Author Report for: Li LContact information:Li LisaSchool of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Room 193; Science Center; Hong KongChinaPhone : +85226037796 Fax : Send E-Mail to Li Lisa
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: Study of Huperzine A derivatives with extended protection against soman intoxication Cui Y, Chen X, Shi J, Jin Q, Zhang R, Shi T, Wang C, Li L Ref: Toxicol Appl Pharmacol, :116646, 2023 : PubMed ESTHER: Cui_2023_Toxicol.Appl.Pharmacol__116646 PubMedSearch: Cui 2023 Toxicol.Appl.Pharmacol 116646 PubMedID: 37517785 Abstract Pre-administration of huperzine A (Hup A) was validated to prevent poisoning from exposure to nerve agents (NAs) by reversibly inhibiting acetylcholinesterase (AChE). However, like the currently commonly used reversible inhibitors, Hup A has a short half-life and is unable to produce a long-term preventative effect. To extend the protective time of Hup A against NAs, 42 derivatives with a CN bond were designed based on the structure of Hup A in this study. All designed derivatives showed good binding capability with AChE via molecular docking. Six compounds (H3, H4, H11, H14, H16, and H25) with representative structures were selected for synthesis by Schiff base reaction, and their structures were stable. The modified Ellman's method showed the six compounds concentration-dependently inhibited AChE, and the half maximal inhibitory concentration (IC(50)) were higher than that of Hup A. Pretreatment of AChE with the derivatives significantly increased the IC(50) of soman. In vivo experiments demonstrated H3, H4, H14, H16, and H25 had longer protective capacities against 1 x LD(95) soman-induced death in mice than Hup A. The 12 h protective index showed that the protective ratios of H3, H4, H14 and H16 were 2.31, 1.85, 2.23 and 1.99 respectively, better than that of Hup A. The extended protection of the derivatives against soman may be explained by their transformation to Hup A in vivo. Furthermore, all six compounds showed lower acute oral toxicity than Hup A. Overall, our study provided an optional strategy to acquire pretreatment agents for NAs with extended action and low toxicity. Title: Targeting soluble epoxide hydrolase promotes osteogenic-angiogenic coupling via activating SLIT3/HIF-1alpha signalling pathway Gao L, Chen W, Li L, Li J, Kongling W, Zhang Y, Yang X, Zhao Y, Bai J, Wang F Ref: Cell Prolif, :e13403, 2023 : PubMed ESTHER: Gao_2023_Cell.Prolif__e13403 PubMedSearch: Gao 2023 Cell.Prolif e13403 PubMedID: 36636821 Inhibitor(s) related to this paper: TPPU Abstract Type H vessels have recently been identified to modulate osteogenesis. Epoxyeicostrioleic acids (EETs) have an essential contribution to vascular homeostasis. However, whether increased EETs with soluble epoxide hydrolase (sEH) inhibitor TPPU enhance the coupling of angiogenesis and osteogenesis remains largely unknown. The effects of TPPU on cross-talk between co-cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs), and on long bone growth and calvarial defect repair in mice were investigated in vitro and in vivo. TPPU enhanced osteogenic differentiation of co-cultured HUVECs and hDPSCs in vitro and increased type H vessels, and long bone growth and bone repair of calvarial defect. Mechanistically, TPPU promoted cell proliferation and angiogenesis, reclined cell apoptosis, and significantly increased CD31(hi) EMCN(hi) endothelial cells (ECs) and SLIT3 and HIF-1alpha expression levels in co-cultured HUVECs and hDPSCs. Knockdown of Slit3 in hDPSCs or Hif-1alpha in HUVECs impaired the formation of CD31(hi) EMCN(hi) ECs and reversed TPPU-induced osteogenesis. We defined a previously unidentified effect of TPPU coupling angiogenesis and osteogenesis. TPPU induced type H vessels by upregulating the expression of hDPSCs-derived SLIT3, which resulted in the activation of ROBO1/YAP1/HIF-1alpha signalling pathway in ECs. Targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a promising therapeutic target for bone regeneration and repair. Title: Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review) Gao J, Li L Ref: Exp Ther Med, 26:444, 2023 : PubMed ESTHER: Gao_2023_Exp.Ther.Med_26_444 PubMedSearch: Gao 2023 Exp.Ther.Med 26 444 PubMedID: 37614437 Abstract Alzheimer's disease (AD), the most common cause of dementia worldwide, has gradually become a global health concern for society and individuals with the process of global ageing. Although extensive research has been carried out on AD, the etiology and pathological mechanism of the disease are still unclear, and there is no specific drug to cure or delay AD progression. The exploration of enhancing nerve regeneration in AD has gradually attracted increasing attention. In the current review, the existing therapeutic strategies were summarized to induce nerve regeneration which can increase the number of neurons, and improve the survival of neurons, the plasticity of synapses and synaptic activity. The strategies include increasing neurotrophic expression (such as brain-derived neurotrophic factor and nerve growth factor), inhibiting acetylcholinesterase (such as donepezil, tacrine, rivastigmine and galanthamine), elevating histone deacetylase levels (such as RGFP-966, Tasquinimod, CM-414 and 44B), stimulating the brain by physiotherapy (such as near-infrared light, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation) and transplanting exogenous neural stem cells. However, further evaluations need to be performed to determine the optimal treatment. The present study reviews recent interventions for enhancing adult neurogenesis and attempts to elucidate their mechanisms of action, which may provide a theoretical basis for inducing nerve regeneration to fight against AD. Title: UNC-43/CaMKII-triggered anterograde signals recruit GABA(A)Rs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs Hao Y, Liu H, Zeng XT, Wang Y, Zeng WX, Qian KY, Li L, Chi MX, Gao S and Tong XJ <1 more author(s)> Hao Y, Liu H, Zeng XT, Wang Y, Zeng WX, Qian KY, Li L, Chi MX, Gao S, Hu Z, Tong XJ (- 1) Ref: Nat Commun, 14:1436, 2023 : PubMed ESTHER: Hao_2023_Nat.Commun_14_1436 PubMedSearch: Hao 2023 Nat.Commun 14 1436 PubMedID: 36918518 Abstract Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABA(A)Rs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABA(A)Rs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABA(A)Rs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1alpha/Neurexin surface delivery. Together, MADD-4B and NRX-1alpha recruit postsynaptic NLG-1/Neuroligin and stabilize GABA(A)Rs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABA(A)Rs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1alpha, which act as anterograde signals to recruit postsynaptic GABA(A)Rs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity. Title: PGC 1alpha-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure Jin Q, Zhang Y, Cui Y, Shi M, Shi J, Zhu S, Shi T, Zhang R, Chen X and Li L <2 more author(s)> Jin Q, Zhang Y, Cui Y, Shi M, Shi J, Zhu S, Shi T, Zhang R, Chen X, Zong X, Wang C, Li L (- 2) Ref: Biol Pharm Bull, 46:563, 2023 : PubMed ESTHER: Jin_2023_Biol.Pharm.Bull_46_563 PubMedSearch: Jin 2023 Biol.Pharm.Bull 46 563 PubMedID: 37005300 Abstract This work aimed to assess whether mitochondrial damage in the liver induced by subacute soman exposure is caused by peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and whether PGC-1alpha regulates mitochondrial respiratory chain damage. Toxicity mechanism research may provide theoretical support for developing anti-toxic drugs in the future. First, a soman animal model was established in male Sprague-Dawley (SD) rats by subcutaneous soman injection. Then, liver damage was biochemically evaluated, and acetylcholinesterase (AChE) activity was also determined. Transmission electron microscopy (TEM) was performed to examine liver mitochondrial damage, and high-resolution respirometry was carried out for assessing mitochondrial respiration function. In addition, complex I-IV levels were quantitatively evaluated in isolated liver mitochondria by enzyme-linked immunosorbent assay (ELISA). PGC-1alpha levels were detected with a Jess capillary-based immunoassay device. Finally, oxidative stress was analyzed by quantifying superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and reactive oxygen species (ROS) levels. Repeated low-level soman exposure did not alter AChE activity, while increasing morphological damage of liver mitochondria and liver enzyme levels in rat homogenates. Complex I, II and I + II activities were 2.33, 4.95, and 5.22 times lower after treatment compared with the control group, respectively. Among complexes I-IV, I-III decreased significantly (p < 0.05), and PGC-1alpha levels were 1.82 times lower after soman exposure than in the control group. Subacute soman exposure significantly increased mitochondrial ROS production, which may cause oxidate stress. These findings indicated dysregulated mitochondrial energy metabolism involves PGC-1alpha protein expression imbalance, revealing non-cholinergic mechanisms for soman toxicity. Title: Effects of Lipid Metabolism-Related Genes PTGIS and HRASLS on Phenotype, Prognosis, and Tumor Immunity in Lung Squamous Cell Carcinoma Lei K, Liang R, Tan B, Li L, Lyu Y, Wang K, Wang W, Hu X, Wu D and Wang M <1 more author(s)> Lei K, Liang R, Tan B, Li L, Lyu Y, Wang K, Wang W, Hu X, Wu D, Lin H, Wang M (- 1) Ref: Oxid Med Cell Longev, 2023:6811625, 2023 : PubMed ESTHER: Lei_2023_Oxid.Med.Cell.Longev_2023_6811625 PubMedSearch: Lei 2023 Oxid.Med.Cell.Longev 2023 6811625 PubMedID: 36703911 Abstract BACKGROUND: Lipid metabolism reprogramming played an important role in cancer occurrence, development, and immune regulation. The aim of this study was to identify and validate lipid metabolism-related genes (LMRGs) associated with the phenotype, prognosis, and immunological characteristics of lung squamous cell carcinoma (LUSC). METHODS: In the TCGA cohort, bioinformatics and survival analysis were used to identify lipid metabolism-related differentially expressed genes (DEGs) associated with the prognosis of LUSC. PTGIS/HRASLS knockdown and overexpression effects on the LUSC phenotype were analyzed in vitro experiments. Based on the expression distribution of PTGIS/HRASLS, LUSC patients were divided into two clusters by consensus clustering. Clinical information, prognosis, immune infiltration, expression of immune checkpoints, and tumor mutation burden (TMB) level were compared between the TCGA and GSE4573 cohorts. The genes related to clustering and tumor immunity were screened by weighted gene coexpression network analysis (WGCNA), and the target module genes were analyzed by functional enrichment analysis, protein-protein interaction (PPI) analysis, and immune correlation analysis. RESULTS: 191 lipid metabolism-related DEGs were identified, of which 5 genes were independent prognostic genes of LUSC. PTGIS/HRASLS were most closely related to LUSC prognosis and immunity. RT-qPCR, western blot (WB) analysis, and immunohistochemistry (IHC) showed that the expression of PTGIS was low in LUSC, while HRASLS was high. Functionally, PTGIS promoted LUSC proliferation, migration, and invasion, while HRASLS inhibited LUSC proliferation, migration, and invasion. The two clusters' expression and distribution of PTGIS/HRASLS had the opposite trend. Cluster 1 was associated with lower pathological staging (pT, pN, and pTNM stages), better prognosis, stronger immune infiltration, higher expression of immune checkpoints, and higher TMB level than cluster 2. WGCNA found that 28 genes including CD4 and IL10RA were related to the expression of PTGIS/HRASLS and tumor immune infiltration. PTGIS/HRASLS in the GSE4573 cohort had the same effect on LUSC prognosis and tumor immunity as the TCGA cohort. CONCLUSIONS: PTGIS and HRASLS can be used as new therapeutic targets for LUSC as well as biomarkers for prognosis and tumor immunity, which has positive significance for guiding the immunotherapy of LUSC. Title: Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes Li Y, Liu X, Li L, Zhang T, Gao Y, Zeng K, Wang Q Ref: Front Pharmacol, 14:1093696, 2023 : PubMed ESTHER: Li_2023_Front.Pharmacol_14_1093696 PubMedSearch: Li 2023 Front.Pharmacol 14 1093696 PubMedID: 36762117 Abstract Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role. Title: Enhancing the Hydrolysis and Acyl Transfer Activity of Carboxylesterase DLFae4 by a Combinational Mutagenesis and In-Silico Method Li L, Ding L, Shao Y, Sun S, Wang M, Xiang J, Zhou J, Wu G, Song Z, Xin Z Ref: Foods, 12:1169, 2023 : PubMed ESTHER: Li_2023_Foods_12_1169 PubMedSearch: Li 2023 Foods 12 1169 PubMedID: 36981096 Abstract In the present study, a feruloyl esterase DLFae4 identified in our previous research was modified by error-prone PCR and site-directed saturation mutation to enhance the catalytic efficiency and acyltransferase activity further. Five mutants with 6.9-118.9% enhanced catalytic activity toward methyl ferulate (MFA) were characterized under the optimum conditions. Double variant DLFae4-m5 exhibited the highest hydrolytic activity (270.97 U/mg), the Km value decreased by 83.91%, and the Kcat/Km value increased by 6.08-fold toward MFA. Molecular docking indicated that a complex hydrogen bond network in DLFae4-m5 was formed, with four of five bond lengths being shortened compared with DLFae4, which might account for the increase in catalytic activity. Acyl transfer activity assay revealed that the activity of DLFae4 was as high as 1550.796 U/mg and enhanced by 375.49% (5823.172 U/mg) toward 4-nitrophenyl acetate when residue Ala-341 was mutated to glycine (A341G), and the corresponding acyl transfer efficiency was increased by 7.7 times, representing the highest acyltransferase activity to date, and demonstrating that the WGG motif was pivotal for the acyltransferase activity in family VIII carboxylesterases. Further experiments indicated that DLFae4 and variant DLFae4 (A341G) could acylate cyanidin-3-O-glucoside effectively in aqueous solution. Taken together, our study suggested the effectiveness of error-prone PCR and site-directed saturation mutation to increase the specific activity of enzymes and may facilitate the practical application of this critical feruloyl esterase. Title: Dissecting the HGT network of carbon metabolic genes in soil-borne microbiota Li L, Liu Y, Xiao Q, Xiao Z, Meng D, Yang Z, Deng W, Yin H, Liu Z Ref: Front Microbiol, 14:1173748, 2023 : PubMed ESTHER: Li_2023_Front.Microbiol_14_1173748 PubMedSearch: Li 2023 Front.Microbiol 14 1173748 PubMedID: 37485539 Abstract The microbiota inhabiting soil plays a significant role in essential life-supporting element cycles. Here, we investigated the occurrence of horizontal gene transfer (HGT) and established the HGT network of carbon metabolic genes in 764 soil-borne microbiota genomes. Our study sheds light on the crucial role of HGT components in microbiological diversification that could have far-reaching implications in understanding how these microbial communities adapt to changing environments, ultimately impacting agricultural practices. In the overall HGT network of carbon metabolic genes in soil-borne microbiota, a total of 6,770 nodes and 3,812 edges are present. Among these nodes, phyla Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes are predominant. Regarding specific classes, Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacteroidia, Actinomycetia, Betaproteobacteria, and Clostridia are dominant. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional assignments of glycosyltransferase (18.5%), glycolysis/gluconeogenesis (8.8%), carbohydrate-related transporter (7.9%), fatty acid biosynthesis (6.5%), benzoate degradation (3.1%) and butanoate metabolism (3.0%) are primarily identified. Glycosyltransferase involved in cell wall biosynthesis, glycosylation, and primary/secondary metabolism (with 363 HGT entries), ranks first overwhelmingly in the list of most frequently identified carbon metabolic HGT enzymes, followed by pimeloyl-ACP methyl ester carboxylesterase, alcohol dehydrogenase, and 3-oxoacyl-ACP reductase. Such HGT events mainly occur in the peripheral functions of the carbon metabolic pathway instead of the core section. The inter-microbe HGT genetic traits in soil-borne microbiota genetic sequences that we recognized, as well as their involvement in the metabolism and regulation processes of carbon organic, suggest a pervasive and substantial effect of HGT on the evolution of microbes. Title: Detection of target site mutations in the acetylcholinesterase and voltage-gated sodium channel in field populations of Culex quinquefasciatus and Cx. tritaeniorhynchus from southern Sichuan region of China Liu J, Wang Y, Liu P, Yu X, Tan AI, Zeng J, Li L, Qiu X Ref: J Am Mosq Control Assoc, :, 2023 : PubMed ESTHER: Liu_2023_J.Am.Mosq.Control.Assoc__ PubMedSearch: Liu 2023 J.Am.Mosq.Control.Assoc PubMedID: 36752737 Abstract Culex quinquefasciatus and Cx. tritaeniorhynchus are 2 dominant disease vectors in Neijiang City, Sichuan Province, China. Although there is evidence of confirmed resistance against insecticides in mosquito vectors, nothing is known about the existing insecticide resistance-conferring mutations in Cx. quinquefasciatus and Cx. tritaeniorhynchu in this region so far. In this study, the G119S mutation in the acetylcholinesterase (AChE) was detected in Cx. quinquefasciatus at a very low frequency (0.9%) with no resistant homozygotes being observed. Two resistance mutations in the voltage-gated sodium channel (VGSC) (L1014F and L1014S) were found in Cx. quinquefasciatus with frequencies of 88.7% and 8.3%, respectively. By contrast, the AChE F455W mutation was found to be fixed (with a frequency of 100%) in 3 of the 5 studied populations, with an overall frequency being 98.1%. In addition, 1 resistance-conferring VGSC mutation (L1014F) was detected with an overall frequency of 15.2% in Cx. tritaeniorhynchus. These results indicate that the well-recognized insecticide resistance-conferring mutations in both AChE and VGSC are present in the 2 Culex species in Neijiang. The contrasting patterns in the frequency of resistance alleles indicate that species-customized strategies of insecticide resistance management should be considered for the 2 species. Title: Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure Luo HY, Gao LC, Long HZ, Zhou ZW, Xu SG, Li FJ, Li HL, Cheng Y, Li CX and Deng P <3 more author(s)> Luo HY, Gao LC, Long HZ, Zhou ZW, Xu SG, Li FJ, Li HL, Cheng Y, Li CX, Peng XY, Li L, Chen R, Deng P (- 3) Ref: European Journal of Clinical Pharmacology, :, 2023 : PubMed ESTHER: Luo_2023_Eur.J.Clin.Pharmacol__ PubMedSearch: Luo 2023 Eur.J.Clin.Pharmacol PubMedID: 36976322 Abstract OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms. 