Gene_667_95 PubMedSearch: Tang 2018 Gene 667 95 PubMedID: 29665449 Gene_locus related to this paper: human-EPHX2 Abstract OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20-30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization. MATERIALS AND METHODS: 167 lipid-related genes of a core FH family were sequenced using a gene-capture chip. Through carrier dependent protein expression, the expression level (western blot), hydrolase activity (fluorescent chemistry) and intracellular localization (immunofluorescence and Confocal Laser Scanning Microscope) of recombinant sEH R287Q in cultured BEL-7402 cells were conducted. The effect of wild type and R287Q of sEH on LDLR expression, LDL binding to LDLR and LDL internalization were also conducted through Flow Cytometry. RESULTS: sEH R287Q was the only gene changes among 167 lipid-related genes in the FH core family. Both expression level and hydrolase activity of recombinant sEH R287Q in cultured cells were significantly declined compared with that of the wild type sEH. sEH R287Q also decreased the binding of LDL to LDLR and LDL internalization and had no effect on cell-surface LDLR protein level. CONCLUSION: Our results suggest that sEH R287Q may have a role in the elevation of blood LDL in FH. The exactly role of sEH R287Q on FH deserves further study. Title: Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane Wang J, Tang X, Li Y, Zhang R, Zhu L, Chen J, Sun Y, Zhang Q, Wang W Ref: Phys Chem Chem Phys, 20:20540, 2018 : PubMed ESTHER: Wang_2018_Phys.Chem.Chem.Phys_20_20540 PubMedSearch: Wang 2018 Phys.Chem.Chem.Phys 20 20540 PubMedID: 30051124 Abstract The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts. Title: Nevadensin is a naturally occurring selective inhibitor of human carboxylesterase 1 Wang YQ, Weng ZM, Dou TY, Hou J, Wang DD, Ding LL, Zou LW, Yu Y, Chen J and Ge GB <1 more author(s)> Wang YQ, Weng ZM, Dou TY, Hou J, Wang DD, Ding LL, Zou LW, Yu Y, Chen J, Tang H, Ge GB (- 1) Ref: Int J Biol Macromol, 120:1944, 2018 : PubMed ESTHER: Wang_2018_Int.J.Biol.Macromol_120_1944 PubMedSearch: Wang 2018 Int.J.Biol.Macromol 120 1944 PubMedID: 30268757 Abstract Human carboxylesterase 1 (hCE1) is a key enzyme responsible for the hydrolysis of a wide range of endogenous and xenobiotic esters, but the highly selective inhibitors against hCE1 are rarely reported. This study aimed to assess the inhibitory effects of natural flavonoids against hCE1 and to find potential specific hCE1 inhibitors. To this end, fifty-eight natural flavonoids were collected and their inhibitory effects against both hCE1 and hCE2 were assayed. Among all tested compounds, nevadensin, an abundant natural constitute from Lysionotus pauciflorus Maxim., displayed the best combination of inhibition potency and selectivity towards hCE1. The inhibition mechanism of nevadensin on hCE1 was further investigated using two site-specific hCE1 substrates including D-luciferin methyl ester (DME) and 2(2benzoyloxy3methoxyphenyl)benzothiazole (BMBT). Furthermore, docking simulations demonstrated that the binding area of nevadensin on hCE1 was highly overlapped with that of DME but was far away from that of BMBT, which was highly consistent with the inhibition modes of nevadensin. These findings found a natural occurring specific inhibitor of hCE1, which could be served as a lead compound for the development of novel hCE1 inhibitor with improved properties, and also hold great promise for investigating hCE1-ligand interactions. Title: Studies on the lipid-regulating mechanism of alisol-based compounds on lipoprotein lipase Xu F, Lu C, Wu Q, Gu W, Chen J, Fang F, Zhao B, Du W, You M Ref: Bioorg Chem, 80:347, 2018 : PubMed ESTHER: Xu_2018_Bioorg.Chem_80_347 PubMedSearch: Xu 2018 Bioorg.Chem 80 347 PubMedID: 29986183 Abstract Studies on the lipid-regulating effects of alisol compounds are reported that include alisol B, alisol A 24-acetate (24A), alisol A and an alisol B - 24A - alisol A mixture (content ratio=1:1:1). The effects on the activity of lipoprotein lipase (LPL), a key lipid-modulating enzyme, were studied to investigate the molecular mechanism of lipid-regulating activity of alisols. The effects of alisols on regulating blood lipids and the activities of LPL were determined using a reagent kit method. The structure of LPL was obtained by homology modeling and the interactive mechanism of alisol monomers and the mixture with LPL was investigated by molecular simulation. The alisol monomer and mixture were shown to regulate blood lipids, suggesting that alisols may decrease the level of triglyceride (TG) by improving the activity of LPL. The order of intensity was: mixture>alisol A>alisol B>24A, indicating that alisols of alismatis rhizoma feature a synergistic effect on LPL. The N- and C-terminus of LPL both represented the catalytic active domains of this lipid-regulating effect. Cys306, Gln129 and Ser166 were the key amino acid residues resulting in the lipid-regulating effect of the alisol monomer while Ser166 and Arg18 were found to be responsible for the lipid-regulating effect of the mixture. The C-terminus of LPL was indirectly involved in the enzymatic process. A folded side chain of alisols or the parent ring was found to bind somewhat weaker to LPL than an open side chain or parent ring. The hydroxyl groups on the C14-, C22-, C28-, C30- and C31-terminus in the side chain, the ring ether structure in C23-position, and the acetyl group in C29-position represented the key sites for the lipid-regulating action of alisols. Meanwhile, the C30-site hydroxyl group played an important role in the synergistic effect of the alisol mixture. Title: Correlation between antibiotic-induced feeding depression and body size reduction in zooplankton (rotifer, Brachionus calyciflorus): Neural response and digestive enzyme inhibition Yan Z, Yang Q, Wang X, Torres OL, Tang S, Zhang S, Guo R, Chen J Ref: Chemosphere, 218:376, 2018 : PubMed ESTHER: Yan_2018_Chemosphere_218_376 PubMedSearch: Yan 2018 Chemosphere 218 376 PubMedID: 30476769 Abstract The study analyzed the correlation between the antibiotic-induced feeding depression and body size reduction in rotifer, Brachionus calyciflorus, involving exposure, post-exposure and re-exposure periods. The filtration and ingestion rates of the rotifers were inhibited in these three exposure periods at any given concentration of the antibiotic sulfamethazine (SMZ). As food for rotifer, the cell size of the green algae was unchanged, which indicated that it could not drive feeding depression. Secondly, several corresponding physiological responses were considered. Reactive oxygen species (ROS) levels increased in the post-exposure and the re-exposure; acetylcholinesterase (AChE) activity was significantly decreased in the exposure and the re-exposure, whereas it was induced in the post-exposure. The activities of amylase and lipase were always inhibited in these three exposure periods. Additionally, significant decreases in lorica length, width and biovolume of rotifers occurred after the feeding depression. Statistical analysis indicated a positive correlation between the activity of the digestive enzyme and the body size. Our results demonstrated that SMZ could influence the neurotransmission, inhibit the activity of the digestive enzyme, and finally result in body size reduction. These results provided an integrated perspective on assessing the toxicity effects of antibiotic in non-lethal dosage on the feeding behavior of non-target aquatic organisms. Title: [MEGDEL syndrome with an SERAC1 mutation: a case report] Chen J, Peng J, Yin F Ref: Zhonghua Er Ke Za Zhi, 55:394, 2017 : PubMed ESTHER: Chen_2017_Zhonghua.Er.Ke.Za.Zhi_55_394 PubMedSearch: Chen 2017 Zhonghua.Er.Ke.Za.Zhi 55 394 PubMedID: 28482397 Gene_locus related to this paper: human-SERAC1 Title: Glycyrrhetinic Acid Liposomes Containing Mannose-Diester Lauric Diacid-Cholesterol Conjugate Synthesized by Lipase-Catalytic Acylation for Liver-Specific Delivery Chen J, Chen Y, Cheng Y, Gao Y Ref: Molecules, 22:, 2017 : PubMed ESTHER: Chen_2017_Molecules_22_E1598 PubMedSearch: Chen 2017 Molecules 22 E1598 PubMedID: 28946644 Abstract Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (RTe) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy. Title: Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease Chen Z, Digiacomo M, Tu Y, Gu Q, Wang S, Yang X, Chu J, Chen Q, Han Y and Pi R <5 more author(s)> Chen Z, Digiacomo M, Tu Y, Gu Q, Wang S, Yang X, Chu J, Chen Q, Han Y, Chen J, Nesi G, Sestito S, Macchia M, Rapposelli S, Pi R (- 5) Ref: Eur Journal of Medicinal Chemistry, 125:784, 2017 : PubMed ESTHER: Chen_2017_Eur.J.Med.Chem_125_784 PubMedSearch: Chen 2017 Eur.J.Med.Chem 125 784 PubMedID: 27736684 Abstract A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Abeta) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Abeta self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD. Title: Selective Inhibitors of Human Liver Carboxylesterase Based on a beta-Lapachone Scaffold: Novel Reagents for Reaction Profiling Hatfield MJ, Chen J, Fratt EM, Chi L, Bollinger JC, Binder RJ, Bowling J, Hyatt JL, Scarborough J and Potter PM <1 more author(s)> Hatfield MJ, Chen J, Fratt EM, Chi L, Bollinger JC, Binder RJ, Bowling J, Hyatt JL, Scarborough J, Jeffries C, Potter PM (- 1) Ref: Journal of Medicinal Chemistry, 60:1568, 2017 : PubMed ESTHER: Hatfield_2017_J.Med.Chem_60_1568 PubMedSearch: Hatfield 2017 J.Med.Chem 60 1568 PubMedID: 28112927 Abstract Carboxylesterases (CEs) are ubiquitous enzymes that are responsible for the metabolism of xenobiotics, including drugs such as irinotecan and oseltamivir. Inhibition of CEs significantly modulates the efficacy of such agents. We report here that beta-lapachone is a potent, reversible CE inhibitor with Ki values in the nanomolar range. A series of amino and phenoxy analogues have been synthesized, and although the former are very poor inhibitors, the latter compounds are highly effective in modulating CE activity. Our data demonstrate that tautomerism of the amino derivatives to the imino forms likely accounts for their loss in biological activity. A series of N-methylated amino derivatives, which are unable to undergo such tautomerism, were equal in potency to the phenoxy analogues and demonstrated selectivity for the liver enzyme hCE1. These specific inhibitors, which are active in cell culture models, will be exceptionally useful reagents for reaction profiling of esterified drugs in complex biological samples. Title: Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice Li N, Liu C, Jing S, Wang M, Wang H, Sun J, Wang C, Chen J, Li H Ref: Evid Based Complement Alternat Med, 2017:8632016, 2017 : PubMed ESTHER: Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016 PubMedSearch: Li 2017 Evid.Based.Complement.Alternat.Med 2017 8632016 PubMedID: 28814961 Abstract Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement. Title: Single and mixture toxicities of BDE-47, 6-OH-BDE-47 and 6-MeO-BDE-47 on the feeding activity of Daphnia magna: From behavior assessment to neurotoxicity Liu Y, Guo R, Tang S, Zhu F, Zhang S, Yan Z, Chen J Ref: Chemosphere, 195:542, 2017 : PubMed ESTHER: Liu_2017_Chemosphere_195_542 PubMedSearch: Liu 2017 Chemosphere 195 542 PubMedID: 29277034 Abstract Although 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47), 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE-47) clearly disrupt the endocrine system, current knowledge of their single and/or mixture toxicities on other behaviors of aquatic organisms remains limited. In the present study, Daphnia magna was used to investigate the single and mixture toxicities of BDE-47, 6-OH-BDE-47 and 6-MeO-BDE-47 as measured by inhibition of feeding during exposure and post-exposure periods. Additionally, the biochemical performance, i.e., the activities of super oxidase dismutase (SOD), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) of the test organism was studied to investigate the potential mechanisms of the toxicity of the target compounds. The three target compounds produced an obvious depressive effect on feeding behavior during the exposure period, and the effect increased with increasing concentrations. D. magna was most sensitive to 6-OH-BDE-47. The toxicity of the ternary mixture showed an obvious concentration-dependent effect, whereas the binary mixture toxicity showed the characteristics of hormesis. During the post-exposure period, overcompensation occurred, indicating a short-term effect of the target compounds on D. magna. Additionally, significant changes occurred in neurological responses, indicating that these compounds might have neurobehavioral toxicity in D. magna. The decrease in oxidative stress enzymes (SOD and GPx) indicated that the antioxidant response of D. magna was destroyed. Title: Organophosphate esters in sediment cores from coastal Laizhou Bay of the Bohai Sea, China Wang Y, Wu X, Zhang Q, Hou M, Zhao H, Xie Q, Du J, Chen J Ref: Sci Total Environ, 607-608:103, 2017 : PubMed ESTHER: Wang_2017_Sci.Total.Environ_607-608_103 PubMedSearch: Wang 2017 Sci.Total.Environ 607-608 103 PubMedID: 28688252 Abstract Concentrations and vertical distributions of organophosphate esters (OPEs) were investigated in the sediment cores collected from the Laizhou Bay, Bohai Sea of China. The total concentrations of OPEs in the sediment core (CA) collected near the Yellow River Estuary were in the range of 11.8-102ng/g, while the total concentrations in the sediment core (CB) near a mariculture area were 6.65-41.5ng/g. Significantly high concentrations of OPEs were found in the sediments near the Yellow River Estuary than those in the mariculture area. Vertical distributions in the sediment cores demonstrated a recent increase of OPE emissions, especially for tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), and tris (2-chloroisopropyl) phosphate (TCPP). Generally, TCEP and TCPP were the dominant congeners in the sediment cores, while the profiles of TnBP were increase in the surface 0-20cm layers of the CA core. OPEs in the CA core may be remarkably influenced by the discharge of Yellow River, whereas OPEs in the CB core may originate from the transport through seawater. The remarkable increase of OPE flame retardants in the surface sediments raises the concern about their emissions and risks to the environment and indicates the need for further monitoring. Title: Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis Whitson JA, Zhang X, Medvedovic M, Chen J, Wei Z, Monnier VM, Fan X Ref: Invest Ophthalmol Vis Sci, 58:2666, 2017 : PubMed ESTHER: Whitson_2017_Invest.Ophthalmol.Vis.Sci_58_2666 PubMedSearch: Whitson 2017 Invest.Ophthalmol.Vis.Sci 58 2666 PubMedID: 28525556 Abstract Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes. Results: RNA-Seq results were in excellent agreement with qPCR (correlation coefficients 0.87-0.94 and P < 5E-6 for a subset of 36 mRNAs). Of 24,415 transcripts mapped to the mouse genome, 441 genes showed significantly modulated expression. Pathway analysis indicated major changes in epithelial-mesenchymal transition (EMT) signaling, visual cycle, small molecule biochemistry, and lipid metabolism. GSH-deficient lenses showed upregulation of detoxification genes, including Aldh1a1, Aldh3a1 (aldehyde dehydrogenases), Mt1, Mt2 (metallothioneins), Ces1g (carboxylesterase), and Slc14a1 (urea transporter UT-B). Genes in canonical EMT pathways, including Wnt10a, showed upregulation in lens epithelia samples. Severely GSH-deficient lens epithelia showed downregulation of vision-related genes (including crystallins). The BSO-treated LEGSKO lens epithelia transcriptome has significant correlation (r = 0.63, P < 0.005) to that of lens epithelia undergoing EMT. Protein expression data correlated with transcriptomic data and confirmed EMT signaling activation. Conclusions: These results show that GSH-deficiency in the lens leads to expression of detoxifying genes and activation of EMT signaling, in addition to changes in transport systems and lipid homeostasis. These data provide insight into the adaptation and consequences of GSH-deficiency in the lens and suggest that GSH plays an important role in lenticular EMT pathology. Title: The impact assessment of anticancer drug imatinib on the feeding behavior of rotifers with an integrated perspective: Exposure, post-exposure and re-exposure Yan Z, Yan K, He X, Liu Y, Zhang J, Lopez Torres O, Guo R, Chen J Ref: Chemosphere, 185:423, 2017 : PubMed ESTHER: Yan_2017_Chemosphere_185_423 PubMedSearch: Yan 2017 Chemosphere 185 423 PubMedID: 28710991 Abstract The anticancer drugs are getting increasing attention as an emerging contaminant in the aquatic environments. In the present study, feeding behavior of the rotifer Brachionus calyciflorus under the impact of anticancer drug imatinib was evaluated. Traditional toxicological studies usually focus on dose-effect relationship at a given exposure time, while ignore the possible impact after the exposure. Thus, how the impact varied in the post-exposure and re-exposure was also considered in the present study. The feeding depression of the rotifers was attributed to the increased concentration of imatinib. Although the filtration and ingestion rate of the rotifers recovered to a certain extent after the exposure, the significant feeding inhibition still persisted even if the exposure was ended. In the re-exposure period, the feeding behavior was less depressed than those of the exposure period, which implied that rotifers might develop a tolerance to the same toxics. The activities of acetylcholine esterase (AchE) and the levels of reactive oxygen species (ROS) in rotifers were also detected. Imatinib inhibited the activities of AchE in the exposure and re-exposure while ROS levels increased significantly in the re-exposure period. Our present study provided an integrated assessment the potential environmental risks of imatinib at a new perspective. Title: Evaluation and application of constitutive promoters for cutinase production by Saccharomyces cerevisiae Zhang J, Cai Y, Du G, Chen J, Wang M, Kang Z Ref: J Microbiol, 55:538, 2017 : PubMed ESTHER: Zhang_2017_J.Microbiol_55_538 PubMedSearch: Zhang 2017 J.Microbiol 55 538 PubMedID: 28664516 Abstract Cutinase as a promising biocatalyst has been intensively studied and applied in processes targeted for industrial scale. In this work, the cutinase gene tfu from Thermobifida fusca was artificially synthesized according to codon usage bias of Saccharomyces cerevisiae and investigated in Saccharomyces cerevisiae. Using the alpha-factor signal peptide, the T. fusca cutinase was successfully overexpressed and secreted with the GAL1 expression system. To increase the cutinase level and overcome some of the drawbacks of induction, four different strong promoters (ADH1, HXT1, TEF1, and TDH3) were comparatively evaluated for cutinase production. By comparison, promoter TEF1 exhibited an outstanding property and significantly increased the expression level. By fed-batch fermentation with a constant feeding approach, the activity of cutinase was increased to 29.7 U/ml. The result will contribute to apply constitutive promoter TEF1 as a tool for targeted cutinase production in S. cerevisiae cell factory. Title: Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism Ahn K, Boehm M, Brown MF, Calloway J, Che Y, Chen J, Fennell KF, Geoghegan KF, Gilbert AM and Yan J <19 more author(s)> Ahn K, Boehm M, Brown MF, Calloway J, Che Y, Chen J, Fennell KF, Geoghegan KF, Gilbert AM, Gutierrez JA, Kalgutkar AS, Lanba A, Limberakis C, Magee TV, O'Doherty I, Oliver R, Pabst B, Pandit J, Parris K, Pfefferkorn JA, Rolph TP, Patel R, Schuff B, Shanmugasundaram V, Starr JT, Varghese AH, Vera NB, Vernochet C, Yan J (- 19) Ref: ACS Chemical Biology, 11:2529, 2016 : PubMed ESTHER: Ahn_2016_ACS.Chem.Biol_11_2529 PubMedSearch: Ahn 2016 ACS.Chem.Biol 11 2529 PubMedID: 27391855 Gene_locus related to this paper: human-LYPLAL1 Inhibitor(s) related to this paper: Piperidinyl-1,2,3-triazole-urea-inhibitor-11, Piperidinyl-1,2,3-triazole-urea-inhibitor-12, Piperidinyl-1,2,3-triazole-urea-inhibitor-2 Abstract Lysophospholipase-like 1 (LYPLAL1) is an uncharacterized metabolic serine hydrolase. Human genome-wide association studies link variants of the gene encoding this enzyme to fat distribution, waist-to-hip ratio, and nonalcoholic fatty liver disease. We describe the discovery of potent and selective covalent small-molecule inhibitors of LYPLAL1 and their use to investigate its role in hepatic metabolism. In hepatocytes, selective inhibition of LYPLAL1 increased glucose production supporting the inference that LYPLAL1 is a significant actor in hepatic metabolism. The results provide an example of how a selective chemical tool can contribute to evaluating a hypothetical target for therapeutic intervention, even in the absence of complete biochemical characterization. Title: NDRG1 Controls Gastric Cancer Migration and Invasion through Regulating MMP-9 Chang X, Xu X, Xue X, Ma J, Li Z, Deng P, Chen J, Zhang S, Zhi Y, Dai D Ref: Pathol Oncol Res, 22:789, 2016 : PubMed ESTHER: Chang_2016_Pathol.Oncol.Res_22_789 PubMedSearch: Chang 2016 Pathol.Oncol.Res 22 789 PubMedID: 27154576 Abstract The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p < 0.01), invasion depth (p < 0.05), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), whereas MMP-9 was positive correlated with the degree of tumor cell differentiation (p < 0.01), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), but not correlated with invasion depth (p>0.05). Furthermore, cell proliferation and invasion effect were remarkably enhanced when NDRG1 was silencing, but MMP-9 expression was increased. NDRG1 silencing enhances gastric cancer cells progression through upregulating MMP-9. It suggests that NDRG1 may inhibit the metastasis of gastric cancer via regulating MMP-9. Title: Multi-biomarker responses as indication of contaminant effects in Gambusia affinis from impacted rivers by municipal effluents Huang GY, Liu YS, Liang YQ, Shi WJ, Hu LX, Tian F, Chen J, Ying GG Ref: Sci Total Environ, 563-564:273, 2016 : PubMed ESTHER: Huang_2016_Sci.Total.Environ_563-564_273 PubMedSearch: Huang 2016 Sci.Total.Environ 563-564 273 PubMedID: 27135591 Abstract This study investigated toxic effects in mosquitofish from two urban rivers of South China impacted by municipal effluents by using multiple biomarkers including fish morphology, biochemical indicators and transcriptional responses, and explored potential cause-effect relationship with a list of chemicals (metals, polycyclic aromatic hydrocarbons (PAHs) and pesticides). The results showed significant alterations in metallothionein (MT) protein and mRNA expression in mosquitofish collected from the two rivers and a strong association between MT protein and mRNA expression levels and heavy metals in the river water. Both ethoxyresorufin-O-deethylase (EROD) activity and cytochromes P450 1A (CYP1A) mRNA expression were significantly enhanced in mosquitofish at most sampling sites. There existed a strong correlation between EROD activity and CYP1A mRNA expression levels, but no clear correlations between these responses and PAHs in the river water possibly because of the presence of many other agonists of the aryl hydrocarbon receptor in the two rivers. Significant acetylcholinesterase (AChE) inhibition was observed in mosquitofish brain samples. The pesticides in the two rivers showed an influence on the AChE activity, which was also found to be significantly negatively correlated to fipronil concentrations. Moreover, the result also indicates that metals and pesticides present in the two rivers might cause the observed estrogenic and androgenic effects in mosquitofish. The findings from this study clearly showed morphological, biochemical and transcriptional responses in mosquitofish due to chemical contamination of the two urban rivers. This multi-biomarker approach using mosquitofish can be applied to evaluate contamination of riverine environments. Title: Parabens inhibit fatty acid amide hydrolase: A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation Kodani SD, Overby HB, Morisseau C, Chen J, Zhao L, Hammock BD Ref: Toxicol Lett, 262:92, 2016 : PubMed ESTHER: Kodani_2016_Toxicol.Lett_262_92 PubMedSearch: Kodani 2016 Toxicol.Lett 262 92 PubMedID: 27659731 Abstract Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1)-selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids. Title: Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats Liu X, Mo Y, Gong J, Li Z, Peng H, Chen J, Wang Q, Ke Z, Xie J Ref: Metabolic Brain Disease, 31:417, 2016 : PubMed ESTHER: Liu_2016_Metab.Brain.Dis_31_417 PubMedSearch: Liu 2016 Metab.Brain.Dis 31 417 PubMedID: 26686502 Abstract Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1beta and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-alpha, IL-1beta