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: Complete degradation of di-n-butyl phthalate by Glutamicibacter sp. strain 0426 with a novel pathway Ren C, Wang Y, Wu Y, Zhao HP, Li L Ref: Biodegradation, :, 2023 : PubMed ESTHER: Ren_2023_Biodegradation__ PubMedSearch: Ren 2023 Biodegradation PubMedID: 37395851 Gene_locus related to this paper: 9micc-a0a5c2fpe7 Abstract Di-n-butyl phthalate (DBP) is widely used as plasticizer that has potential carcinogenic, teratogenic, and endocrine effects. In the present study, an efficient DBP-degrading bacterial strain 0426 was isolated and identified as a Glutamicibacter sp. strain 0426. It can utilize DBP as the sole source of carbon and energy and completely degraded 300 mg/L of DBP within 12 h. The optimal conditions (pH 6.9 and 31.7 degreesC) for DBP degradation were determined by response surface methodology and DBP degradation well fitted with the first-order kinetics. Bioaugmentation of contaminated soil with strain 0426 enhanced DBP (1 mg/g soil) degradation, indicating the application potential of strain 0426 for environment DBP removal. Strain 0426 harbors a distinctive DBP hydrolysis mechanism with two parallel benzoate metabolic pathways, which may account for the remarkable performance of DBP degradation. Sequences alignment has shown that an alpha/beta fold hydrolase (WP_083586847.1) contained a conserved catalytic triad and pentapeptide motif (GX1SX2G), of which function is similar to phthalic acid ester (PAEs) hydrolases and lipases that can efficiently catalyze hydrolysis of water-insoluble substrates. Furthermore, phthalic acid was converted to benzoate by decarboxylation, which entered into two different pathways: one is the protocatechuic acid pathway under the role of pca cluster, and the other is the catechol pathway. This study demonstrates a novel DBP degradation pathway, which broadens our understanding of the mechanisms of PAE biodegradation. Title: Vincamine, from an antioxidant and a cerebral vasodilator to its anticancer potential Ren Y, DeRose K, Li L, Gallucci JC, Yu J, Douglas Kinghorn A Ref: Bioorganic & Medicinal Chemistry, 92:117439, 2023 : PubMed ESTHER: Ren_2023_Bioorg.Med.Chem_92_117439 PubMedSearch: Ren 2023 Bioorg.Med.Chem 92 117439 PubMedID: 37579526 Abstract Vincamine is a naturally occurring indole alkaloid showing antioxidant activity and has been used clinically for the prevention and treatment of cerebrovascular disorders and insufficiencies. It has been well documented that antioxidants may contribute to cancer treatment, and thus, vincamine has been investigated recently for its potential antitumor activity. Vincamine was found to show cancer cell cytotoxicity and to modulate several important proteins involved in tumor growth, including acetylcholinesterase (AChE), mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-kappaB), nuclear factor erythroid 2-related factor 2 (Nrf2), and T-box 3 (TBX3). Several bisindole alkaloids, including vinblastine and vincristine and their synthetic derivatives, vindesine, vinflunine, and vinorelbine, have been used as clinically effective cancer chemotherapeutic agents. In the present review, the discovery and development of vincamine as a useful therapeutic agent and its antioxidant and antitumor activity are summarized, with its antioxidant-related mechanisms of anticancer potential being described. Also, discussed herein are the design of the potential vincamine-based oncolytic agents, which could contribute to the discovery of further new agents for cancer treatment. Title: Effect of substrate composition on physicochemical properties of the medium-long-medium structured triacylglycerol Tian Y, Zhou Y, Li L, Huang C, Lin L, Li C, Ye Y Ref: J Sci Food Agric, :, 2023 : PubMed ESTHER: Tian_2023_J.Sci.Food.Agric__ PubMedSearch: Tian 2023 J.Sci.Food.Agric PubMedID: 37708388 Abstract BACKGROUND: Nutritional and functional qualities and applications of structured lipids (SL) depend on the composition and molecular structure of fatty acids in the glycerol backbone of triacylglycerol (TAG). However, the relationship between the substrate composition and physicochemical qualities of SL has not been revealed. The investigation aims to disclose the effect of substrate composition on the physicochemical properties of medium-long-medium structured lipids (MLM-SLs) by enzymatic interesterification of Lipozyme TLIM/RMIM. RESULTS: The medium-long chain triacylglycerol (MLCT) yield could reach 70.32% including 28.98% CaLCa (1,3-dioctonyl-2-linoleoyl glyceride) and 24.34% CaOCa (1,3-didecanoyl-2-oleoyl glyceride). The sn-2 unsaturated fatty acids composition mainly depended on long chain triacylglycerol (LCT) in the substrate. The increased carbon chain length and double bond in triacylglycerol decreased its melting and crystallization temperature. The balanced substrate composition of MCT/LCT increased the size and finer crystals. Molecular docking simulation revealed that the MLCT molecule was mainly interacted with the catalytic triplets of Lipozyme TLIM (Arg81-Ser83-Arg84) and the Lipozyme RMIM (Tyr183-Thr226-Arg262) by O...H bond. The oxygen atom of the ester on the MLCT molecule was primarily bound to the hydrogen of hydroxyl and amino groups on the binding sites of Lipozyme TLIM/RMIM. The intermolecular interplay between MLCT and Lipozyme RMIM is stable than Lipozyme TLIM due to the formation of lower binding affinity energy. CONCLUSION: This research clarifies the interaction mechanism between MLCT molecules and lipases, and provides in-deep understanding the relationship between substrate composition, molecular structure and physicochemical property of MLM-SLs. This article is protected by copyright. All rights reserved. Title: Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana Wei J, Li Z, Shan M, Wu F, Li L, Ma Y, Wu J, Li X, Liu Y and Wu Z <2 more author(s)> Wei J, Li Z, Shan M, Wu F, Li L, Ma Y, Wu J, Li X, Liu Y, Hu Z, Zhang Y, Wu Z (- 2) Ref: Org Biomol Chem, :, 2023 : PubMed ESTHER: Wei_2023_Org.Biomol.Chem__ PubMedSearch: Wei 2023 Org.Biomol.Chem PubMedID: 37581482 Abstract Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh(2)(OCOCF(3))(4)-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC(50) = 2.13 +/- 0.06 microM and K(i) = 0.058 microM), which was five times stronger than that of the positive control (rivastigmine, IC(50) = 12.46 +/- 0.82 microM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism. Title: Chromium exposure altered metabolome and microbiome-associated with neurotoxicity in zebrafish Yan T, Xu Y, Zhu Y, Jiang P, Zhang Z, Li L, Wu Q Ref: J Appl Toxicol, :, 2023 : PubMed ESTHER: Yan_2023_J.Appl.Toxicol__ PubMedSearch: Yan 2023 J.Appl.Toxicol PubMedID: 36727205 Abstract In recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1mg/L Cr (III) and 1mg/L Cr (VI) for seven days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr- exposed groups, as compared to that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification. Title: Synthesis, Bioactivity and Molecular Docking of Nereistoxin Derivatives Containing Phosphonate Yan Q, Lu X, Zhang Z, Jin Q, Gao R, Li L, Wang H Ref: Molecules, 28:, 2023 : PubMed ESTHER: Yan_2023_Molecules_28_ PubMedSearch: Yan 2023 Molecules 28 PubMedID: 37375402 Abstract Novel nereistoxin derivatives containing phosphonate were synthesized and characterized via (31)P, (1)H and (13)C NMR and HRMS. The anticholinesterase activity of the synthesized compounds was evaluated on human acetylcholinesterase (AChE) using the in vitro Ellman method. Most of the compounds exhibited good inhibition of acetylcholinesterase. All of these compounds were selected to assess their insecticidal activity (in vivo) against Mythimna separata Walker, Myzus persicae Sulzer and Rhopalosiphum padi. Most of the tested compounds displayed potent insecticidal activity against these three species. Compound 7f displayed good activity against all three insect species, showing LC(50) values of 136.86 microg/mL for M. separata, 138.37 microg/mL for M. persicae and 131.64 microg/mL for R. padi. Compound 7b had the highest activity against M. persicae and R. padi, with LC(50) values of 42.93 microg/mL and 58.19 microg/mL, respectively. Docking studies were performed to speculate the possible binding sites of the compounds and explain the reasons for the activity of the compounds. The results showed that the compounds had lower binding energies with AChE than with the acetylcholine receptor (AchR), suggesting that compounds are more easily bound with AChE. Title: Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors Yu D, Yang C, Liu Y, Lu T, Li L, Chen G, Liu Z, Li Y Ref: Sci Rep, 13:4877, 2023 : PubMed ESTHER: Yu_2023_Sci.Rep_13_4877 PubMedSearch: Yu 2023 Sci.Rep 13 4877 PubMedID: 36966194 Abstract Alzheimer's disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC(50) values of 3.94 microM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor. Title: Dissecting the Effect of Temperature on Hyperthermophilic Pf2001 Esterase Dimerization by Molecular Dynamics Zhang X, Li L, Zheng Q Ref: J Chem Inf Model, :, 2023 : PubMed ESTHER: Zhang_2023_J.Chem.Inf.Model__ PubMedSearch: Zhang 2023 J.Chem.Inf.Model PubMedID: 37452749 Gene_locus related to this paper: pyrfu-PF2001 Abstract Pf2001 esterase (Pf2001) from Pyrococcus furiosus has hyperthermophilic properties and exerts a biocatalytic function in a dimeric state. Crystal structures revealed that the structural rearrangement of the cap domain is responsible for the Pf2001 dimer formation. However, the details of the cap domain remodeling and the effects of temperature on the dimerization process remain elusive at the molecular level, taking into account that experimental methods are difficult to capture the dynamic process of dimerization to some extent. Herein, four dimer models based on the monomeric crystal structure (PDB ID: 5G59) were constructed to investigate the conformational transition details and temperature effects in the dimerization by conventional molecular dynamics and accelerated molecular dynamics simulations. Our simulation results indicate that the monomer undergoes a conformational change into a "preparatory state" at high temperatures, which is more favorable for its transformation into a stable dimer. The subsequent free energy landscape analysis further identifies four intermediate states (from separated state to dimeric state) and discloses that a more accessible alpha-helix driven by stronger hydrophobic interactions induces a rearrangement of the cap domain, displaying a "tic-tac-toe" activation feature that is important for stabilizing the dimer interface and facilitating the formation of hydrophobic pockets. In addition, the electrostatic potential surface analysis illustrates that the weaker electrostatic repulsion (Lys and Arg) in the dimer interface at high temperatures is also a key factor for dimer stabilization. Altogether, our results can provide molecular-level insight into the dimer formation process of hyperthermophilic esterase and would be useful to understand the enzymatic specificity of alpha/beta-hydrolase. Title: Single and Combined Effects of Chlorpyrifos and Glyphosate on the Brain of Common Carp: Based on Biochemical and Molecular Perspective Zhang D, Ding W, Liu W, Li L, Zhu G, Ma J Ref: Int J Mol Sci, 24:, 2023 : PubMed ESTHER: Zhang_2023_Int.J.Mol.Sci_24_ PubMedSearch: Zhang 2023 Int.J.Mol.Sci 24 PubMedID: 37629125 Abstract Chlorpyrifos (CPF) and glyphosate (GLY) are the most widely used organophosphate insecticide and herbicide worldwide, respectively; co-occurrence of CPF and GLY in aquatic environments occurs where they inevitably have potential hazards to fish. However, the potential mechanisms of CPF and GLY to induce toxicity have not been fully explored. To identify the adverse impacts of CPF and GLY on fish, either alone or in combination (MIX), CPF (25 microg/L) and GLY (3.5 mg/L) were set up according to an environmentally relevant concentration to expose to common carp for 21 days. After exposure, CPF and GLY decreased the activities of acetylcholinesterase and Na(+)/K(+)-ATPase, altered monoamine oxidase levels, decreased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase and glutamic reductase), and induced the accumulation of malondialdehyde in the carp brain. The parameters in the MIX groups had a greater impact compared to that in the CPF or GLY group, suggesting that both single and combined exposure could affect neurological signaling systems and cause oxidative stress and lipid peroxidation damage in carp brains, and that MIX exposure increases the impact of each pollutant. RNA-seq results showed that single or combined exposure to CPF and GLY induced global transcriptomic changes in fish brains, and the number of differentially expressed genes in MIX-treated carp brains were globally increased compared to either the CPF or GLY groups, suggesting that the effects of co-exposure were greater than single exposure. Further analysis results revealed that the global transcriptomic changes participated in oxidative stress, immune dysfunction, and apoptosis of fish brains, and identified that the P13k-Akt signaling pathway participates in both single and combined exposure of CPF- and GLY-induced toxicity. Taken together, our results demonstrated that the interaction of CPF and GLY might be synergic and provided novel insights into the molecular mechanisms of fish brains coping with CPF and GLY. 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: Nanobodies as binding-chaperones stabilize the recombinant Bombyx mori acetylcholinesterase and protect the enzyme activity in pesticide detection Cai J, Romao E, Wu G, Li J, Li L, Wang Z, Li Y, Yang J, Shen Y and Wang H <2 more author(s)> Cai J, Romao E, Wu G, Li J, Li L, Wang Z, Li Y, Yang J, Shen Y, Xu Z, Muyldermans S, Wang H (- 2) Ref: Enzyme Microb Technol, 155:109992, 2022 : PubMed ESTHER: Cai_2022_Enzyme.Microb.Technol_155_109992 PubMedSearch: Cai 2022 Enzyme.Microb.Technol 155 109992 PubMedID: 35114480 Abstract In our previous study, the recombinant type II acetylcholinesterase from Bombyx mori (rBmAChE) presented outstanding sensitivity to pesticides, which exhibited great potential in pesticides detection. However, the poor stability of rBmAChE and also the unclear mechanism of its sensitivity hindered the applications in on-site testing of pesticides residues. In this study, we constructed an immune nanobody library, in which we obtained 48 rBmAChE-specific nanobodies. Among them, Nb4 and Nb9 were verified as the most prominent enhancers of the enzyme activity and stabilizers under thermal stress, which indicated their usage as protective reagents for rBmAChE. The simultaneously addition of the two Nbs enhanced the thermal-stability of rBmAChE against exposure to 50-70 degreesC, and also remained 100% residual activity after 30 days storage at - 20 degreesC or 4 degreesC, whereas 80% and 62% at - 80 degreesC and 25 degreesC. The homologous modeling and docking of Nb4 and Nb9 to rBmAChE indicated the stabilization of Nb4 to the peripheral anion site (PAS) of rBmAChE while Nb9 protected the C-terminal structure. Substrate docking demonstrated the importance of electrostatic attraction during catalytic process, that might be enhanced by Nbs. As a result, Nb4 and Nb9 were proved to have great potential on rBmAChE applications due to their regulation on enzyme activity and protection against thermal-inactivation and long-term storage of rBmAChE. Title: 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: miRNA-Mediated Low Expression of EPHX3 Is Associated with Poor Prognosis and Tumor Immune Infiltration in Head and Neck Squamous Cell Carcinomas Ding S, Hong Q, Duan T, Xu Z, He Q, Qiu D, Li L, Yan J, Zhang Q, Mu Z Ref: J Oncol, 2022:7633720, 2022 : PubMed ESTHER: Ding_2022_J.Oncol_2022_7633720 PubMedSearch: Ding 2022 J.Oncol 2022 7633720 PubMedID: 35401746 Abstract The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration. Title: Individualized regimen of low-dose rituximab monotherapy for new-onset AChR-positive generalized myasthenia gravis Du Y, Li C, Hao YF, Zhao C, Yan Q, Yao D, Li L, Zhang W Ref: Journal of Neurology, :, 2022 : PubMed ESTHER: Du_2022_J.Neurol__ PubMedSearch: Du 2022 J.Neurol PubMedID: 35243555 Abstract BACKGROUND: Generalized AChR-MG is an archetype of B cell-mediated autoimmune disorders, and use of biologic agent rituximab (RTX) for B cell depletion is generally limited to immunosuppressive therapy-refractory cases. However, benefit of RTX monotherapy and individualized regimen with optimal dosage in early stage of new-onset generalized AChR-MG still remains to be elucidated. In this retrospective study, we explore the efficacy and safety of personalized regimen of 100 mg low-dose rituximab monotherapy in treating new-onset generalized AChR-MG. METHODS: Thirteen new-onset generalized AChR-MG patients were enrolled for the study, initiating RTX treatment from November 2017 to August 2020. The individualized low-dose RTX monotherapy protocol consisted of 100 mg induction treatment weekly with no more than three circles, followed by reinfusion (100 mg once) sequentially according to whether achieving primary endpoint and peripheral CD19 + B-cell repopulation <= 1% of total lymphocytes at each visit (every 3 months). Outcome measures included MGFA-PIS Minimal Manifestation (MM) or better status (primary endpoint), changes in QMG, MMT, MG-ADL and MGQOL-15 scores (secondary endpoint), as well as cholinesterase inhibitors dosage. RESULTS: All 13 patients achieved the primary endpoint in parallel with significant improvement of QMG, MMT, MG-ADL MGQOL-15 scores, and reduction of cholinesterase inhibitors dose. A total of 52 visits were performed during follow-up, and only 10 assessments presenting peripheral CD19 + B-cell repopulation (<= 1%) without "MM or better status" were followed by RTX reinfusions (100 mg once) for clinical remission. The total dosage of RTX was only 346.15 +/- 96.74 mg (including 269.23 +/- 63.04 mg for induction and 76.92 +/- 59.91 mg for reinfusion), which seemed to be much lower than those dosages used in new-onset generalized AChR-MG as described previously. Moreover, compared with patients without thymoma, thymectomy markedly delayed initiation of RTX for patients with thymoma (log-rank test, p = 0.0002), but the delaying treatments showed no influence on the time for achieving primary outcome (log-rank test, p = 0.2517). CONCLUSION: Our study firstly showed that individualized regimen of low-dose RTX monotherapy is effective and safe for early treatment of new-onset generalized AChR-MG, and practicable for directing RTX reinfusion and withdrawal. Moreover, the monotherapy protocol was also indicated to be extensively applicable in both new-onset AChR-MG with thymoma (thymectomy) and without thymoma. Title: Phytochemical profiling and antioxidant, enzyme-inhibitory, and toxic activities of extracts from Adonis ramosa Franch Guo X, Chen M, He X, Zhao Y, Yu J, Zhu J, Li L, Xia G, Zang H Ref: Nat Prod Res, :1, 2022 : PubMed ESTHER: Guo_2022_Nat.Prod.Res__1 PubMedSearch: Guo 2022 Nat.Prod.Res 1 PubMedID: 35045779 Abstract This study investigated the content and biological activity of three solvent extracts of Adonis ramosa Franch (AR), which contains 12 types of phytochemicals. The overall yield and total protein content of the aqueous extract were the highest, and it exhibited the highest hydroxyl and superoxide radical-scavenging abilities, copper chelating abilities, and cupric reducing antioxidant capacity. Ethanol extract had the highest total phenolic, flavonoid, and carbohydrate contents, and it showed the highest iron chelating activity, and HClO- and nitrite-scavenging abilities. Methanol AR extract contained the highest total steroid and tannin contents; it also demonstrated high radical- and reactive oxygen species-scavenging abilities and had the best ferric reducing antioxidant power, which allowed it to effectively prevent beta-carotene bleaching. Methanol extract also showed good stability and low toxicity. All tested solvent extracts of AR exhibited weak enzyme-inhibitory activities for four enzymes (alpha-glucosidase, alpha-amylase, acetylcholinesterase and butyrylcholinesterase). Overall, AR can serve as a natural antioxidant. Title: Maternal Low-Protein Diet during Puberty and Adulthood Aggravates Lipid Metabolism of Their Offspring Fed a High-Fat Diet in Mice Huang X, Zhuo Y, Jiang D, Zhu Y, Fang Z, Che L, Lin Y, Xu S, Hua L and Feng B <4 more author(s)> Huang X, Zhuo Y, Jiang D, Zhu Y, Fang Z, Che L, Lin Y, Xu S, Hua L, Zou Y, Huang C, Li L, Wu D, Feng B (- 4) Ref: Nutrients, 14:, 2022 : PubMed ESTHER: Huang_2022_Nutrients_14_ PubMedSearch: Huang 2022 Nutrients 14 PubMedID: 36235710 Abstract A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring's liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7alpha hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD. Title: Narciclasine inhibits phospholipase A2 and regulates phospholipid metabolism to ameliorate psoriasis-like dermatitis Kong Y, Jiang J, Huang Y, Liu X, Jin Z, Li L, Wei F, Yin J, Zhang Y and Chen H <1 more author(s)> Kong Y, Jiang J, Huang Y, Liu X, Jin Z, Li L, Wei F, Yin J, Zhang Y, Tong Q, Chen H (- 1) Ref: Front Immunol, 13:1094375, 2022 : PubMed ESTHER: Kong_2022_Front.Immunol_13_1094375 PubMedSearch: Kong 2022 Front.Immunol 13 1094375 PubMedID: 36700214 Abstract INTRODUCTION: Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling disease." The fact that metabolic syndrome (MetS) is the most common and important comorbidities of psoriasis suggests an important role of lipid metabolism in the pathogenesis of psoriasis. Narciclasine (Ncs) is an alkaloid isolated from the Amaryllidaceae plants. Its biological activities include antitumor, antibacterial, antiinflammatory, anti-angiogenic and promoting energy expenditure to improve dietinduced obesity. Here, we report that Ncs may be a potential candidate for psoriasis, acting at both the organismal and cellular levels. METHODS: The therapeutic effect of Ncs was assessed in IMQ-induced psoriasis-like mouse model. Then, through in vitro experiments, we explored the inhibitory effect of Ncs on HaCaT cell proliferation and Th17 cell polarization; Transcriptomics and lipidomics were used to analyze the major targets of Ncs; Single-cell sequencing data was used to identify the target cells of Ncs action. RESULTS: Ncs can inhibit keratinocyte proliferation and reduce the recruitment of immune cells in the skin by inhibiting psoriasis-associated inflammatory mediators. In addition, it showed a direct repression effect on Th17 cell polarization. Transcriptomic and lipidomic data further revealed that Ncs extensively regulated lipid metabolismrelated genes, especially the Phospholipase A2 (PLA2) family, and increased antiinflammatory lipid molecules. Combined with single-cell data analysis, we confirmed that keratinocytes are the main cells in which Ncs functions. DISCUSSION: Taken together, our findings indicate that Ncs alleviates psoriasiform skin inflammation in mice, which is associated with inhibition of PLA2 in keratinocytes and improved phospholipid metabolism. Ncs has the potential for further development as a novel anti-psoriasis drug. Title: Pest Biological Control: Goals Throughout My Life Li L Ref: Annual Review of Entomology, 67:1, 2022 : PubMed ESTHER: Li_2022_Annu.Rev.Entomol_67_1 PubMedSearch: Li 2022 Annu.Rev.Entomol 67 1 PubMedID: 34995090 Abstract This autobiography documents the life and accomplishments of Li Liying. Born into a poor family in China, she eventually became director of Guangdong Entomological Institute. After graduating middle school (1949), she was admitted to the Agronomy Faculty at Beijing Agricultural University but was shortly after redirected by the Chinese Government to Timiryazev Agricultural Academy, Moscow, Russia. The last year of her study at Timiryazev Agricultural Academy was a pivotal experience. She had the opportunity to conduct fieldwork on cotton pest control and became aware of the harmful practice of aerially spraying highly toxic organophosphates with workers present. She decided to dedicate herself to finding safer alternatives and became a leader in the development of mass-rearing techniques for insects beneficial to agriculture. She traveled to laboratories in several foreign countries to foster collaboration and exchange of ideas among colleagues. She is recognized for her service to entomological societies, teaching at universities, and love of entomology. Title: Two Extracellular Poly(sigma-caprolactone)-Degrading Enzymes From Pseudomonas hydrolytica sp. DSWY01(T): Purification, Characterization, and Gene Analysis Li L, Lin X, Bao J, Xia H, Li F Ref: Front Bioeng Biotechnol, 10:835847, 2022 : PubMed ESTHER: Li_2022_Front.Bioeng.Biotechnol_10_835847 PubMedSearch: Li 2022 Front.Bioeng.Biotechnol 10 835847 PubMedID: 35372294 Gene_locus related to this paper: psemy-a4xvf4, psemy-a4y035 Abstract Poly(sigma-caprolactone) (PCL) is an artificial polyester with commercially promising application. In this study, two novel PCL-degrading enzymes named PCLase I and PCLase II were purified to homogeneity from the culture supernatant of an effective polyester-degrading bacterium, Pseudomonas hydrolytica sp. DSWY01(T). The molecular masses of PCLase I and PCLase II were determined to be 27.5 and 30.0 kDa, respectively. The optimum temperatures for the enzyme activities were 50 and 40 degreesC, and the optimum pH values were 9.0 and 10.0, respectively. The two enzymes exhibited different physical and chemical properties, but both enzymes could degrade PCL substrates into monomers and oligomers. Weight loss detection and scanning electron microscopy revealed that PCLase I had more effective degradation ability than PCLase II. The genes of the two enzymes were cloned on the basis of the peptide fingerprint analysis results. The sequence analysis and substrate specificity analysis results showed that PCLase I and PCLase II were cutinase and lipase, respectively. Interface activation experiment also confirmed this conclusion. Structural analysis and modeling were further performed to obtain possible insights on the mechanism. Title: Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6 Li R, Ye Z, She D, Fang P, Zong G, Hu K, Kong D, Xu W, Li L and Xue Y <2 more author(s)> Li R, Ye Z, She D, Fang P, Zong G, Hu K, Kong D, Xu W, Li L, Zhou Y, Zhang K, Xue Y (- 2) Ref: Drug Des Devel Ther, 16:3557, 2022 : PubMed ESTHER: Li_2022_Drug.Des.Devel.Ther_16_3557 PubMedSearch: Li 2022 Drug.Des.Devel.Ther 16 3557 PubMedID: 36238196 Abstract OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. RESULTS: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD. Title: Engineering the Thermostability of the Mono- and Diacylglycerol Lipase SMG1 for the Synthesis of Diacylglycerols Li L, Wang Y, Cui R, Wang F, Lan D Ref: Foods, 11:4069, 2022 : PubMed ESTHER: Li_2022_Foods_11_4069 PubMedSearch: Li 2022 Foods 11 4069 PubMedID: 36553811 Gene_locus related to this paper: malgo-a8puy1 Abstract Diacylglycerols (DAGs) display huge application prospectives in food industries. Therefore, new strategies to produce diacylglycerides are needed. Malassezia globose lipase (SMG1) could be used to synthesize DAGs. However, the poor thermostability of SMG1 seriously hampers its application. Herein, a rational design was used to generate a more thermostable SMG1. Compared with the wild type (WT), the M5D mutant (Q34P/A37P/M176V/G177A/M294R/ G28C-P206C), which contains five single-point mutations and one additional disulfide bond, displayed a 14.0 degreesC increase in the melting temperature (T(m)), 5 degreesC in the optimal temperature, and 1154.3-fold in the half-life (t(1/2)) at 55 degreesC. Meanwhile, the specific activity towards DAGs of the M5D variant was improved by 3.0-fold compared to the WT. Molecular dynamics (MD) simulations revealed that the M5D mutant showed an improved rigid structure. Additionally, the WT and the M5D variants were immobilized and used for the production of DAGs. Compared with the WT, the immobilized M5D-catalyzed esterification showed a 9.1% higher DAG content and a 22.9% increase in residual activity after nine consecutive cycles. This study will pave the way for the industrial application of SMG1. Title: A carboxylesterase-activatable near-infrared phototheranostic probe for tumor fluorescence imaging and photodynamic therapy Li L, Zhang Q, Li J, Tian Y, Liu W, Diao H Ref: RSC Adv, 12:35477, 2022 : PubMed ESTHER: Li_2022_RSC.Adv_12_35477 PubMedSearch: Li 2022 RSC.Adv 12 35477 PubMedID: 36540215 Abstract Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics. Title: Identification of novel immune-related targets mediating disease progression in acute pancreatitis Liu Q, Li L, Xu D, Zhu J, Huang Z, Yang J, Cheng S, Gu Y, Zheng L and Shen H <1 more author(s)> Liu Q, Li L, Xu D, Zhu J, Huang Z, Yang J, Cheng S, Gu Y, Zheng L, Zhang X, Shen H (- 1) Ref: Front Cell Infect Microbiol, 12:1052466, 2022 : PubMed ESTHER: Liu_2022_Front.Cell.Infect.Microbiol_12_1052466 PubMedSearch: Liu 2022 Front.Cell.Infect.Microbiol 12 1052466 PubMedID: 36590588 Abstract INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear. METHODS: An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo. RESULTS: The numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 x 10(-3)), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 x 10(-8)), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation. DISCUSSION: In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression. Title: Characterization of a new chlorimuron-ethyl-degrading strain Cedecea sp. LAM2020 and biodegradation pathway revealed by multiomics analysis Ma Q, Han X, Song J, Wang J, Li Q, Parales RE, Li L, Ruan Z Ref: J Hazard Mater, 443:130197, 2022 : PubMed ESTHER: Ma_2022_J.Hazard.Mater_443_130197 PubMedSearch: Ma 2022 J.Hazard.Mater 443 130197 PubMedID: 36272371 Gene_locus related to this paper: 9entr-CarHBioH Abstract The widespread use of the herbicide chlorimuron-methyl is hazard to rotational crops and causes soil degradation problems. Biodegradation is considered a promising way for removing herbicide residues from the environment. Here, a new isolated strain, Cedecea sp. LAM2020, enabled complete degradation of 100 mg/L chlorimuron-methyl within five days. Transcriptome analysis revealed that ABC transporters, atrazine degradation and purine metabolism were enriched in the KEGG pathway. Integrating GO and KEGG classification with related reports, we predict that carboxylesterases are involved in the biodegradation of chlorimuron-methyl by LAM2020. Heterologous expression of the carboxylesterase gene carH showed 26.67% degradation of 50 mg/L chlorimuron-methyl within 6 h. The intracellular potential biological response and extracellular degradation process of chlorimuron-ethyl were analyzed by the nontarget metabolomic and mass spectrometry respectively, and the biodegradation characteristics and complete mineralization pathway was revealed. The cleavage of the sulfonylurea bridge and the ester bond achieved the first step in the degradation of chlorimuron-methyl. Together, these results reveal the presence of acidolysis and enzymatic degradation of chlorimuron-methyl by strain LAM2020. Hydroponic corn experiment showed that the addition of strain LAM2020 alleviated the toxic effects of chlorimuron-ethyl on the plants. Collectively, strain LAM2020 may be a promising microbial agent for plants chlorimuron-ethyl detoxification and soil biofertilizer. Title: Branched poly(ethylenimine) carbon dots-MnO(2) nanosheets based fluorescent sensory system for sensing of malachite green in fish samples Mu X, Liu X, Ye X, Zhang W, Li L, Ma P, Song D Ref: Food Chem, 394:133517, 2022 : PubMed ESTHER: Mu_2022_Food.Chem_394_133517 PubMedSearch: Mu 2022 Food.Chem 394 133517 PubMedID: 35749877 Abstract Malachite green (MG) is an organic dye compound that is frequently used as a fungicide and antiseptic in aquaculture. However, human or animal exposure to MG causes carcinogenic, teratogenic and mutagenic effects. Herein, a novel fluorescent assay was designed for the detection of MG using manganese dioxide nanosheets (MnO(2) NS) as an energy acceptor to quench the fluorescence of branched poly(ethylenimine) carbon dots (BPEI-CDs) via Forster resonance energy transfer. When butyrylcholinesterase is introduced to form thiocholine in the presence of S-butyrylthiocholine iodide, MnO(2) NS can be recovered by thiocholine to Mn(2+), resulting in restoration of the fluorescence of BPEI-CDs. Exploiting these changes in fluorescence intensity in the above system, a fluorescence probe was successfully developed for the quantitative detection of MG. Besides, this assay was applied to fish samples, verifying the high potential for practical application of the proposed sensor for the monitoring of MG in aquatic products. 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: Development of indole-2-carbonyl piperazine urea derivatives as selective FAAH inhibitors for efficient treatment of depression and pain Shang Y, Wang M, Hao Q, Meng T, Li L, Shi J, Yang G, Zhang Z, Yang K, Wang J Ref: Bioorg Chem, 128:106031, 2022 : PubMed ESTHER: Shang_2022_Bioorg.Chem_128_106031 PubMedSearch: Shang 2022 Bioorg.Chem 128 106031 PubMedID: 36037600 Abstract Fatty acid amide hydrolase (FAAH), aserinehydrolase with significant role in thehydrolysis of endocannabinoids, is a promising therapeutic target for peripheral and central nervous system related disorders, including pain, neuroinflammation and depression. Employing a structure-based approach, a novel series of indole-2-carbonyl piperazine urea derivatives were designed and synthesized as FAAH inhibitors for the treatment of pain-depression comorbidity. Among them, compound 4i emerged as the most potent inhibitor (IC(50) = 0.12 microM) with fine selectivity versus CES2, ABHD6, MAGL and the cannabinoid receptor, which also displayed superior metabolic stability in human liver microsome and an adequate pharmacokinetic profile in rodents. Treatment of depressed rats with 4i demonstrated favorable antidepressant-like effects not only by increasing the level of BDNF in the hippocampus but also by restraining the apoptosis of hippocampal neurons. Also, 4i effectively suppressed the LPS-induced neuroinflammation in vitro. Moreover, 4i exhibited potent analgesic activity, which indicated its promising therapeutical application for pain and depression. These meaningful results shed light on FAAH inhibitors as promising pain-depression comorbidity therapeutics. Title: Comparative Study of the Molecular Characterization, Evolution, and Structure Modeling of Digestive Lipase Genes Reveals the Different Evolutionary Selection Between Mammals and Fishes Tang SL, Liang XF, He S, Li L, Alam MS, Wu J Ref: Front Genet, 13:909091, 2022 : PubMed ESTHER: Tang_2022_Front.Genet_13_909091 PubMedSearch: Tang 2022 Front.Genet 13 909091 PubMedID: 35991544 Abstract Vertebrates need suitable lipases to digest lipids for the requirement of energy and essential nutrients; however, the main digestive lipase genes of fishes have certain controversies. In this study, two types of digestive lipase genes (pancreatic lipase (pl) and bile salt-activated lipase (bsal)) were identified in mammals and fishes. The neighborhood genes and key active sites of the two lipase genes were conserved in mammals and fishes. Three copies of PL genes were found in mammals, but only one copy of the pl gene was found in most of the fish species, and the pl gene was even completely absent in some fish species (e.g., zebrafish, medaka, and common carp). Additionally, the hydrophobic amino acid residues (Ile and Leu) which are important to pancreatic lipase activity were also absent in most of the fish species. The PL was the main digestive lipase gene in mammals, but the pl gene seemed not to be the main digestive lipase gene in fish due to the absence of the pl gene sequence and the important amino acid residues. In contrast, the bsal gene existed in all fish species, even two to five copies of bsal genes were found in most of the fishes, but only one copy of the BSAL gene was found in mammals. The amino acid residues of bile salt-binding sites and the three-dimensional (3D) structure modeling of Bsal proteins were conserved in most of the fish species, so bsal might be the main digestive lipase gene in fish. The phylogenetic analysis also indicated that pl or bsal showed an independent evolution between mammals and fishes. Therefore, we inferred that the evolutionary selection of the main digestive lipase genes diverged into two types between mammals and fishes. These findings will provide valuable evidence for the study of lipid digestion in fish. Title: Improvement of methanol tolerance and catalytic activity of Rhizomucor miehei lipase for one-step synthesis of biodiesel by semi-rational design Tian M, Yang L, Lv P, Wang Z, Fu J, Miao C, Li Z, Li L, Liu T and Luo W <1 more author(s)> Tian M, Yang L, Lv P, Wang Z, Fu J, Miao C, Li Z, Li L, Liu T, Du W, Luo W (- 1) Ref: Bioresour Technol, :126769, 2022 : PubMed ESTHER: Tian_2022_Bioresour.Technol__126769 PubMedSearch: Tian 2022 Bioresour.Technol 126769 PubMedID: 35092821 Abstract Exploiting highly active and methanol-resistant lipase is of great significance for biodiesel production. A semi-rational directed evolution method combined with N-glycosylation is reported, and all mutants exhibiting higher catalytic activity and methanol tolerance than the wild type (WT). Mutant N267 retained 64% activity after incubation in 50% methanol for 8 h, which was 48% greater than that of WT. The catalytic activity of mutants N267 and N167 was 30- and 71- fold higher than that of WT. Molecular dynamics simulations of N267 showed that the formation of new strong hydrogen bonds between glycan and the protein stabilized the structure of lipase and improved its methanol tolerance. N267 achieved biodiesel yields of 99.33% (colza oil) and 81.70% (waste soybean oil) for 24 h, which was much higher than WT (51.6% for rapeseed oil and 44.73% for wasted soybean oil). The engineered ProRML mutant has high potential for commercial biodiesel production. Title: Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-kB/miR-155-5p/eNOS/NO/IkB Cycle in Hypertensive Rats Wang X, Han W, Zhang Y, Zong Y, Tan N, Li L, Liu C, Liu L Ref: Antioxidants (Basel), 11:, 2022 : PubMed ESTHER: Wang_2022_Antioxidants.