and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects. Title: alpha/beta-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors Wei M, Zhang J, Jia M, Yang C, Pan Y, Li S, Luo Y, Zheng J, Ji J and Zhang C <4 more author(s)> Wei M, Zhang J, Jia M, Yang C, Pan Y, Li S, Luo Y, Zheng J, Ji J, Chen J, Hu X, Xiong J, Shi Y, Zhang C (- 4) Ref: Proc Natl Acad Sci U S A, 113:E2695, 2016 : PubMed ESTHER: Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695 PubMedSearch: Wei 2016 Proc.Natl.Acad.Sci.U.S.A 113 E2695 PubMedID: 27114538 Gene_locus related to this paper: human-ABHD6 Abstract In the brain, AMPA-type glutamate receptors are major postsynaptic receptors at excitatory synapses that mediate fast neurotransmission and synaptic plasticity. alpha/beta-Hydrolase domain-containing 6 (ABHD6), a monoacylglycerol lipase, was previously found to be a component of AMPA receptor macromolecular complexes, but its physiological significance in the function of AMPA receptors (AMPARs) has remained unclear. The present study shows that overexpression of ABHD6 in neurons drastically reduced excitatory neurotransmission mediated by AMPA but not by NMDA receptors at excitatory synapses. Inactivation of ABHD6 expression in neurons by either CRISPR/Cas9 or shRNA knockdown methods significantly increased excitatory neurotransmission at excitatory synapses. Interestingly, overexpression of ABHD6 reduced glutamate-induced currents and the surface expression of GluA1 in HEK293T cells expressing GluA1 and stargazin, suggesting a direct functional interaction between these two proteins. The C-terminal tail of GluA1 was required for the binding between of ABHD6 and GluA1. Mutagenesis analysis revealed a GFCLIPQ sequence in the GluA1 C terminus that was essential for the inhibitory effect of ABHD6. The hydrolase activity of ABHD6 was not required for the effects of ABHD6 on AMPAR function in either neurons or transfected HEK293T cells. Thus, these findings reveal a novel and unexpected mechanism governing AMPAR trafficking at synapses through ABHD6. Title: A liquid chromatography tandem mass spectrometric method on in vitro nerve agents poisoning characterization and reactivator efficacy evaluation by determination of specific peptide adducts in acetylcholinesterase Yan L, Chen J, Xu B, Guo L, Xie Y, Tang J, Xie J Ref: Journal of Chromatography A, 1450:86, 2016 : PubMed ESTHER: Yan_2016_J.Chromatogr.A_1450_86 PubMedSearch: Yan 2016 J.Chromatogr.A 1450 86 PubMedID: 27179675 Abstract The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified. A key termination procedure is focused to make the reaction system "frozen" and precisely "capture" the poisoning, aging and spontaneous reactivation status of AChE, and the abundance of such specific peptides can thus be simultaneously measured. In our established method, as low as 0.72% and 0.84% inhibition level of AChE induced by 0.5nM sarin and VX can be detected from the measurement of peptide adducts, which benefits a confirmation of NAs exposure, especially at extremely low levels. Comparing with conventional colorimetric Ellman assays, our method provides not only enzyme activity and inhibition rate, but also the precise poisoning status of NAs exposed AChE. Based on the full information provided by this method, the efficacy of reactivators, such as HI-6, obidoxime and pralidoxime, in the typical treatment of NAs poisoned AChE in in vitro was further evaluated. Our results showed that this method is a promising tool for the characterization of NAs poisoning and the evaluation of reactivator efficacy. Title: Antifungal Indole Alkaloids from Winchia calophylla Yang ML, Chen J, Sun M, Zhang DB, Gao K Ref: Planta Med, 82:712, 2016 : PubMed ESTHER: Yang_2016_Planta.Med_82_712 PubMedSearch: Yang 2016 Planta.Med 82 712 PubMedID: 27002397 Abstract Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 microM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 microM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 microM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 microM, respectively. Title: Increased serum level of Lp-PLA2 is independently associated with the severity of coronary artery diseases: a cross-sectional study of Chinese population Cai A, Li G, Chen J, Li X, Li L, Zhou Y Ref: BMC Cardiovasc Disord, 15:14, 2015 : PubMed ESTHER: Cai_2015_BMC.Cardiovasc.Disord_15_14 PubMedSearch: Cai 2015 BMC.Cardiovasc.Disord 15 14 PubMedID: 25879827 Abstract BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays complex and adverse roles on atherosclerosis. Current study was to investigate whether increased plasma Lp-PLA2 level is independently associated with the severity of coronary artery diseases (CAD). Title: In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl-/-) mice Chen J, Kaiyala KJ, Lam J, Agrawal N, Nguyen L, Ogimoto K, Spencer D, Morton GJ, Schwartz MW, Dichek HL Ref: Physiol Rep, 3:, 2015 : PubMed ESTHER: Chen_2015_Physiol.Rep_3_ PubMedSearch: Chen 2015 Physiol.Rep 3 PubMedID: 25862097 Gene_locus related to this paper: mouse-1hlip Abstract The lean body weight phenotype of hepatic lipase (HL)-deficient mice (hl(-/-)) suggests that HL is required for normal weight gain, but the underlying mechanisms are unknown. HL plays a unique role in lipoprotein metabolism performing bridging as well as catalytic functions, either of which could participate in energy homeostasis. To determine if both the catalytic and bridging functions or the catalytic function alone are required for the effect of HL on body weight, we studied (hl(-/-)) mice that transgenically express physiologic levels of human (h)HL (with catalytic and bridging functions) or a catalytically-inactive (ci)HL variant (with bridging function only) in which the catalytic Serine 145 was mutated to Alanine. As expected, HL activity in postheparin plasma was restored to physiologic levels only in hHL-transgenic mice (hl(-/-)hHL). During high-fat diet feeding, hHL-transgenic mice exhibited increased body weight gain and body adiposity relative to hl(-/-)ciHL mice. A similar, albeit less robust effect was observed in female hHL-transgenic relative to hl(-/-)ciHL mice. To delineate the basis for this effect, we determined cumulative food intake and measured energy expenditure using calorimetry. Interestingly, in both genders, food intake was 5-10% higher in hl(-/-)hHL mice relative to hl(-/-)ciHL controls. Similarly, energy expenditure was ~10% lower in HL-transgenic mice after adjusting for differences in total body weight. Our results demonstrate that (1) the catalytic function of HL is required to rescue the lean body weight phenotype of hl(-/-) mice; (2) this effect involves complementary changes in both sides of the energy balance equation; and (3) the bridging function alone is insufficient to rescue the lean phenotype of hl(-/-)ciHL mice. Title: Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution Chen XG, Jiang X, Gu J, Xu M, Wu Y, Deng Y, Zhang C, Bonizzoni M, Dermauw W and James AA <21 more author(s)> Chen XG, Jiang X, Gu J, Xu M, Wu Y, Deng Y, Zhang C, Bonizzoni M, Dermauw W, Vontas J, Armbruster P, Huang X, Yang Y, Zhang H, He W, Peng H, Liu Y, Wu K, Chen J, Lirakis M, Topalis P, Van Leeuwen T, Hall AB, Thorpe C, Mueller RL, Sun C, Waterhouse RM, Yan G, Tu ZJ, Fang X, James AA (- 21) Ref: Proc Natl Acad Sci U S A, 112:E5907, 2015 : PubMed ESTHER: Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907 PubMedSearch: Chen 2015 Proc.Natl.Acad.Sci.U.S.A 112 E5907 PubMedID: 26483478 Gene_locus related to this paper: aedae-q177c7, aedal-a0a182gwe3, aedal-a0a182gwt8, aedal-a0a023eq67 Abstract The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species. 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: A general method to improve fluorophores for live-cell and single-molecule microscopy Grimm JB, English BP, Chen J, Slaughter JP, Zhang Z, Revyakin A, Patel R, Macklin JJ, Normanno D and Lavis LD <2 more author(s)> Grimm JB, English BP, Chen J, Slaughter JP, Zhang Z, Revyakin A, Patel R, Macklin JJ, Normanno D, Singer RH, Lionnet T, Lavis LD (- 2) Ref: Nat Methods, 12:244, 2015 : PubMed ESTHER: Grimm_2015_Nat.Methods_12_244 PubMedSearch: Grimm 2015 Nat.Methods 12 244 PubMedID: 25599551 Abstract Specific labeling of biomolecules with bright fluorophores is the keystone of fluorescence microscopy. Genetically encoded self-labeling tag proteins can be coupled to synthetic dyes inside living cells, resulting in brighter reporters than fluorescent proteins. Intracellular labeling using these techniques requires cell-permeable fluorescent ligands, however, limiting utility to a small number of classic fluorophores. Here we describe a simple structural modification that improves the brightness and photostability of dyes while preserving spectral properties and cell permeability. Inspired by molecular modeling, we replaced the N,N-dimethylamino substituents in tetramethylrhodamine with four-membered azetidine rings. This addition of two carbon atoms doubles the quantum efficiency and improves the photon yield of the dye in applications ranging from in vitro single-molecule measurements to super-resolution imaging. The novel substitution is generalizable, yielding a palette of chemical dyes with improved quantum efficiencies that spans the UV and visible range. Title: Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence Hancock DB, Reginsson GW, Gaddis NC, Chen X, Saccone NL, Lutz SM, Qaiser B, Sherva R, Steinberg S and Stefansson K <24 more author(s)> Hancock DB, Reginsson GW, Gaddis NC, Chen X, Saccone NL, Lutz SM, Qaiser B, Sherva R, Steinberg S, Zink F, Stacey SN, Glasheen C, Chen J, Gu F, Frederiksen BN, Loukola A, Gudbjartsson DF, Bruske I, Landi MT, Bickeboller H, Madden P, Farrer L, Kaprio J, Kranzler HR, Gelernter J, Baker TB, Kraft P, Amos CI, Caporaso NE, Hokanson JE, Bierut LJ, Thorgeirsson TE, Johnson EO, Stefansson K (- 24) Ref: Transl Psychiatry, 5:e651, 2015 : PubMed ESTHER: Hancock_2015_Transl.Psychiatry_5_e651 PubMedSearch: Hancock 2015 Transl.Psychiatry 5 e651 PubMedID: 26440539 Abstract We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerstrom Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 x 10(-9) across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 x 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences. Title: The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin Lin NN, Chen J, Xu B, Wei X, Guo L, Xie JW Ref: Mil Med Res, 2:13, 2015 : PubMed ESTHER: Lin_2015_Mil.Med.Res_2_13 PubMedSearch: Lin 2015 Mil.Med.Res 2 13 PubMedID: 26140218 Abstract BACKGROUND: T-2 toxin poses a great threat to human health because it has the highest toxicity of the currently known trichothecene mycotoxins. To understand the in vivo toxicity and transformation mechanism of T-2 toxin, we investigated the role of one kind of principal phase I drug-metabolizing enzymes (cytochrome P450 [CYP450] enzymes) on the metabolism of T-2 toxin, which are crucial to the metabolism of endogenous substances and xenobiotics. We also investigated carboxylesterase, which also plays an important role in the metabolism of toxic substances. Title: Inhibition of monoacylglycerol lipase reduces nicotine withdrawal Muldoon PP, Chen J, Harenza JL, Abdullah RA, Sim-Selley LJ, Cravatt BF, Miles MF, Chen X, Lichtman AH, Damaj MI Ref: British Journal of Pharmacology, 172:869, 2015 : PubMed ESTHER: Muldoon_2015_Br.J.Pharmacol_172_869 PubMedSearch: Muldoon 2015 Br.J.Pharmacol 172 869 PubMedID: 25258021 Gene_locus related to this paper: human-MGLL Abstract BACKGROUND AND PURPOSE: Abrupt discontinuation of nicotine, the main psychoactive component in tobacco, induces a withdrawal syndrome in nicotine-dependent animals, consisting of somatic and affective signs, avoidance of which contributes to drug maintenance. While blockade of fatty acid amide hydrolase, the primary catabolic enzyme of the endocannabinoid arachidonoylethanolamine (anandamide), exacerbates withdrawal responses in nicotine-dependent mice, the role of monoacylglycerol lipase (MAGL), the main hydrolytic enzyme of a second endocannabinoid 2-arachidonylglycerol (2-AG), in nicotine withdrawal remains unexplored. EXPERIMENTAL APPROACH: To evaluate the role of MAGL enzyme inhibition in nicotine withdrawal, we initially performed a genetic correlation approach using the BXD recombinant inbred mouse panel. We then assessed nicotine withdrawal intensity in the mouse after treatment with the selective MAGL inhibitor, JZL184, and after genetic deletion of the enzyme. Lastly, we assessed the association between genotypes and smoking withdrawal phenotypes in two human data sets. KEY Title: Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure Pan H, Piermartiri TC, Chen J, McDonough J, Oppel C, Driwech W, Winter K, McFarland E, Black K and Marini AM <2 more author(s)> Pan H, Piermartiri TC, Chen J, McDonough J, Oppel C, Driwech W, Winter K, McFarland E, Black K, Figueiredo T, Grunberg N, Marini AM (- 2) Ref: Neurotoxicology, 51:38, 2015 : PubMed ESTHER: Pan_2015_Neurotoxicol_51_38 PubMedSearch: Pan 2015 Neurotoxicol 51 38 PubMedID: 26386148 Abstract Exposure to nerve agents results in severe seizures or status epilepticus caused by the inhibition of acetylcholinesterase, a critical enzyme that breaks down acetylcholine to terminate neurotransmission. Prolonged seizures cause brain damage and can lead to long-term consequences. Current countermeasures are only modestly effective against the brain damage supporting interest in the evaluation of new and efficacious therapies. The nutraceutical alpha-linolenic acid (LIN) is an essential omega-3 polyunsaturated fatty acid that has a wide safety margin. Previous work showed that a single intravenous injection of alpha-linolenic acid (500nmol/kg) administered before or after soman significantly protected against soman-induced brain damage when analyzed 24h after exposure. Here, we show that administration of three intravenous injections of alpha-linolenic acid over a 7 day period after soman significantly improved motor performance on the rotarod, enhanced memory retention, exerted an anti-depressant-like activity and increased animal survival. This dosing schedule significantly reduced soman-induced neuronal degeneration in four major vulnerable brain regions up to 21 days. Taken together, alpha-linolenic acid reduces the profound behavioral deficits induced by soman possibly by decreasing neuronal cell death, and increases animal survival. Title: Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure Piermartiri TC, Pan H, Chen J, McDonough J, Grunberg N, Apland JP, Marini AM Ref: Neuromolecular Med, 17:251, 2015 : PubMed ESTHER: Piermartiri_2015_Neuromolecular.Med_17_251 PubMedSearch: Piermartiri 2015 Neuromolecular.Med 17 251 PubMedID: 25920465 Abstract Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naive animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism. Title: A simple electrochemical biosensor based on AuNPs/MPS/Au electrode sensing layer for monitoring carbamate pesticides in real samples Song Y, Chen J, Sun M, Gong C, Shen Y, Wang L Ref: J Hazard Mater, 304:103, 2015 : PubMed ESTHER: Song_2015_J.Hazard.Mater_304_103 PubMedSearch: Song 2015 J.Hazard.Mater 304 103 PubMedID: 26547618 Abstract A simple electrochemical biosensor for quantitative determination of carbamate pesticide was developed based on a sensing interface of citrate-capped gold nanoparticles (AuNPs)/(3-mercaptopropyl)-trimethoxysilane (MPS)/gold electrode (Au). The biosensor was fabricated by firstly assembling three-dimensional (3D) MPS networks on Au electrode and subsequently assembling citrate-capped AuNPs on 3D MPS network via AuS bond. The interface of AuNPs/MPS/Au was negatively charged originating from the citrate coated on AuNPs that would repulse the negatively charged ferricyanide ([Fe(CN)6]3-/4-) to produce a negative response. In the presence of acetylcholinesterase (AChE) and acetylthiocholine (ATCl), the AChE catalyzes the hydrolysis of ATCl into positively charged thiocholine which would replace the citrate on AuNPs through the strong AuS bond and convert the negative charged surface to be positively charged. The resulted positively charged AuNPs/MPS/Au then attracted the [Fe(CN)6]3-/4- to produce a positive response. Based on the inhibition of carbamate pesticides on the activity of AChE, the pesticide could be quantitatively determined at a very low potential. The linear range was from 0.003 to 2.00muM. The sensing platform was also proved to be suitable for carbamate pesticides detection in practical sample. Title: Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits Xu H, Tao X, Wei Y, Chen J, Xing S, Cen W, Wen A, Zhu L, Tang G and Li X <3 more author(s)> Xu H, Tao X, Wei Y, Chen J, Xing S, Cen W, Wen A, Zhu L, Tang G, Li M, Jiang A, Jiang Y, Li X (- 3) Ref: Gene, 557:146, 2015 : PubMed ESTHER: Xu_2015_Gene_557_146 PubMedSearch: Xu 2015 Gene 557 146 PubMedID: 25498336 Abstract Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits. Title: Novibacillus thermophilus gen. nov., sp. nov., a Gram-staining-negative and moderately thermophilic member of the family Thermoactinomycetaceae Yang G, Chen J, Zhou S Ref: Int J Syst Evol Microbiol, 65:2591, 2015 : PubMed ESTHER: Yang_2015_Int.J.Syst.Evol.Microbiol_65_2591 PubMedSearch: Yang 2015 Int.J.Syst.Evol.Microbiol 65 2591 PubMedID: 25951858 Gene_locus related to this paper: 9bacl-a0a1u9k3n4 Abstract Two Gram-staining-negative, facultatively anaerobic bacterial strains, SG-1T and SG-2, were isolated from a saline soil sample and a compost sample, respectively. The cells were non-motile rods that occurred singly or in chains, and endospores were not observed under tested growth conditions. Optimum growth occurred at 50 degreesC, pH 7.5-8.0 and with 5-7% (w/v) NaCl. The DNA G+C content was 49.5-50.5mol%. The strains contained MK-7 as the predominant menaquinone and iso-C15 : 0 and anteiso-C15 : 0 as the major fatty acids. The polar lipids consisted mainly of diphosphatidylglycerol and phosphatidylglycerol. The cell-wall peptidoglycan type was A1gamma (meso-DAP direct). Phylogenetic analyses revealed that the new isolates belonged to the family Thermoactinomycetaceae, exhibiting low 16S rRNA gene sequence similarity (90.8-91.3%) to the nearest type strain, Mechercharimyces asporophorigenens YM11-542T, and formed a well-supported lineage that was clearly distinguished from all currently described genera in this family. Based on our polyphasic taxonomic characterization, we propose that strains SG-1T and SG-2 represent a novel genus and species within the family Thermoactinomycetaceae, for which we propose the name Novibacillus thermophilus gen. nov., sp. nov. The type strain of Novibacillus thermophilus is SG-1T ( = KCTC 33118T = CGMCC 1.12771T). Title: Complete Genome Sequence of Rhodococcus sp. B7740, a Carotenoid-Producing Bacterium Isolated from the Arctic Sea Zhang D, Li L, Zhu S, Zhang N, Yang J, Ma X, Chen J Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Zhang_2015_Genome.Announc_3_e00333 PubMedSearch: Zhang 2015 Genome.Announc 3 e00333 PubMedID: 25931596 Gene_locus related to this paper: 9noca-a0a0d5a5c6, 9noca-a0a0d5abf5, 9noca-a0a0d5ae28, 9noca-a0a0d5ahw4 Abstract Rhodococcus sp. B7740 was isolated from Arctic seawater and selected for its capacity to synthesize carotenoids. Here, we report the complete genome sequence of Rhodococcus sp. B7740 to provide the genetic basis for a better understanding of its carotenoid-accumulating capabilities, and we describe the major features of the genome. Title: NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells Chang X, Xu X, Ma J, Xue X, Li Z, Deng P, Zhang S, Zhi Y, Chen J, Dai D Ref: Mol Biol Rep, 41:6215, 2014 : PubMed ESTHER: Chang_2014_Mol.Biol.Rep_41_6215 PubMedSearch: Chang 2014 Mol.Biol.Rep 41 6215 PubMedID: 24985974 Abstract N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer. Title: (-)-phenserine attenuates soman-induced neuropathology Chen J, Pan H, Chen C, Wu W, Iskandar K, He J, Piermartiri T, Jacobowitz DM, Yu QS and Marini AM <2 more author(s)> Chen J, Pan H, Chen C, Wu W, Iskandar K, He J, Piermartiri T, Jacobowitz DM, Yu QS, McDonough JH, Greig NH, Marini AM (- 2) Ref: PLoS ONE, 9:e99818, 2014 : PubMed ESTHER: Chen_2014_PLoS.One_9_e99818 PubMedSearch: Chen 2014 PLoS.One 9 e99818 PubMedID: 24955574 Abstract Organophosphorus (OP) nerve agents are deadly chemical weapons that pose an alarming threat to military and civilian populations. The irreversible inhibition of the critical cholinergic degradative enzyme acetylcholinesterase (AChE) by OP nerve agents leads to cholinergic crisis. Resulting excessive synaptic acetylcholine levels leads to status epilepticus that, in turn, results in brain damage. Current countermeasures are only modestly effective in protecting against OP-induced brain damage, supporting interest for evaluation of new ones. (-)-Phenserine is a reversible AChE inhibitor possessing neuroprotective and amyloid precursor protein lowering actions that reached Phase III clinical trials for Alzheimer's Disease where it exhibited a wide safety margin. This compound preferentially enters the CNS and has potential to impede soman binding to the active site of AChE to, thereby, serve in a protective capacity. Herein, we demonstrate that (-)-phenserine protects neurons against soman-induced neuronal cell death in rats when administered either as a pretreatment or post-treatment paradigm, improves motoric movement in soman-exposed animals and reduces mortality when given as a pretreatment. Gene expression analysis, undertaken to elucidate mechanism, showed that (-)-phenserine pretreatment increased select neuroprotective genes and reversed a Homer1expression elevation induced by soman exposure. These studies suggest that (-)-phenserine warrants further evaluation as an OP nerve agent protective strategy. Title: Synaptic proteins and receptors defects in autism spectrum disorders Chen J, Yu S, Fu Y, Li X Ref: Front Cell Neurosci, 8:276, 2014 : PubMed ESTHER: Chen_2014_Front.Cell.Neurosci_8_276 PubMedSearch: Chen 2014 Front.Cell.Neurosci 8 276 PubMedID: 25309321 Abstract Recent studies have found that hundreds of genetic variants, including common and rare variants, rare and de novo mutations, and common polymorphisms contribute to the occurrence of autism spectrum disorders (ASDs). The mutations in a number of genes such as neurexin, neuroligin, postsynaptic density protein 95, SH3, and multiple ankyrin repeat domains 3 (SHANK3), synapsin, gephyrin, cadherin, and protocadherin, thousand-and-one-amino acid 2 kinase, and contactin, have been shown to play important roles in the development and function of synapses. In addition, synaptic receptors, such as gamma-aminobutyric acid receptors and glutamate receptors, have also been associated with ASDs. This review will primarily focus on the defects of synaptic proteins and receptors associated with ASDs and their roles in the pathogenesis of ASDs via synaptic pathways. Title: The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1alpha in Cultured Hep3B Cells Chen J, Lam CT, Kong AY, Zhang WL, Zhan JY, Bi CWC, Chan GK, Lam KY, Yao P and Tsim KWK <1 more author(s)> Chen J, Lam CT, Kong AY, Zhang WL, Zhan JY, Bi CWC, Chan GK, Lam KY, Yao P, Dong TTX, Tsim KWK (- 1) Ref: Planta Med, 80:1622, 2014 : PubMed ESTHER: Chen_2014_Planta.Med_80_1622 PubMedSearch: Chen 2014 Planta.Med 80 1622 PubMedID: 25184890 Abstract The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement or herbal medicine worldwide. To study the beneficial role of jujube in enhancing hematopoietic function, we investigated its roles on the expression of erythropoietin in cultured Hep3B human hepatocellular carcinoma cells. Application of chemically standardized jujube water extract stimulated erythropoietin expression in a dose-dependent manner, with the highest response by ~ 100 % of increase. A plasmid containing hypoxia response element, a critical regulator for erythropoietin transcription, was transfected into Hep3B cells. Application of jujube water extract onto the transfected cells induced the transcriptional activity of the hypoxia response element. To account for its transcriptional activation, the expression of hypoxia-inducible factor-1alpha was increased after treatment with jujube water extract: the increase was in both mRNA and protein levels. These results confirmed the hematopoietic function of jujube in the regulation of erythropoietin expression in liver cells. Title: Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization Lin Y, Chen J, Yan L, Guo L, Wu B, Li C, Feng J, Liu Q, Xie J Ref: Anal Bioanal Chem, 406:5213, 2014 : PubMed ESTHER: Lin_2014_Anal.Bioanal.Chem_406_5213 PubMedSearch: Lin 2014 Anal.Bioanal.Chem 406 5213 PubMedID: 24633564 Abstract A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples. Title: High-resolution melting analysis reveals genetic polymorphisms in MicroRNAs confer hepatocellular carcinoma risk