(Basel)_11_ PubMedSearch: Wang 2022 Antioxidants.(Basel) 11 PubMedID: 35883863 Abstract Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-kappaB/miR-155-5p/eNOS/NO/IkappaB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy. Title: Comprehensive analysis of the carboxylesterase gene reveals that NtCXE22 regulates axillary bud growth through strigolactone metabolism in tobacco Wang L, Xie X, Xu Y, Li Z, Xu G, Cheng L, Yang J, Li L, Pu W, Cao P Ref: Front Plant Sci, 13:1019538, 2022 : PubMed ESTHER: Wang_2022_Front.Plant.Sci_13_1019538 PubMedSearch: Wang 2022 Front.Plant.Sci 13 1019538 PubMedID: 36600915 Gene_locus related to this paper: tobac-NtCXE49, tobac-NtCXE48, tobac-NtCXE46, tobac-NtCXE44, tobac-NtCXE41, tobac-NtCXE40, tobac-NtCXE39, tobac-NtCXE38, tobac-NtCXE36, tobac-NtCXE34, tobac-NtCXE33, tobac-NtCXE28, tobac-NtCXE27, tobac-NtCXE26, tobac-NtCXE25, tobac-NtCXE24, tobac-NtCXE23, tobac-NtCXE21, tobac-NtCXE19, tobac-NtCXE18, tobac-NtCXE17, tobac-NtCXE15, tobac-NtCXE14, tobac-NtCXE13, tobac-NtCXE12, tobac-NtCXE11, tobac-NtCXE10, tobac-NtCXE8, tobac-NtCXE7, tobac-NtCXE6, tobac-NtCXE5, tobac-NtCXE4, tobac-NtCXE3, tobac-NtCXE2, tobac-NtCXE1, tobac-NtCXE30, tobac-NtCXE32, tobac-NtCXE22, tobac-NtCXE29, tobac-NtCXE35, tobac-NtCXE45 Abstract Carboxylesterases (CXE) are a class of hydrolytic enzymes with alpha/beta-folding domains that play a vital role in plant growth, development, stress response, and activation of herbicide-active substances. In this study, 49 Nicotiana tabacum L. CXE genes (NtCXEs) were identified using a sequence homology search. The basic characteristics, phylogenetic evolution, gene structure, subcellular location, promoter cis-elements, and gene expression patterns of the CXE family were systematically analyzed. RNA-seq data and quantitative real-time PCR showed that the expression level of CXEs was associated with various stressors and hormones; gene expression levels were significantly different among the eight tissues examined and at different developmental periods. As a new class of hormones, strigolactones (SLs) are released from the roots of plants and can control the germination of axillary buds.NtCXE7, NtCXE9, NtCXE22, and NtCXE24 were homologous to Arabidopsis SLs hydrolase AtCXE15, and changes in their expression levels were induced by topping and by GR24 (a synthetic analogue of strigolactone). Further examination revealed that NtCXE22-mutant (ntcxe22) plants generated by CRISPR-Cas9 technology had shorter bud outgrowth with lower SLs content. Validation of NtCXE22 was also performed in NtCCD8-OE plants (with fewer axillary buds) and in ntccd8 mutant plants (with more axillary buds). The results suggest that NtCXE22 may act as an efficient SLs hydrolase and affects axillary bud development, thereby providing a feasible method for manipulating endogenous SLs in crops and ornamental plants. Title: Millions of microplastics released from a biodegradable polymer during biodegradation/enzymatic hydrolysis Wei XF, Capezza AJ, Cui Y, Li L, Hakonen A, Liu B, Hedenqvist MS Ref: Water Res, 211:118068, 2022 : PubMed ESTHER: Wei_2022_Water.Res_211_118068 PubMedSearch: Wei 2022 Water.Res 211 118068 PubMedID: 35066257 Abstract In this article, we show that enzymatic hydrolysis of a biodegradable polyester (poly(sigma-caprolactone)) by Amano Lipase PS in an aqueous (buffer) environment yielded rapidly an excessive number of microplastic particles; merely 0.1 g of poly(sigma-caprolactone) film was demonstrated to yield millions of particles. There were also indications of non-enzymatic hydrolysis at the same conditions, but this did not yield any particles within the time frame of the experiment (up to 6 days). Microplastic particles formed had irregular shapes with an average size of around 10 microm, with only a few reaching 60 microm. The formation of microplastic particles resulted from the uneven hydrolysis/erosion rate across the polymer film surface, which led to a rough and undulating surface with ridge, branch, and rod-shaped micro-protruding structures. The consequent detachment and fragmentation of these micro-sized protruding structures resulted in the release of microplastics to the surroundings. Together with microplastics, hydrolysis products such as acidic monomers and oligomers were also released during the enzymatic hydrolysis process, causing a pH decrease in the surrounding liquid. The results suggest that the risk of microplastic pollution from biodegradable plastics is notable despite their biodegradation. Special attention needs to be paid when using and disposing of biodegradable plastics, considering the enormous impact of the paradigm shift towards more biodegradable products on the environment. 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: Genome-wide analysis of the strigolactone biosynthetic and signaling genes in grapevine and their response to salt and drought stresses Yu Y, Xu J, Wang C, Pang Y, Li L, Tang X, Li B, Sun Q Ref: PeerJ, 10:e13551, 2022 : PubMed ESTHER: Yu_2022_PeerJ_10_e13551 PubMedSearch: Yu 2022 PeerJ 10 e13551 PubMedID: 35712547 Abstract Strigolactones (SLs) are a novel class of plant hormones that play critical roles in regulating various developmental processes and stress tolerance. Although the SL biosynthetic and signaling genes were already determined in some plants such as Arabidopsis and rice, the information of SL-related genes in grapevine (Vitis vinifera L.) remains largely unknown. In this study, the SL-related genes were identified from the whole grapevine genome, and their expression patterns under salt and drought stresses were determined. The results indicated that the five genes that involved in the SL biosynthesis included one each of the D27, CCD7, CCD8, MAX1 and LBO genes, as well as the three genes that involved in the SL signaling included one each of the D14, MAX2, D53 genes. Phylogenetic analysis suggested that these SL-related proteins are highly conserved among different plant species. Promoter analysis showed that the prevalence of a variety of cis-acting elements associated with hormones and abiotic stress existed in the promoter regions of these SL-related genes. Furthermore, the transcription expression analysis demonstrated that most SL-related genes are involved in the salt and drought stresses response in grapevine. These findings provided valuable information for further investigation and functional analysis of SL biosynthetic and signaling genes in response to salt and drought stresses in grapevine. 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: SERS-ELISA determination of human carboxylesterase 1 using metal-organic framework doped with gold nanoparticles as SERS substrate Feng J, Lu H, Yang Y, Huang W, Cheng H, Kong H, Li L Ref: Mikrochim Acta, 188:280, 2021 : PubMed ESTHER: Feng_2021_Mikrochim.Acta_188_280 PubMedSearch: Feng 2021 Mikrochim.Acta 188 280 PubMedID: 34331134 Abstract By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 x 10(-13) mol.L(-1), and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determine hCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1-120 ng.mL(-1), the SERS signal intensity of benzidine at 1609 cm(-1) gradually decreases with the increase of hCE 1 concentration (R(2) = 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed. Title: Preparation of a Bombyx mori acetylcholinesterase enzyme reagent through chaperone protein disulfide isomerase co-expression strategy in Pichia pastoris for detection of pesticides Li J, Cai J, Ma M, Li L, Lu L, Wang Y, Wang C, Yang J, Xu Z and Wang H <2 more author(s)> Li J, Cai J, Ma M, Li L, Lu L, Wang Y, Wang C, Yang J, Xu Z, Yao M, Shen X, Wang H (- 2) Ref: Enzyme Microb Technol, 144:109741, 2021 : PubMed ESTHER: Li_2021_Enzyme.Microb.Technol_144_109741 PubMedSearch: Li 2021 Enzyme.Microb.Technol 144 109741 PubMedID: 33541576 Gene_locus related to this paper: boomi-ACHE2 Abstract The cholinesterase-based spectrophotometric methods for detection of organophosphate pesticides (OPs) and carbamate pesticides (CPs) have been proposed as a good choice for their high efficiency, simplicity and low cost. The enzyme, as a core reagent, is of great importance for the developed method. In this study, a protein disulfide isomerase (PDI) co-expression strategy in Pichia pastoris was employed to enhance the yield of recombinant Bombyx mori acetylcholinesterase 2 (rBmAChE2). Subsequently, the prepared enzyme reagent was used to detect the pesticides in real samples. The results showed that the co-expression of rBmAChE2 with PDI increased the enzyme activity of the supernatant and the yield of purified rBmAChE2 up to 60 U/mL and 6 mg/L respectively, both almost 5-fold higher than those of original recombinant strain. In addition, 5 g/L gelatin reagent could help to preserve nearly 90% of the rBmAChE2 activity for 90 days in 4 degreesC and the limits of detections (LODs) of the rBmAChE2-based assay for 20 kinds of OPs or CPs ranged from 0.010 to 2.725 mg/kg, which were lower than most of indexes present in current Chinese National Standard (GB/T 5009.199-2003) or the maximum residue limits (GB 2763-2019). Furthermore, the detection results of 23 vegetable samples were verified by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, which indicated that the rBmAChE2-based assay in this work is suitable for pesticide residues rapid detection. Title: Key Metabolic Enzymes Involved in Remdesivir Activation in Human Lung Cells Li R, Liclican A, Xu Y, Pitts J, Niu C, Zhang J, Kim C, Zhao X, Soohoo D and Feng JY <14 more author(s)> Li R, Liclican A, Xu Y, Pitts J, Niu C, Zhang J, Kim C, Zhao X, Soohoo D, Babusis D, Yue Q, Ma B, Murray BP, Subramanian R, Xie X, Zou J, Bilello JP, Li L, Schultz BE, Sakowicz R, Smith BJ, Shi PY, Murakami E, Feng JY (- 14) Ref: Antimicrobial Agents & Chemotherapy, :AAC0060221, 2021 : PubMed ESTHER: Li_2021_Antimicrob.Agents.Chemother__AAC0060221 PubMedSearch: Li 2021 Antimicrob.Agents.Chemother AAC0060221 PubMedID: 34125594 Inhibitor(s) related to this paper: Remdesivir Abstract Remdesivir (RDV; GS-5734; Veklury(a)), the first FDA-approved antiviral to treat COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. RDV is taken up in the target cells and metabolized in multiple steps to form the active nucleoside triphosphate (TP) (GS-443902), which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. In this report, we profiled the key enzymes involved in the RDV metabolic pathway with multiple parallel approaches: (1) bioinformatic analysis of nucleoside/tide metabolic enzyme mRNA expression using public human tissue and lung single-cell RNAseq datasets; (2) protein and mRNA quantification of enzymes in human lung tissue and primary lung cells; (3) biochemical studies on the catalytic rate of key enzymes; (4) effects of specific enzyme inhibitors on the GS-443902 formation; and (5) the effects of these inhibitors on RDV antiviral activity against SARS-CoV-2 in cell culture. Our data collectively demonstrated that carboxylesterase 1 (CES1) and cathepsin A (CatA) are enzymes involved in hydrolyzing RDV to its alanine intermediate Met X, which is further hydrolyzed to the monophosphate form by histidine triad nucleotide-binding protein 1 (HINT1). The monophosphate is then consecutively phosphorylated to diphosphate and triphosphate by cellular phosphotransferases. Our data support the hypothesis that the unique properties of RDV prodrug not only allow lung-specific accumulation critical for the treatment of respiratory viral infection such as COVID-19, they also enable efficient intracellular metabolism of RDV and its Met X to monophosphate and successive phosphorylation to form the active TP in disease-relevant cells. Title: Morphine increases myocardial triacylglycerol through regulating adipose triglyceride lipase S406 phosphorylation Li L, Wang J, Li D, Zhang H Ref: Life Sciences, 283:119866, 2021 : PubMed ESTHER: Li_2021_Life.Sci_283_119866 PubMedSearch: Li 2021 Life.Sci 283 119866 PubMedID: 34352257 Abstract AIMS: Morphine, a commonly used drug for anesthesia, affects lipid metabolism in different tissues, but the mechanism is currently unclear. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme responsible for the first step of triglyceride (TG) hydrolysis. Here we aim to investigate whether ATGL phosphorylation is involved in morphine-induced TG accumulation. MAIN METHODS: Oil red O staining and TG content analysis were used to detect the effect of morphine on lipid storage. A series of ATGL phosphoamino acid site mutant plasmids were constructed by gene synthesis and transfected to HL-1 cells to evaluate the phosphorylation levels of ATGL phosphoamino acid in morphine-treated HL-1 cells with immunoprecipitation and immunoblotting assay. KEY FINDINGS: Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. Of note, the phosphorylation positive mutation of ATGL Ser406 to aspartic acid effectively reversed morphine-induced excessive accumulation of TG in HL-1 cells. SIGNIFICANCE: This discovery will help to fully understand the lipid regulation function of morphine in a new scope. In addition, it will expand the phosphorylation research of ATGL more comprehensively and provide powerful clues for lipid metabolism regulation. Title: Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer's Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit Li L, Li J, Dai Y, Yang M, Liang S, Wang Z, Liu W, Chen L, Tao J Ref: Front Aging Neurosci, 13:770948, 2021 : PubMed ESTHER: Li_2021_Front.Aging.Neurosci_13_770948 PubMedSearch: Li 2021 Front.Aging.Neurosci 13 770948 PubMedID: 35185516 Abstract OBJECTIVES: To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 x FAD) mice. METHODS: Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions. (1)H-MRS, Nissl staining, immunohistochemistry, and immunofluorescence were performed to examine the cholinergic system alteration. Thioflavin S staining and 6E10 immunofluorescence were performed to detect the amyloid-beta (Abeta). Furthermore, hM4Di designer receptors exclusively activated by designer drugs (DREADDs) virus and long-term clozapine-N-oxide injection were used to inhibit the medial septal and vertical limb of the diagonal band and dentate gyrus (MS/VDB-DG) cholinergic neural circuit. Cognitive-behavioral tests and immunofluorescence were performed to investigate the cholinergic neural circuit mechanism of EA treatment improving cognition in 5 x FAD mice. RESULTS: Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 x FAD mice. Abeta deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG). CONCLUSION: Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 x FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment. Title: Juvenile hormone regulates the reproductive diapause through Methoprene-tolerant gene in Galeruca daurica Ma HY, Li YY, Li L, Tan Y, Pang BP Ref: Insect Molecular Biology, :, 2021 : PubMed ESTHER: Ma_2021_Insect.Mol.Biol__ PubMedSearch: Ma 2021 Insect.Mol.Biol PubMedID: 33949026 Abstract Juvenile hormone (JH) signaling plays an important role in regulation of reproductive diapause in insects. However, its underlying molecular mechanism has been unclear. Methoprene-tolerant (Met), as a universal JH receptor, is involved in JH action. To gain some insight into its function in the reproductive diapause of Galeruca daurica, a serious pest on the Inner Mongolia grasslands undergoing obligatory summer diapause at the adult stage, we cloned the complete open-reading frame (ORF) sequences of Met and other 7 JH signaling-related genes, including JH acid methyltransferase (JHAMT), JH esterase (JHE), JH epoxide hydrolase (JHEH), Kruppel homolog 1 (Kr-h1), vitellogenin (Vg), forkhead box O (FOXO), and fatty acid synthase 2 (FAS2), from this species. GdMet encoded a putative protein, which contained three domains typical of the bHLH-PAS family. Expression patterns of these 8 genes were developmentally regulated during adult development. Topical application of JH analog (JHA) methoprene into the 3-day-old and 5-day-old adults induced the expression of GdMet. Silencing GdMet by RNAi inhibited the expression of JHBP, JHE, Kr-h1, and Vg, whereas promoted the FAS2 expression, which enhanced lipid accumulation and fat body development, and finally induced the adults into diapause ahead. Combining with our previous results, we conclude that JH may regulate reproductive diapause through a conserved Met-dependent pathway in G. daurica. Title: Repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus Shi M, Deng S, Cui Y, Chen X, Shi T, Song L, Zhang R, Zhang Y, Xu J and Li L <2 more author(s)> Shi M, Deng S, Cui Y, Chen X, Shi T, Song L, Zhang R, Zhang Y, Xu J, Shi J, Wang C, Li L (- 2) Ref: Toxicol Lett, 338:32, 2021 : PubMed ESTHER: Shi_2021_Toxicol.Lett_338_32 PubMedSearch: Shi 2021 Toxicol.Lett 338 32 PubMedID: 33253782 Abstract Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4xLD(50) (16.8 microg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly (p < 0.05) longer while the crossing times were significantly decreased in the Morris water task (p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 +/- 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 +/- 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure. Title: Plasma cholinesterase activity is influenced by interactive effect between omethoate exposure and CYP2E1 polymorphisms Wang T, Zhang H, Li L, Zhang W, Wang Q, Wang W Ref: J Environ Sci Health B, :1, 2021 : PubMed ESTHER: Wang_2021_J.Environ.Sci.Health.B__1 PubMedSearch: Wang 2021 J.Environ.Sci.Health.B 1 PubMedID: 33872129 Abstract The aim of this study was to explore the association between metabolizing enzyme gene polymorphisms and the decrease in cholinesterase activity induced by omethoate