in Chinese patients Qi JH, Wang J, Chen J, Shen F, Huang JT, Sen S, Zhou X, Liu SM Ref: BMC Cancer, 14:643, 2014 : PubMed ESTHER: Qi_2014_BMC.Cancer_14_643 PubMedSearch: Qi 2014 BMC.Cancer 14 643 PubMedID: 25176041 Abstract BACKGROUND: Although several single-nucleotide polymorphisms in microRNA (miRNA) genes have been associated with primary hepatocellular carcinoma, published findings regarding this relationship are inconsistent and inconclusive. Title: Identification of effective combinatorial markers for quality standardization of herbal medicines Shi ZQ, Song DF, Li RQ, Yang H, Qi LW, Xin GZ, Wang DQ, Song HP, Chen J and Li P <1 more author(s)> Shi ZQ, Song DF, Li RQ, Yang H, Qi LW, Xin GZ, Wang DQ, Song HP, Chen J, Hao H, Li P (- 1) Ref: Journal of Chromatography A, 1345:78, 2014 : PubMed ESTHER: Shi_2014_J.Chromatogr.A_1345_78 PubMedSearch: Shi 2014 J.Chromatogr.A 1345 78 PubMedID: 24794938 Abstract Quality standardization of herbal medicines (HMs) is an important task with great challenges. Selection of abundant compounds as markers is currently a major approach for the quality control of HMs; however, such marker compounds are irrelevant to the bioactivities in many cases. Taking Lycoridis Radiatae Bulbus (LRB) as an example, we proposed a universal strategy to identify the effective combinatorial markers (ECMs) that are representative of the bioactivities of HMs, and took them as chemical markers for quality standardization. Fingerprinting and quantification were employed to find out the common components in various batches of medicines. The contribution of each common compound to the overall bioactivity was determined through fingerprint-bioactivity modeling, which based on the absolute quantification of each compound and the acetylcholinesterase (AChE) inhibitory activity of LRB. Two most effective compounds, ungerimine and galanthamine, were therefore proposed as ECMs. Interestingly, these two compounds could synergistically inhibit AChE. This approach demonstrated its strong advantage of the bioactivity relevant quality assessment when compared with conventional methods. And the success of applying this ECMs-based method to the quality assessment of unknown LRB samples proved that our approach was reliable and reproducible. In conclusion, this approach is not only useful for the bioactivity relevant quality control of HMs but also helpful for the discovery of ECMs as new drug candidates. Title: Draft Genome Sequence of Xylella fastidiosa Pear Leaf Scorch Strain in Taiwan Su CC, Deng WL, Jan FJ, Chang CJ, Huang H, Chen J Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Su_2014_Genome.Announc_2_e00166 PubMedSearch: Su 2014 Genome.Announc 2 e00166 PubMedID: 24652975 Gene_locus related to this paper: xylfs-z9jn15, 9gamm-z9jk30, 9gamm-z9jmt7 Abstract The draft genome sequence of Xylella fastidiosa pear leaf scorch strain PLS229, isolated from the pear cultivar Hengshan (Pyrus pyrifolia) in Taiwan, is reported here. The bacterium has a genome size of 2,733,013 bp, with a G+C content of 53.1%. The PLS229 genome was annotated and has 3,259 open reading frames and 50 RNA genes. Title: Association between copy number variation losses and alcohol dependence across African American and European American ethnic groups Ulloa AE, Chen J, Vergara VM, Calhoun V, Liu J Ref: Alcohol Clin Exp Res, 38:1266, 2014 : PubMed ESTHER: Ulloa_2014_Alcohol.Clin.Exp.Res_38_1266 PubMedSearch: Ulloa 2014 Alcohol.Clin.Exp.Res 38 1266 PubMedID: 24512105 Abstract BACKGROUND: Copy number variations (CNVs) are structural genetic mutations consisting of segmental gains or losses in DNA sequence. Although CNVs contribute substantially to genomic variation, few genetic and imaging studies report association of CNVs with alcohol dependence (AD). Our purpose is to find evidence of this association across ethnic populations and genders. This work is the first AD-CNV study across ethnic groups and the first to include the African American (AA) population. Title: Whole-Genome Sequence of Streptococcus suis Serotype 4 Reference Strain 6407 Wang K, Chen J, Yao H, Lu C Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Wang_2014_Genome.Announc_2_e00770 PubMedSearch: Wang 2014 Genome.Announc 2 e00770 PubMedID: 25125641 Gene_locus related to this paper: strsu-b9wvz1 Abstract We report here the second complete genome sequence of Streptococcus suis serotype 4 (strain 6407). The genome is 2,292,360 bp in length, covering 2,239 coding sequences, 58 tRNAs, and 4 rRNA loci. Title: Structural insights into enzymatic degradation of oxidized polyvinyl alcohol Yang Y, Ko TP, Liu L, Li J, Huang CH, Chan HC, Ren F, Jia D, Wang AH and Du G <2 more author(s)> Yang Y, Ko TP, Liu L, Li J, Huang CH, Chan HC, Ren F, Jia D, Wang AH, Guo RT, Chen J, Du G (- 2) Ref: Chembiochem, 15:1882, 2014 : PubMed ESTHER: Yang_2014_Chembiochem_15_1882 PubMedSearch: Yang 2014 Chembiochem 15 1882 PubMedID: 25044912 Gene_locus related to this paper: psesp-OPH, sphs1-OPH Inhibitor(s) related to this paper: Diethylene-glycol-monoethyl-ether, Acetylacetone, Octanoate Abstract The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our environment. Yet PVA can be assimilated by microbes in two steps: oxidation and cleavage. Here we report novel alpha/beta-hydrolase structures of oxidized PVA hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3 and Pseudomonas sp. VM15C, including complexes with substrate analogues, acetylacetone and caprylate. The active site is covered by a lid-like beta-ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the CC bond of beta-diketone, although it has a catalytic triad similar to that of most alpha/beta-hydrolases. Analysis of the crystal structures suggests a double-oxyanion-hole mechanism, previously only found in thiolase cleaving beta-ketoacyl-CoA. Three mutations in the lid region showed enhanced activity, with potential in industrial applications. Title: Roles of tryptophan residue and disulfide bond in the variable lid region of oxidized polyvinyl alcohol hydrolase Yang Y, Ko TP, Liu L, Li J, Huang CH, Chen J, Guo RT, Du G Ref: Biochemical & Biophysical Research Communications, 452:509, 2014 : PubMed ESTHER: Yang_2014_Biochem.Biophys.Res.Commun_452_509 PubMedSearch: Yang 2014 Biochem.Biophys.Res.Commun 452 509 PubMedID: 25173935 Gene_locus related to this paper: sphs1-OPH Inhibitor(s) related to this paper: Diethylene-glycol-monoethyl-ether, DMSO Abstract Oxidized polyvinyl alcohol hydrolase (OPH) catalyzes the cleavage of C-C bond in beta-diketone. It belongs to the alpha/beta-hydrolase family and contains a unique lid region that covers the active site. The lid is the most variable region when pOPH from Pseudomonas sp. VM15C and sOPH from Sphingopyxis sp. 113P3 are compared. The wild-type enzymes and the pOPH mutants W255A, W255Y and W255F were analyzed for lipase activity by using p-nitrophenyl (pNP) esters as the substrates. The wild-type enzymes showed increased Km and decreased kcat/Km with the acyl chain length, and the mutants showed reduced kcat/Km for pNP acetate, indicating the importance of Trp255 in sequestering the active site from solvent. The significantly lower activity for pNP butyrate can be a result of product inhibition, as suggested by the complex crystal structures, in which butyric acid, DMSO or PEG occupied the same substrate-binding cleft. The mutant activity was retained with pNP caprylate and pNP laurate as the substrates, reflecting the amphipathic nature of the cleft. Moreover, the disulfide bond formation of Cys257/267 is important for the activity of pOPH, but it is not essential for sOPH, which has a shorter lid structure. Title: Biochemical characterization and high-level production of oxidized polyvinyl alcohol hydrolase from Sphingopyxis sp. 113P3 expressed in methylotrophic Pichia pastoris Yang Y, Liu L, Li J, Du G, Chen J Ref: Bioprocess Biosyst Eng, 37:777, 2014 : PubMed ESTHER: Yang_2014_Bioprocess.Biosyst.Eng_37_777 PubMedSearch: Yang 2014 Bioprocess.Biosyst.Eng 37 777 PubMedID: 24068496 Abstract The Sphingopyxis sp. 113P3 gene oph, encoding oxidized polyvinyl alcohol hydrolase (OPH), was optimized with the preferred codons of Pichia pastoris and ligated into the pPIC9K vector behind the alpha-factor signal sequence. The vector was then transfected into P. pastoris GS115 and genomic integration was confirmed. Large-scale production of recombinant protein was performed by induction with 14.4 g/L methanol at 22 degrees C in a 3-L bioreactor. The maximal OPH activity obtained was 68.4 U/mL, which is the highest activity reported. The optimal pH and temperature of recombinant OPH were 8.0 and 45 degrees C, respectively. OPH activity was stable over a pH range of 5.0-8.5, and at a maximal temperature of 45 degrees C. The K cat /K m of recombinant OPH was 598 mM(-1) s(-1), which was 4.27-fold higher than that of recombinant OPH derived from Escherichia coli. The improved catalytic efficiency of OPH expressed in recombinant P. pastoris makes it favorable for industrial applications. Title: Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W and Shi Q <31 more author(s)> You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W, Zhang X, Sun Y, Chen S, Hong W, Li Y, Cheng S, Fan G, Shi C, Liang J, Tom Tang Y, Yang C, Ruan Z, Bai J, Peng C, Mu Q, Lu J, Fan M, Yang S, Huang Z, Jiang X, Fang X, Zhang G, Zhang Y, Polgar G, Yu H, Li J, Liu Z, Ravi V, Coon SL, Yang H, Venkatesh B, Shi Q (- 31) Ref: Nat Commun, 5:5594, 2014 : PubMed ESTHER: You_2014_Nat.Commun_5_5594 PubMedSearch: You 2014 Nat.Commun 5 5594 PubMedID: 25463417 Gene_locus related to this paper: 9gobi-a0a3b4bh68, 9gobi-a0a3b4bmj6, 9gobi-a0a3b4alj9, 9gobi-a0a3b4biy6, 9gobi-a0a3b4ah01, 9gobi-a0a3b3z8m7, 9gobi-a0a3b4aaj5, 9gobi-a0a3b4b6y7 Abstract Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. Title: Lipase immobilized catalytically active membrane for synthesis of lauryl stearate in a pervaporation membrane reactor Zhang W, Qing W, Ren Z, Li W, Chen J Ref: Bioresour Technol, 172C:16, 2014 : PubMed ESTHER: Zhang_2014_Bioresour.Technol_172C_16 PubMedSearch: Zhang 2014 Bioresour.Technol 172C 16 PubMedID: 25218626 Abstract A composite catalytically active membrane immobilized with Candida rugosa lipase has been prepared by immersion phase inversion technique for enzymatic synthesis of lauryl stearate in a pervaporation membrane reactor. SEM images showed that a "sandwich-like" membrane structure with a porous lipase-PVA catalytic layer uniformly coated on a polyvinyl alcohol (PVA)/polyethersulfone (PES) bilayer was obtained. Optimum conditions for lipase immobilization in the catalytic layer were determined. The membrane was proved to exhibit superior thermal stability, pH stability and reusability than free lipase under similar conditions. In the case of pervaporation coupled synthesis of lauryl stearate, benefited from in-situ water removal by the membrane, a conversion enhancement of approximately 40% was achieved in comparison to the equilibrium conversion obtained in batch reactors. In addition to conversion enhancement, it was also found that excess water removal by the catalytically active membrane appears to improve activity of the lipase immobilized. Title: [Cloning of feruloyl esterase gene from Aspergillus niger h408 and high-efficient expression in Pichia pastoris] Zhou Y, Liu X, Chen J, Hu H, Hou Y Ref: Wei Sheng Wu Xue Bao, 54:876, 2014 : PubMed ESTHER: Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876 PubMedSearch: Zhou 2014 Wei.Sheng.Wu.Xue.Bao 54 876 PubMedID: 25345018 Abstract OBJECTIVE: To achieve the high-efficiency expression of feruloyl estrase gene (AnfaeA) from Aspergillus niger h408 in Pichia pastoris and characterize the recombinant feruloyl esterase (FAE). Title: Free energy landscape for the binding process of Huperzine A to acetylcholinesterase Bai F, Xu Y, Chen J, Liu Q, Gu J, Wang X, Ma J, Li H, Onuchic JN, Jiang H Ref: Proc Natl Acad Sci U S A, 110:4273, 2013 : PubMed ESTHER: Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273 PubMedSearch: Bai 2013 Proc.Natl.Acad.Sci.U.S.A 110 4273 PubMedID: 23440190 Abstract Drug-target residence time (t = 1/k(off), where k(off) is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, k(off) and activation free energy of dissociation (DeltaG(off) not equal). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated. We applied this method to simulate the binding event of the anti-Alzheimer's disease drug (-)-Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/mol. The method also provides atomic resolution information for the (-)-Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect this methodology to be widely applicable to drug discovery and development. Title: Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens Chang X, Zhang S, Ma J, Li Z, Zhi Y, Chen J, Lu Y, Dai D Ref: Cell Biochem Biophys, 66:93, 2013 : PubMed ESTHER: Chang_2013_Cell.Biochem.Biophys_66_93 PubMedSearch: Chang 2013 Cell.Biochem.Biophys 66 93 PubMedID: 23099645 Abstract NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer. Title: A randomized, 4-week double-blind placebo control study on the efficacy of donepezil augmentation of lithium for treatment of acute mania Chen J, Lu Z, Zhang M, Zhang J, Ni X, Jiang X, Xu H, Heeramun-Aubeeluck A, Hu Q and Davis JM <1 more author(s)> Chen J, Lu Z, Zhang M, Zhang J, Ni X, Jiang X, Xu H, Heeramun-Aubeeluck A, Hu Q, Jin H, Davis JM (- 1) Ref: Neuropsychiatr Dis Treat, 9:839, 2013 : PubMed ESTHER: Chen_2013_Neuropsychiatr.Dis.Treat_9_839 PubMedSearch: Chen 2013 Neuropsychiatr.Dis.Treat 9 839 PubMedID: 23807849 Abstract INTRODUCTION: A significant number of mania patients fail to respond to current pharmacotherapy, thereby there is need for novel augmentation strategies. The results of some early studies showed the effectiveness of cholinomimetics in the treatment of mania. One open case series suggested the efficacy of donepezil in the treatment of bipolar disorder. Our aim was to explore whether an oral cholinesterase inhibitor, donepezil, administered during a 4-week treatment period, would benefit patients with acute mania. Title: Microcystin-LR-induced phytotoxicity in rice crown root is associated with the cross-talk between auxin and nitric oxide Chen J, Zhang HQ, Hu LB, Shi ZQ Ref: Chemosphere, 93:283, 2013 : PubMed ESTHER: Chen_2013_Chemosphere_93_283 PubMedSearch: Chen 2013 Chemosphere 93 283 PubMedID: 23726011 Abstract Irrigation with cyanobacterial-blooming water containing microcystin-LR (MC-LR) poses threat to the growth of agricultural plants. Large amounts of rice (Oryza sativa) field in the middle part of China has been irrigating with cyanobacterial-blooming water. Nevertheless, the mechanism of MC-LR-induced phytotoxicity in the root of monocot rice remains unclear. In the present study, we demonstrate that MC-LR stress significantly inhibits the growth of rice root by impacting the morphogenesis rice crown root. MC-LR treatment results in the decrease in IAA (indole-3-acetic acid) concentration as well as the expression of CRL1 and WOX11 in rice roots. The application of NAA (1-naphthylacetic acid), an IAA homologue, is able to attenuate the inhibitory effect of MC-LR on rice root development. MC-LR treatment significantly inhibits OsNia1-dependent NO generation in rice roots. The application of NO donor SNP (sodium nitroprusside) is able to partially reverse the inhibitory effects of MC-LR on the growth of rice root and the expression of CRL1 and WOX11 by enhancing endogenous NO level in rice roots. The application of NO scavenger cPTIO [2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide] eliminates the effects of SNP. Treatment with NAA stimulates the generation of endogenous NO in MC-LR-treated rice roots. Treatment with NO scavenger cPTIO abolishes the ameliorated effect of NAA on MC-LR-induced growth inhibition of rice root. Treatment with SNP enhanced IAA concentration in MC-LR-treated rice roots. Altogether, our data suggest that NO acts both downstream and upstream of auxin in regulating rice root morphogenesis under MC-LR stress. Title: Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution Chen J, Huang Q, Gao D, Wang J, Lang Y, Liu T, Li B, Bai Z, Luis Goicoechea J and Chen M <30 more author(s)> Chen J, Huang Q, Gao D, Wang J, Lang Y, Liu T, Li B, Bai Z, Luis Goicoechea J, Liang C, Chen C, Zhang W, Sun S, Liao Y, Zhang X, Yang L, Song C, Wang M, Shi J, Liu G, Liu J, Zhou H, Zhou W, Yu Q, An N, Chen Y, Cai Q, Wang B, Liu B, Min J, Huang Y, Wu H, Li Z, Zhang Y, Yin Y, Song W, Jiang J, Jackson SA, Wing RA, Chen M (- 30) Ref: Nat Commun, 4:1595, 2013 : PubMed ESTHER: Chen_2013_Nat.Commun_4_1595 PubMedSearch: Chen 2013 Nat.Commun 4 1595 PubMedID: 23481403 Gene_locus related to this paper: orysa-Q6ZDG3, orysa-q6h415, orysj-q6yse8, orysa-q33aq0, orybr-j3l7k2, orybr-j3m138, orybr-j3l6m8, orybr-j3m3b3, orybr-j3l8d1, orybr-j3kza5, orybr-j3mnb5, orybr-j3n4p4, orybr-j3lg73, orybr-j3l342, orybr-j3msi2, orybr-j3nb83, orybr-j3mpc5 Abstract The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza. Title: Cutinase: Characteristics, preparation, and application Chen S, Su L, Chen J, Wu J Ref: Biotechnol Adv, 31:1754, 2013 : PubMed ESTHER: Chen_2013_Biotechnol.Adv_31_1754 PubMedSearch: Chen 2013 Biotechnol.Adv 31 1754 PubMedID: 24055682 Abstract Cutinases (E.C. 3.1.1.74) belong to the alpha/beta-hydrolase superfamily. They were initially discovered because they are secreted by fungi to hydrolyze the ester bonds of the plant polymer cutin. Since then, they have been shown to catalyze the hydrolysis of a variety of polymers, insoluble triacylglycerols, and low-molecular-weight soluble esters. Cutinases are also capable of catalyzing esterification and transesterification reactions. These relatively small, versatile, secreted catalysts have shown promise in a number of industrial applications. This review begins by describing the characteristics of cutinases, pointing out key differences among cutinases, esterases and lipases, and reviewing recent progress in engineering improved cutinases. It continues with a review of the methods used to produce cutinases, with the goal of obtaining sufficient quantities of material for use in industrial processes. Finally, the uses of cutinases in the textile industry are described. The studies presented here demonstrate that the cutinases are poised to become important industrial catalysts, replacing older technologies with more environmentally friendly processes. Title: Draft Genome Sequence of Xylella fastidiosa subsp. multiplex Strain Griffin-1 from Quercus rubra in Georgia Chen J, Huang H, Chang CJ, Stenger DC Ref: Genome Announc, 1:e00756, 2013 : PubMed ESTHER: Chen_2013_Genome.Announc_1_e00756 PubMedSearch: Chen 2013 Genome.Announc 1 e00756 PubMedID: 24115539 Gene_locus related to this paper: xylfa-pip Abstract The draft genome sequence of Xylella fastidiosa subsp. multiplex strain Griffin-1, isolated from a red oak tree (Quercus rubra) in Georgia, is reported here. The bacterium has a genome size of 2,387,314 bp, with a G+C content of 51.7%. The Griffin-1 strain genome contains 2,903 predicted open reading frames and 50 RNA genes. Title: In situ formation of metal coordination polymer: a strategy for fluorescence turn-on assay of acetylcholinesterase activity and inhibitor screening Liao D, Chen J, Zhou H, Wang Y, Li Y, Yu C Ref: Analytical Chemistry, 85:2667, 2013 : PubMed ESTHER: Liao_2013_Anal.Chem_85_2667 PubMedSearch: Liao 2013 Anal.Chem 85 2667 PubMedID: 23379662 Abstract A novel method for the sensing of acetylcholinesterase (AChE) activity and inhibitor screening based on the formation of metal coordination polymer has been developed. Acetylthiocholine (ATCh) was selected as the substrate. In the presence of AChE, ATCh was hydrolyzed to thiocholine and acetate. Thiocholine interacted with Ag(I) to form a metal coordination polymer. A positively charged perylene probe (probe 1) was employed. The fluorescence of probe 1 was very efficiently quenched by a polyanion [PVS, poly(vinyl sulfonate)]. In the presence of acetylcholinesterase, the positively charged metal coordination polymer newly formed in situ would interact with PVS, probe 1 monomer molecules were released, and a turn on fluorescence signal was detected. The assay is highly sensitive, a limit of detection of 0.04 mU/mL AChE was obtained. The assay is also highly selective, a number of potential interference proteins (enzymes) were tested, and none of them show noticeable interference. Sensing of AChE inhibitor was also demonstrated. Our assay is fairly simple and inexpensive. We envision that it could be used for the sensitive detection of other hydrolytic enzyme activities with properly selected substrates and for the screening of potential inhibitor drugs. Title: Whole-Genome Sequencing of Lactobacillus shenzhenensis Strain LY-73T Lin Z, Liu Z, Yang R, Zou Y, Wan D, Chen J, Guo M, Zhao J, Fang C, Liu F Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Lin_2013_Genome.Announc_1_e00972 PubMedSearch: Lin 2013 Genome.Announc 1 e00972 PubMedID: 24265500 Gene_locus related to this paper: 9laco-u4tvs6, 9laco-u4ti93 Abstract Lactobacillus shenzhenensis strain LY-73(T) is a novel species which was first isolated from fermented goods. Here, we report the draft genome sequence of Lactobacillus shenzhenensis LY-73(T). Title: Draft genome of the wheat A-genome progenitor Triticum urartu Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L and Zhang A <39 more author(s)> Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L, Tao Y, Gao C, Wu H, Li Y, Cui Y, Guo X, Zheng S, Wang B, Yu K, Liang Q, Yang W, Lou X, Chen J, Feng M, Jian J, Zhang X, Luo G, Jiang Y, Liu J, Wang Z, Sha Y, Zhang B, Tang D, Shen Q, Xue P, Zou S, Wang X, Liu X, Wang F, Yang Y, An X, Dong Z, Zhang K, Luo MC, Dvorak J, Tong Y, Yang H, Li Z, Wang D, Zhang A (- 39) Ref: Nature, 496:87, 2013 : PubMed ESTHER: Ling_2013_Nature_496_87 PubMedSearch: Ling 2013 Nature 496 87 PubMedID: 23535596 Gene_locus related to this paper: triua-m8a764, triua-m8ag96, triua-m7zp69, wheat-w5d1z6, wheat-w5d232, wheat-w5bnf5, triua-t1nm05, wheat-w5cae4, triua-m7ytf7, wheat-w5f1j8, triua-m8ad49, wheat-a0a077s1q2, wheat-a0a3b6c2m6, triua-m7zi26, wheat-a0a3b6at77 Abstract Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat. Title: 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: Song bu li decoction, a traditional uyghur medicine, protects cell death by regulation of oxidative stress and differentiation in cultured PC12 cells Maiwulanjiang M, Zhu KY, Chen J, Miernisha A, Xu SL, Du CY, Lau KK, Choi RC, Dong TTX and Tsim KWK <1 more author(s)> Maiwulanjiang M, Zhu KY, Chen J, Miernisha A, Xu SL, Du CY, Lau KK, Choi RC, Dong TTX, Aisa HA, Tsim KWK (- 1) Ref: Evid Based Complement Alternat Med, 2013:687958, 2013 : PubMed ESTHER: Maiwulanjiang_2013_Evid.Based.Complement.Alternat.Med_2013_687958 PubMedSearch: Maiwulanjiang 2013 Evid.Based.Complement.Alternat.Med 2013 687958 PubMedID: 24198845 Abstract Song Bu Li decoction (SBL) is a traditional Uyghur medicinal herbal preparation, containing Nardostachyos Radix et Rhizoma. Recently, SBL is being used to treat neurological disorders (insomnia and neurasthenia) and heart disorders (arrhythmia and palpitation). Although this herbal extract has been used for many years, there is no scientific basis about its effectiveness. Here, we aimed to evaluate the protective and differentiating activities of SBL in cultured PC12 cells. The pretreatment of SBL protected the cell against tBHP-induced cell death in a dose-dependent manner. In parallel, SBL suppressed intracellular reactive oxygen species (ROS) formation. The transcriptional activity of antioxidant response element (ARE), as well as the key antioxidative stress proteins, was induced in dose-dependent manner by SBL in the cultures. In cultured PC12 cells, the expression of neurofilament, a protein marker for neuronal differentiation, was markedly induced by applied herbal extract. Moreover, the nerve growth factor- (NGF-) induced neurite outgrowth in cultured PC12 cells was significantly potentiated by the cotreatment of SBL. In accord, the expression of neurofilament was increased in the treatment of SBL. These results therefore suggested a possible role of SBL by its effect on neuron differentiation and protection against oxidative stress. Title: Novel tacrine-ebselen hybrids with improved cholinesterase inhibitory, hydrogen peroxide and peroxynitrite scavenging activity Mao F, Chen J, Zhou Q, Luo Z, Huang L, Li X Ref: Bioorganic & Medicinal Chemistry Lett, 23:6737, 2013 : PubMed ESTHER: Mao_2013_Bioorg.Med.Chem.Lett_23_6737 PubMedSearch: Mao 2013 Bioorg.Med.Chem.Lett 23 6737 PubMedID: 24220172 Inhibitor(s) related to this paper: Ebselen Abstract A series of tacrine-ebselen hybrids were synthesised and evaluated as possible multifunctional anti-Alzheimer's disease (AD) agents. Compound 6i, which is tacrine linked with 5,6-dimethoxybenzo[d][1,2]selenazol-3(2H)-one by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) and butylcholinesterase (BCHE) inhibitor, with IC50 values of 2.55 and 2.80nM, respectively. Furthermore, this compound demonstrated similar hydrogen peroxide and peroxynitrite scavenging activity as ebselen by horseradish peroxidase assay and peroxynitrite scavenging activity assay, indicating that this hybrid is a good multifunctional drug candidate for the treatment of AD. Title: Draft Genome Sequence of Pseudomonas plecoglossicida Strain NB2011, the Causative Agent of White Nodules in Large Yellow Croaker (Larimichthys crocea) Mao Z, Li M, Chen J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Mao_2013_Genome.Announc_1_e00586 PubMedSearch: Mao 2013 Genome.Announc 1 e00586 PubMedID: 23929479 Gene_locus related to this paper: 9psed-s2k464, psepu-PIP, 9psed-s2k0h8, 9psed-s2jxx1, 9psed-s2kmi2 Abstract We describe the draft genome sequence of Pseudomonas plecoglossicida strain NB2011, the causative agent of white nodules in cultured large yellow croaker (Larimichthys crocea) in China. The draft genome sequence of the bacterium consists of 5.41 million bp, with a G+C content of 62.8%. A total of 4,952 genes were identified. Title: Poster: In vitro exposure to nicotine modulate the function of presynaptic NMDA receptors present on dopaminergic terminals in rat Nucleus Accumbens Marchi M, Salamone A, Zappettini S, Grilli M, Olivero G, Chen J, Cunha R, Pittaluga A Ref: Biochemical Pharmacology, 86:1228, 2013 : PubMed ESTHER: Marchi_2013_Biochem.Pharmacol_86(8)_1228 PubMedSearch: Marchi 2013 Biochem.Pharmacol 86(8) 1228 Title: Association of lipoprotein lipase polymorphism rs2197089 with serum lipid concentrations and LPL gene expression Mo X, Liu X, Wang L, Lu X, Chen S, Li H, Huang J, Chen J, Cao J and Gu D <2 more author(s)> Mo X, Liu X, Wang L, Lu X, Chen S, Li H, Huang J, Chen J, Cao J, Li J, Tang Y, Gu D (- 2) Ref: J Hum Genet, 58:160, 2013 : PubMed ESTHER: Mo_2013_J.Hum.Genet_58_160 PubMedSearch: Mo 2013 J.Hum.Genet 58 160 PubMedID: 23344322 Abstract Many single-nucleotide polymorphisms (SNPs) have been reported to be associated with lipid concentrations in recent genome-wide association studies. The aim of this study was to validate the associations of rs2197089 in the lipoprotein lipase (LPL) gene with serum lipid concentrations and gene expression levels in the Chinese Han population and examine the potential interactions. A total of 9339 participants were recruited and genotyped for rs2197089. Gene expression levels of LPL in blood cells of 309 participants were evaluated by real-time PCR. We observed significant associations between rs2197089 and decreased triglycerides (TG) (P=0.0006), but not high-density lipoprotein cholesterol (HDL-C) concentration (P=0.0881). However, weak evidence of interaction between cigarette smoking and rs2197089 was detected (P=0.0362). In smokers, significant association between rs2197089 and increased HDL-C concentration was found (P=0.0068). Participants with the minor allele A had higher expression levels of LPL (P=0.0243). The results of our study indicated that rs2197089 was significantly associated with TG but it was associated with HDL-C only in smokers. This SNP seemed to have influence on the expression level of LPL. Title: Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H and Ehringer MA <116 more author(s)> Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Han Y, Hansel NN, Jiang C, Korhonen T, Lind PA, Liu J, Lyytikainen LP, Michel M, Shaffer JR, Short SE, Sun J, Teumer A, Thompson JR, Vogelzangs N, Vink JM, Wenzlaff A, Wheeler W, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty TH, Benjamin DJ, Bergen AW, Broms U, Cesarini D, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gillespie NA, Gu F, Hall AS, Hallfors J, Han S, Hartmann AM, Heikkila K, Hickie IB, Hottenga JJ, Jousilahti P, Kaakinen M, Kahonen M, Koellinger PD, Kittner S, Konte B, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Murray T, Nauck M, North KE, Pare PD, Pergadia M, Ruczinski I, Salomaa V, Viikari J, Willemsen G, Barnes KC, Boerwinkle E, Boomsma DI, Caporaso N, Edenberg HJ, Francks C, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Johannesson M, Kendler KS, Lehtimaki T, Magnusson PK, Marazita ML, Marchini J, Mitchell BD, Nothen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Schwartz AG, Shete S, Spitz M, Swan GE, Volzke H, Veijola J, Wei Q, Amos C, Cannon DS, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Weiss RB, Kraft P, Bierut LJ, Ehringer MA (- 116) Ref: Genet Epidemiol, 37:846, 2013 : PubMed ESTHER: Stephens_2013_Genet.Epidemiol_37_846 PubMedSearch: Stephens 2013 Genet.Epidemiol 37 846 PubMedID: 24186853 Abstract Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype. Title: Extracellular location of Thermobifida fusca cutinase expressed in Escherichia coli BL21(DE3) without mediation of a signal peptide Su L, Woodard RW, Chen J, Wu J Ref: Applied Environmental Microbiology, 79:4192, 2013 : PubMed ESTHER: Su_2013_Appl.Environ.Microbiol_79_4192 PubMedSearch: Su 2013 Appl.Environ.Microbiol 79 4192 PubMedID: 23603671 Abstract Cutinase is a multifunctional esterase with potential industrial applications. In the present study, a truncated version of the extracellular Thermobifida fusca cutinase without a signal peptide (referred to as cutinase(NS)) was heterologously expressed in Escherichia coli BL21(DE3). The results showed that the majority of the cutinase activity was located in the culture medium. In a 3-liter fermentor, the cutinase activity in the culture medium reached 1,063.5 U/ml (2,380.8 mg/liter), and the productivity was 40.9 U/ml/h. Biochemical characterization of the purified cutinase(NS) showed that it has enzymatic properties similar to those of the wild-type enzyme. In addition, E. coli cells producing inactive cutinase(NS)S130A were constructed, and it was found that the majority of the inactive enzyme was located in the cytoplasm. Furthermore, T. fusca cutinase was confirmed to have hydrolytic activity toward phospholipids, an important component of the cell membrane. Compared to the cells expressing the inactive cutinase(NS)S130A, the cells expressing cutinase(NS) showed increased membrane permeability and irregular morphology. Based on these results, a hypothesis of "cell leakage induced by the limited phospholipid hydrolysis of cutinase(NS)" was proposed to explain the underlying mechanism for the extracellular release of cutinase(NS). Title: A novel strategy for enhancing extracellular secretion of recombinant proteins in Escherichia coli Su L, Xu C, Woodard RW, Chen J, Wu J Ref: Applied Microbiology & Biotechnology, 97:6705, 2013 : PubMed ESTHER: Su_2013_Appl.Microbiol.Biotechnol_97_6705 PubMedSearch: Su 2013 Appl.Microbiol.Biotechnol 97 6705 PubMedID: 23722267 Abstract Secretion of cytoplasmic expressed proteins into culture medium has significant commercial advantages in large-scale production of proteins. Our previous study demonstrated that the membrane permeability of Escherichia coli could be significantly improved when Thermobifida fusca cutinase, without a signal peptide, was expressed in cytoplasm. This study investigated the extracellular production of other recombinant proteins, including both secretory and cytosolic proteins, with co-expression of cutinase. When the secretory enzymes, xylanase and alpha-amylase, were co-expressed with cutinase, the culture period was shortened by half, and the productivity was 7.9 and 2.0-fold to that of their individual control without co-expression, respectively. When the normally cytosolic proteins, xylose isomerase and trehalose synthase, were co-expressed with cutinase, more than half of the target proteins were "secreted" into the culture medium. Moreover, by using beta-galactosidase to detect membrane leakage, the improved secretion of the above model proteins was confirmed not to be due to cell lysis. The study provides a novel strategy for enhancing extracellular secretion of recombinant proteins in E. coli. Title: Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine-Homoisoflavonoid hybrids Sun Y, Chen J, Chen X, Huang L, Li X Ref: Bioorganic & Medicinal Chemistry, 21:7406, 2013 : PubMed ESTHER: Sun_2013_Bioorg.Med.Chem_21_7406 PubMedSearch: Sun 2013 Bioorg.Med.Chem 21 7406 PubMedID: 24128814 Abstract A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9nM and 0.401muM, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD). Title: Triptolide inhibits amyloid-beta production and protects neural cells by inhibiting CXCR2 activity Wang J, Shi ZQ, Xu X, Xin GZ, Chen J, Qi LW, Li P Ref: J Alzheimers Dis, 33:217, 2013 : PubMed ESTHER: Wang_2013_J.Alzheimers.Dis_33_217 PubMedSearch: Wang 2013 J.Alzheimers.Dis 33 217 PubMedID: 22986777 Abstract Triptolide, a biologically active natural product from Tripterygium wilfordii, protects neurons from inflammation-mediated damage. Our results showed for the first time that triptolide inhibited the expression of CXCR2 and presenilin in a neuroblastoma cell line SHSY5Ysw. Moreover, triptolide potently inhibited amyloid-beta1-42 production with IC50 value of 30 pM in HEK293sw cells or 2 nM in SHSY5Ysw cells, respectively. We also demonstrated that triptolide prevented primary cortical neurons from chemokine CXCL1-induced cytotoxicity. Therefore, our study indicates that the neural protective effect of triptolide is largely mediated by inhibiting CXCR2 activity. Title: Whole-Genome Sequence of Streptococcus suis Serotype 3 Strain YB51 Wang K, Chen J, Yao H, Lu C Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Wang_2013_Genome.Announc_1_e00884 PubMedSearch: Wang 2013 Genome.Announc 1 e00884 PubMedID: 24179118 Gene_locus related to this paper: strsu-b9wvz1 Abstract We report here the second complete genome sequence of Streptococcus suis serotype 3 (strain YB51). The genome is 2,043,655 bp in length, which is 14,840 bp longer than the first reported genome of the same serotype, and it covers 2,012 coding sequences, 56 tRNAs, and 4 rRNA loci. Title: Complete Genome Sequence of Streptococcus suis Serotype 16 Strain TL13 Wang K, Yao H, Lu C, Chen J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Wang_2013_Genome.Announc_1_e00394 PubMedSearch: Wang 2013 Genome.Announc 1 e00394 PubMedID: 23814033 Gene_locus related to this paper: strsu-b9wvz1 Abstract We report here the first complete genome sequence of Streptococcus suis serotype 16, which has been identified to be zoonotic. The sequenced strain TL13 was isolated from a pig in China. The genome is 2,038,146 bp in length, covering 1,950 coding sequences, 53 tRNAs, and 4 rRNA loci. Title: In vivo readout of CFTR function: ratiometric measurement of CFTR-dependent secretion by individual, identifiable human sweat glands Wine JJ, Char JE, Chen J, Cho HJ, Dunn C, Frisbee E, Joo NS, Milla C, Modlin SE and Wolfe MH <4 more author(s)> Wine JJ, Char JE, Chen J, Cho HJ, Dunn C, Frisbee E, Joo NS, Milla C, Modlin SE, Park IH, Thomas EA, Tran KV, Verma R, Wolfe MH (- 4) Ref: PLoS ONE, 8:e77114, 2013 : PubMed ESTHER: Wine_2013_PLoS.One_8_e77114 PubMedSearch: Wine 2013 PLoS.One 8 e77114 PubMedID: 24204751 Abstract To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a beta-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics. Title: Complete Genome Sequence of Glaciecola psychrophila Strain 170T Yin J, Chen J, Liu G, Yu Y, Song L, Wang X, Qu X Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Yin_2013_Genome.Announc_1_E00199 PubMedSearch: Yin 2013 Genome.Announc 1 E00199 PubMedID: 23640379 Gene_locus related to this paper: 9alte-k7ach6, 9alte-k7ahj1, 9alte-k7ava9, 9alte-k6ynu0, 9alte-k6z391, 9alte-k7a5n7, 9alte-k7a8i8 Abstract Here, we report the complete genome sequence of Glaciecola psychrophila strain 170(T), a novel species of the genus Glaciecola, isolated from sea ice at high-latitude Arctic locations. The genome consists of a single chromosome (5,413,691 bp) and 5,363 genes. The genomics information will facilitate the study of the physiology, cold adaptation, and evolution of this genus. Title: Enhanced activity toward PET by site-directed mutagenesis of Thermobifida fusca cutinase-CBM fusion protein Zhang Y, Wang L, Chen J, Wu J Ref: Carbohydr Polym, 97:124, 2013 : PubMed ESTHER: Zhang_2013_Carbohydr.Polym_97_124 PubMedSearch: Zhang 2013 Carbohydr.Polym 97 124 PubMedID: 23769527 Abstract In the present study, cutinase-CBMCenA fusion protein was genetically modified in the carbohydrate-binding module (CBM) binding sites, by site-directed mutagenesis, to enhance its activity toward polyethylene terephthalate (PET) fiber. The effects of tryptophan at particular positions of CBMCenA on the binding and hydrolysis of polyester substrate were investigated by replacing each of Trp14, Trp50 and Trp68 with leucine or tyrosine, respectively. All the mutants were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that the mutants displayed similar thermostability and pH stabilities in response to the native enzyme. Furthermore, W68L and W68Y, among all the mutants, exhibited significant improvement in binding and catalytic efficiency (1.4-1.5 fold) toward PET fiber when compared to that of the native enzyme. The enhanced binding and hydrolytic activity might be a result of creating new hydrogen bond or hydrophobic interaction between the enzyme and PET fiber. Title: Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X and Meng J <2 more author(s)> Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X, Allard M, Brown E, Meng J (- 2) Ref: Genome Announc, 1:E00213, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00213 PubMedSearch: Zhang 2013 Genome.Announc 1 E00213 PubMedID: 23661485 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China. Title: The genome of the hydatid tapeworm Echinococcus granulosus Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y and Wang S <21 more author(s)> Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y, Liu J, Kang H, Chen J, Wang L, Chen A, Yu S, Gao Z, Jin L, Gu W, Wang Z, Zhao L, Shi B, Wen H, Lin R, Jones MK, Brejova B, Vinar T, Zhao G, McManus DP, Chen Z, Zhou Y, Wang S (- 21) Ref: Nat Genet, 45:1168, 2013 : PubMed ESTHER: Zheng_2013_Nat.Genet_45_1168 PubMedSearch: Zheng 2013 Nat.Genet 45 1168 PubMedID: 24013640 Gene_locus related to this paper: echgr-k4epc5, echmu-u6hbw4, echgr-w6ugl0, echgr-w6u7y4, echgr-w6vaq5, echgr-a0a068wxj3, echgr-a0a068wgw1, echgr-a0a068wl60 Abstract Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control. Title: D14-SCFD3-dependent degradation of D53 regulates strigolactone signalling Zhou F, Lin Q, Zhu L, Ren Y, Zhou K, Shabek N, Wu F, Mao H, Dong W and Wan J <24 more author(s)> Zhou F, Lin Q, Zhu L, Ren Y, Zhou K, Shabek N, Wu F, Mao H, Dong W, Gan L, Ma W, Gao H, Chen J, Yang C, Wang D, Tan J, Zhang X, Guo X, Wang J, Jiang L, Liu X, Chen W, Chu J, Yan C, Ueno K, Ito S, Asami T, Cheng Z, Lei C, Zhai H, Wu C, Wang H, Zheng N, Wan J (- 24) Ref: Nature, 504:406, 2013 : PubMed ESTHER: Zhou_2013_Nature_504_406 PubMedSearch: Zhou 2013 Nature 504 406 PubMedID: 24336215 Abstract Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the alpha/beta hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses. Title: Nicotine normalizes event related potentials in COMT-Val-tg mice and increases gamma and theta spectral density Cao YA, Featherstone RE, Gandal MJ, Liang Y, Jutzeler C, Saunders J, Tatard-Leitman V, Chen J, Weinberger DR and Siegel SJ <1 more author(s)> Cao YA, Featherstone RE, Gandal MJ, Liang Y, Jutzeler C, Saunders J, Tatard-Leitman V, Chen J, Weinberger DR, Lerman C, Siegel SJ (- 1) Ref: Behavioral Neuroscience, 126:332, 2012 : PubMed ESTHER: Cao_2012_Behav.Neurosci_126_332 PubMedSearch: Cao 2012 Behav.Neurosci 126 332 PubMedID: 22309446 Abstract Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high-activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high-activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT-Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele. Title: Active zone density is conserved during synaptic growth but impaired in aged mice Chen J, Mizushige T, Nishimune H Ref: Journal of Comparative Neurology, 520:434, 2012 : PubMed ESTHER: Chen_2012_J.Comp.Neurol_520_434 PubMedSearch: Chen 2012 J.Comp.Neurol 520 434 PubMedID: 21935939 Abstract Presynaptic active zones are essential structures for synaptic vesicle release, but the developmental regulation of their number and maintenance during aging at mammalian neuromuscular junctions (NMJs) remains unknown. Here, we analyzed the distribution of active zones in developing, mature, and aged mouse NMJs by immunohistochemical detection of the active zone-specific protein Bassoon. Bassoon is a cytosolic scaffolding protein essential for the active zone assembly in ribbon synapses and some brain synapses. Bassoon staining showed a punctate pattern in nerve terminals and axons at the nascent NMJ on embryonic days 16.5-18.5. Three-dimensional reconstruction of NMJs revealed that the majority of Bassoon puncta within an NMJ were attached to the presynaptic membrane from postnatal day 0 to adulthood, and colocalized with another active zone protein, Piccolo. During postnatal development, the number of Bassoon puncta increased as the size of the synapses increased. Importantly, the density of Bassoon puncta remained relatively constant from postnatal day 0 to 54 at 2.3 puncta/mum(2) , while the synapse size increased 3.3-fold. However, Bassoon puncta density and signal intensity were significantly attenuated at the NMJs of 27-month-old aged mice. These results suggest that synapses maintain the density of synaptic vesicle release sites while the synapse size changes, but this density becomes impaired during aging. Title: Presynaptic Active Zone Density during Development and Synaptic Plasticity Clarke GL, Chen J, Nishimune H Ref: Front Mol Neurosci, 5:12, 2012 : PubMed ESTHER: Clarke_2012_Front.Mol.Neurosci_5_12 PubMedSearch: Clarke 2012 Front.Mol.Neurosci 5 12 PubMedID: 22438837 Abstract Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and beta-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated. Title: Enhancement of nose-to-brain delivery of basic fibroblast growth factor for improving rat memory impairments induced by co-injection of beta-amyloid and ibotenic acid into the bilateral hippocampus Feng C, Zhang C, Shao X, Liu Q, Qian Y, Feng L, Chen J, Zha Y, Zhang Q, Jiang X Ref: Int J Pharm, 423:226, 2012 : PubMed ESTHER: Feng_2012_Int.J.Pharm_423_226 PubMedSearch: Feng 2012 Int.J.Pharm 423 226 PubMedID: 22193058 Abstract Basic fibroblast growth factor (bFGF) delivery to the brain of animals appears to be an emerging potential therapeutic approach to neurodegenerative diseases, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion. A nasal spray of bFGF had been developed previously and the objective of the present study was to investigate whether bFGF nasal spray could enhance brain uptake of bFGF and ameliorate memory impairment induced by co-injection of beta-amyloid(25-35) and ibotenic acid into bilateral hippocampus of rats. The results of brain uptake study showed that the AUC(0-12h) of bFGF nasal spray in olfactory bulb, cerebrum, cerebellum and hippocampus was respectively 2.47, 2.38, 2.56 and 2.19 times that of intravenous bFGF solution, and 1.11, 1.95, 1.40 and 1.93 times that of intranasal bFGF solution, indicating that intranasal administration of bFGF nasal spray was an effective means of delivering bFGF to the brain, especially to cerebrum and hippocampus. In Morris water maze tasks, intravenous administration of bFGF solution at high dose (40 mug/kg) showed little improvement on spatial memory impairment. In contrast, bFGF solution of the same dose following intranasal administration could significantly ameliorate spatial memory impairment. bFGF nasal spray obviously improved spatial memory impairment even at a dose half (20 mug/kg) of bFGF solution, recovered their acetylcholinesterase and choline acetyltransferase activity to the sham control level, and alleviated neuronal degeneration in rat hippocampus, indicating neuroprotective effects on the central nerve system. In a word, bFGF nasal spray may be a new formulation of great potential for treating AD. Title: Effects of AIBL on Oncomelania hupensis, the intermediate snail host of Schistosoma japonicum: An enzyme histochemical study Han BX, Guo DZ, Chen J, Mao J Ref: Asian Pac J Trop Med, 5:966, 2012 : PubMed ESTHER: Han_2012_Asian.Pac.J.Trop.Med_5_966 PubMedSearch: Han 2012 Asian.Pac.J.Trop.Med 5 966 PubMedID: 23199715 Abstract OBJECTIVE: To explore the effect of AIBL on Oncomelania hupensis, the intermediate snail host of Schistosoma japonicum. Title: Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH and Bierut LJ <142 more author(s)> Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikainen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hallfors J, Han S, Hartmann AM, Hayward C, Heikkila K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkarsdottir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeboller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kahonen M, Kendler KS, Lehtimaki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nothen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Volzke H, Wei Q, Wichmann HE, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ (- 142) Ref: Arch Gen Psychiatry, 69:854, 2012 : PubMed ESTHER: Hartz_2012_Arch.Gen.Psychiatry_69_854 PubMedSearch: Hartz 2012 Arch.Gen.Psychiatry 69 854 PubMedID: 22868939 Abstract CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD </=10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset </=16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. Title: On-line immobilized acetylcholinesterase microreactor for screening of inhibitors from natural extracts by capillary electrophoresis Min W, Wang W, Chen J, Wang A, Hu Z Ref: Anal Bioanal Chem, 404:2397, 2012 : PubMed ESTHER: Min_2012_Anal.Bioanal.Chem_404_2397 PubMedSearch: Min 2012 Anal.Bioanal.Chem 404 2397 PubMedID: 22932810 Abstract In this study we developed a simple capillary electrophoresis (CE) method with an on-line acetylcholinesterase (AChE) microreactor at the inlet of capillary for inhibitor screening. The fused-silica capillary surface was modified with a polycationic polyethylenimine coating. Solutions of the enzyme and chitosan were then injected to immobilize the enzyme in approximately 2.9 cm of the capillary inlet (total length of capillary 60.2 cm) by electrostatic interaction and the film overlay technique. Separation of enzyme reaction product (thiocholine, ThCh) and unreacted substrate (acetylthiocholine, AThCh) was achieved within 3.0 min. The conditions affecting the efficiency of reaction of the enzyme were optimized by measuring the peak area of ThCh. Under the optimum conditions, using Huperzine-A as model inhibitor, K (i) and IC (50) were 0.551 mumol L(-1) and 1.52 mumol L(-1), respectively, for immobilized AChE. Finally, screening of a small compound library containing two known AChE inhibitors and 30 natural extracts was conducted, and species with inhibition activity were directly identified. Compared with previous publications on screening for AChE inhibitors in natural products based on CE methods, the method developed in this work has the advantages of lower cost per analysis, less leakage, and better bioaffinity for the immobilized enzyme because of the unique properties of sodium alginate and chitosan. Title: Active zone protein Bassoon co-localizes with presynaptic calcium channel, modifies channel function, and recovers from aging related loss by exercise Nishimune H, Numata T, Chen J, Aoki Y, Wang Y, Starr MP, Mori Y, Stanford JA Ref: PLoS ONE, 7:e38029, 2012 : PubMed ESTHER: Nishimune_2012_PLoS.One_7_e38029 PubMedSearch: Nishimune 2012 PLoS.One 7 e38029 PubMedID: 22701595 Abstract The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca(2+) influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise. Title: Extracellular overexpression of recombinant Thermobifida fusca cutinase by alpha-hemolysin secretion system in E. coli BL21(DE3) Su L, Chen S, Yi L, Woodard RW, Chen J, Wu J Ref: Microb Cell Fact, 11:8, 2012 : PubMed ESTHER: Su_2012_Microb.Cell.Fact_11_8 PubMedSearch: Su 2012 Microb.Cell.Fact 11 8 PubMedID: 22239833 Abstract BACKGROUND: Extracellular expression of proteins has an absolute advantage in a large-scale industrial production. In our previous study, Thermobifida fusca cutinase, an enzyme mainly utilized in textile industry, was expressed via type II secretory system in Escherichia coli BL21(DE3), and it was found that parts of the expressed protein was accumulated in the periplasmic space. Due to the fact that alpha-hemolysin secretion system can export target proteins directly from cytoplasm across both cell membrane of E. coli to the culture medium, thus in the present study we investigated the expression of cutinase using this alpha-hemolysin secretion