exposure. A total of 180 workers exposed to omethoate over an extended period were recruited along with 115 healthy controls. Cholinesterase activity in whole blood, erythrocyte, and plasma was detected using acetylthiocholine and the dithio-bis-(nitrobenzoic acid) method. Six polymorphic loci of GSTT1(+/-), GSTM1(+/-), GSTP1 rs1695, CYP2E1 rs6413432, CYP2E1 rs3813867, and PON2 rs12026 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The gene-environment interactions were analyzed using the generalized linear model method. The cholinesterase activity of erythrocyte and plasma in the exposure group was significantly lower than that in the control group (P < 0.001) in general. The plasma cholinesterase activity in the TT + AT genotype in CYP2E1 rs6413432 was lower than that in the AA genotype in the exposure group (P = 0.016). Interaction between the AA genotype in CYP2E1 rs6413432 and omethoate exposure had a significant effect on plasma cholinesterase activity (P = 0.079). The decrease in plasma cholinesterase activity was associated with interaction between the AA genotypes in rs6413432 and omethoate exposure. Title: Two novel Mutations of the LPL Gene in two Chinese family cases with Familial Chylomicronemia Syndrome Wang M, Zhou Y, He X, Deng C, Liu X, Li J, Zhou L, Li Y, Zhang Y and Li L <1 more author(s)> Wang M, Zhou Y, He X, Deng C, Liu X, Li J, Zhou L, Li Y, Zhang Y, Liu H, Li L (- 1) Ref: Clinica Chimica Acta, :, 2021 : PubMed ESTHER: Wang_2021_Clin.Chim.Acta__ PubMedSearch: Wang 2021 Clin.Chim.Acta PubMedID: 34324844 Abstract The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429+1G>T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome. Title: Characterization of a novel carboxylesterase with catalytic activity toward di(2-ethylhexyl) phthalate from a soil metagenomic library Yan Z, Ding L, Zou D, Qiu J, Shao Y, Sun S, Li L, Xin Z Ref: Sci Total Environ, 785:147260, 2021 : PubMed ESTHER: Yan_2021_Sci.Total.Environ_785_147260 PubMedSearch: Yan 2021 Sci.Total.Environ 785 147260 PubMedID: 33957585 Abstract A novel carboxylesterase gene estyz5 was isolated from a soil metagenomic library. The recombinant enzyme EstYZ5 is 298 amino acids in length with a predicted molecular weight of 32 kDa. Sequence alignment and phylogenetic analysis revealed that EstYZ5 belongs to the hormone-sensitive lipase (HSL) family with a deduced catalytic triad of Ser144-Glu238-His268. EstYZ5 contains two conserved motifs, a pentapeptide motif GDSAG and a HGGG motif, which are typically found in members of the HSL family. Esterolytic activity of the recombinant enzyme was optimal at 30 degreesC and pH 8.0, and the kcat/Km value of the enzyme for the optimum substrate p-nitrophenyl butyrate was as high as 1272 mM(-)(1).s(-1). Importantly, EstYZ5 showed activity toward di(2-ethylhexyl) phthalate with complex side chains, which is rare for HSLs. Molecular docking simulations revealed that the catalytic triad and an oxyanion hole likely play vital roles in enzymatic activity and specificity. The phthalate-degrading activity of EstYZ5, combined with its high levels of esterolytic activity, render this new enzyme a candidate for biotechnological applications. Title: Neurotoxicity induced by combined exposure of microcystin-LR and nitrite in male zebrafish (Danio rerio): Effects of oxidant-antioxidant system and neurotransmitter system Yang L, Guo H, Kuang Y, Yang H, Zhang X, Tang R, Li D, Li L Ref: Comparative Biochemistry & Physiology C Toxicol Pharmacol, 253:109248, 2021 : PubMed ESTHER: Yang_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_253_109248 PubMedSearch: Yang 2021 Comp.Biochem.Physiol.C.Toxicol.Pharmacol 253 109248 PubMedID: 34826614 Abstract With the intensification of water eutrophication around the world, cyanobacterial blooms have been becoming a common environmental pollution problem. The levels of microcystin-LR (MC-LR) and nitrite rise sharply during the cyanobacterial bloom period, which may have potential joint toxicity on aquatic organisms. In this study, adult male zebrafish were immersed into different joint solutions of MC-LR (0, 3, 30 microg/L) and nitrite (0, 2, 20 mg/L) for 30 days to explore the neurotoxic effects and underlying mechanisms. The results showed that single factor MC-LR or nitrite caused a concentration-dependent damage in brain ultrastructure and the effects of their joint exposure were much more intense. Downregulated expression of mbp and bdnf associated with myelination of nerve fibers further confirmed that MC-LR and nitrite could damage the structure and function of neuron. The decreases in dopamine content, acetylcholinesterase activity and related gene mRNA levels indicated that MC-LR and nitrite adversely affected the normal function of the dopaminergic and cholinergic systems in zebrafish brain. In addition, the significant increase in malondialdehyde content suggested the occurrence of oxidative stress caused by MC-LR, nitrite and their joint-exposure, which paralleled a significant decrease in antioxidant enzymemanganese superoxide dismutase activity and its transcription level. In conclusion, MC-LR + Nitrite joint-exposure has synergistic neurotoxic effects on the structure and neurotransmitter systems of fish brain, and antioxidant capacity disruption caused by these two factors might be one of the underlying synergistic mechanisms. Therefore, there is a risk of being induced neurotoxicity in fish during sustained cyanobacterial bloom events. Title: Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder Zou M, Liu Y, Xie S, Wang L, Li D, Li L, Wang F, Zhang Y, Xia W and Wu L <1 more author(s)> Zou M, Liu Y, Xie S, Wang L, Li D, Li L, Wang F, Zhang Y, Xia W, Sun C, Wu L (- 1) Ref: Open Biol, 11:200306, 2021 : PubMed ESTHER: Zou_2021_Open.Biol_11_200306 PubMedSearch: Zou 2021 Open.Biol 11 200306 PubMedID: 33529552 Abstract Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system-endogenous cannabinoids, their receptors and associated enzymes-in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg(-1), which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment. Title: A magnetic SERS immunosensor for highly sensitive and selective detection of human carboxylesterase 1 in human serum samples Feng J, Xu Y, Huang W, Kong H, Li Y, Cheng H, Li L Ref: Anal Chim Acta, 1097:176, 2020 : PubMed ESTHER: Feng_2020_Anal.Chim.Acta_1097_176 PubMedSearch: Feng 2020 Anal.Chim.Acta 1097 176 PubMedID: 31910958 Abstract Hepatocellular carcinoma (HCC) is a common and lethal cancer. New serum markers for detecting HCC are urgently needed. Human carboxylesterase 1 (hCE1) is an important member of the serine hydrolase superfamily and is closely related to the occurrence of HCC. It can be used as a good serum marker for early diagnosis of HCC. Here, we developed a surface enhanced Raman scattering (SERS)- based magnetic immunosensor that specifically recognizes and detects trace amounts of hCE1 in human serum via a sandwich structure consisting of a SERS tags, magnetic supporting substrates, and target antigen (hCE1). The SERS tags are 4-mercaptobenzoic acid (4-MBA)-labeled AgNPs, and the SERS supporting substrates are composed of a raspberry-like morphology of Fe3O4@SiO2@AgNPs magnetic nanocomposites surface-functionalized with a hCE1 antibody. The prepared SERS magnetic immunosensor exhibits excellent selectivity and extremely high sensitivity for hCE1 detection. The SERS signal and logarithm of hCE1 concentration presented a wide linear response range of 0.1ngmL(-1) to 1.0mgmL(-1), and the detection limit of hCE1 was 0.1ngmL(-1). The results indicate that the immunosensor can be used for the rapid determination of hCE1 in human serum without a complicated sample pre-treatment. Furthermore, the immunosensor has good reproducibility and stability, and has a promising prospect for the quantitative detection of other tumor markers in early clinical diagnosis. Title: Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure Fu F, Liu H, Lu X, Zhang R, Li L, Gao R, Xie J, Wang H, Pei C Ref: Rapid Commun Mass Spectrom, :e8721, 2020 : PubMed ESTHER: Fu_2020_Rapid.Commun.Mass.Spectrom__e8721 PubMedSearch: Fu 2020 Rapid.Commun.Mass.Spectrom e8721 PubMedID: 31899842 Abstract RATIONALE: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. This appears to be more effective than the fluoride reactivation method, based on acetylcholinesterase. METHODS: After the exposure of human serum albumin to nine nerve agents, human serum albumin was denatured, reduced, alkylated and digested with trypsin according to standard mass spectrometry-based proteomics procedures. The phosphonylated peptides of human serum albumin were identified using positive ion electrospray ionization with a quadrupole orbitrap mass spectrometer. RESULTS: The peptide KVPQVSTPTLVESR showed a good mass spectrometric response to the nine nerve agents. The tendency of sarin and cyclosarin was to bind to S419 on the peptide, while the other nerve agents (tabun, soman, and V-type nerve agents) were shown to bind more readily to K414 on the peptide. CONCLUSIONS: This research revealed the new site, S419, of the tryptic peptide KVPQVSTPTLVEVSR on human albumin to be a valuable biomarker for sarin/cyclosarin exposure, helping to further distinguish sarin and cyclosarin poisoning from nerve agents and providing an important tool for identification of sarin or cyclosarin in terrorist attacks. Title: Enantioselective disposition and metabolic products of isofenphos-methyl in rats and the hepatotoxic effects Gao B, Zhao S, Shi H, Zhang Z, Li L, He Z, Wen Y, Covaci A, Wang M Ref: Environ Int, 143:105940, 2020 : PubMed ESTHER: Gao_2020_Environ.Int_143_105940 PubMedSearch: Gao 2020 Environ.Int 143 105940 PubMedID: 32663714 Abstract Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on vegetables and fruits has been prohibited due to its high toxicity. In this study, we investigated the enantioselective distribution and metabolism of IFP and its metabolites, namely, isofenphos-methyl oxon (IFPO) and isocarbophos oxon (ICPO), in male Sprague Dawley (SD) rats. Forty eight hours (48 h) after exposure, ICPO was the main detectable compound in blood (up to 75%) and urine (up to 77%), and we found that (S)-ICPO was significantly more stable than (R)-ICPO (p < 0.05). Therefore, (S)-ICPO was proposed as a suitable candidate biomarker for the biomonitoring of IFP in human urine and blood. After 48 h exposure, 21.2-41.0%, 4.1-15.1%, and 8.6-18.7% of dosed IFP was detected in the liver of racemic, R and S enantiomer-exposed rats, respectively, and R-IFP and R-IFPO showed a faster degradation (p < 0.05). Our results showed that after one week of consecutive exposure to IFP, ICPO was accumulated in the liver of rats in both racemic and enantiopure groups (no difference between the groups, p > 0.05). We found that cytochrome P450 (CYP) (i.e. CYP2C11, CYP2D2 and CYP3A2 enzymes and carboxylesterases) is responsible for the enantioselective metabolism of IFP in liver. In addition, rats exposed to (S)-IFP exhibited hepatic lipid peroxidation, liver inflammation and hepatic fibrosis. This study provides useful information and a reference for the biomonitoring and risk assessment of IFP and organophosphorus pesticide exposure. Title: Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects Han Y, Huang D, Xu S, Li L, Tian Y, Li S, Chen C, Li Y, Sun Y and Zhao Y <4 more author(s)> Han Y, Huang D, Xu S, Li L, Tian Y, Li S, Chen C, Li Y, Sun Y, Hou Y, Qin M, Gong P, Gao Z, Zhao Y (- 4) Ref: Eur Journal of Medicinal Chemistry, :113028, 2020 : PubMed ESTHER: Han_2020_Eur.J.Med.Chem__113028 PubMedSearch: Han 2020 Eur.J.Med.Chem 113028 PubMedID: 33248848 Abstract Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC(50) value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a "prodrug". In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation. Title: Chiral organophosphorous pesticides fosthiazate: absolute configuration, stereoselective bioactivity, toxicity, and degradation in vegetables Li L, Xu JY, Lv B, Kaziem AE, Liu F, Shi HY, Wang M Ref: Journal of Agricultural and Food Chemistry, 68:7609, 2020 : PubMed ESTHER: Li_2020_J.Agric.Food.Chem_68_7609 PubMedSearch: Li 2020 J.Agric.Food.Chem 68 7609 PubMedID: 32598147 Abstract Fosthiazate is a widely used chiral organophosphorous nematicide with four stereoisomers. The present study systemically assessed the stereoselectivity of fosthiazate for the first time, including absolute configuration confirmation, stereoselective bioactivity toward nematode and aphid, toxicity to honeybees, and the stereoselective degradation in cucumber and pepper under field conditions. The absolute configurations of the four stereoisomers that eluted on the Superchiral IG-3 column were confirmed as (1S,3R)-(-)-fosthiazate, (1S,3S)-(-)-fosthiazate, (1R,3S)-(+)-fosthiazate, and (1R,3R)-(+)-fosthiazate. Compared with other two stereoisomers, (1S,3R)-fosthiazate and (1S,3S)-fosthiazate possess more than 100 times bioactive and 10 times toxic toward the target and non-target organisms, respectively. The molecular docking found that (1S,3R)-fosthiazate and (1S,3S)-fosthiazate had shorter binding distances and lower energies with acetylcholinesterase (AChE) which illuminated the mechanism of the experimental results. In addition, both the high-bioactive stereoisomers had faster degradation rates in cucumber and pepper. Based on the results of bioactivity, toxicity, and degradation behavior, the stereoisomer mixture of (1S,3R)-fosthiazate and (1S,3S)-fosthiazate will be a better option than the racemic fosthiazate to increase the bioactivity and reduce application dosage. Title: Functional analysis of a carboxylesterase gene involved in beta-cypermethrin and phoxim resistance in Plutella xylostella (L.) Li R, Zhu B, Shan J, Li L, Liang P, Gao X Ref: Pest Manag Sci, 77"":2097, 2020 : PubMed ESTHER: Li_2020_Pest.Manag.Sci_77_2097 PubMedSearch: Li 2020 Pest.Manag.Sci 77 2097 PubMedID: 33342080 Gene_locus related to this paper: pluxy-PxalphaE8 Abstract BACKGROUND: Carboxylesterases (CarEs) have been acquainted with their detoxification of xenobiotics in organism bodies, including insecticides. Overexpression of CarE genes has been considered playing important roles in insecticide resistance in insects, however it's involvement in multi-insecticide resistance have been rarely reported. This study aimed to assess the function of a CarE gene (PxalphaE8) in resistance to five insecticides in Plutella xylostella. RESULTS: The relative expressions of PxalphaE8 in three multi-insecticide-resistant populations including GD-2017, GD-2019 and HN were 14.8-, 19.5- and 28.0-fold higher than that in the susceptible one. Exposure to LC(25) of beta-cypermethrin, chlorantraniliprole, metaflumizone, phoxim and tebufenozide could induce the specific activity of CarEs and the relative expression of PxalphaE8 increase, while knockdown of PxalphaE8 expression dramatically reduced the activity of CarEs and increased the resistance of P. xylostella (GD-2019) larvae to beta-cypermethrin and phoxim by 47.4% and 45.5%, respectively. Further, a transgenic line of Drosophila melanogaster overexpressing PxalphaE8 was constructed and the bioassay results showed that the tolerance of the transgenic Drosophila to beta-cypermethrin and phoxim were 3.93- and 3.98-fold higher than that of the untransgenic line, respectively. CONCLUSION: These results provided the evidence that overexpression of PxalphaE8 is involved in resistance at least to both beta-cypermethrin and phoxim in multi-insecticide resistant P. xylostella populations, which would help in further understanding the molecular mechanisms of multi-insecticide resistance in this pest. This article is protected by copyright. All rights reserved. Title: Identification and characterization of a novel phthalate-degrading hydrolase from a soil metagenomic library Qiu J, Zhang Y, Shi Y, Jiang J, Wu S, Li L, Shao Y, Xin Z Ref: Ecotoxicology & Environmental Safety, 190:110148, 2020 : PubMed ESTHER: Qiu_2020_Ecotoxicol.Environ.Saf_190_110148 PubMedSearch: Qiu 2020 Ecotoxicol.Environ.Saf 190 110148 PubMedID: 31911388 Gene_locus related to this paper: 9zzzz-EstJ6 Abstract Phthalate esters have raised public concerns owing to their effects on the environment and human health. We identified a novel phthalate-degrading hydrolase, EstJ6, from a metagenomic library using function-driven screening. Phylogenetic analysis indicated that EstJ6 is a member of family IV esterases. EstJ6 hydrolyzed various dialkyl and monoalkyl phthalate esters, and exhibited high hydrolytic activity (128 U/mg) toward dibutyl phthalate at 40 degrees C and pH 7.5. EstJ6 hydrolyzed not only common phthalate esters with simple side chains but also diethylhexyl phthalate and monoethylhexyl phthalate, which have complex and long side chains. Site-directed mutagenesis indicated that the catalytic triad residues of EstJ6 consists of Ser146, Glu240, and His270. EstJ6 is therefore a promising biodegradation enzyme, and our study illustrates the advantages of a metagenomic approach in identifying enzyme-coding genes for agricultural, food, and biotechnological applications. Title: Characterization of XtjR8: A novel esterase with phthalate-hydrolyzing activity from a metagenomic library of lotus pond sludge Qiu J, Yang H, Yan Z, Shi Y, Zou D, Ding L, Shao Y, Li L, Khan U and Xin Z <1 more author(s)> Qiu J, Yang H, Yan Z, Shi Y, Zou D, Ding L, Shao Y, Li L, Khan U, Sun S, Xin Z (- 1) Ref: Int J Biol Macromol, 164:1510, 2020 : PubMed ESTHER: Qiu_2020_Int.J.Biol.Macromol_164_1510 PubMedSearch: Qiu 2020 Int.J.Biol.Macromol 164 1510 PubMedID: 32755708 Gene_locus related to this paper: 9zzzz-XtjR8 Abstract A fosmid metagenomic library containing 9.7 x 10(4) clones was constructed. A novel esterase, XtjR8, was isolated through functional screening. XtjR8 shared the maximum amino acid identity (44%) with acetyl-hydrolase from Streptomyces hygroscopicus, and was classified into family IV esterase. XtjR8 exhibited the highest hydrolytic activity for p-nitrophenyl acetate at 40 degreesC and pH 8.0, and presented more than 40% activity from 20 degreesC to 80 degreesC. More importantly, XtjR8 displayed the ability to hydrolyze both phthalate monoesters and diesters, this feature is extremely rare among previously reported esterases. Site-directed mutagenesis experiments revealed that the catalytic triad residues were Ser152, Glu246, and His276. Among them, Ser152 formed a hydrogen bond with dibutyl phthalate (DBP) by molecular docking, Gly84, Gly85, and Leu248 of conserved motifs formed hydrophobic interactions with DBP, respectively, which were important for the catalytic activity. Considering its wide range of temperature and hydrolytic potential toward phthalate esters, XtjR8 