system. RESULTS: T. fusca cutinase was fused with the specific signal peptide of alpha-hemolysin scretion system and expressed in E. coli BL21(DE3). In addition, HlyB and HlyD, strain-specific translocation components of alpha-hemolysin secretion system, were coexpressed to facilitate the enzyme expression. The cultivation of this engineered cell showed that cutinase activity in the culture medium reached 334 U/ml, which is 2.5 times that from type II secretion pathway under the same culture condition. The recombinant cutinase was further purified. Biochemical characterization of purified enzyme, which had an alpha-hemolysin secretion pathway signal peptide attached, had substrate specificity, pH and temperature profile, as well as application capability in bioscouring similar to that of wild-type cutinase. CONCLUSIONS: In the present study, T. fusca cutinase was successfully secreted to the culture media by alpha-hemolysin secretion system. This is the first report of cutinase being efficiently secreted by this pathway. Due to the limited cases of successful expression of industrial enzyme by E. coli alpha-hemolysin secretion system, our study further explored the utilization of this pathway in industrial enzymes. Title: Direct pharmacokinetic analysis of puqietinone by in vivo microdialysis sampling and turbulent-flow chromatography coupled with liquid chromatography-mass spectrometry Xin GZ, Cao L, Shi ZQ, Li HJ, Wen XD, Chen J, Qi LW, Li P Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 899:127, 2012 : PubMed ESTHER: Xin_2012_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_899_127 PubMedSearch: Xin 2012 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 899 127 PubMedID: 22658466 Abstract Sample pretreatment is a key step in bioanalytical process because of possible interference and matrix effects in mass spectrometry analysis. In this work, a novel strategy towards high speed and sensitivity was developed combining in vivo microdialysis (MD) sampling, turbulent-flow chromatography (TFC), and liquid chromatography-mass spectrometry (LC-MS). The procedures of cleanup, preconcentration, and separation were completed on-line in one step within 10min. During the MD optimization procedure, 1% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used to improve the relative recovery of the analyte. Untreated MD samples were directly injected, and a TFC precolumn was flushed for 1min with aqueous phase of 4mL/min flow rate to desalt and concentrate biosamples. The retained analytes were then back-flushed by a switching valve onto a fast LC column (4.6mmx50mm, 1.8mum) for separation. Another diverter valve was employed to prevent the HP-beta-CD that interferes with the ESI process from entering the MS. Puqietinone, a lipophilic alkaloid from Fritillaria puqiensis, was used as a case for validation. Results showed that the limit of quantification for puqietinone was 0.10ng/mL, and good linearity (R(2)=0.9993) was maintained over the range of 1.02-200.02ng/mL. Accuracy and precision were satisfactory within the range of the standard curve. This approach was able to effectively eliminate the influences of matrix effect and carry-over as the injection volume increased up to 20muL. The developed method was successfully applied to pharmacokinetic study of puqietinone after intravenous administration to rat. Results demonstrate the potential of using MD with TFC-LC/MS for in vivo monitoring experiments. Title: [Relation between HBsAg levels during the immune clearance phase of hepatitis B virus infection and liver pathological stages of chronic hepatitis B] Zeng DW, Dong J, Chen LH, Zhu YY, Chen J, Zheng Q, Liu YR, Jiang JJ Ref: Zhonghua Gan Zang Bing Za Zhi, 20:746, 2012 : PubMed ESTHER: Zeng_2012_Zhonghua.Gan.Zang.Bing.Za.Zhi_20_746 PubMedSearch: Zeng 2012 Zhonghua.Gan.Zang.Bing.Za.Zhi 20 746 PubMedID: 23207334 Abstract To investigate whether the level of hepatitis B surface antigen (HBsAg) represents the status of inflammation and stages of fibrosis in livers of patients with chronic hepatitis B (CHB) during the immune clearance phase (IC). Liver biopsy samples and sera were collected from 165 consecutive patients (136 males; 29 females) with CHB in IC who were treated in our hospital between March 2009 and June 2011. Routine biochemical tests were carried out to measure indicators of liver function. The relation between HBsAg level and liver pathological stages were determined by Spearman's rank correlation analysis. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBsAg level for liver pathological stages. Binary logistic regression was used to analyze potentially relevant indicators, and liver pathology-predicting models were built and analyzed by the ROC method. The mean values of HBsAg (IU/mL) were significantly different at the different liver inflammation stages: G1, 27 716.07+/-32 870.69; G2, 34 478.75+/-40 899.55; G3, 19 408.09+/-24 881.07; G4, 14 286.31+/-28 610.14. Likewise, the mean values of HBsAg (IU/mL) were significantly different at the different liver fibrosis stages: S1, 41 337.23+/-43 236.39; S2, 27 264.32+/-32 517.29; S3, 111 541.77+/-11 538.93; S4, 11 447.37+/-22215.44. Spearman's rank correlation analysis indicated a significant correlation between HBsAg level and liver inflammation stage (rs = -0.244) and fibrosis stage (rs = -0.365). ROC curve analysis of the diagnostic value of HBsAg for inflammation stages S more than or equal to 4 revealed that the area under the curve (AUC) was 0.70. The specificity of diagnosing S more than or equal to 4 was > 95.16% when HBsAg was less than or equal to 32995 IU/mL. Binary logistic regression analysis identified age, serum albumin, cholinesterase, and HBsAg as independent predictors of liver fibrosis. HBsAg level is negatively correlated with liver inflammation and fibrosis stages for patients with CHB in the IC phase, and might represent a useful noninvasive marker of the degree of hepatic fibrosis. 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: Assessing the role of the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) three-finger domain in binding lipoprotein lipase Beigneux AP, Davies BS, Tat S, Chen J, Gin P, Voss CV, Weinstein MM, Bensadoun A, Pullinger CR and Young SG <1 more author(s)> Beigneux AP, Davies BS, Tat S, Chen J, Gin P, Voss CV, Weinstein MM, Bensadoun A, Pullinger CR, Fong LG, Young SG (- 1) Ref: Journal of Biological Chemistry, 286:19735, 2011 : PubMed ESTHER: Beigneux_2011_J.Biol.Chem_286_19735 PubMedSearch: Beigneux 2011 J.Biol.Chem 286 19735 PubMedID: 21478160 Abstract Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) is an endothelial cell protein that transports lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lumen. GPIHBP1 contains two main structural motifs, an amino-terminal acidic domain enriched in aspartates and glutamates and a lymphocyte antigen 6 (Ly6) motif containing 10 cysteines. All of the cysteines in the Ly6 domain are disulfide-bonded, causing the protein to assume a three-fingered structure. The acidic domain of GPIHBP1 is known to be important for LPL binding, but the involvement of the Ly6 domain in LPL binding requires further study. To assess the importance of the Ly6 domain, we created a series of GPIHBP1 mutants in which each residue of the Ly6 domain was changed to alanine. The mutant proteins were expressed in Chinese hamster ovary (CHO) cells, and their expression level on the cell surface and their ability to bind LPL were assessed with an immunofluorescence microscopy assay and a Western blot assay. We identified 12 amino acids within GPIHBP1, aside from the conserved cysteines, that are important for LPL binding; nine of those were clustered in finger 2 of the GPIHBP1 three-fingered motif. The defective GPIHBP1 proteins also lacked the ability to transport LPL from the basolateral to the apical surface of endothelial cells. Our studies demonstrate that the Ly6 domain of GPIHBP1 is important for the ability of GPIHBP1 to bind and transport LPL. Title: ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure Chen J, Brunzell DH, Jackson K, van der Vaart A, Ma JZ, Payne TJ, Sherva R, Farrer LA, Gejman P and Chen X <11 more author(s)> Chen J, Brunzell DH, Jackson K, van der Vaart A, Ma JZ, Payne TJ, Sherva R, Farrer LA, Gejman P, Levinson DF, Holmans P, Aggen SH, Damaj MI, Kuo PH, Webb BT, Anton R, Kranzler HR, Gelernter J, Li MD, Kendler KS, Chen X (- 11) Ref: PLoS ONE, 6:e28790, 2011 : PubMed ESTHER: Chen_2011_PLoS.One_6_e28790 PubMedSearch: Chen 2011 PLoS.One 6 e28790 PubMedID: 22205969 Abstract Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions. Title: Genome sequence of the nonpathogenic Listeria monocytogenes serovar 4a strain M7 Chen J, Xia Y, Cheng C, Fang C, Shan Y, Jin G, Fang W Ref: Journal of Bacteriology, 193:5019, 2011 : PubMed ESTHER: Chen_2011_J.Bacteriol_193_5019 PubMedSearch: Chen 2011 J.Bacteriol 193 5019 PubMedID: 21742872 Gene_locus related to this paper: lisin-LIN2544, lismo-LMO0857, lismo-LMO1674, lismo-LMO2452 Abstract This report presents the complete and annotated genome sequence of the naturally nonpathogenic Listeria monocytogenes serovar 4a strain M7, isolated from cow's milk in Zhejiang province, China. Title: Study on improvement of extracellular production of recombinant Thermobifida fusca cutinase by Escherichia coli Chen S, Liu Z, Chen J, Wu J Ref: Appl Biochem Biotechnol, 165:666, 2011 : PubMed ESTHER: Chen_2011_Appl.Biochem.Biotechnol_165_666 PubMedSearch: Chen 2011 Appl.Biochem.Biotechnol 165 666 PubMedID: 21594592 Abstract Escherichia coli is one of the most commonly used host strains for recombinant protein production. More and more research works on the production of recombinant protein indicate that extracellular production throughout a culture medium is more convenient and attractive compared to intracellular production. In present work, inducing temperature and isopropyl beta-D: -1-thiogalactopyranoside (IPTG) concentration were investigated to decrease the formation of inclusion body and increase the amount of soluble recombinant cutinase initially. Enzyme activity in the culture medium reached to 118.9 U/ml at 64 h of culture, and no inclusion body was detected in cytoplasm under the inducement condition of 0.2 mM IPTG and 30 degrees C. In addition, it was found that a large amount of cutinase had been accumulated in periplasm since 16-h cultivation under the same inducement condition. Therefore, glycine and surfactant sodium taurodeoxycholate (TDOC) were further used to promote the leakage of recombinant cutinase from periplasm. Supplied with 100 mM glycine and 1 mM TDOC, the amount of cutinase in periplasm decreased remarkably, and the activity in the culture medium reached to 146.2 and 149.2 U/ml after 54 h of culturing, respectively. Title: Effect of Silent Mutations in Translational Initial Region on the Production of Recombinant Cutinase in Escherichia coli Liu ZG, Zhu L, Zhu KL, Chen S, Chen J, Wu J Ref: Curr Microbiol, 62:1302, 2011 : PubMed ESTHER: Liu_2011_Curr.Microbiol_62_1302 PubMedSearch: Liu 2011 Curr.Microbiol 62 1302 PubMedID: 21212953 Abstract Translational Initial Region (TIR) is the threshold of an intracellular translation process, and tiny alterations in this region are reported to intensely influence the downstream expression. Such property provides a potential utilization in extracellular production of recombinant enzyme. As an esterase, cutinase is an essential catalyst in the process of textile scouring, and has a potential application in food and chemical industry. In the present study, a bacterial cutinase (Tfu_0883) from Thermobifida fusca was expressed in Escherichia coli with pelB as its signal peptide using trc as its promoter. A subsequent TIR degeneracy mutagenesis was then carried out in the initial sequence of pelB. A fast screening method for these mutants was developed and a series of strains with different expression strengths were accordingly obtained. Among these mutants, a high cutinase production level of 38.0 U/ml was achieved, which is three times that of the control group. This study explored the potential utilization of TIR degeneracy mutagenesis in the production of industrial enzymes. Title: Complete genome sequence of the industrial strain Ketogulonicigenium vulgare WSH-001 Liu L, Li Y, Zhang J, Zhou Z, Liu J, Li X, Zhou J, Du G, Wang L, Chen J Ref: Journal of Bacteriology, 193:6108, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_6108 PubMedSearch: Liu 2011 J.Bacteriol 193 6108 PubMedID: 21994934 Gene_locus related to this paper: ketvy-e3f614, ketvw-f9yby2 Abstract Ketogulonicigenium vulgare is an industrial organism commonly used in the vitamin C industry. Here, we report the finished, annotated, and compared 3.28-Mbp high-quality genome sequence of Ketogulonicigenium vulgare WSH-001, a 2-keto-l-gulonic acid-producing industrial strain stocked in our laboratory. Title: Complete genome sequence of the industrial strain Bacillus megaterium WSH-002 Liu L, Li Y, Zhang J, Zou W, Zhou Z, Liu J, Li X, Wang L, Chen J Ref: Journal of Bacteriology, 193:6389, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_6389 PubMedSearch: Liu 2011 J.Bacteriol 193 6389 PubMedID: 22038958 Gene_locus related to this paper: bacmd-d5dhr4, bacmd-d5dlu4, bacmd-d5dna5, bacme-g2rqm9, bacme-g2rsv7, bacme-g9bex6 Abstract Bacillus megaterium, an industrial strain, has been widely used in protein production and the vitamin C industry. Here we reported a finished, annotated, and compared 4.14-Mbp high-quality genome sequence of B. megaterium WSH-002, which is the companion strain for Ketogulonicigenium vulgare in the vitamin C industry and is stocked in our laboratory. Title: In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain Liu Q, Shao X, Chen J, Shen Y, Feng C, Gao X, Zhao Y, Li J, Zhang Q, Jiang X Ref: Toxicol Appl Pharmacol, 251:79, 2011 : PubMed ESTHER: Liu_2011_Toxicol.Appl.Pharmacol_251_79 PubMedSearch: Liu 2011 Toxicol.Appl.Pharmacol 251 79 PubMedID: 21163285 Abstract Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-alpha level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain. Title: Two-step synthesis of fatty acid ethyl ester from soybean oil catalyzed by Yarrowia lipolytica lipase Meng Y, Wang G, Yang N, Zhou Z, Li Y, Liang X, Chen J, Li J Ref: Biotechnol Biofuels, 4:6, 2011 : PubMed ESTHER: Meng_2011_Biotechnol.Biofuels_4_6 PubMedSearch: Meng 2011 Biotechnol.Biofuels 4 6 PubMedID: 21366905 Abstract BACKGROUND: Enzymatic biodiesel production by transesterification in solvent media has been investigated intensively, but glycerol, as a by-product, could block the immobilized enzyme and excess n-hexane, as a solution aid, would reduce the productivity of the enzyme. Esterification, a solvent-free and no-glycerol-release system for biodiesel production, has been developed, and two-step catalysis of soybean oil, hydrolysis followed by esterification, with Yarrowia lipolytica lipase is reported in this paper. RESULTS: First, soybean oil was hydrolyzed at 40 degrees C by 100 U of lipase broth per 1 g of oil with approximately 30% to 60% (vol/vol) water. The free fatty acid (FFA) distilled from this hydrolysis mixture was used for the esterification of FFA to fatty acid ethyl ester by immobilized lipase. A mixture of 2.82 g of FFA and equimolar ethanol (addition in three steps) were shaken at 30 degrees C with 18 U of lipase per 1 gram of FFA. The degree of esterification reached 85% after 3 hours. The lipase membranes were taken out, dehydrated and subjected to fresh esterification so that over 82% of esterification was maintained, even though the esterification was repeated every 3 hours for 25 batches. CONCLUSION: The two-step enzymatic process without glycerol released and solvent-free demonstrated higher efficiency and safety than enzymatic transesterification, which seems very promising for lipase-catalyzed, large-scale production of biodiesel, especially from high acid value waste oil. Title: Engineered Thermobifida fusca cutinase with increased activity on polyester substrates Silva C, Da S, Silva N, Matama T, Araujo R, Martins M, Chen S, Chen J, Wu J and Cavaco-Paulo A <1 more author(s)> Silva C, Da S, Silva N, Matama T, Araujo R, Martins M, Chen S, Chen J, Wu J, Casal M, Cavaco-Paulo A (- 1) Ref: Biotechnol J, 6:1230, 2011 : PubMed ESTHER: Silva_2011_Biotechnol.J_6_1230 PubMedSearch: Silva 2011 Biotechnol.J 6 1230 PubMedID: 21751386 Gene_locus related to this paper: thefu-q6a0i4 Abstract A bacterial cutinase from Thermobifida fusca, named Tfu_0883, was genetically modified by site-directed mutagenesis to enhance its activity on poly(ethylene terephthalate) (PET). The new mutations tailored the catalytic site for PET, increasing the affinity of cutinase to this hydrophobic substrate and the ability to hydrolyze it. The mutation I218A was designed to create space and the double mutation Q132A/T101A was designed both to create space and to increase hydrophobicity. The activity of the double mutant on the soluble substrate p-nitrophenyl butyrate increased two-fold compared to wild-type cutinase, while on PET both single and double mutants exhibited considerably higher hydrolysis efficiency. The replacement of specific amino acids at the active site was an effective approach for the improvement of the Tfu_0883 cutinase capacity to hydrolyze polyester surfaces. Thus, this study provides valuable insight on how the function and stability of enzymes can be improved by molecular engineering for their application in synthetic fiber biotransformation. Title: Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil Su D, Zhao Y, Wang B, Xu H, Li W, Chen J, Wang X Ref: PLoS ONE, 6:e27632, 2011 : PubMed ESTHER: Su_2011_PLoS.One_6_e27632 PubMedSearch: Su 2011 PLoS.One 6 e27632 PubMedID: 22114680 Abstract Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and alpha7 nicotinic receptor (alpha7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or alpha7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. Title: Linking emulsion PCR haplotype analysis Wetmur JG, Chen J Ref: Methods Mol Biol, 687:165, 2011 : PubMed ESTHER: Wetmur_2011_Methods.Mol.Biol_687_165 PubMedSearch: Wetmur 2011 Methods.Mol.Biol 687 165 PubMedID: 20967607 Abstract The experimental measurement of haplotype requires the determination of two or more genotypes on the same DNA molecule. Because such measurements are much more complicated than measurements of genotypes, haplotypes are typically inferred using population data for linkage disequilibrium between the markers of interest. We have developed a method for molecular haplotyping, linking emulsion PCR (LE-PCR), and have demonstrated that the method is sufficiently robust to determine haplotypes for multiple markers in a population setting. LE-PCR uses emulsion PCR to isolate single template molecules for simultaneous PCR of widely spaced markers and uses linking PCR to fuse these amplicons into one short amplicon, which maintains the phase of the markers. LE-PCR is illustrated for polymorphisms in human paraoxonase 1 (PON1) that have been shown to affect transcriptional activity and substrate specificity in the detoxification of organophosphates. Title: Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y and Wang X <32 more author(s)> Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y, van Gool AJ, Du H, Chen J, Chen R, Zhang P, Huang Z, Thompson JR, Meng Y, Bai Y, Wang J, Zhuo M, Wang T, Huang Y, Wei L, Li J, Wang Z, Hu H, Yang P, Le L, Stenson PD, Li B, Liu X, Ball EV, An N, Huang Q, Fan W, Zhang X, Wang W, Katze MG, Su B, Nielsen R, Yang H, Wang X (- 32) Ref: Nat Biotechnol, 29:1019, 2011 : PubMed ESTHER: Yan_2011_Nat.Biotechnol_29_1019 PubMedSearch: Yan 2011 Nat.Biotechnol 29 1019 PubMedID: 22002653 Gene_locus related to this paper: macfa-BCHE, macfa-g7nzc0, macfa-g7nze2, macfa-g7p4b9, macfa-g7pa87, macfa-g7pd01, macfa-g7q259, macfa-3neur, macfa-g8f585, macfa-KANSL3, macfa-q4r8p0, macfa-SPG21, macfa-TEX30, macmu-3neur, macmu-ACHE, macmu-BCHE, macmu-f6sz31, macmu-f6the6, macmu-f6zkq5, macmu-f7buk8, macmu-f7cfi8, macmu-f7flv1, macmu-f7ggk1, macmu-f7hir7, macmu-g7n054, macmu-g7npb8, macmu-g7nq39, macmu-KANSL3, macmu-TEX30, macfa-g7pgg6, macmu-g7n4x3, macfa-g7nzx2, macfa-g8f4f7, macmu-f7ba84, macfa-g7psx7, macmu-h9er02, macfa-g8f3k0, macfa-a0a2k5w1n7, macmu-g7mxj6, macfa-g7pbk1, macfa-a0a2k5urk5, macfa-a0a2k5wye4, macfa-g7pe14, macmu-f7hkw9, macmu-f7hm08, macmu-g7mke4, macfa-g7nxn9, macmu-a0a1d5rh04, macmu-h9fud6, macfa-g8f3e1, macfa-i7gcw6, macmu-f6qwx1, macmu-f7h4t2, macfa-a0a2k5wkd0, macfa-a0a2k5v7v4, macfa-g7p7y3, macfa-a0a2k5uqq3, macmu-i2cu80, macfa-g8f5i1, macmu-f7h550, macmu-f7gkb9, macfa-a0a2k5tui1 Abstract The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. Title: High level expression, purification and activation of human dipeptidyl peptidase I from mammalian cells Yang W, Xia W, Mao J, Xu D, Chen J, Feng S, Wang J, Li H, Theisen CF and Su J <5 more author(s)> Yang W, Xia W, Mao J, Xu D, Chen J, Feng S, Wang J, Li H, Theisen CF, Petersen JM, Thorolfsson M, Rasmussen HB, Junker F, Boel E, Su J (- 5) Ref: Protein Expr Purif, 76:59, 2011 : PubMed ESTHER: Yang_2011_Protein.Expr.Purif_76_59 PubMedSearch: Yang 2011 Protein.Expr.Purif 76 59 PubMedID: 20828618 Abstract Dipeptidyl peptidase I (DPPI) plays a crucial role in maturation of many regulatory peptides and has been suggested as a pharmaceutical target in several inflammatory diseases. It is also a useful processing enzyme for the generation of authentic protein products by catalyzing the removal of N-terminal fusion peptides. We used a robust transient transfection system in human embryonic kidney 293 cells to exploit expression and activation of DPPI from chicken, rat and man for the development of an industrial production process. The expression of human and rat DPPI was significantly higher in the human HEK293 cell line than that obtained with avian DPPI. A CHO K1SV stable cell line was selected as the optimal stable host system for production of human DPPI yielding expression levels higher than 1.5 g/L. The secreted pro-DPPI underwent auto-maturation during defined buffer conditions during the purification steps. Active human DPPI was purified with a three-step purification strategy employing: Butyl Sepharose 4 Fast Flow, Sephadex G-25 Medium and Q Sepharose Fast Flow chromatography. The final yield of active enzyme was approximately 1 g/L cell culture. The enzyme exhibited exopeptidase activity against both a dipeptide-p-nitroanilide substrate and N-terminally extended MEAE-hGH (Met-Glu-Ala-Glu-human growth hormone). In conclusion, an efficient production process for recombinant human DPPI has been developed including a highly efficient and stable CHO cell system and an efficient purification procedure, which is simple and easy to scale for industrial purposes. The present data facilitates not only industrial applications of DPPI as a processing enzyme, but also provides active enzyme useful in the identification of small molecule inhibitors. Title: Oxidative injury in the brain of mice caused by lanthanid Zhao H, Cheng Z, Hu R, Chen J, Hong M, Zhou M, Gong X, Wang L, Hong F Ref: Biol Trace Elem Res, 142:174, 2011 : PubMed ESTHER: Zhao_2011_Biol.Trace.Elem.Res_142_174 PubMedSearch: Zhao 2011 Biol.Trace.Elem.Res 142 174 PubMedID: 20614199 Abstract The organ toxicity of lanthanides (Ln) on organisms had been recognized, but very little is known about the oxidative injury of brain caused by Ln. In order to study the mechanisms underlying the effects of Ln on the brain, ICR mice were injected with a single 20 mg/kg body weight dose of LaCl(3), CeCl(3), and NdCl(3) into the abdominal cavity daily for 14 days. We then examined the coefficient of the brain, the brain pathological changes and oxidative stress-mediated responses, and the accumulation of Ln and levels of neurochemicals in the brain. The results showed that CeCl(3) and NdCl(3) could induce some neurons to turn inflammatory cells and slight edema but did not observe the brain pathological changes from LaCl(3)-treated group. The concentrations of La, Ce, and Nd in the brain were significantly different and ranked in the order of Ce, Nd, and La. The injury of the brain and oxidative stress occurred as Ln appeared to trigger a cascade of reactions such as lipid peroxidation, the decreases of the total antioxidation capacity and activities of antioxidative enzymes, the excessive release of nitric oxide, the increase of glutamic acid, and the downregulated level of acetylcholinesterase activities. Furthermore, both Ce(3+) and Nd(3+) exhibited higher oxidative stress and toxicity on brain than La(3+), and Ce(3+) caused more severe brain injuries and oxidative stress than Nd(3+), implying that the differences in the brain injuries caused by Ln might be related to the number of 4f electrons of Ln. Title: Enhanced performance of lipase-catalyzed kinetic resolution of secondary alcohols in monoether-functionalized