will be served as an interesting candidate for biodegradation and industrial applications. Title: Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z and Du G <3 more author(s)> Shen Y, Zhang B, Pang X, Yang R, Chen M, Zhao J, Wang J, Wang Z, Yu Z, Wang Y, Li L, Liu A, Du G (- 3) Ref: Front Pharmacol, 11:595254, 2020 : PubMed ESTHER: Shen_2020_Front.Pharmacol_11_595254 PubMedSearch: Shen 2020 Front.Pharmacol 11 595254 PubMedID: 33390981 Abstract Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD. Title: Irinotecan-mediated diarrhea is mainly correlated with intestinal exposure to SN-38: Critical role of gut Ugt Sun R, Zhu L, Li L, Song W, Gong X, Qi X, Wang Y, Ghose R, Gao S and Liu Z <1 more author(s)> Sun R, Zhu L, Li L, Song W, Gong X, Qi X, Wang Y, Ghose R, Gao S, Hu M, Liu Z (- 1) Ref: Toxicol Appl Pharmacol, :115032, 2020 : PubMed ESTHER: Sun_2020_Toxicol.Appl.Pharmacol__115032 PubMedSearch: Sun 2020 Toxicol.Appl.Pharmacol 115032 PubMedID: 32387182 Inhibitor(s) related to this paper: SN-38 Abstract BACKGROUND AND PURPOSE: Irinotecan-induced diarrhea (IID) results from intestinal damages by its active metabolite SN-38. Alleviation of these damages has focused on lowering luminal SN-38 concentrations. However, it is unclear if the enteric bioavailability of SN-38 is mostly dependent on luminal SN-38 concentrations. EXPERIMENTAL APPROACH: Irinotecan (50mg/kg, i.p. once daily for 6days) was administered to female wildtype FVB, Mdr1a (-/-), Mrp2 (-/-) and Bcrp1 (-/-) mice for pharmacokinetic (PK), toxicokinetic (TK) and biodistribution studies. Plasma PK/TK profiles and tissues drug distribution were determined after first or sixth daily doses, along with activities of blood and gut esterases and intestinal Ugts. Caco-2 cells and bile-cannulate mice were used to further investigate intestinal and biliary disposition of irinotecan and its metabolites. KEY RESULTS: Significant differences in IID severity were observed with the susceptible rank of Bcrp1(-/-)>wildtype FVB>Mdr1a(-/-)>Mrp2(-/-). This rank order did not correlate with biliary excretion rates of SN-38/SN-38G. Rather, the severity was best correlated (R=0.805) with the intestinal ratio of Css SN-38/SN-38G, a measure of gut Ugt activity. On the contrary, IID was poorly correlated with plasma AUC ratio of SN-38/SN-38G (R=0.227). Increased intestinal esterase activities due to repeated dosing and gut efflux transporter functionality are the other key factors that determine SN-38 enteric exposures. CONCLUSION AND IMPLICATIONS: Intestinal SN-38 exposure is mainly affected by intestinal Ugt activities and blood esterase activities, and strongly correlated with severity of IID. Modulating intestinal SN-38 concentration and gut Ugt expression should be the focus of future studies to alleviate IID. Title: Characteristics of lipid droplets and the expression of proteins involved in lipolysis in the murine cervix during mid-pregnancy Tao L, Zhang H, Wang H, Li L, Huang L, Su F, Yuan X, Luo M, Ge L Ref: Reprod Fertil Dev, 32:967, 2020 : PubMed ESTHER: Tao_2020_Reprod.Fertil.Dev_32_967 PubMedSearch: Tao 2020 Reprod.Fertil.Dev 32 967 PubMedID: 32693909 Abstract Lipid droplets (LDs) are reservoirs of arachidonoyl lipids for prostaglandin (PG) E2 synthesis, and progesterone can stimulate PGE2 synthesis; however, the relationship between progesterone and LD metabolism in the murine cervix remains unclear. In the present study we examined LD distribution and changes in the expression of proteins involved in lipolysis and autophagy in the murine cervix during pregnancy, and compared the findings with those in dioestrous mice. During mid-pregnancy, LDs were predominantly distributed in the cervical epithelium. Electron microscopy revealed the transfer of numerous LDs from the basal to apical region in the luminal epithelium, marked catabolism of LDs, an elevated number of LDs and autophagosomes and a higher LD:mitochondrion size ratio in murine cervical epithelial cells (P<0.05). In addition, immunohistochemical and western blotting analyses showed significantly higher cAMP-dependent protein kinase, adipose triglyceride lipase and hormone-sensitive lipase expression, and a higher light chain 3 (LC3) II:LC3I ratio in the stroma and smooth muscles and, particularly, in murine cervical epithelial cells, during mid-pregnancy than late dioestrus. In conclusion, these results suggest that the enhanced lipolysis of LDs and autophagy in murine cervical tissues were closely related to pregnancy and were possibly controlled by progesterone because LD catabolism may be necessary for energy provision and PGE2 synthesis to maintain a closed pregnant cervix. Title: Congenital myasthenic syndrome with novel pathogenic variants in the COLQ gene associated with the presence of antibodies to acetylcholine receptors Tay CG, Fong CY, Li L, Ganesan V, Teh CM, Gan CS, Thong MK Ref: J Clin Neurosci, 72:468, 2020 : PubMed ESTHER: Tay_2020_J.Clin.Neurosci_72_468 PubMedSearch: Tay 2020 J.Clin.Neurosci 72 468 PubMedID: 31831253 Abstract Congenital myasthenic syndrome (CMS) is a heterogeneous group of inherited disorder which does not associate with anti-acetylcholine receptor (AChR) antibody. The presence of AChR autoantibody is pathogenic and highly sensitive and specific for autoimmune myasthenia gravis (MG). We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical presentation of early onset phenotype, and refractoriness to acetylcholinesterase inhibitor and immunotherapy should prompt CMS as a differential diagnosis. Title: Cancer-related fatigue and biochemical parameters among cancer patients with different stages of sarcopenia Wang B, Thapa S, Zhou T, Liu H, Li L, Peng G, Yu S Ref: Support Care Cancer, 28:581, 2020 : PubMed ESTHER: Wang_2020_Support.Care.Cancer_28_581 PubMedSearch: Wang 2020 Support.Care.Cancer 28 581 PubMedID: 31102055 Abstract PURPOSE: Cancer-related fatigue (CRF) is a pervasive symptom experienced by cancer patients. Sarcopenia has been suggested as a treatment target of CRF. This study aims to assess the differences of CRF and biochemical markers among different stages of sarcopenia which remain poorly delineated. METHODS: A total of 187 patients were included in this cross-sectional study. Based on muscle mass (skeletal muscle index, SMI), muscle strength (handgrip strength), and physical performance (SARC-F score), patients were divided into four groups (non-sarcopenia, pre-sarcopenia, sarcopenia, and severe sarcopenia). Cancer-related fatigue was measured by the Brief Fatigue Inventory (BFI). Biochemical markers were measured by routine blood tests. RESULTS: The BFI score was significantly associated with sarcopenia stage (r=0.500; P<0.001). Cancer patients in severe sarcopenia group suffered from worse CRF than those in non-sarcopenia, pre-sarcopenia, and sarcopenia groups (P<0.001). In the multivariate linear regression model (R(2)=0.542), CRF was significantly correlated with SARC-F score (standardized B=0.519; P<0.001) and high-sensitivity C-reactive protein (standardized B=0.389; P=0.004). Serum albumin and cholinesterase were statistically correlated with both sarcopenia stage and CRF. CONCLUSIONS: The significantly increased occurrence and severity of CRF in cancer patients with sarcopenia suggest that sarcopenia may be a crucial target to improve the management of CRF. Circulating albumin and cholinesterase have the potential to predicting sarcopenia as biomarkers. Title: Symbiotic Fungus Affected the Asian Citrus Psyllid (ACP) Resistance to Imidacloprid and Thiamethoxam Yi T, Lei L, He L, Yi J, Li L, Dai L, Hong Y Ref: Front Microbiol, 11:522164, 2020 : PubMed ESTHER: Yi_2020_Front.Microbiol_11_522164 PubMedSearch: Yi 2020 Front.Microbiol 11 522164 PubMedID: 33391190 Abstract The Asian citrus psyllid (ACP), Diaphorina citri (Kuwayama) (Hemiptera: Liviidae), is a notorious Rutaceae plant pest. Frequent and extensive use of pesticides has resulted in severe insecticide resistance in ACP populations. Fully understanding the mechanism of ACP resistance to pesticides is vital for us to control or delay the development of resistance. Therefore, we compared the difference in resistance to imidacloprid and thiamethoxam between Hunan (Yongzhou, Chenzhou) and Guangdong (Guangzhou) ACP populations and analyzed the correlations between the resistance level and genes and symbiotic fungi. The results showed that the resistance of the Guangdong ACP population to imidacloprid and thiamethoxam was lower than that of Hunan ACP population, and the relative expression of genes associated with P450 mono-oxygenase and acetylcholinesterase was significantly lower in the Guangdong ACP population than in Hunan ACP population. The differences of mean relative abundances of four symbiotic bacteria among three populations were marginally significant; however, the mean relative abundance of 16 fungi among three populations was significantly different, and positive linear correlations were observed between the resistance level and two fungi (Aspergillus niger and Aureobasidium pullulans) and two genes (CYP4C70 and CYP4DB1). Negative correlations were only observed between the resistance level and two fungi (Golubevia pallescens and Acremonium sclerotigenum). Moreover, four fungi were unique to the Chenzhou population which was the highest resistance to imidacloprid and thiamethoxam. These findings suggested the P450 mono-oxygenase and symbiotic fungi together affected ACP resistance to imidacloprid and thiamethoxam. In the future, we may use environmental G. pallescens and A. sclerotigenum to control or delay ACP resistance. Title: Effect of Tannic Acid on Nutrition and Activities of Detoxification Enzymes and Acetylcholinesterase of the Fall Webworm (Lepidoptera: Arctiidae) Yuan Y, Li L, Zhao J, Chen M Ref: J Insect Sci, 20:, 2020 : PubMed ESTHER: Yuan_2020_J.Insect.Sci_20_ PubMedSearch: Yuan 2020 J.Insect.Sci 20 PubMedID: 32061083 Abstract Plant tannins, polyphenolic plant secondary metabolites are involved in important chemical defense processes in plants. In this study, tannic acid was used as the standard of plant tannins to determine the effects on nutritional indices and activities of glutathione S-transferases (GSTs), cytochrome P450 monooxygenase (CYP450), carboxylesterase (CarE), and acetylcholinesterase (AChE) in fourth-instar larvae of Hyphantria cunea (Drury) by feeding on an artificial diet containing tannic acid under different treatments. We found that tannic acid significantly affected the digestive capacity and food utilization rate of H. cunea larvae. A tannic acid concentration of less than 2.0% promoted feeding and the utilization of undesirable food by H. cunea larvae, while inhibitory effects were observed at high concentrations (>2.5%). Tannic acid had a significant effect on the activity of detoxification enzymes and AChE in H. cunea larvae in concentration-dependent and time-dependent manners (P < 0.05). These results provide new insights into the potential mechanisms underlying detoxification in H. cunea larvae against tannic acid in host plants. Title: Aptamer-functionalized magnetic nanoparticles conjugated organic framework for immobilization of acetylcholinesterase and its application in inhibitors screening Zhao L, Yang G, Li L, Zhu C, Ma Y, Qu F Ref: Anal Chim Acta, 1140:228, 2020 : PubMed ESTHER: Zhao_2020_Anal.Chim.Acta_1140_228 PubMedSearch: Zhao 2020 Anal.Chim.Acta 1140 228 PubMedID: 33218485 Abstract Construction of new enzyme reactor based on aptamer functionalized magnetic nanoparticles conjugated organic framework (COF) for acetylcholinesterase immobilization has been an enabling endeavor in this work. The aptamer against acetylcholinesterase was selected through a method based on capillary electrophoresis in one round. A new magnetic COF material rich of carboxyl groups was firstly synthesized, and its surface was then modified with the selected aptamer through covalently linking. Acetylcholinesterase was immobilized to fabricate the enzyme reactor Fe(3)O(4)@COF-Apt-AChE through the high affinity and specificity with its binding aptamer. The as constructed enzyme reactor was comprehensively characterized and the key factors that affected its catalysis efficiency were investigated in detail. Owing to the surface modification of the magnetic COF materials by aptamer for acetylcholinesterase immobilization, the immobilized enzyme exhibited improved substrates affinity. What's more, good reusability (more than 8 times) and prolonged stability (enzyme activity still kept at 90% after 42 days) were also achieved. Finally, the enzyme reactor could be applied in AChE inhibitors screening, which expanded its application capability. The proposed protocol not only paves a new way for fabrication of novel aptamer functionalized magnetic COF materials as enzyme reactors, but also indicates a broadened application of the integration of aptamer and its enzyme. Title: Metabolism and pharmacological activities of the natural health-benefiting compound diosmin Zheng Y, Zhang R, Shi W, Li L, Liu H, Chen Z, Wu L Ref: Food Funct, 11:8472, 2020 : PubMed ESTHER: Zheng_2020_Food.Funct_11_8472 PubMedSearch: Zheng 2020 Food.Funct 11 8472 PubMedID: 32966476 Abstract Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKbeta, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed. Title: The Trp183 is essential in lactonohydrolase ZHD detoxifying zearalenone and zearalenols Zhou H, Li L, Zhan B, Wang S, Li J, Hu XJ Ref: Biochemical & Biophysical Research Communications, 522:986, 2020 : PubMed ESTHER: Zhou_2020_Biochem.Biophys.Res.Commun_522_986 PubMedSearch: Zhou 2020 Biochem.Biophys.Res.Commun 522 986 PubMedID: 31810602 Gene_locus related to this paper: biooc-ZHD101 Abstract Lactonohydrolase ZHD can detoxify oestrogenic mycotoxin zearalenone and zearalenols through hydrolysis and decarboxylation. The detail mechanism, especially the role of Trp183, which interacts with substrate through p-pi interaction and one hydrogen bond, is still unknown. The Trp183 mutants abolished activity to ZEN, alpha-ZOL and beta-ZOL, except that W183F mutant retained about 40% activity against alpha-ZOL. In two W183F-reactant complex structures the reactants still bind at the active position and it suggested that this p-pi interaction takes responsible for the reactants recognization and allocation. Further, the ZHD-productant complex structures showed that the resorcinol ring of hydrolysed alpha-ZOL and hydrolysed beta-ZOL move a distance of one ring as compare to the resorcinol ring of reactant alpha-ZOL and beta-ZOL. The same movement also found in comparison of hydrolysed ZEN and ZEN. In the structure of W183F complex with hydrolysed alpha-ZOL the resorcinol ring of hydrolysed alpha-ZOL doesn't move as compare to the resorcinol ring of reactant alpha-ZOL. It suggested the Trp183 coordinated hydrogen bond takes responsible for the movement of the hydrolysed product. These functional and structural results suggested that Trp183 is essential for ZHD detoxifying zearalenone and zearalenols. Title: Significant association between GPR50 hypomethylation and AD in males Chen W, Ji H, Li L, Xu C, Zou T, Cui W, Xu S, Zhou X, Duan S, Wang Q Ref: Mol Med Rep, 20:1085, 2019 : PubMed ESTHER: Chen_2019_Mol.Med.Rep_20_1085 PubMedSearch: Chen 2019 Mol.Med.Rep 20 1085 PubMedID: 31173244 Abstract Alzheimer's disease (AD) is a chronic neurodegenerative disease. G protein coupled receptor 50 (GPR50) is a candidate gene for AD. The present study was designed to determine the association between GPR50 methylation and AD. The methylation levels of the GPR50 promoter in 51 patients with AD and 61 healthy controls were determined by bisulfite pyrophosphate sequencing. All participants were Han Chinese, living in Ningbo. It was identified that the GPR50 promoter methylation level was significantly decreased in the male AD group compared with the male control group (9.15 vs. 16.67%, P=0.002). In addition, it was observed that the GPR50 methylation levels of the females was significantly increased compared with that of males in both the patients with AD and the healthy control group (AD patient group: 33.00 vs. 9.15%, P<0.0001; healthy control group: 29.41 vs. 16.67%, P<0.0001). This may be explained by the fact that GPR50 is located on the X chromosome. In addition, GPR50 methylation was positively correlated with plasma cholinesterase levels in female patients with AD (r=0.489, P=0.039). The present study demonstrated that hypomethylation of the GPR50 promoter in peripheral blood may be a potential biomarker for the diagnosis of AD in Chinese Han males. Title: A potential biomarker of isofenphos-methyl in humans: A chiral view Gao B, Zhao S, Zhang Z, Li L, Hu K, Kaziem AE, He Z, Hua X, Shi H, Wang M Ref: Environ Int, 127:694, 2019 : PubMed ESTHER: Gao_2019_Environ.Int_127_694 PubMedSearch: Gao 2019 Environ.Int 127 694 PubMedID: 30991225 Inhibitor(s) related to this paper: Isocarbophos, Isofenphos-methyl Abstract Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was confirmed that phosphorothioate organophosphorus pesticides with N-alkyl (POPN) require activation by oxidative desulfuration and N-dealkylation. In this work, we demonstrated that IFP could be metabolized in human liver microsomes to isofenphos-methyl oxon (IFPO, 52.7%), isocarbophos (ICP, 14.2%) and isocarbophos oxon (ICPO, 11.2%). It was found that (R)-IFP was preferentially degraded compared to the (S)-enantiomer, and the enantiomeric fraction (EF) value reached 0.61 at 60min. However, (S)-enantiomers of the three metabolites, were degraded preferentially, and the EF values ranged from 0.34 to 0.45. Cytochrome P450 (CYP) isoforms CYP3A4, CYP2E1, and CYP1A2 and carboxylesterase enzyme have an essential role in the enantioselective metabolism of IFP; but, the enzymes that participate in the degradation of IFP metabolites are different. The AChE inhibition bioassay indicated that ICPO is the only effective inhibitor of AChE. The covalent molecular docking has proposed that the metabolites of IFP and its analogs after N-dealkylation and oxidative desulfuration will possess the highest inhibitory activity against AChE. This study is the first to demonstrate that ICPO can be regarded as a potential biomarker for the biomonitoring of IFP and ICP exposure in humans. Title: Candida sp. 99-125 lipase-catalyzed synthesis of ergosterol linolenate and its characterization He WS, Li L, Zhao J, Xu H, Rui J, Cui D, Li H, Zhang H, Liu X Ref: Food Chem, 280:286, 2019 : PubMed ESTHER: He_2019_Food.Chem_280_286 PubMedSearch: He 2019 Food.Chem 280 286 PubMedID: 30642499 Abstract As a major sterol in edible mushroom, ergosterol has gained much attention owing to its potential bioactivities. However, ergosterol has a high melting point, poor oil