ionic liquids Zhou H, Chen J, Ye L, Lin H, Yuan Y Ref: Bioresour Technol, 102:5562, 2011 : PubMed ESTHER: Zhou_2011_Bioresour.Technol_102_5562 PubMedSearch: Zhou 2011 Bioresour.Technol 102 5562 PubMedID: 21388804 Abstract Several cationic monoether-functionalized ionic liquids (MEF-ILs) with different substituents were synthesized and used as media for kinetic resolution of secondary alcohols catalyzed by several lipases. The results indicate that Novozym 435 (an immobilized Candida antarctica Lipase B) had higher efficiency compared to other lipases in deracemization. The alkyl substituents at the 2- and 3-positions in the imidazolium ring of MEF-ILs were found to contribute to the increased enantioselectivity and enhancement of the reaction rate, respectively, while the higher stereo-hindrance of ether bonds decreased the activity. An enantioselectivity higher than 99% with 50% conversion of rac-1-phenylethanol was achieved using the catalyst system comprised of Novozym 435 and the MEF-IL 1-(3-ethoxypropyl)-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide. The catalytic system could be separated and reused without considerable activity loss. MEF-ILs can be a new class of enzyme-benign media suitable for lipase-catalyzed kinetic resolution of secondary alcohols. Title: Whole genome sequences of two Xylella fastidiosa strains (M12 and M23) causing almond leaf scorch disease in California Chen J, Xie G, Han S, Chertkov O, Sims D, Civerolo EL Ref: Journal of Bacteriology, 192:4534, 2010 : PubMed ESTHER: Chen_2010_J.Bacteriol_192_4534 PubMedSearch: Chen 2010 J.Bacteriol 192 4534 PubMedID: 20601474 Gene_locus related to this paper: xylfa-cxest, xylfa-metx, xylfa-pip, xylfa-XF0015, xylfa-XF1029, xylfa-XF1253, xylfa-XF1282, xylfa-XF1356, xylfa-XF2330, xylfa-XF2551 Abstract Xylella fastidiosa is a Gram-negative plant-pathogenic bacterium causing many economically important diseases, including almond leaf scorch disease (ALSD) in California. Genome information greatly facilitates research on this nutritionally fastidious organism. Here we report the complete genome sequences of two ALSD strains of this bacterium, M12 and M23. Title: Biochemical characterization of the cutinases from Thermobifida fusca Chen S, Su L, Billig S, Zimmermann W, Chen J, Wu J Ref: J Mol Catal B Enzym, 63:121, 2010 : PubMed ESTHER: Chen_2010_J.Mol.Catal.B.Enzym_63_121 PubMedSearch: Chen 2010 J.Mol.Catal.B.Enzym 63 121 Gene_locus related to this paper: thefu-q6a0i4, thefu-q6a0i3 Abstract Thermobifida fusca produces two cutinases which share 93% identity in amino acid sequence. In the present study, we investigated the detailed biochemical properties of T. fusca cutinases for the first time. For a better comparison between bacterial and fungal cutinases, recombinant Fusarium solani pisi cutinase was subjected to the similar analysis. The results showed that both bacterial and fungal cutinases are monomeric proteins in solution. The bacterial cutinases exhibited a broad substrate specificity against plant cutin, synthetic polyesters, insoluble triglycerides, and soluble esters. In addition, the two isoenzymes of T. fusca and the F.solani pisi cutinase are similar in substrate kinetics, the lack of interfacial activation, and metal ion requirements. However, the T.fusca cutinases showed higher stability in the presence of surfactants and organic solvents. Considering the versatile hydrolytic activity, good tolerance to surfactants, superior stability in organic solvents, and thermostability demonstrated by T. fusca cutinases, they may have promising applications in related industries. Title: Measures of bulbar and spinal motor function, muscle innervation, and mitochondrial function in ALS rats Smittkamp SE, Spalding HN, Brown JW, Gupte AA, Chen J, Nishimune H, Geiger PC, Stanford JA Ref: Behavioural Brain Research, 211:48, 2010 : PubMed ESTHER: Smittkamp_2010_Behav.Brain.Res_211_48 PubMedSearch: Smittkamp 2010 Behav.Brain.Res 211 48 PubMedID: 20211206 Abstract Symptom onset in amyotrophic lateral sclerosis (ALS) may occur in the muscles of the limbs (spinal onset) or those of the head and neck (bulbar onset). Most preclinical studies have focused on spinal symptoms, despite the prevalence of and increased morbidity and mortality associated with bulbar disease. We measured lick rhythm and tongue force to evaluate bulbar disease in the SOD1-G93A rat model of familial ALS. Body weight and grip strength were measured concomitantly. Testing spanned the early (maturation), middle (pre-symptomatic), and late (symptomatic and end-stage) phases of the disease. We measured a persistent tongue motility deficit that became apparent in the early phase of the disease, providing behavioral evidence of bulbar pathology. At end-stage, however, cytochrome oxidase (CO) activity was normal in the hypoglossal nucleus, and in the tongue, neuromuscular innervation, citrate synthase (CS) protein levels and activity, and uncoupling protein 3 (UCP3) protein levels remained unchanged. Interestingly, significant denervation and atrophy were evident in the end-stage sternomastoid muscle, providing peripheral anatomical evidence of bulbar pathology. Changes in body weight and grip strength occurred in the late phase of the disease. Extensive atrophy and denervation were observed in the end-stage gastrocnemius muscle. In contrast to our findings in the tongue, CS protein levels were decreased in the extensor digitorum longus (EDL) and soleus, although CS activity was maintained or increased. UCP3 protein was decreased also in the EDL. These data provide evidence of differential effects in muscles that were more or less affected by disease. Title: Identifying unexpected therapeutic targets via chemical-protein interactome Yang L, Chen J, Shi L, Hudock MP, Wang K, He L Ref: PLoS ONE, 5:e9568, 2010 : PubMed ESTHER: Yang_2010_PLoS.One_5_e9568 PubMedSearch: Yang 2010 PLoS.One 5 e9568 PubMedID: 20221449 Abstract Drug medications inevitably affect not only their intended protein targets but also other proteins as well. In this study we examined the hypothesis that drugs that share the same therapeutic effect also share a common therapeutic mechanism by targeting not only known drug targets, but also by interacting unexpectedly on the same cryptic targets. By constructing and mining an Alzheimer's disease (AD) drug-oriented chemical-protein interactome (CPI) using a matrix of 10 drug molecules known to treat AD towards 401 human protein pockets, we found that such cryptic targets exist. We recovered from CPI the only validated therapeutic target of AD, acetylcholinesterase (ACHE), and highlighted several other putative targets. For example, we discovered that estrogen receptor (ER) and histone deacetylase (HDAC), which have recently been identified as two new therapeutic targets of AD, might already have been targeted by the marketed AD drugs. We further established that the CPI profile of a drug can reflect its interacting character towards multi-protein sets, and that drugs with the same therapeutic attribute will share a similar interacting profile. These findings indicate that the CPI could represent the landscape of chemical-protein interactions and uncover "behind-the-scenes" aspects of the therapeutic mechanisms of existing drugs, providing testable hypotheses of the key nodes for network pharmacology or brand new drug targets for one-target pharmacology paradigm. Title: Molecular cloning and characterization of an acetylcholinesterase cDNA in the brown planthopper, Nilaparvata lugens Yang Z, Chen J, Chen Y, Jiang S Ref: J Insect Sci, 10:102, 2010 : PubMed ESTHER: Yang_2010_J.Insect.Sci_10_102 PubMedSearch: Yang 2010 J.Insect.Sci 10 102 PubMedID: 20874389 Gene_locus related to this paper: nillu-ACHE2 Abstract A full cDNA encoding an acetylcholinesterase (AChE, EC 3.1.1.7) was cloned and characterized from the brown planthopper, Nilaparvata lugens Stal (Hemiptera: Delphacidae). The complete cDNA (2467 bp) contains a 1938-bp open reading frame encoding 646 amino acid residues. The amino acid sequence of the AChE deduced from the cDNA consists of 30 residues for a putative signal peptide and 616 residues for the mature protein with a predicted molecular weight of 69,418. The three residues (Ser242, Glu371, and His485) that putatively form the catalytic triad and the six Cys that form intra-subunit disulfide bonds are completely conserved, and 10 out of the 14 aromatic residues lining the active site gorge of the AChE are also conserved. Northern blot analysis of poly(A)+ RNA showed an approximately 2.6-kb transcript, and Southern blot analysis revealed there likely was just a single copy of this gene in N. lugens. The deduced protein sequence is most similar to AChE of Nephotettix cincticeps with 83% amino acid identity. Phylogenetic analysis constructed with 45 AChEs from 30 species showed that the deduced N. lugens AChE formed a cluster with the other 8 insect AChE2s. Additionally, the hypervariable region and amino acids specific to insect AChE2 also existed in the AChE of N. lugens. The results revealed that the AChE cDNA cloned in this work belongs to insect AChE2 subgroup, which is orthologous to Drosophila AChE. Comparison of the AChEs between the susceptible and resistant strains revealed a point mutation, Gly185Ser, is likely responsible for the insensitivity of the AChE to methamidopho in the resistant strain. Title: Characterization of Thermobifida fusca cutinase-carbohydrate-binding module fusion proteins and their potential application in bioscouring Zhang Y, Chen S, Xu M, Cavaco-Paulo A, Wu J, Chen J Ref: Applied Environmental Microbiology, 76:6870, 2010 : PubMed ESTHER: Zhang_2010_Appl.Environ.Microbiol_76_6870 PubMedSearch: Zhang 2010 Appl.Environ.Microbiol 76 6870 PubMedID: 20729325 Abstract Cutinase from Thermobifida fusca is thermally stable and has potential application in the bioscouring of cotton in the textile industry. In the present study, the carbohydrate-binding modules (CBMs) from T. fusca cellulase Cel6A (CBM(Cel6A)) and Cellulomonas fimi cellulase CenA (CBM(CenA)) were fused, separately, to the carboxyl terminus of T. fusca cutinase. Both fusion enzymes, cutinase-CBM(Cel6A) and cutinase-CBM(CenA), were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that both displayed similar catalytic properties and pH stabilities in response to T. fusca cutinase. In addition, both fusion proteins displayed an activity half-life of 53 h at their optimal temperature of 50 degrees C. Compared to T. fusca cutinase, in the absence of pectinase, the binding activity on cotton fiber was enhanced by 2% for cutinase-CBM(Cel6A) and by 28% for cutinase-CBM(CenA), whereas in the presence of pectinase, the binding activity was enhanced by 40% for the former and 45% for the latter. Notably, a dramatic increase of up to 3-fold was observed in the amount of released fatty acids from cotton fiber by both cutinase-CBM fusion proteins when acting in concert with pectinase. This is the first report of improving the scouring efficiency of cutinase by fusing it with CBM. The improvement in activity and the strong synergistic effect between the fusion proteins and pectinase suggest that they may have better applications in textile bioscouring than the native cutinase. Title: [Mathematical models using conventional laboratory indicators to predict hepatic fibrosis progressing in chronic hepatitis B] Chen J, Jiang JJ, Zheng Q, Zhu YY Ref: Zhonghua Yi Xue Za Zhi, 89:2349, 2009 : PubMed ESTHER: Chen_2009_Zhonghua.Yi.Xue.Za.Zhi_89_2349 PubMedSearch: Chen 2009 Zhonghua.Yi.Xue.Za.Zhi 89 2349 PubMedID: 20095359 Abstract OBJECTIVE: To build a mathematical model for diagnosing liver fibrosis progression by using conventional laboratory indicators, and to evaluate its clinical value of predicting hepatic fibrosis and hepatocirrhosis in chronic hepatitis B. METHODS: Liver biopsy and routine laboratory tests were performed in 391 patients with chronic hepatitis B. Using Multiple logistic regression to analyse evidently relevant indicators,then the models predicting for different stages of liver fibrosis were built and analyzed by receiver operating characteristic (ROC) curve. RESULTS: Age, platelet (PLT), international rate (INR), total bilirubin, albumin (ALB), aspartate aminotransferase, gamma-glutamyltranspeptidase (GGT), total bile acid and cholinesterase (CHE) were correlated with liver fibrosis stage. Multiple Logistic regression analysis showed that PLT, INR, ALB, GGT and CHE were independent predictors of three models ( S > or = 2, S > or = 3, S = 4). We finally built the predicting models and got Fibrosis scores (FS). ROC curve analysis revealed that the area under the curve was 0.784 in model-1 (S > or = 2), 0.768 in model-2 (S > or = 3) and 0.806 in model-3 (S = 4). A FS, cutoff point of 7.09 had 67.4% sensitivity, 79.3% specificity and 71.1% accuracy in Model-1. A FS2 cutoff point of 5.67 had 75.0% sensitivity, 67.7% specificity and 72.9% accuracy in Model-2. A FS3 cutoff point of 3.65 had 71.4% sensitivity, 78.5% specificity and 73.7% accuracy in Model-3. CONCLUSION: The mathematical models using conventional laboratory indicators have fairly well value for predicting hepatic fibrosis progressing in chronic hepatitis B. Title: Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in Pichia pastoris Gao Z, Bai G, Chen J, Zhang Q, Pan P, Bai F, Geng P Ref: Biosci Biotechnol Biochem, 73:688, 2009 : PubMed ESTHER: Gao_2009_Biosci.Biotechnol.Biochem_73_688 PubMedSearch: Gao 2009 Biosci.Biotechnol.Biochem 73 688 PubMedID: 19270384 Abstract Glucagon-like peptide-1 (GLP-1) has considerable potential as a possible therapeutic agent for type-2 diabetes. Unfortunately, this glucoincretin is short lived due to degradation by dipeptidyl-peptidase IV and rapid clearance by renal filtration. In this study, we attempted to extend GLP-1 action through the attachment of a lysine residue at the N-terminal of GLP-1 (named KGLP-1), and to make a fusion protein with human serum albumin (HSA) in Pichia pastoris. The protein, designated KGLP-1/HSA, was purified by an immunomagnetic separation technique. High performance liquid chromatography (HPLC) showed that the purified protein had an overall purity of 92.0%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the expected molecular mass of 70,297.8 Da. Additionally, the N-terminal sequence of KGLP-1/HSA was confirmed by N-terminal sequencing. The stability and biological activity of KGLP-1/HSA were then evaluated in vitro and in vivo. The findings indicated that fusion KGLP-1/HSA preserved the action of native GLP-1, and the active duration was greatly prolonged. Title: Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study Hou L, Chen S, Yu H, Lu X, Chen J, Wang L, Huang J, Fan Z, Gu D Ref: Hum Genet, 125:11, 2009 : PubMed ESTHER: Hou_2009_Hum.Genet_125_11 PubMedSearch: Hou 2009 Hum.Genet 125 11 PubMedID: 19034521 Gene_locus related to this paper: human-PLA2G7 Abstract The human PLA2G7 gene encodes lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an emerging risk factor for cardiovascular diseases. In the present study, seven single nucleotide polymorphisms (SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease (CHD), of which 512 were patients with myocardial infarction (MI), and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA(2) activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients, including 423 MI patients. Lp-PLA(2) activity in CHD and MI cases was significantly higher (233.42+/-57.66 and 234.27+/-59.51 nmol ml(-1) min(-1), respectively) than in controls (211.47+/-58.61 nmol ml(-1) min(-1)). After adjusting for traditional risk factors by logistic regression, the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA(2) activity were 1.27 (95% CI, 1.07-1.50) and 1.27 (95% CI, 1.05-1.54), respectively. Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA(2) activity, but neither was associated with increased CHD risk. Both univariate and multivariate analyses, adjusting effects of conventional factors, indicated that the rs13210554 T allele increased the risk of MI in this Chinese Han population. In summary, an independent association of increased plasma Lp-PLA(2) activity with CHD and MI existed in this Chinese Han Population. Although V279F and I198T mutations significantly decreased the activity of Lp-PLA(2), only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA(2) activity appears to influence the CHD and MI risk in Chinese Han population. Title: Identification of a new functional domain in angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) involved in binding and inhibition of lipoprotein lipase (LPL) Lee EC, Desai U, Gololobov G, Hong S, Feng X, Yu XC, Gay J, Wilganowski N, Gao C and Sonnenburg WK <9 more author(s)> Lee EC, Desai U, Gololobov G, Hong S, Feng X, Yu XC, Gay J, Wilganowski N, Gao C, Du LL, Chen J, Hu Y, Zhao S, Kirkpatrick L, Schneider M, Zambrowicz BP, Landes G, Powell DR, Sonnenburg WK (- 9) Ref: Journal of Biological Chemistry, 284:13735, 2009 : PubMed ESTHER: Lee_2009_J.Biol.Chem_284_13735 PubMedSearch: Lee 2009 J.Biol.Chem 284 13735 PubMedID: 19318355 Gene_locus related to this paper: human-LPL Abstract Angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are secreted proteins that regulate triglyceride (TG) metabolism in part by inhibiting lipoprotein lipase (LPL). Recently, we showed that treatment of wild-type mice with monoclonal antibody (mAb) 14D12, specific for ANGPTL4, recapitulated the Angptl4 knock-out (-/-) mouse phenotype of reduced serum TG levels. In the present study, we mapped the region of mouse ANGPTL4 recognized by mAb 14D12 to amino acids Gln(29)-His(53), which we designate as specific epitope 1 (SE1). The 14D12 mAb prevented binding of ANGPTL4 with LPL, consistent with its ability to neutralize the LPL-inhibitory activity of ANGPTL4. Alignment of all angiopoietin family members revealed that a sequence similar to ANGPTL4 SE1 was present only in ANGPTL3, corresponding to amino acids Glu(32)-His(55). We produced a mouse mAb against this SE1-like region in ANGPTL3. This mAb, designated 5.50.3, inhibited the binding of ANGPTL3 to LPL and neutralized ANGPTL3-mediated inhibition of LPL activity in vitro. Treatment of wild-type as well as hyperlipidemic mice with mAb 5.50.3 resulted in reduced serum TG levels, recapitulating the lipid phenotype found in Angptl3(-/-) mice. These results show that the SE1 region of ANGPTL3 and ANGPTL4 functions as a domain important for binding LPL and inhibiting its activity in vitro and in vivo. Moreover, these results demonstrate that therapeutic antibodies that neutralize ANGPTL4 and ANGPTL3 may be useful for treatment of some forms of hyperlipidemia. Title: Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells Li H, Wang L, Ye L, Mao Y, Xie X, Xia C, Chen J, Lu Z, Song J Ref: Med Microbiol Immunol, 198:113, 2009 : PubMed ESTHER: Li_2009_Med.Microbiol.Immunol_198_113 PubMedSearch: Li 2009 Med.Microbiol.Immunol 198 113 PubMedID: 19337750 Abstract Quorum sensing system is a cell-to-cell communication system that plays a pivotal role in virulence expression in bacteria. Recent advances have demonstrated that the Pseudomonas aeruginosa quorum sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC(12)-HSL), exerts effects on mammalian cells and modulates host immune response. Mast cells (MCs) are strategically located in the tissues that are constantly exposed to external stimulus. Therefore, it is very much possible that 3OC(12)-HSL may interact with MCs. Little is known, however, about specific effects of 3OC(12)-HSL on MCs. To address this, we investigated the influence of 3OC(12)-HSL on cell viability, apoptosis, intracellular calcium and cytokine release in MCs. We found that at high concentrations (100 microM), 3OC(12)-HSL inhibited proliferation and induced apoptosis in P815. The 3OC(12)-HSL treatment significantly increased intracellular calcium release in both P815 and HMC-1. We also observed that 3OC(12)-HSL-induced histamine release and degranulation in HMC-1 cells. Furthermore, 3OC(12)-HSL-induced IL-6 production at lower concentrations (6.25-12.5 microM) but steadily reduced IL-6 production at high concentration (50-100 muM). These data demonstrate that P. aeruginosa 3OC(12)-HSL affects MCs function. Title: Development of square wave voltammetry method for the assessment of organophosphorus compound impact on the cholinesterase of Pheretima with 2,6-dichloroindophenol as a redox indicator Qiu J, Chen J, Ma Q, Miao Y Ref: Chemosphere, 77:129, 2009 : PubMed ESTHER: Qiu_2009_Chemosphere_77_129 PubMedSearch: Qiu 2009 Chemosphere 77 129 PubMedID: 19487014 Abstract A square wave voltammetry method was developed for the assessment of organophosphorus (OPs) compound impact on the cholinesterase of Pheretima with 2,6-dichloroindophenol (2,6-DCIP) as a redox indicator. The substrate of acetylthiocholine is hydrolysed by the cholinesterase (ChE) from soil animal pheretima, and the produced thiocholine reacts with the 2,6-DCIP to give obvious shift of electrochemical signal. The inhibition of ChE was assessed by measuring the enzyme activity before and after incubating with parathion-methyl. The reduction peak current of 2,6-DCIP decreases with the time of enzymatical reaction. The ChE loses almost 32.74% activity after 10 min incubation with 1ng mL(-1) paraoxon and 54.62% with 10 microg mL(-1) paraoxon, while the activity that corresponds to 100 microg mL(-1) paraoxon was nearly completely inhibited. This method can be employed to assess the inhibition of ChE and investigate OPs impact on environmental animals. Title: Cutinase-like proteins of Mycobacterium tuberculosis: characterization of their variable enzymatic functions and active site identification West NP, Chow FM, Randall EJ, Wu J, Chen J, Ribeiro JM, Britton WJ Ref: FASEB Journal, 23:1694, 2009 : PubMed ESTHER: West_2009_Faseb.J_23_1694 PubMedSearch: West 2009 Faseb.J 23 1694 PubMedID: 19225166 Gene_locus related to this paper: myctu-cut3, myctu-cutas1, myctu-cutas2, myctu-RV1758, myctu-RV3452, myctu-RV3724, myctu-Rv3802c Abstract Discovery and characterization of novel secreted enzymes of Mycobacterium tuberculosis are important for understanding the pathogenesis of one of the most important human bacterial pathogens. The proteome of M. tuberculosis contains over 400 potentially secreted proteins, the majority of which are uncharacterized. A family of seven cutinase-like proteins (CULPs) was identified by bioinformatic analysis, expressed and purified from Escherichia coli, and characterized in terms of their enzymatic activities. These studies revealed a functional diversity of enzyme classes based on differential preferences for substrate chain length. One member, Culp1, exhibited strong esterase activity, 40-fold higher than that of Culp6, which had strong activity as a lipase. Another, Culp4, performed moderately as an esterase and weakly as a lipase. Culp6 lipase activity was optimal above pH 7.0, and fully maintained to pH 8.5. None of the CULP members exhibited cutinase activity. Site-directed mutagenesis of each residue of the putative catalytic triad in Culp6 confirmed that each was essential for activity toward all fatty acid chain lengths of nitrophenyl esters and lipolytic function. Culp1 and Culp2 were present only in culture supernatants of M. tuberculosis, while Culp6, which is putatively essential for mycobacterial growth, was retained in the cell wall, suggesting the proteins play distinct roles in mycobacterial biology. Title: Dynamic evolution of oryza genomes is revealed by comparative genomic analysis of a genus-wide vertical data set Ammiraju JS, Lu F, Sanyal A, Yu Y, Song X, Jiang N, Pontaroli AC, Rambo T, Currie J and Wing RA <9 more author(s)> Ammiraju JS, Lu F, Sanyal A, Yu Y, Song X, Jiang N, Pontaroli AC, Rambo T, Currie J, Collura K, Talag J, Fan C, Goicoechea JL, Zuccolo A, Chen J, Bennetzen JL, Chen M, Jackson S, Wing RA (- 9) Ref: Plant Cell, 20:3191, 2008 : PubMed ESTHER: Ammiraju_2008_Plant.Cell_20_3191 PubMedSearch: Ammiraju 2008 Plant.Cell 20 3191 PubMedID: 19098269 Abstract Oryza (23 species; 10 genome types) contains the world's most important food crop - rice. Although the rice genome serves as an essential tool for biological research, little is known about the evolution of the other Oryza genome types. They contain a historical record of genomic changes that led to diversification of this genus around the world as well as an untapped reservoir of agriculturally important traits. To investigate the evolution of the collective Oryza genome, we sequenced and compared nine orthologous genomic regions encompassing the Adh1-Adh2 genes (from six diploid genome types) with the rice reference sequence. Our analysis revealed the architectural complexities and dynamic evolution of this region that have occurred over the past approximately 15 million years. Of the 46 intact genes and four pseudogenes