solubility and stability, which restrict its scope of application. In this study, an ergosterol ester of alpha-linolenic acid was successfully and efficiently prepared using Candida sp. 99-125 lipase as a biocatalyst. The desired product was confirmed to be ergosterol linolenate using MS, FT-IR, and NMR analyses. Using Candida sp. 99-125 lipase, the product conversion exceeded 92% in 12h under the following optimized parameters: 75mmol/L ergosterol, 40g/L lipase, 1:1.25 ergosterol-to-alpha-linolenic acid molar ratio, and 45 degrees C. The results confirmed that Candida sp. 99-125 lipase has good reusability and stability and is also relatively low cost, suggesting its great potential for large-scale production of ergosterol ester. Most importantly, the physiochemical properties (oil solubility and melting point) of ergosterol significantly improved after esterification with alpha-linolenic acid, thus facilitating its application in oil-based systems. Title: Enhancing thermostability of Yarrowia lipolytica lipase 2 through engineering multiple disulfide bonds and mitigating reduced lipase production associated with disulfide bonds Li L, Zhang S, Wu W, Guan W, Deng Z, Qiao H Ref: Enzyme Microb Technol, 126:41, 2019 : PubMed ESTHER: Li_2019_Enzyme.Microb.Technol_126_41 PubMedSearch: Li 2019 Enzyme.Microb.Technol 126 41 PubMedID: 31000163 Abstract The limited thermostability of Yarrowia lipolytica lipase 2 (Lip2) hampers its industrial application. To improve its thermostability, we combined single disulfide bonds which our group identified previously. In this study, combining different regional disulfide bonds had greater effect than combining same regional disulfide bonds. Furthermore, mutants with 4, 5, and 6 disulfide bonds exhibited dramatically enhanced thermostability. Compared with the wild-type, sextuple mutant 6s displayed a 22.53 and 31.23 degC increase in the melting temperature (T(m)) and the half loss temperature at 15 min (T15 50), respectively, with greater pH stability and a wider reaction pH range. Molecular dynamics simulation revealed that multiple disulfide bonds resulted in more rigid structures of mutants 4s, 5s and 6s, and prolonged enzyme unfolding times. Moreover, secretions of mutants 5s and 6s were significantly increased by 60% and 80% by co-expressing with the chaperone protein disulfide isomerase (PDI), which mitigated the reduced production issue caused by multiple disulfide bonds. Results of this study indicated that enhanced heat endurance giving more potential for industrial application. Title: Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis Liu Y, Feng W, Liu W, Kong X, Li L, He J, Wang D, Zhang M, Zhou G and Xu M <3 more author(s)> Liu Y, Feng W, Liu W, Kong X, Li L, He J, Wang D, Zhang M, Zhou G, Xu W, Chen W, Gong A, Xu M (- 3) Ref: J Cancer, 10:3746, 2019 : PubMed ESTHER: Liu_2019_J.Cancer_10_3746 PubMedSearch: Liu 2019 J.Cancer 10 3746 PubMedID: 31333792 Gene_locus related to this paper: human-ABHD11 Abstract Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening. Title: mir-234 controls neuropeptide release at the Caenorhabditis elegans neuromuscular junction Snieckute G, Baltaci O, Liu H, Li L, Hu Z, Pocock R Ref: Molecular & Cellular Neurosciences, 98:70, 2019 : PubMed ESTHER: Snieckute_2019_Mol.Cell.Neurosci_98_70 PubMedSearch: Snieckute 2019 Mol.Cell.Neurosci 98 70 PubMedID: 31200102 Abstract miR-137 is a highly conserved microRNA (miRNA) that is associated with the control of brain function and the etiology of psychiatric disorders including schizophrenia and bipolar disorder. The Caenorhabditis elegans genome encodes a single miR-137 ortholog called mir-234, the function of which is unknown. Here we show that mir-234 is expressed in a subset of sensory, motor and interneurons in C. elegans. Using a mir-234 deletion strain, we systematically examined the development and function of these neurons in addition to global C. elegans behaviors. We were however unable to detect phenotypes associated with loss of mir-234, possibly due to genetic redundancy. To circumvent this issue, we overexpressed mir-234 in mir-234-expressing neurons to uncover possible phenotypes. We found that mir-234-overexpression endows resistance to the acetylcholinesterase inhibitor aldicarb, suggesting modification of neuromuscular junction (NMJ) function. Further analysis revealed that mir-234 controls neuropeptide levels, therefore positing a cause of NMJ dysfunction. Together, our data suggest that mir-234 functions to control the expression of target genes that are important for neuropeptide maturation and/or transport in C. elegans. SIGNIFICANCE STATEMENT: The miR-137 family of miRNAs is linked to the control of brain function in humans. Defective regulation of miR-137 is associated with psychiatric disorders that include schizophrenia and bipolar disorder. Previous studies have revealed that miR-137 is required for the development of dendrites and for controlling the release of fast-acting neurotransmitters. Here, we analyzed the function a miR-137 family member (called mir-234) in the nematode animal model using anatomical, behavioral, electrophysiological and neuropeptide analysis. We reveal for the first time that mir-234/miR-137 is required for the release of slow-acting neuropeptides, which may also be of relevance for controlling human brain function. Title: High-level expression of Thermomyces dupontii thermo-alkaline lipase in Pichia pastoris under the control of different promoters Wang J, Zhang T, Li Y, Li L, Wang Y, Yang B Ref: 3 Biotech, 9:33, 2019 : PubMed ESTHER: Wang_2019_3.Biotech_9_33 PubMedSearch: Wang 2019 3.Biotech 9 33 PubMedID: 30622871 Gene_locus related to this paper: talth-f6lqk7 Abstract In this study, 15 methanol-inducible and 9 constitutive promoters were used to drive the expression of Thermomyces dupontii lipase (TDL) in Pichia pastoris. Of the 15 methanol-inducible promoters, formaldehyde dehydrogenase promoter (PFLD1) showed the highest efficiency in driving lipase production, followed by alcohol oxidase 1 (PAOX1) and dihydroxyacetone synthase (PDAS1) promoters. The maximum lipase activity of transformants with PFLD1, PAOX1 and PDAS1 promoters in 5-l bioreactor was 27,076, 24,159 and 22,342 U/ml, respectively. For the nine constitutive promoters, glycosyl phosphatidyl inositol-anchored protein promoter (PGCW14) produced the highest amount of lipases in a medium containing glucose or glycerol as the only carbon source, followed by mitochondrial alcohol dehydrogenase isozyme (P0472) and glyceraldehyde-3-phosphate dehydrogenase (PGAP) promoters. The maximum lipase yields in 5-l bioreactors under the control of PGCW14, P0472 and PGAP promoters were 17,353, 15,046 and 14,276 U/ml, respectively. The result of this study not only identifies a few highly efficient promoters for the heterologous expression of TDL in P. pastoris, but also casts some insight into the optimization of protein production in heterologous systems. Title: Epoxyeicosatrienoic acids alleviate methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in mice Wang X, Li L, Wang H, Xiao F, Ning Q Ref: Scand J Immunol, :e12791, 2019 : PubMed ESTHER: Wang_2019_Scand.J.Immunol__e12791 PubMedSearch: Wang 2019 Scand.J.Immunol e12791 PubMedID: 31132306 Abstract The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases and have recently been found to have an anti-inflammatory activity. However, the role of EETs in non-alcoholic steatohepatitis has not been fully understood. In this study, we investigated the protective role of EETs in methionine-choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) in mice and the potential mechanisms. We used 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea(TPPU), a soluble epoxide hydrolase inhibitor, to increase the endogenous EET level in mice. Upon TPPU treatment, the liver steatosis and inflammatory damage were significantly ameliorated in mice with steatohepatitis, paralleled by the downregulation of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) as well as chemokines (CXCL1, MCP-1). Compared with untreated NASH mice, mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and inflammation relevant adhesion molecules (ICAM-1, VCAM-1) were downregulated, whereas mRNA level of peroxisome proliferator-activated receptor alpha(PPAR-alpha) was elevated in TPPU-treated mice. In vitro, 11,12-EET treatment remarkably attenuated free fatty acid (FFA)-induced inflammation in HepG2 and THP-1 cells. Further, 11,12-EET inhibited the activation of NF-kappaB signalling pathway in macrophages from mice with steatohepatitis. Collectively, these results suggest that EETs play a protective role and alleviate the MCD diet-induced steatohepatitis in mice mainly by downregulating activation of NF-kappaB pathway in macrophages. Title: Antioxidant Profile of 1-Monocaffeoyl Glycerol in Lipophobic/Lipophilic Media Weng L, Li L, Ji L, Zhao D, Xu Z, Su J, Li B, Zhang X Ref: J Food Sci, 84:2091, 2019 : PubMed ESTHER: Weng_2019_J.Food.Sci_84_2091 PubMedSearch: Weng 2019 J.Food.Sci 84 2091 PubMedID: 31313325 Abstract Oxidative stress has been generally considered as one trigger of organism imbalance, resulting in lipid peroxidation, DNA damage and protein oxidation, which could be relieved by antioxidant supplement or endogenous antioxidant system. In present study, 1-monocaffeoyl glycerol (1-MCG), an amphipathic caffeic acid natural derivative, was enzymatically synthesized by Lipozyme 435, and its antioxidant profile in both lipophilic and lipophobic media was evaluated. The 1-MCG was identified by HPLC-UV, HPLC-ESI-MS, and (1) H/(13) C-NMR. Subsequently, antioxidant assays in lipophilic (DPPH assay) and lipophobic (ABTS, ORAC, erythrocyte hemolysis, ROS, MDA, and GPx assays) systems were explored. The better and lasting DPPH. and ABTS(+.) inhibitions of 1-MCG than caffeic acid (CA) were related to its better solubilities in ethanol/water media and electron transfer ability. ORAC results suggested the radical scavenging activities of 1-MCG (5 to 40 microM) were higher than Trolox. Furthermore, the effectiveness of 1-MCG against AAPH-induced erythrocytes oxidation indicated that 1-MCG can effectively inhibit hemolysis. ESEM was also applied to verify the hemolysis inhibition and morphology preservation abilities of 1-MCG. Besides, results showed 1-MCG was able to prevent ROS from invasion, reduce production of MDA, up-regulated GPx activity, terminate lipid peroxidation, and maintain the integrity of the structure and function of erythrocytes. PRACTICAL APPLICATION: As an amphiphilic caffeic acid derivative, 1-monocaffeoyl glycerol was synthesized, purified, and identified. 1-Monocaffeoyl glycerol could significantly eliminate radicals including DPPH., ABTS(+.) , and AAPH in ethanol, water, and PBS system, respectively. 1-Monocaffeoyl glycerol could protect erythrocyte from AAPH induced hemolysis. Title: HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure Wu J, Guo N, Zhang X, Xiong C, Liu J, Xu Y, Fan J, Yu J, Zhao X and Li L <4 more author(s)> Wu J, Guo N, Zhang X, Xiong C, Liu J, Xu Y, Fan J, Yu J, Zhao X, Liu B, Wang W, Zhang J, Cao H, Li L (- 4) Ref: J Viral Hepat, 26:1334, 2019 : PubMed ESTHER: Wu_2019_J.Viral.Hepat_26_1334 PubMedSearch: Wu 2019 J.Viral.Hepat 26 1334 PubMedID: 31294523 Abstract A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages. Title: The genome of broomcorn millet Zou C, Li L, Miki D, Li D, Tang Q, Xiao L, Rajput S, Deng P, Peng L and Zhu JK <14 more author(s)> Zou C, Li L, Miki D, Li D, Tang Q, Xiao L, Rajput S, Deng P, Peng L, Jia W, Huang R, Zhang M, Sun Y, Hu J, Fu X, Schnable PS, Chang Y, Li F, Zhang H, Feng B, Zhu X, Liu R, Schnable JC, Zhu JK (- 14) Ref: Nat Commun, 10:436, 2019 : PubMed ESTHER: Zou_2019_Nat.Commun_10_436 PubMedSearch: Zou 2019 Nat.Commun 10 436 PubMedID: 30683860 Gene_locus related to this paper: panmi-a0a3l6qvl9, 9poal-a0a2s3hbt0, panmi-a0a3l6sxg5, 9poal-a0a2t7cdl4, panmi-a0a3l6ta96, panmi-a0a3l6qv47 Abstract Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology. Title: Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers Ding M, Yang Y, Duan X, Wang S, Feng X, Wang T, Wang P, Liu S, Li L and Wang W <7 more author(s)> Ding M, Yang Y, Duan X, Wang S, Feng X, Wang T, Wang P, Liu S, Li L, Liu J, Tang L, Niu X, Zhang Y, Li G, Yao W, Cui L, Wang W (- 7) Ref: Ecotoxicology & Environmental Safety, 161:563, 2018 : PubMed ESTHER: Ding_2018_Ecotoxicol.Environ.Saf_161_563 PubMedSearch: Ding 2018 Ecotoxicol.Environ.Saf 161 563 PubMedID: 29929132 Abstract Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P<0.001). Multivariate analysis indicates that exposure group (b=-1.016, P<0.001), agender (b=0.365, P<0.001), drinking (b=0.271, P=0.004) and TERF1rs3863242 (b=-0.368, P=0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate. Title: Schisanhenol improves learning and memory in scopolamine-treated mice by reducing acetylcholinesterase activity and attenuating oxidative damage through SIRT1-PGC-1alpha-Tau signaling pathway Han Y, Yang H, Li L, Du X, Sun C Ref: International Journal of Neuroscience, :1, 2018 : PubMed ESTHER: Han_2018_Int.J.Neurosci__1 PubMedSearch: Han 2018 Int.J.Neurosci 1 PubMedID: 30033800 Abstract Schisanhenol is a compound derived from the fruit of a traditional Chinese herb Schisandra rubriflora. The aim of the present study was to evaluate the effect of Schisanhenol on the cognitive impairment induced by scopolamine. The learning and memorial ability of mice was monitored by water morris maze. Hippocampus of mice were collected after behavioral testing and the activity of SOD, MDA, GSH-px, AChE were measured with standard biochemical procedures. Western blotting was used to analyze the expression of SIRT1, PGC-1alpha, phosphorylated Tau proteins. Intraperitoneal administration of Schisanhenol (10, 30 or 100 mg/kg) significantly attenuated scopolamine-induced cognitive impairment in water morris maze. In addition, Schisanhenol increased the activity of SOD and GSH-px while decreased the content of AChE and MDA. Furthermore, western blotting analysis revealed that Schisanhenol increased the levels of SIRT1 and PGC-1alpha and decreased the level of phosphorylated Tau protein (Ser 396) significantly in the hippocampal tissues. Taken together, the present study suggests that Schisanhenol may block scopolamine-induced learning deficit and enhance cognitive function, the mechanism via improve the cholinergic system and antioxidant ability, activate SIRT1-PGC1alpha signaling, inhibit the phosphorylation of Tau, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease. Title: Long non-coding RNA ABHD11-AS1 promotes colorectal cancer development through regulation of miR-133a/SOX4 axis Lei X, Li L, Duan X Ref: Bioscience Reports, 38:, 2018 : PubMed ESTHER: Lei_2018_Biosci.Rep_38_ PubMedSearch: Lei 2018 Biosci.Rep 38 PubMedID: 30429229 Gene_locus related to this paper: human-ABHD11 Abstract Recently, lncRNA has been verified to regulate the development and progression of tumor. LncRNA ABHD11-AS1 has been proven to serve as an oncogene in several cancers. However, the role of ABHD11-AS1 in colorectal cancer remains totally unknown. In the present study, qRT-PCR assay revealed that ABHD11-AS1 expression was markedly higher in colorectal cancer tissues and cell lines. In addition, patients who displayed overexpression of ABHD11-AS1 showed a significantly poorer progression free survival (PFS) and overall survival (OS) by Kaplan-Meier analysis. Loss-of-function experiments suggested that silencing of ABHD11-AS1 expression could significantly reduce the proliferation, colony formation, migration and invasion of colorectal cancer cells, and increase cell apoptosis. Moreover, bioinformatics analysis, biotin pull-down assay, luciferase reporter assay, and RIP assay disclosed that ABHD11-AS1 straightly interacted with miR-133a. We also found that SOX4 was a downstream target of miR-133a and ABHD11-AS1 subsequently exerted its biological effects via modulating the expression of SOX4 in colorectal cancer cells. Collectively, these findings manifested that the ABHD11-AS1/miR-133a/SOX4 axis may be a cogitable and promising therapeutic target for colorectal cancer. Title: De novo transcriptomic analysis of the alimentary tract of the tephritid gall fly, Procecidochares utilis Li L, Lan M, Lu W, Li Z, Xia T, Zhu J, Ye M, Gao X, Wu G Ref: PLoS ONE, 13:e0201679, 2018 : PubMed ESTHER: Li_2018_PLoS.One_13_e0201679 PubMedSearch: Li 2018 PLoS.One 13 e0201679 PubMedID: 30138350 Abstract The tephritid gall fly, Procecidochares utilis, is an important obligate parasitic insect of the malignant weed Eupatorium adenophorum which biosynthesizes toxic secondary metabolites. Insect alimentary tracts secrete several enzymes that are used for detoxification, including cytochrome P450s, glutathione S-transferases, and carboxylesterases. To explore the adaptation of P. utilis to its toxic host plant, E. adenophorum at molecular level, we sequenced the transcriptome of the alimentary tract of P. utilis using Illumina sequencing. Sequencing and de novo assembly yielded 62,443 high-quality contigs with an average length of 604 bp that were further assembled into 45,985 unigenes with an average length of 674 bp and an N50 of 983 bp. Among the unigenes, 30,430 (66.17%) were annotated by alignment against the NCBI non-redundant protein (Nr) database, while 16,700 (36.32%), 16,267 (35.37%), and 11,530 (25.07%) were assigned functions using the Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) databases, respectively. Using the comprehensive transcriptome data set, we manually identified several important gene families likely to be involved in the detoxification of toxic compounds including 21 unigenes within the glutathione S-transferase (GST) family, 22 unigenes within the cytochrome P450 (P450) family, and 16 unigenes within the carboxylesterase (CarE) family. Quantitative PCR was used to verify eight, six, and two genes of GSTs, P450s, and CarEs, respectively, in different P. utilis tissues and at different developmental stages. The detoxification enzyme genes were mainly expressed in the foregut and midgut. Moreover, the unigenes were higher expressed in the larvae, pupae, and 3-day adults, while they were expressed at lower levels in eggs. These transcriptomic data provide a valuable molecular resource for better understanding the function of the P. utilis alimentary canal. These identified genes could be pinpoints to address the molecular mechanisms of P. utilis interacting with toxic plant host. Title: Sublethal effects of imidacloprid on the performance of the bird cherry-oat aphid Rhopalosiphum padi Li W, Lu Z, Li L, Yu Y, Dong S, Men X, Ye B Ref: PLoS ONE, 13:e0204097, 2018 : PubMed ESTHER: Li_2018_PLoS.One_13_e0204097 