in the japonica genome, 38 (76%) fell into eight multigene families. Analysis of the evolutionary history of each family revealed independent and lineage-specific gain and loss of gene family members as frequent causes of synteny disruption. Transposable elements were shown to mediate massive replacement of intergenic space (>95%), gene disruption, and gene/gene fragment movement. Three cases of long-range structural variation (inversions/deletions) spanning several hundred kilobases were identified that contributed significantly to genome diversification. Title: Toxicological analysis of low-nicotine and nicotine-free cigarettes Chen J, Higby R, Tian D, Tan D, Johnson MD, Xiao Y, Kellar KJ, Feng S, Shields PG Ref: Toxicology, 249:194, 2008 : PubMed ESTHER: Chen_2008_Toxicology_249_194 PubMedSearch: Chen 2008 Toxicology 249 194 PubMedID: 18599178 Abstract Low-nicotine and nicotine-free cigarettes are commercially available under the brand-name Quest. Some consumers may believe that these are safer cigarettes, and they may smoke more cigarettes or inhale more smoke to compensate for low nicotine yields. Thus, we have studied the toxicological effects of these two cigarettes and compared them with the Kentucky reference cigarette 2R4F. Also, the availability of nicotine-free cigarettes allows for the assessing the role of nicotine in cigarette smoke. In addition to nicotine, some tobacco-specific nitrosamines, aldehydes, and volatile organic compounds were also reduced in the Quest cigarettes compared to the 2R4F. However, aromatic amines were higher in the nicotine-free compared with low nicotine cigarettes. The Ames test revealed that cigarette smoke condensates from the nicotine-free (CSC-F), low nicotine (CSC-L) and 2R4F (CSC-R) cigarettes had a similar mutagenic potency. Exposure to any CSC caused a similar dose-dependent LDH leakage from normal human bronchial epithelial cells. However, CSC-F had more inhibitory effects on the cell growth than CSC-L and CSC-R. Adding nicotine to the CSC-F attenuated this inhibition. Both Quest CSCs decreased gap junction intercellular communication and caused cell cycle arrest. CSC exposure increased cytoplasmic nucleosomes, sub-G1/G0 population and apoptotic comet tails. Proapoptotic protein Bax increased independent of p53 induction after exposure to CSC-F. In conclusion, these studies are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells. Nicotine, as it exists in CSC, attenuates cytotoxicity possibly in part through inhibition of apoptotic pathways. Title: Water-soluble derivative of propolis mitigates scopolamine-induced learning and memory impairment in mice Chen J, Long Y, Han M, Wang T, Chen Q, Wang R Ref: Pharmacol Biochem Behav, 90:441, 2008 : PubMed ESTHER: Chen_2008_Pharmacol.Biochem.Behav_90_441 PubMedSearch: Chen 2008 Pharmacol.Biochem.Behav 90 441 PubMedID: 18485465 Abstract The water-soluble derivative of propolis (WSDP) was prepared from fresh Chinese propolis. Its major constituents were identified by high performance liquid chromatography (HPLC) analysis. It has been reported that propolis possessed a broad spectrum of biological activities but including few studies on learning and memory by now. Thus, this study was aimed to investigate the effect of WSDP on scopolamine-induced learning and memory impairment in mice. WSDP (50 mg/kg, 100 mg/kg) was given by intragastric administration (i.g.) 40 min prior to the intraperitoneal (i.p.) injection of scopolamine (1 mg/kg). The effect on amnesia was investigated with both hidden-platform acquisition training and probe trial testing in Morris water maze test. The results from 100 mg/kg WSDP group showed significant mitigation scopolamine-induced amnesia in mice. Furthermore, WSDP's effect on the acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus was also assayed. As a result, WSDP (100 mg/kg) significantly inhibited AChE activity in the hippocampus of scopolamine-treated mice. These results indicated that WSDP may mitigate amnesia in vivo through inhibition of AChE activity in the hippocampus, which suggested propolis may have potential as a pharmaceutical of brain protection with elderly population for preventing Alzheimer's disease (AD) and other neurodegenerative diseases. Title: Identification and characterization of bacterial cutinase Chen S, Tong X, Woodard RW, Du G, Wu J, Chen J Ref: Journal of Biological Chemistry, 283:25854, 2008 : PubMed ESTHER: Chen_2008_J.Biol.Chem_283_25854 PubMedSearch: Chen 2008 J.Biol.Chem 283 25854 PubMedID: 18658138 Gene_locus related to this paper: thefu-q6a0i4, thefu-q6a0i3 Abstract Cutinase, which exists in both fungi and bacteria, catalyzes the cleavage of the ester bonds of cutin. Fungal cutinases have been extensively studied, however, reports on bacterial cutinases have been limited due to the lack of knowledge concerning the identity of their open reading frames. In the present study, the cutinase from Thermobifida fusca was induced by cutin and purified to homogeneity by following p-nitrophenyl butyrate hydrolyzing activity. Peptide mass fingerprinting analysis of the wild-type enzyme matched two proteins, Tfu_0883 and Tfu_0882, which are 93% identical in sequence. Both proteins were cloned and overexpressed in their mature form. Recombinant Tfu_0883 and Tfu_0882 display very similar enzymatic properties and were confirmed to be cutinases by their capability to hydrolyze the ester bonds of cutin. Comparative characterization of Fusarium solani pisi and T. fusca cutinases indicated that they have similar substrate specificity and catalytic properties except that the T. fusca enzymes are thermally more stable. Homology modeling revealed that T. fusca cutinases adopt an alpha/beta-hydrolase fold that exhibits both similarities and variations from the fungal cutinase structure. A serine hydrolase catalytic mechanism involving a Ser(170)-His(248)-Asp(216) (Tfu_0883 numbering) catalytic triad was supported by active site-directed inhibition studies and mutational analyses. This is the first report of cutinase encoding genes from bacterial sources. Title: [Cutinase production from short-chain organic acids by Thermobifida fusca] He G, Du G, Liu L, Liu H, Huo G, Chen J Ref: Sheng Wu Gong Cheng Xue Bao, 24:821, 2008 : PubMed ESTHER: He_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_821 PubMedSearch: He 2008 Sheng.Wu.Gong.Cheng.Xue.Bao 24 821 PubMedID: 18724703 Abstract We studied cutinase production from short-chain organic acids by Thermobifida fusca WSH03-11 to evaluate the possibility of converting municipal sludge to high value-added products. The optimum organic acid (8.0 g/L) and nitrogen source (1.5 g/L) concentrations were determined by the single factor experiments with butyric acid, propionic acid and acetic acid as the carbon sources. When lactic acid was used as the carbon source, the optimum organic acid (3.0 g/L) and nitrogen source (1.0 g/L) concentrations were obtained. Cutinase production by T. fusca WSH03-11 was further improved with butyric acid (by 31.0%), propionic acid (by 13.3%), acetic acid (by 43.8%) and lactic acid (by 73.2%) as carbon source, respectively, with the optimized cutin concentrations. Among these four short-chain organic acids, the average specific consumption rate of acetic acid was the highest, higher than that of propionic acid 1.3-folds, butyric acid 2.0-folds and lactic acid 2.2-folds. The highest cutinase activity reached 52.4 u/mL with butyric acid (8 g/L) as the sole carbon source, higher than that of lactic acid (3 g/L) 1.7-folds, acetic acid (8 g/L) 2.5-folds and propionic acid (8 g/L) 3.2-folds. The yield of cutinase activity on lactic acid (12.70 u/mg) higher than that of butyric acid 1.4-folds, propionic acid 3.0-folds and acetic acid 3.8-folds. T. fusca WSH03-11 consumed acetic acid firstly in mixed acids carbon sources, and the consumption of butyric acid was inhibited. Further studies indicated that the consumption rate of butyrate was decreased by 66.7% in the presence of 0.5 g/L acetic acid in the mixed acids. This was the first report concerning the production of cutinase by T. fusca with mixed organic acids as the carbon sources. The results presented here provided a novel and efficient approach to produce high value-add products from municipal sludge, and also established a foundation for the industrial production of cutinase by T. fusca WSH03-11 with cheap carbon sources from the processing of municipal sludge. Title: Acute toxicity of the pesticide methomyl on the topmouth gudgeon (Pseudorasbora parva): mortality and effects on four biomarkers Li H, Jiang H, Gao X, Wang X, Qu W, Lin R, Chen J Ref: Fish Physiol Biochem, 34:209, 2008 : PubMed ESTHER: Li_2008_Fish.Physiol.Biochem_34_209 PubMedSearch: Li 2008 Fish.Physiol.Biochem 34 209 PubMedID: 18665458 Abstract In this study, the acute toxicity of the pesticide methomyl on the topmouth gudgeon (Pseudorasbora parva) was evaluated using mortality and the activity of the enzymes acetylcholinesterase (AChE), glutathione S-transferases (GSTs), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) as endpoints. LC50 values were 1.228, 0.782, 0.538, and 0.425 mg/l at 24, 48, 72, and 96 h of exposure, respectively. Methomyl caused a sharp decrease in specific activity of brain AChE around 48% at concentrations between 0.043 and 0.213 mg/l. A reduction higher than 40% in liver GST activity at concentrations between 0.085 and 0.213 mg/l was found, whereas no significant effects were observed in intestinal GST. A significant concentration-dependent decrease of GOT activity was found after 24 h of exposure to the pesticide but not after 96 h. No significant effects on GPT activity were observed. These results indicate that at the concentrations tested, methomyl is acutely toxic to the species P. parva, causing mortality, neurotoxic effects, and changes in some hepatic enzymes. Title: Genetic variation in genes for the xenobiotic-metabolizing enzymes CYP1A1, EPHX1, GSTM1, GSTT1, and GSTP1 and susceptibility to colorectal cancer in Lynch syndrome Pande M, Amos CI, Osterwisch DR, Chen J, Lynch PM, Broaddus R, Frazier ML Ref: Cancer Epidemiol Biomarkers Prev, 17:2393, 2008 : PubMed ESTHER: Pande_2008_Cancer.Epidemiol.Biomarkers.Prev_17_2393 PubMedSearch: Pande 2008 Cancer.Epidemiol.Biomarkers.Prev 17 2393 PubMedID: 18768509 Abstract Individuals with Lynch syndrome are predisposed to cancer due to an inherited DNA mismatch repair gene mutation. However, there is significant variability observed in disease expression likely due to the influence of other environmental, lifestyle, or genetic factors. Polymorphisms in genes encoding xenobiotic-metabolizing enzymes may modify cancer risk by influencing the metabolism and clearance of potential carcinogens from the body. In this retrospective analysis, we examined key candidate gene polymorphisms in CYP1A1, EPHX1, GSTT1, GSTM1, and GSTP1 as modifiers of age at onset of colorectal cancer among 257 individuals with Lynch syndrome. We found that subjects heterozygous for CYP1A1 I462V (c.1384A>G) developed colorectal cancer 4 years earlier than those with the homozygous wild-type genotype (median ages, 39 and 43 years, respectively; log-rank test P = 0.018). Furthermore, being heterozygous for the CYP1A1 polymorphisms, I462V and Msp1 (g.6235T>C), was associated with an increased risk for developing colorectal cancer [adjusted hazard ratio for AG relative to AA, 1.78; 95% confidence interval, 1.16-2.74; P = 0.008; hazard ratio for TC relative to TT, 1.53; 95% confidence interval, 1.06-2.22; P = 0.02]. Because homozygous variants for both CYP1A1 polymorphisms were rare, risk estimates were imprecise. None of the other gene polymorphisms examined were associated with an earlier onset age for colorectal cancer. Our results suggest that the I462V and Msp1 polymorphisms in CYP1A1 may be an additional susceptibility factor for disease expression in Lynch syndrome because they modify the age of colorectal cancer onset by up to 4 years. Title: An emulsion polymerase chain reaction-based method for molecular haplotyping Wetmur JG, Chen J Ref: Methods Mol Biol, 410:351, 2008 : PubMed ESTHER: Wetmur_2008_Methods.Mol.Biol_410_351 PubMedSearch: Wetmur 2008 Methods.Mol.Biol 410 351 PubMedID: 18642608 Abstract Genotypes are easily measured using a variety of experimental methods. However, experimental methods for measuring haplotypes, i.e., molecular haplotyping, are limited. Instead, haplotypes often are statistically inferred from genotype data with varying degrees of confidence, depending on the extent of linkage disequilibrium (LD) between markers. We have developed a method for molecular haplotyping, linking-emulsion polymerase chain reaction (LE-PCR), that should find application in studies where LD is limited, especially when the polymorphisms in question affect the function of a single gene product. We have illustrated this technology with the human paraoxonase 1 gene (PON1), where polymorphisms affecting transcription and enzymatic activity show incomplete LD. PON1 is an enzyme with multiple activities, including detoxification of organophosphates. Title: The complete genome sequence of Bacillus thuringiensis Al Hakam Challacombe JF, Altherr MR, Xie G, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML, Chen J and Brettin TS <38 more author(s)> Challacombe JF, Altherr MR, Xie G, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML, Chen J, Chertkov O, Cleland C, Dimitrijevic M, Doggett NA, Fawcett JJ, Glavina T, Goodwin LA, Green LD, Han CS, Hill KK, Hitchcock P, Jackson PJ, Keim P, Kewalramani AR, Longmire J, Lucas S, Malfatti S, Martinez D, McMurry K, Meincke LJ, Misra M, Moseman BL, Mundt M, Munk AC, Okinaka RT, Parson-Quintana B, Reilly LP, Richardson P, Robinson DL, Saunders E, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Ticknor LO, Wills PL, Gilna P, Brettin TS (- 38) Ref: Journal of Bacteriology, 189:3680, 2007 : PubMed ESTHER: Challacombe_2007_J.Bacteriol_189_3680 PubMedSearch: Challacombe 2007 J.Bacteriol 189 3680 PubMedID: 17337577 Gene_locus related to this paper: bacah-a0rcd1, bacah-a0rer5, bacah-a0rev7, bacan-BA1019, bacan-BA1242, bacan-BA2392, bacan-BA2607, bacan-BA3343, bacan-BA3863, bacan-BA3877, bacan-BA4324, bacan-BA4338, bacan-BA4577, bacan-BA5009, bacan-BA5110, bacan-BA5136, bacan-DHBF, bacc1-q73a27, bacc1-q73c93, bacce-BC0192, bacce-BC1788, bacce-BC1954, bacce-BC2141, bacce-BC2171, bacce-BC4730, bacce-BC4862, bacce-BC5130, bacce-PHAC, bacce-q72yu1, baccr-pepx, bachk-q6hcl3, bachk-q6hgn4, bachk-q6hgp9, bachk-q6hig3, bachk-q6hit8 Abstract Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62:775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69:2755-2764, 2003). Title: One-step purification of a fusion protein of glucagon-like peptide-1 and human serum albumin expressed in pichia pastoris by an immunomagnetic separation technique Chen J, Bai G, Cao Y, Gao Z, Zhang Q, Zhu Y, Yang W Ref: Biosci Biotechnol Biochem, 71:2655, 2007 : PubMed ESTHER: Chen_2007_Biosci.Biotechnol.Biochem_71_2655 PubMedSearch: Chen 2007 Biosci.Biotechnol.Biochem 71 2655 PubMedID: 17986790 Abstract Glucagon-like peptide-1 (GLP-1) has great therapeutic potential to treat diabetes type 2, mainly due to its unique glucose-dependent stimulation of insulin secretion profiles, but its clinical application is limited by its short half-life in vivo, which resultes from degradation by dipeptidyl peptidase IV and/or renal clearance. Developing long-acting GLP-1 analogs is therefore an important step toward using them therapeutically. In this study, the GLP-1/human serum albumin (HSA) fusion protein gene was cloned into the secretor type expression vector pPIC9K and subsequently expressed in Pichia pastoris. The expression quantity reached 58.5 mg/l in small-scale incubation. After optimization and characterization, the GLP-1/HSA fusion protein was successfully purified from the supernatant of the broth using immunomagnetic cellulose microspheres. HPLC showed that the purified GLP-1/HSA had an overall purity of 93.9%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the fusion protein exhibited the expected molecular mass of 70 kDa. Furthermore, that analysis of in vivo activity indicated that GLP-1/HSA reduced the blood glucose level after intraperitoneal administration to Chinese Kunming mice in a dose-dependent manner, and the effects held significantly 4 h after administration. Overall, this study illustrates the development of a long-acting GLP-1/HSA fusion protein expressed in Pichia pastoris. Title: Identifying glucagon-like peptide-1 mimetics using a novel functional reporter gene high-throughput screening assay Chen J, Bai G, Yang Y, Geng P, Cao Y, Zhu Y Ref: Peptides, 28:928, 2007 : PubMed ESTHER: Chen_2007_Peptides_28_928 PubMedSearch: Chen 2007 Peptides 28 928 PubMedID: 17267075 Abstract Glucagon-like peptide-1 (GLP-1) stimulates insulin and inhibits glucagon secretion and therefore could potentially be used to treat diabetes type II. However, its therapeutic use is limited by its short half-life in vivo, due mainly to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV). Developing GLP-1 analogs with greater bioactivity is therefore an important step toward using them therapeutically. Accordingly, we aimed to identify GLP-1 mimetic peptides by creating a high-throughput screening (HTS) assay of a phage displayed (PhD) peptide library. This assay was functionally based using the GLP-1 receptor (GLP-1R) gene. Rat GLP-1R cDNA was transfected into CHO/enhanced green fluorescent protein (EGFP) cells by lipofection. The resulting stable, recombinant cell line functionally expressed the GLP-1R and a cAMP-responsive EGFP reporter gene, to monitor receptor activation, and was used to screen a PhD dodecapeptide library. After four rounds of selection, 10 positive clones were selected based on functional evaluation and sequenced. Three sequences were obtained, corresponding to three different domains of GLP-1 (Group 1: 22-34; Group 2: 18-29; and Group 3: 6-17). The Group 3 peptide had the highest bioactivity, was synthesized, and designated KS-12. Importantly, KS-12 activated GLP-1R in vitro and reduced blood glucose levels in a dose-dependent manner when administered to Chinese Kunming mice. Although KS-12 was not as effective as GLP-1, it was significantly resistant to DPP-IV both in vitro and in vivo. Thus, this study provides a novel way to screen DPP-IV resistant agonist peptides of GLP-1 from a PhD peptide library using the functional reporter gene HTS assay. Title: Enhanced cutinase production with Thermobifida fusca by two-stage pH control strategy Du GC, Zhang SL, Hua ZZ, Zhu Y, Chen J Ref: Biotechnol J, 2:365, 2007 : PubMed ESTHER: Du_2007_Biotechnol.J_2_365 PubMedSearch: Du 2007 Biotechnol.J 2 365 PubMedID: 17309045 Abstract A mutant of Thermobifida fusca ATCC 27730 was used for cutinase production. Acetate was the most suitable carbon source for cell growth and cutinase production compared with others. The pH was one of the most important factors affecting cutinase yield and productivity. Batch cutinase fermentations by mutant Thermobifida fusca WSH04 at various pH values ranging from 7.0 to 7.9 were studied. Based on the effects of different pH values on the specific cell growth rate and specific cutinase formation rate, a two-stage pH control strategy was developed, in which the pH was set at 7.3 for the first 20 h, and switched to 7.6 afterwards. By applying this two-stage pH control strategy for cutinase fermentation, the maximal cutinase activity reached 19.8 U/mL. Title: Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains Rohmer L, Fong C, Abmayr S, Wasnick M, Larson Freeman TJ, Radey M, Guina T, Svensson K, Hayden HS and Brittnacher MJ <25 more author(s)> Rohmer L, Fong C, Abmayr S, Wasnick M, Larson Freeman TJ, Radey M, Guina T, Svensson K, Hayden HS, Jacobs M, Gallagher LA, Manoil C, Ernst RK, Drees B, Buckley D, Haugen E, Bovee D, Zhou Y, Chang J, Levy R, Lim R, Gillett W, Guenthener D, Kang A, Shaffer SA, Taylor G, Chen J, Gallis B, D'Argenio DA, Forsman M, Olson MV, Goodlett DR, Kaul R, Miller SI, Brittnacher MJ (- 25) Ref: Genome Biol, 8:R102, 2007 : PubMed ESTHER: Rohmer_2007_Genome.Biol_8_R102 PubMedSearch: Rohmer 2007 Genome.Biol 8 R102 PubMedID: 17550600 Gene_locus related to this paper: fratn-a0q8l8, fratt-q5ngu5 Abstract BACKGROUND Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans. RESULTS: Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation. CONCLUSION: The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species. Title: A novel enantioselective epoxide hydrolase for (R)-phenyl glycidyl ether to generate (R)-3-phenoxy-1,2-propanediol Wu S, Shen J, Zhou X, Chen J Ref: Applied Microbiology & Biotechnology, 76:1281, 2007 : PubMed ESTHER: Wu_2007_Appl.Microbiol.Biotechnol_76_1281 PubMedSearch: Wu 2007 Appl.Microbiol.Biotechnol 76 1281 PubMedID: 17710393 Gene_locus related to this paper: tsupd-d5us69 Abstract Bacillus sp. Z018, a novel strain producing epoxide hydrolase, was isolated from soil. The epoxide hydrolase catalyzed the stereospecific hydrolysis of (R)-phenyl glycidyl ether to generate (R)-3-phenoxy-1,2-propanediol. Epoxide hydrolase from Bacillus sp. Z018 was inducible, and (R)-phenyl glycidyl ether was able to act as an inducer. The fermentation conditions for epoxide hydrolase were 35 degrees C, pH 7.5 with glucose and NH(4)Cl as the best carbon and nitrogen source, respectively. Under optimized conditions, the biotransformation yield of 45.8% and the enantiomeric excess of 96.3% were obtained for the product (R)-3-phenoxy-1,2-propanediol. Title: N, N -disubstituted piperazines and homopiperazines: synthesis and affinities at alpha4beta2* and alpha7* neuronal nicotinic acetylcholine receptors Chen J, Deaciuc AG, Dwoskin LP, Crooks PA, Bai D Ref: J Enzyme Inhib Med Chem, 21:667, 2006 : PubMed ESTHER: Chen_2006_J.Enzyme.Inhib.Med.Chem_21_667 PubMedSearch: Chen 2006 J.Enzyme.Inhib.Med.Chem 21 667 PubMedID: 17252939 Abstract A series of N, N- disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural alpha4beta2* and alpha7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for alpha4beta2* nAChRs and did not interact with the alpha7* nAChRs subtype. The most potent analogs were compounds 8-19 (K(i) = 10.4 microM), 8-13 (K(i) = 12.0 microM), and 8-24 (K(i) = 12.8 microM). Thus, linking together a pyridine pi-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for alpha4beta2* nAChRs. Title: Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis Han CS, Xie G, Challacombe JF, Altherr MR, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML and Gilna P <38 more author(s)> Han CS, Xie G, Challacombe JF, Altherr MR, Bhotika SS, Brown N, Bruce D, Campbell CS, Campbell ML, Chen J, Chertkov O, Cleland C, Dimitrijevic M, Doggett NA, Fawcett JJ, Glavina T, Goodwin LA, Green LD, Hill KK, Hitchcock P, Jackson PJ, Keim P, Kewalramani AR, Longmire J, Lucas S, Malfatti S, McMurry K, Meincke LJ, Misra M, Moseman BL, Mundt M, Munk AC, Okinaka RT, Parson-Quintana B, Reilly LP, Richardson P, Robinson DL, Rubin E, Saunders E, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Ticknor LO, Wills PL, Brettin TS, Gilna P (- 38) Ref: Journal of Bacteriology, 188:3382, 2006 : PubMed ESTHER: Han_2006_J.Bacteriol_188_3382 PubMedSearch: Han 2006 J.Bacteriol 188 3382 PubMedID: 16621833 Gene_locus related to this paper: bacan-BA0954, bacan-BA2607, bacce-BC0968, bacce-BC3133, bacce-BC5130, bacce-c2mr40, baccz-q63gk2 Abstract Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates, appear closely related to B. anthracis. The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms. Title: Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells Tu Q, Valverde P, Chen J Ref: Biochemical & Biophysical Research Communications, 341:1257, 2006 : PubMed ESTHER: Tu_2006_Biochem.Biophys.Res.Commun_341_1257 PubMedSearch: Tu 2006 Biochem.Biophys.Res.Commun 341 1257 PubMedID: 16466699 Abstract Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of alpha1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively. Title: Comparison of statistical models for analyzing genotype, inferred haplotype, and molecular haplotype data Wallenstein S, Chen J, Wetmur JG Ref: Mol Genet Metab, 89:270, 2006 : PubMed ESTHER: Wallenstein_2006_Mol.Genet.Metab_89_270 PubMedSearch: Wallenstein 2006 Mol.Genet.Metab 89 270 PubMedID: 16782380 Abstract This report compares statistical models based on molecular and inferred haplotypes of the human paraoxonase-1 gene (PON1). In a study of 402 women comprising three race/ethnicities, 137 women had ambiguous inferred haplotypes. The inferred haplotypes (the one with highest posterior probability) for 20 of these women differed from molecular haplotypes, while based on the posterior distribution from the imputation method, 30 discrepancies were expected. We examined the proportion of the variance in PON1 enzymatic activity (phenotype) explained by genotype, and by inferred and molecular haplotype information. For Caucasians, there was an improvement in adjusted R(2) from 16% for the genotype count model, to 29% for imputed haplotypes, and a further improvement to 33% for molecular haplotypes. For Hispanics and African-Americans, there was no indication that haplotypes helped in explaining PON1 activity, and the imputed model gave essentially the same R(2) as the molecular model. For African-Americans, none of the models had adjusted R(2) that exceeded 4%, while for Hispanics they were all about 21-22%. We propose a new parsimonious model which uses all the genotype information and selected haplotype information. For PON1, this model achieves essentially the same adjusted R(2) as the all-haplotype model, with a potential cost savings and without giving the extreme predictions for uncommon haplotype combinations that the all-haplotype models provides. Title: Haplotype-phenotype relationships of paraoxonase-1 Chen J, Chan W, Wallenstein S, Berkowitz G, Wetmur JG Ref: Cancer Epidemiol Biomarkers Prev, 14:731, 2005 : PubMed ESTHER: Chen_2005_Cancer.Epidemiol.Biomarkers.Prev_14_731 PubMedSearch: Chen 2005 Cancer.Epidemiol.Biomarkers.Prev 14 731 PubMedID: 15767359 Abstract Paraoxonase 1 (PON1) is an enzyme with multiple activities, including detoxification of organophosphates. It is believed to be important in preventing neurotoxic damage and has also been implicated in atherosclerosis. The PON1 gene contains five common polymorphisms, three in the promoter (-909G > C, -162A > G, -108C > T) and two in the coding region (M55L, Q192R) with varying but incomplete linkage disequilibrium. Our previous study showed that functional polymorphisms in PON1 were strongly associated with enzymatic activity in both pregnant women [26-30 weeks of gestation] and neonates. However, there was substantial overlapping of enzyme activities between genotypes. In this study, we investigated whether haplotype (genotype + phase) information would strengthen the genotype-phenotype relationship for PON1. The study consisted of a multiethnic population of 402 mothers and 229 neonates. Haplotypes were imputed by two widely used programs, PHASE and tagSNPs, which yielded very similar results. There were seven haplotypes with a frequency of 5% or higher in at least one ethnic group of the study population. Haplotype composition varied substantially with respect to ethnicity. Haplotypes in Caucasians and African-Americans showed the largest difference, and Caribbean Hispanics seemed to be a mixture of Caucasian and African ancestry. Collectively, the genetic (genotype or haplotype) contribution to PON1 enzymatic activity (measured as phenylacetate hydrolysis) was greater in neonates compared with mothers. Specifically, 16.6% of PON1 variability was explained by genotypes in mothers compared with 30.9% in neonates. Haplotype information offered a slightly increased power in predicting PON1 activity; they explained 35.5% and 19.3% of PON1 variability in neonates and mothers, respectively. Title: Synthesis of linoleoyl disaccharides through lipase-catalyzed condensation and their surface activities Chen J, Kimura Y, Adachi S Ref: J Biosci Bioeng, 100:274, 2005 : PubMed ESTHER: Chen_2005_J.Biosci.Bioeng_100_274 PubMedSearch: Chen 2005 J.Biosci.Bioeng 100 274 PubMedID: 16243276 Abstract Monolinoleoyl trehalose, maltose and cellobiose were synthesized by Candida antarctica lipase-catalyzed condensation in an organic solvent with a low water content. The use of a mixture of pyridine and tert-butanol as the reaction medium resulted in a high product concentration on the order of mmol/l for the synthesis of linoleoyl trehalose and maltose. The highest product concentration was achieved with the 0.4 volumetric fraction of pyridine. Linoleoyl cellobiose was also synthesized although its concentration was approximately one tenth the concentrations of linoleoyl trehalose and maltose. The surfactant properties of linoleoyl trehalose, maltose and cellobiose were measured. Among the esters, linoleoyl trehalose showed the strongest surface activity. Title: Molecular haplotyping by linking emulsion PCR: analysis of paraoxonase 1 haplotypes and phenotypes Wetmur JG, Kumar M, Zhang L, Palomeque C, Wallenstein S, Chen J Ref: Nucleic Acids Research, 33:2615, 2005 : PubMed ESTHER: Wetmur_2005_Nucleic.Acids.Res_33_2615 PubMedSearch: Wetmur 2005 Nucleic.Acids.Res 33 2615 PubMedID: 15886392 Abstract Linking emulsion PCR (LE-PCR) enables formation of minichromosomes preserving phase information of two polymorphic loci, hence the haplotype. Emulsion PCR confines two amplicons of two linked polymorphic sites on a single template molecule to one aqueous-phase droplet. Linking PCR uses biotinylated, overlapping linking primers to connect these amplicons in the droplet. After LE-PCR, unlinked amplicons are removed on streptavidin-coated magnetic beads and single-stranded runoff products are capped by primer extension. Quantitative ASPCR can then be used to ascertain the haplotypes of the two polymorphic loci on the minichromosomes. Using LE-PCR, we determined the human paraoxonase-1 [PON1] molecular haplotypes at three loci (-909g>c, L55M, Q192R) in women who were compound heterozygotes for -909g>c/L55M (n = 89), -909g>c/Q192R (n = 77) and L55M/Q192R (n = 68). We observed a strong association between PON1 substrate specificity (paraoxon/phenylacetate substrate activity ratios) and -909g>c/Q192R haplotype. We have demonstrated here a powerful molecular haplotyping technology that can be applied in population studies. Title: The genomic sequence of the accidental pathogen Legionella pneumophila Chien M, Morozova I, Shi S, Sheng H, Chen J, Gomez SM, Asamani G, Hill K, Nuara J and Russo JJ <27 more author(s)> Chien M, Morozova I, Shi S, Sheng H, Chen J, Gomez SM, Asamani G, Hill K, Nuara J, Feder M, Rineer J, Greenberg JJ, Steshenko V, Park SH, Zhao B, Teplitskaya E, Edwards JR, Pampou S, Georghiou A, Chou IC, Iannuccilli W, Ulz ME, Kim DH, Geringer-Sameth A, Goldsberry C, Morozov P, Fischer SG, Segal G, Qu X, Rzhetsky A, Zhang P, Cayanis E, de Jong PJ, Ju J, Kalachikov S, Shuman HA, Russo JJ (- 27) Ref: Science, 305:1966, 2004 : PubMed ESTHER: Chien_2004_Science_305_1966 PubMedSearch: Chien 2004 Science 305 1966 PubMedID: 15448271 Gene_locus related to this paper: legph-q5zsu4, legpa-q5x2r4, legpa-q5x3a5, legpa-q5x3d6, legpa-q5x4r4, legpa-q5x4t1, legpa-q5x5b2, legpa-q5x5z2, legpa-q5x7f5, legpa-q5x8e6, legpa-q5x8m4, legpa-q5x322, legpa-q5x405, legpa-q5x424, legpa-q5x473, legpa-q5x590, legpa-q5x611, legpa-q5x819, legpc-a5iar0, legph-q5zrh1, legph-q5zsb5, legph-q5zv00, legph-q5zwi8, legph-q5zze3, legpl-q5wtd3, legpl-q5wua5, legpl-q5wvw9, legpn-Q8KU34, legpn-Q8RNQ1, legpn-SBPA, legpn-i7i328, legpl-q5wsw9 Abstract We present the genomic sequence of Legionella pneumophila, the bacterial agent of Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes a 45-kilobase pair element that can exist in chromosomal and episomal forms, selective expansions of important gene families, genes for unexpected metabolic pathways, and previously unknown candidate virulence determinants. We highlight the genes that may account for Legionella's ability to survive in protozoa, mammalian macrophages, and inhospitable environmental niches and that may define new therapeutic targets. Title: Two-dimensional protein database of human pancreas Hu L, Evers S, Lu ZH, Shen Y, Chen J Ref: Electrophoresis, 25:512, 2004 : PubMed ESTHER: Hu_2004_Electrophoresis_25_512 PubMedSearch: Hu 2004 Electrophoresis 25 512 PubMedID: 14760645 Abstract We report here the two-dimensional protein database of human pancreas. The proteins were analyzed by two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Totally, 302 proteins were identified, of which about 27% were enzymes with a broad range of catalytic activities. Several of these are specifically expressed in pancreas, such as pancreatic amylase, pancreatic stone protein, pancreatitis-associated protein, pancreatic lipase, pancreatic elastase, etc. Structural and cytoskeletal proteins are also strongly represented on the gels. Thus, the pancreatic proteome reflects the organ's function. This work paves the way for further studies on pancreatic protein expression in health and disease, such as diabetes and pancreatic cancer. Title: Injection of okadaic acid into the meynert nucleus basalis of rat brain induces decreased acetylcholine level and spatial memory deficit Tian Q, Lin ZQ, Wang XC, Chen J, Wang Q, Gong CX, Wang JZ Ref: Neuroscience, 126:277, 2004 : PubMed ESTHER: Tian_2004_Neurosci_126_277 PubMedSearch: Tian 2004 Neurosci 126 277 PubMedID: 15207345 Abstract Abnormal hyperphosphorylation of tau and cholinergic deficit occur in the early stage of Alzheimer's disease (AD) and relate to the dementia symptom. Hyperphosphorylation of tau, neurofilament (NF) and other proteins in AD brain appears to be caused by a down-regulation of protein phosphatase 2A (PP2A), but the mechanism leading to cholinergic deficit is still unknown. In this study, we selectively inhibited PP2A by injection of okadaic acid (OA) into the Meynert nucleus basalis of rats. We found that injection of OA induced hyperphosphorylation of tau and NF and decreased acetylcholine (ACh) level in the nucleus basalis of Meynert. These alterations were accompanied by spatial memory deficit in OA-injected rats. We also demonstrated that the OA-induced ACh reduction may be due to a failure of intraneuronal transport of choline acetyltransferase (ChAT) from cell body to the neuronal terminals rather than an alteration of activity of ChAT or acetylcholinesterase. This study suggests that a down-regulation of PP2A may underlie both abnormal hyperphosphorylation of cytoskeletal proteins leading to neurofibrillary degeneration and cholinergic deficiency in AD. Title: Increased influence of genetic variation on PON1 activity in neonates Chen J, Kumar M, Chan W, Berkowitz G, Wetmur JG Ref: Environmental Health Perspectives, 111:1403, 2003 : PubMed ESTHER: Chen_2003_Environ.Health.Perspect_111_1403 PubMedSearch: Chen 2003 Environ.Health.Perspect 111 1403 PubMedID: 12928148 Abstract PON1 (paraoxonase-1) detoxifies organophosphates by cleavage of active oxons before they have a chance to inhibit cholinesterases. The corresponding gene PON1 has common polymorphisms in both the promoter (-909, -162, -108) and the coding region (L55M, Q192R). The five PON1 genotypes were determined for maternal blood (n= 402) and cord blood (n= 229) as part of a study of the effects of organophosphate pesticide exposure on infant growth and neurodevelopment. PON1 enzymatic activities were determined for a majority of subjects. The population contained Caucasians, Caribbean Hispanics, and African Americans. PON1 activity was strongly dependent upon the promoter alleles in both maternal and cord blood. For example, PON1 activities for position -108CC, CT, and TT mothers were 146, 128, and 109 arylesterase U/mL (analysis of variance, p< 0.0001), whereas the same PON1 activities for the respective cord bloods were 49.0, 32.4, and 23.2 U/mL (p < 0.0001). Compared with adults, neonates had lower PON1 activity, implying reduced capacity to detoxify organophosphates. In addition there was a larger difference in activity between genotype groups in neonates than in adults. Because the five polymorphisms in PON1 occur in a short stretch of DNA, they were tested for linkage disequilibrium (LD). Significant LD was found among all three promoter polymorphisms as well as between promoter polymorphisms and L55M, with the strongest LD for Caucasians and the weakest for African Americans. The Caribbean Hispanics fall between these two groups. Surprisingly, significant LD also was observed between the promoter polymorphisms and C311S in PON2. LD between the promoter polymorphisms and Q192R was not significant. Title: N,N-disubstituted piperazines: synthesis and affinities at alpha4beta2(*) and alpha7(*) neuronal nicotinic acetylcholine receptors Chen J, Norrholm S, Dwoskin LP, Crooks PA, Bai D Ref: Bioorganic & Medicinal Chemistry Lett, 13:97, 2003 : PubMed ESTHER: Chen_2003_Bioorg.Med.Chem.Lett_13_97 PubMedSearch: Chen 2003 Bioorg.Med.Chem.Lett 13 97 PubMedID: 12467625 Abstract A series of N,N-disubstituted piperazines were prepared and evaluated for binding to alpha4beta2(*) and alpha7(*) neuronal nicotinic acetylcholine receptors using rat striatum and whole brain membrane preparations, respectively. This series of compounds exhibited selectivity for alpha4beta2(*) nAChRs and did not interact with the alpha7(*) nAChRs subtype. The most potent analogues were compounds 8b and 8f (K(i)=32 microM). Thus, linking together a pyridine pi-system and a cyclic amine moiety via a piperazine ring affords compounds with low affinity, but good selectivity for alpha4beta2(*) nicotinic receptors. Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C and Gray A <42 more author(s)> Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (- 42) Ref: Genome Res, 13:2265, 2003 : PubMed ESTHER: Clark_2003_Genome.Res_13_2265 PubMedSearch: Clark 2003 Genome.Res 13 2265 PubMedID: 12975309 Gene_locus related to this paper: human-CES3, human-CES4A Abstract A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics. Title: Kinetic polymerase chain reaction on pooled DNA: a high-throughput, high-efficiency alternative in genetic epidemiological studies Chen J, Germer S, Higuchi R, Berkowitz G, Godbold J, Wetmur JG Ref: Cancer Epidemiol Biomarkers Prev, 11:131, 2002 : PubMed ESTHER: Chen_2002_Cancer.Epidemiol.Biomarkers.Prev_11_131 PubMedSearch: Chen 2002 Cancer.Epidemiol.Biomarkers.Prev 11 131 PubMedID: 11815411 Abstract The ideal technology for screening single-nucleotide polymorphisms requires high throughput with minimal cost per sample, minimal usage of valuable DNA resources, and maximal flexibility for assessment of new polymorphisms. We demonstrate here the feasibility of kinetic allele-specific PCR with DNA pooling (S. Germer et al., Genome Res., 10: 258-266, 2000) in a population study that satisfies all of the mentioned criteria and offers a powerful new tool for detecting meaningful polymorphic differences in candidate gene association studies and genome-wide linkage dysequilibrium scans. Three individuals prepared pooled DNA samples from 269 individuals separated into three racial/ethnic groups: Caucasians (n = 56), African-Americans (n = 86), and Hispanics (n = 127). We used kinetic allele-specific PCR to determine the allele frequencies of the common paraoxonase 1 polymorphism, PON1 Q191R, in these pools. Paraoxonase 1 is a critical enzyme for inactivating neurotoxic intermediates in the metabolism of organophosphates. In a blinded test of the technology, these nine pooled DNA samples were sent to Roche for genotyping by kinetic allele-specific PCR. The allele frequencies found were 0.266 +/- 0.011, 0.386 +/- 0.011, and 0.617 +/- 0.010, respectively, which were comparable to the frequencies of 0.269, 0.403, and 0.622 determined by PCR-restriction fragment length polymorphism analysis. These same samples were genotyped on two kinetic PCR platforms from different manufacturers, using three different DNA polymerases. The results were comparable between both platforms and among all three polymerases. The results demonstrate a powerful new technology for determining frequencies of single-nucleotide polymorphisms in an epidemiological study. Title: Sequence and analysis of rice chromosome 4 Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y and Han B <61 more author(s)> Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y, Hu X, Jia P, Zhao Q, Ying K, Yu S, Tang Y, Weng Q, Zhang L, Lu Y, Mu J, Zhang LS, Yu Z, Fan D, Liu X, Lu T, Li C, Wu Y, Sun T, Lei H, Li T, Hu H, Guan J, Wu M, Zhang R, Zhou B, Chen Z, Chen L, Jin Z, Wang R, Yin H, Cai Z, Ren S, Lv G, Gu W, Zhu G, Tu Y, Jia J, Chen J, Kang H, Chen X, Shao C, Sun Y, Hu Q, Zhang X, Zhang W, Wang L, Ding C, Sheng H, Gu J, Chen S, Ni L, Zhu F, Chen W, Lan L, Lai Y, Cheng Z, Gu M, Jiang J, Li J, Hong G, Xue Y, Han B (- 61) Ref: Nature, 420:316, 2002 : PubMed ESTHER: Feng_2002_Nature_420_316 PubMedSearch: Feng 2002 Nature 420 316 PubMedID: 12447439 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q7F959, orysa-q7f9i3, orysa-q7x7y5, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-Q7XTM8, orysa-q7xts6, orysa-q7xue7, orysa-q7xv53, orysa-Q7XVB5, orysa-Q7XVG5, orysj-q0jaf0, orysj-q7f8x1 Abstract Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis. Title: [The acute effects of dimethoate on the muscarinic-receptors of rat brains and the relationship between muscarinic-receptors and cholinesterase] Sun Y, Zhou Z, Hu Y, Chen J, Jin T Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 20:293, 2002 : PubMed ESTHER: Sun_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_293 PubMedSearch: Sun 2002 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 20 293 PubMedID: 14694657 Abstract OBJECTIVE: To study the acute effects of dimethoate on the muscarinic-receptors(M1, M2) in the brain of rats. Title: [Single factor study of prognosis from 520 cases with chronic severe hepatitis] Zou Z, Chen J, Xin S, Xing H, Li B, Li J, Shen H, Liu Y Ref: Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 16:246, 2002 : PubMed ESTHER: Zou_2002_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_16_246 PubMedSearch: Zou 2002 Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi 16 246 PubMedID: 12665931 Abstract OBJECTIVE: To further understand chronic severe hepatitis (CSH) and to improve the level of diagnosis and treatment and to explore the methods to reduce the fatality rate of CSH through analysing the factors related to prognosis of CSH. Title: Cloning of a novel retinoid-inducible serine carboxypeptidase from vascular smooth muscle cells Chen J, Streb JW, Maltby KM, Kitchen CM, Miano JM Ref: Journal of Biological Chemistry, 276:34175, 2001 : PubMed ESTHER: Chen_2001_J.Biol.Chem_276_34175 PubMedSearch: Chen 2001 J.Biol.Chem 276 34175 PubMedID: 11447226 Gene_locus related to this paper: mouse-RISC, ratno-RISC Abstract Retinoids block smooth muscle cell (SMC) proliferation and attenuate neointimal formation after vascular injury, presumably through retinoid receptor-mediated changes in gene expression. To identify target genes in SMC whose encoded proteins could contribute to such favorable biological effects, we performed a subtractive screen for retinoid-inducible genes in cultured SMC. Here, we report on the cloning and initial characterization of a novel retinoid-inducible serine carboxypeptidase (RISC). Expression of RISC is low in cultured SMC but progressively increases over a 5-day time-course treatment with all-trans-retinoic acid. A near full-length rat RISC cDNA was cloned and found to have a 452-amino acid open reading frame containing an amino-terminal signal sequence, followed by several conserved domains comprising the catalytic triad common to members of the serine carboxypeptidase family. In vitro transcription and translation experiments showed that the rat RISC cDNA generates an approximately 51-kDa protein. Confocal immunofluorescence microscopy of COS-7 cells transiently transfected with a RISC-His tag plasmid revealed cytosolic localization of the fusion protein. Western blotting studies using conditioned medium from transfected COS-7 cells suggest that RISC is a secreted protein. Tissue Northern blotting studies demonstrated robust expression of RISC in rat aorta, bladder, and kidney with much lower levels in all other tissues analyzed; high level RISC expression was also observed in human kidney. In situ hybridization verified the localization of RISC to medial SMC of the adult rat aorta. Interestingly, expression in kidney was restricted to proximal convoluted tubules; little or no expression was observed in glomerular cells, distal convoluted and collecting tubules, or medullary cells. Radiation hybrid mapping studies placed the rat RISC locus on chromosome 10q. These studies reveal a novel retinoid-inducible protease whose activity may be involved in vascular wall and kidney homeostasis. Title: Transgenic animals with inducible, targeted gene expression in brain Chen J, Kelz MB, Zeng G, Sakai N, Steffen C, Shockett PE, Picciotto MR, Duman RS, Nestler EJ Ref: Molecular Pharmacology, 54:495, 1998 : PubMed ESTHER: Chen_1998_Mol.Pharmacol_54_495 PubMedSearch: Chen 1998 Mol.Pharmacol 54 495 PubMedID: 9730908 Abstract Several inducible gene expression systems have been developed in vitro in recent years to overcome limitations with traditional transgenic mice. One of these, the tetracycline-regulated system, has been used successfully in vivo. Nevertheless, concerns remain about the ability of this system to direct high levels of transgene expression in vivo and to enable such expression to be turned on and off effectively. We report here the generation, using a modified tetracycline-regulated system under the control of the neuron-specific enolase promoter, of several lines of mice that direct transgene expression to specific brain regions, including the striatum, cerebellum, CA1 region of the hippocampus, or deep layers of cerebral neocortex. Transgene expression in these mice can be turned off completely with low doses of doxycycline (a tetracycline derivative) and driven to very high levels in the absence of doxycycline. We demonstrate this tissue-specific, inducible expression for three transgenes: those that encode luciferase (a reporter protein) or DeltaFosB or the cAMP-response element binding protein (CREB) (two transcription factors). The various lines of transgenic mice demonstrate an inducible system that generates high levels of transgene expression in specific brain regions and represent novel and powerful tools with which to study the functioning of these (or potentially any other) genes in the brain. Title: Discovery of a novel tetrahydroacridine acetylcholinesterase inhibitor through an indexed combinatorial library Pirrung MC, Chau JH, Chen J Ref: Chemistry & Biology, 2:621, 1995 : PubMed ESTHER: Pirrung_1995_Chem.Biol_2_621 PubMedSearch: Pirrung 1995 Chem.Biol 2 621 PubMedID: 9383467 Inhibitor(s) related to this paper: 7-Nitrotacrine, Tacrine Abstract BACKGROUND: Methods for the rapid and efficient preparation of drug candidates through combinatorial chemistry are of increasing interest. We have previously reported an indexed combinatorial library method that allows both the preparation and testing of compounds in solution. We set out to apply this method to develop more effective analogs of the known, marketed drug tacrine, an acetylcholinesterase inhibitor. RESULTS: A one-step condensation of cyclohexanones with cyanoanilines to generate tetrahydroacridine pools was developed. The resulting library of (formally) 72 tetrahydroacridines was screened against acetylcholinesterase, and a compound 10-fold more potent than tacrine, 7-nitrotacrine, was discovered. Its increased potency could be readily explained by examining the known structure of the complex of acetylcholinesterase with tetrahydroacridine. CONCLUSIONS: In this work, we have provided a relatively rare example of carbon-carbon bond formation in a pool synthesis and have discovered a potentially useful acetylcholinesterase inhibitor. Title: Characterization of muscarinic receptors in cultured human iris sphincter and ciliary smooth muscle cells WoldeMussie E, Feldmann BJ, Chen J Ref: Experimental Eye Research, 56:385, 1993 : PubMed ESTHER: Woldemussie_1993_Exp.Eye.Res_56_385 PubMedSearch: Woldemussie 1993 Exp.Eye.Res 56 385 PubMedID: 8388802 Abstract Muscarinic receptors present in cultured human iris sphincter and ciliary smooth muscle cells were characterized by both ligand ([3H]QNB binding) and functional (phosphoinositide hydrolysis) studies. Ligand binding studies showed that [3H]QNB represented a single population of binding sites with KD values of 4.02 x 10(-11) M in the ciliary and 5.6 x 10(-11) M in the iris sphincter cells. In competition studies, the selective antagonist, 4-diphenylacetoxy-N-methylpiperidine-methobromide (4-DAMP) was the most potent in displacing [3H]QNB with selectivity of 150-350-fold over pirenzepine (M1) and 450-1700-fold over AF-DX 116 (M2). 4-DAMP recognized one site in the iris sphincter cells (Ki = 0.34 nM) but two sites in the ciliary cells (KH = 0.9 nM and KL = 49 nM). 4-DAMP was also the most potent in inhibiting carbachol-induced hydrolysis of inositol phospholipids (PI) in both cell types. However, the IC50 values for PI hydrolysis were several fold lower than those for [3H]QNB binding. Using these selective antagonists, our data supports the presence of functional muscarinic receptors of M3 subtype in human iris sphincter and ciliary cells. It also shows the presence of a second low affinity site in the ciliary smooth muscle cells that is recognized by 4-DAMP. | |||||||
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