PubMedSearch: Li 2018 PLoS.One 13 e0204097 PubMedID: 30235260 Abstract The bird cherry-oat aphid, Rhopalosiphum padi (L.), is a major insect pest of cereal crops in many countries. Imidacloprid has been widely used for controlling piercing-sucking insect pests worldwide, but its sublethal effects on R. padi have not been well addressed. In this study, we investigated the sublethal effects of imidacloprid on biological parameters and five enzyme activities of R. padi. The LC10, LC20, and LC25 of imidacloprid to adult aphids were 0.0053, 0.0329 and 0.0659 mg L-1, respectively. These concentrations significantly decreased pre-adult survival rate, but prolonged the development duration of 1st instar nymphs, pre-oviposition period, and adult longevity. Adult oviposition period was also extended by LC20. The intrinsic rate of increase (r), net reproductive rate (R0), and finite rate (lambda) decreased at all three concentrations, whereas mean generation time (T) increased. Moreover, LC20 and LC25 significantly inhibited superoxide dismutase (SOD) activity, but increased catalase (CAT) activity. Acetylcholinesterase (AChE) activity also increased at LC20. However, cytochrome P450 enzyme and peroxidase (POD) activity did not differ between imidacloprid treatments and the control. In conclusion, the imidacloprid concentrations tested here have negative impacts on the performance of R. padi by reducing its nymphal survival, extending the development duration of some stages, decreasing the rate of population growth, and altering enzyme activities. Title: Genome Mining and Assembly-Line Biosynthesis of the UCS1025A Pyrrolizidinone Family of Fungal Alkaloids Li L, Tang MC, Tang S, Gao S, Soliman S, Hang L, Xu W, Ye T, Watanabe K, Tang Y Ref: Journal of the American Chemical Society, 140:2067, 2018 : PubMed ESTHER: Li_2018_J.Am.Chem.Soc_140_2067 PubMedSearch: Li 2018 J.Am.Chem.Soc 140 2067 PubMedID: 29373009 Gene_locus related to this paper: acrsp-ucsc Abstract UCS1025A is a fungal polyketide/alkaloid that displays strong inhibition of telomerase. The structures of UCS1025A and related natural products are featured by a tricyclic furopyrrolizidine connected to a trans-decalin fragment. We mined the genome of a thermophilic fungus and activated the ucs gene cluster to produce UCS1025A at a high titer. Genetic and biochemical analysis revealed a PKS-NRPS assembly line that activates 2S,3S-methylproline derived from l-isoleucine, followed by Knoevenagel condensation to construct the pyrrolizidine moiety. Oxidation of the 3S-methyl group to a carboxylate leads to an oxa-Michael cyclization and furnishes the furopyrrolizidine. Our work reveals a new strategy used by nature to construct heterocyclic alkaloid-like ring systems using assembly line logic. Title: Genetic variation in human carboxylesterase CES1 confers resistance to hepatic steatosis Lian J, Bahitham W, Panigrahi R, Nelson R, Li L, Watts R, Thiesen A, Lemieux MJ, Lehner R Ref: Biochimica & Biophysica Acta, 1863:688, 2018 : PubMed ESTHER: Lian_2018_Biochim.Biophys.Acta_1863_688 PubMedSearch: Lian 2018 Biochim.Biophys.Acta 1863 688 PubMedID: 29631096 Gene_locus related to this paper: human-CES1 Abstract Obesity often leads non-alcoholic fatty liver disease, insulin resistance and hyperlipidemia. Expression of carboxylesterase CES1 is positively correlated with increased lipid storage and plasma lipid concentration. Here we investigated structural and metabolic consequences of a single nucleotide polymorphism in CES1 gene that results in p.Gly143Glu amino acid substitution. We generated a humanized mouse model expressing CES1(WT) (control), CES1(G143E) and catalytically dead CES1(S221A) (negative control) in the liver in the absence of endogenous expression of the mouse orthologous gene. We show that the CES1(G143E) variant exhibits only 20% of the wild-type lipolytic activity. High-fat diet fed mice expressing CES1(G143E) had reduced liver and plasma triacylglycerol levels. The mechanism by which decreased CES1 activity exerts this hypolipidemic phenotype was determined to include decreased very-low density lipoprotein secretion, decreased expression of hepatic lipogenic genes and increased fatty acid oxidation as determined by increased plasma ketone bodies and hepatic mitochondrial electron transport chain protein abundance. We conclude that attenuation of human CES1 activity provides a beneficial effect on hepatic lipid metabolism. These studies also suggest that CES1 is a potential therapeutic target for non-alcoholic fatty liver disease management. Title: The Claudin-like Protein HPO-30 Is Required to Maintain LAChRs at the C. elegans Neuromuscular Junction Sharma P, Li L, Liu H, Tikiyani V, Hu Z, Babu K Ref: Journal of Neuroscience, 38:7072, 2018 : PubMed ESTHER: Sharma_2018_J.Neurosci_38_7072 PubMedSearch: Sharma 2018 J.Neurosci 38 7072 PubMedID: 29950505 Abstract Communications across chemical synapses are primarily mediated by neurotransmitters and their postsynaptic receptors. There are diverse molecular systems to localize and regulate the receptors at the synapse. Here, we identify HPO-30, a member of the claudin superfamily of membrane proteins, as a positive regulator for synaptic localization of levamisole-dependent AChRs (LAChRs) at the Caenorhabditis elegans neuromuscular junction (NMJ). The HPO-30 protein localizes at the NMJ and shows genetic and physical association with the LAChR subunits LEV-8, UNC-29, and UNC-38. Using genetic and electrophysiological assays in the hermaphrodite C. elegans, we demonstrate that HPO-30 functions through Neuroligin at the NMJ to maintain postsynaptic LAChR levels at the synapse. Together, this work suggests a novel function for a tight junction protein in maintaining normal receptor levels at the NMJ.SIGNIFICANCE STATEMENT Claudins are a large superfamily of membrane proteins. Their role in maintaining the functional integrity of tight junctions has been widely explored. Our experiments suggest a critical role for the claudin-like protein, HPO-30, in maintaining synaptic levamisole-dependent AChR (LAChR) levels. LAChRs contribute to <20% of the acetylcholine-mediated conductance in adult Caenorhabditis elegans; however, they play a significant functional role in worm locomotion. This study provides a new perspective in the study of LAChR physiology. Title: The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis Shen Q, Zhang L, Liao Z, Wang S, Yan T, Shi P, Liu M, Fu X, Pan Q and Tang K <15 more author(s)> Shen Q, Zhang L, Liao Z, Wang S, Yan T, Shi P, Liu M, Fu X, Pan Q, Wang Y, Lv Z, Lu X, Zhang F, Jiang W, Ma Y, Chen M, Hao X, Li L, Tang Y, Lv G, Zhou Y, Sun X, Brodelius PE, Rose JKC, Tang K (- 15) Ref: Mol Plant, 11:776, 2018 : PubMed ESTHER: Shen_2018_Mol.Plant_11_776 PubMedSearch: Shen 2018 Mol.Plant 11 776 PubMedID: 29703587 Gene_locus related to this paper: artan-a0a2u1ns65, artan-a0a2u1nuf0, artan-a0a2u1pw87, artan-a0a2u1ql98, artan-a0a2u1n9p7.2, artan-a0a2u1ky94, artan-a0a2u1pvq0, artan-a0a2u1q8x4, artan-a0a2u1mtd1, artan-a0a2u1l9j8, artan-a0a2u1lak5, artan-a0a2u1lfl1, artan-a0a2u1lzs1, artan-a0a2u1m5v6, artan-a0a2u1n4s5, artan-a0a2u1qgg7 Abstract Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin. Title: Recovery of respiratory function and autonomic diaphragm movement following unilateral recurrent laryngeal nerve to phrenic nerve anastomosis in rabbits Wen J, Han Y, Guo S, Yang M, Li L, Sun G, Wang J, Hu F, Liang J and Tan J <3 more author(s)> Wen J, Han Y, Guo S, Yang M, Li L, Sun G, Wang J, Hu F, Liang J, Wei L, Zhou Q, Zhang W, Tan J (- 3) Ref: Journal of Neurosurgery Spine, :1, 2018 : PubMed ESTHER: Wen_2018_J.Neurosurg.Spine__1 PubMedSearch: Wen 2018 J.Neurosurg.Spine 1 PubMedID: 29979142 Abstract OBJECTIVE Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). The authors' previous study suggested that vagus nerve (VN) and phrenic nerve (PN) anastomosis could partially improve respiratory function in rabbits that had been subjected to PN transection. As a branch of the VN and a motor fiber-dominated nerve, the recurrent laryngeal nerve (RLN) seems a better choice to anastomose with the PN for respiratory function restoration after upper cervical SCI. This study was designed to determine whether RLN-PN anastomosis could restore the respiratory function after upper cervical SCI in rabbits. METHODS Twelve male New Zealand rabbits were randomly divided into 3 groups: 1) sham group (no injury), 2) transection group (right RLN and PN were transected), and 3) bridge group (transected right RLN and PN were immediately anastomosed). Spontaneous discharges of the RLN and PN were compared using a bio-signal collection system. RLN and PN cross sections were stained for acetylcholinesterase (AChE), and the numbers of motor fibers were compared. Three months after the initial surgical procedures, the movement of the diaphragm was assessed using a digital subtraction angiography (DSA) system, and discharges from the right diaphragm muscle were recorded. Toluidine blue staining, electron microscopy, and staining for AChE were used to assess whether motor fibers from the RLN regenerated into the PN, and sections of diaphragm were examined after AChE staining to assess the motor endplates. RESULTS Both the RLN and PN exhibited highly rhythmic discharges, synchronized with respiration, and most fibers in the RLN and PN were found to be motor fibers. Numerous myelinated fibers were observed in anastomosed PN using toluidine blue staining and electron microscopy. Staining for AChE showed that those regenerated fibers had typical characteristics of motor fibers, and motor endplates with typical morphological characteristics were observed in the diaphragm. Reestablished rhythmic contraction of the hemidiaphragm was directly observed using the DSA system, and rhythmic spontaneous discharge was recorded from the reinnervated hemidiaphragm using the bio-signal collection system. CONCLUSIONS Motor fibers from the RLN could regenerate into the PN after end-to-end anastomosis and reinnervate the denervated hemidiaphragm in rabbits. Those regenerated motor fibers restored rhythmic and autonomic movement of the paralyzed diaphragm. These results suggest that the RLN is an optimal donor nerve to anastomose with the PN in order to reestablish the autonomic movement of paralyzed diaphragms after high-level SCI. Title: Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B Wu D, Rao Q, Chen W, Ji F, Xie Z, Huang K, Chen E, Zhao Y, Ouyang X and Li L <5 more author(s)> Wu D, Rao Q, Chen W, Ji F, Xie Z, Huang K, Chen E, Zhao Y, Ouyang X, Zhang S, Jiang Z, Zhang L, Xu L, Gao H, Li L (- 5) Ref: Liver Int, 38:1930, 2018 : PubMed ESTHER: Wu_2018_Liver.Int_38_1930 PubMedSearch: Wu 2018 Liver.Int 38 1930 PubMedID: 29654711 Abstract BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis. Title: Z-Ligustilide Exerted Hormetic Effect on Growth and Detoxification Enzymes of Spodoptera litura Larvae Yi Y, Dou G, Yu Z, He H, Wang C, Li L, Zhou J, Liu D, Shi J and Qi H <4 more author(s)> Yi Y, Dou G, Yu Z, He H, Wang C, Li L, Zhou J, Liu D, Shi J, Li G, Pang L, Yang N, Huang Q, Qi H (- 4) Ref: Evid Based Complement Alternat Med, 2018:7104513, 2018 : PubMed ESTHER: Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513 PubMedSearch: Yi 2018 Evid.Based.Complement.Alternat.Med 2018 7104513 PubMedID: 30057645 Abstract Plants have evolved a variety of phytochemicals to defense insect feeding, whereas insects have also evolved diverse detoxification enzymes, which are adaptively induced as a prosurvival mechanism. Herein, Z-ligustilide in Ligusticum chuanxiong Hort. was found to exhibit a similar trend in the accumulation from December to May as the occurrence of Spodoptera litura (Fabricius) larvae. Importantly, S. litura larvae feeding enhanced Z-ligustilide level in the stem and leaf (p < 0.01). Moreover, Z-ligustilide ranging from 1 to 5 mg.g(-1) exhibited remarkable larvicidal activity, antifeedant activity, and growth inhibition against S. litura larvae. The LC50 values of larvicidal activity for phthalides in L. chuanxiong were compared as follows: Z-ligustilide > levistilide A > senkyunolide A > 3-butylidenephthalide > senkyunolide I, implicating the critical role of conjugated structure. Notably, there was a biphasic dose response for glutathione S-transferase (GST), cytochrome P450 (CYP) 450, Acetylcholinesterase (AChE), and Carboxylesterase (CarE) activities and GSTs1, cytochrome P450 (CYP) 4S9, and CYP4M14 mRNA expression. Particularly, low dose (0.1 mg.g(-1)) of Z-ligustilide conferred the resistance of S. litura larvae against chlorpyrifos (p < 0.05). Together, our data suggest that Z-ligustilide may function in a hormetic way in the chemical defense of L. chuanxiong against S. litura larvae. Title: Effects of repetitive transcranial magnetic stimulation on cognitive function and cholinergic activity in the rat hippocampus after vascular dementia Zhang XQ, Li L, Huo JT, Cheng M, Li LH Ref: Neural Regen Res, 13:1384, 2018 : PubMed ESTHER: Zhang_2018_Neural.Regen.Res_13_1384 PubMedSearch: Zhang 2018 Neural.Regen.Res 13 1384 PubMedID: 30106050 Abstract Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown. In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were administered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1.33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotrophic factor (BDNF)-immunoreactive cells in the hippocampal CA1 region. rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia. The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA1 region. Title: Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy Zhang W, Teng M, Liu B, Liu Q, Liu X, Si Y, Li L Ref: Gastroenterol Res Pract, 2018:4136082, 2018 : PubMed ESTHER: Zhang_2018_Gastroenterol.Res.Pract_2018_4136082 PubMedSearch: Zhang 2018 Gastroenterol.Res.Pract 2018 4136082 PubMedID: 30510572 Abstract Objective: This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods: A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), alpha-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results: Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions: Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592. Title: A pooled analysis of mesenchymal stem cell-based therapy for liver disease Zhao L, Chen S, Shi X, Cao H, Li L Ref: Stem Cell Res Ther, 9:72, 2018 : PubMed ESTHER: Zhao_2018_Stem.Cell.Res.Ther_9_72 PubMedSearch: Zhao 2018 Stem.Cell.Res.Ther 9 72 PubMedID: 29562935 Abstract BACKGROUND: Liver disease is a major cause of death and disability. Mesenchymal stem cells (MSCs) show promise for the treatment of liver disease. However, whether MSC-based therapy is more effective than conventional treatment is unclear, as are the optimal MSC source, the administration frequency, and the most effective MSC delivery route. We therefore undertook a systematic review and meta-analysis of the therapeutic efficacy of MSCs against liver disease and the related factors. METHODS: We systematically searched Medline (PubMed), Cochrane Library, EMBASE, ClinicalTrials.gov, and SinoMed CBM to identify studies published up to June 2017 involving liver disease patients receiving MSC-based therapy and which reported estimates of liver function during the follow-up period. RESULTS: Thirty-nine studies were selected from 672 publications. According to a meta-analysis of 23 controlled studies, compared with conventional treatment MSC therapy significantly improves liver function in patients with liver disease in terms of the model of end-stage liver disease score, albumin, alanine aminotransferase, and total bilirubin levels, and prothrombin time, up to 6 months after administration. However, it has no beneficial effects in terms of prothrombin activity, international normalized ratio, or cholinesterase level. Considerable heterogeneity was identified at most time points. Subgroup analyses showed that a single MSC injection was more effective than multiple injections, MSC administration was more effective via the hepatic artery than the peripheral vein, and MSCs derived from bone marrow were more effective than those derived from the umbilical cord. CONCLUSIONS: MSC-based therapy is relatively safe and improves liver function during the first 6 months after administration. A single injection administration via the hepatic artery and MSCs derived from bone marrow are optimal in terms of improving liver function. However the significant heterogeneity among studies and discontinuous results of the subgroup meta-analysis should be addressed; moreover the long-term efficacy of MSC therapy warrants further investigation. Title: Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial Campbell NL, Perkins AJ, Gao S, Skaar TC, Li L, Hendrie HC, Fowler N, Callahan CM, Boustani MA Ref: J Am Geriatr Soc, 65:1497, 2017 : PubMed ESTHER: Campbell_2017_J.Am.Geriatr.Soc_65_1497 PubMedSearch: Campbell 2017 J.Am.Geriatr.Soc 65 1497 PubMedID: 28295141 Abstract BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686). Title: Salvia miltiorrhiza Roots against Cardiovascular Disease: Consideration of Herb-Drug Interactions Chen F, Li L, Tian DD Ref: Biomed Res Int, 2017:9868694, 2017 : PubMed ESTHER: Chen_2017_Biomed.Res.Int_2017_9868694 PubMedSearch: Chen 2017 Biomed.Res.Int 2017 9868694 PubMedID: 28473993 Abstract Salvia miltiorrhiza root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. This review summarized the effects of these bioactive components from S. miltiorrhiza roots on pharmacokinetics of comedicated drugs with mechanic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on the published data stemming from both in vitro and in vivo human studies. In vitro studies indicated that cytochrome P450 (CYP450), carboxylesterase enzyme, catechol-O-methyltransferase, organic anion transporter 1 (OAT1) and OAT3, and P-glycoprotein were the major targets involved in S. miltiorrhiza-drug interactions. Lipophilic tanshinones had much more potent inhibitory effects towards CYPs activities compared to hydrophilic phenolic acids, evidenced by much lower Ki values of the former. Clinical S. miltiorrhiza-drug interaction studies were mainly conducted using CYP1A2 and CYP3A4 probe substrates. In addition, the effects of coexisting components on the pharmacokinetic behaviors of those noted bioactive compounds were also included herein. Title: MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice Cheng HP, Gong D, Zhao ZW, He PP, Yu XH, Ye Q, Huang C, Zhang X, Chen LY and Tang CK <10 more author(s)> Cheng HP, Gong D, Zhao ZW, He PP, Yu XH, Ye Q, Huang C, Zhang X, Chen LY, Xie W, Zhang M, Li L, Xia XD, Ouyang XP, Tan YL, Wang ZB, Tian GP, Zheng XL, Yin WD, Tang CK (- 10) Ref: Circ J, 82:28, 2017 : PubMed ESTHER: Cheng_2017_Circ.J_82_28 PubMedSearch: Cheng 2017 Circ.J 82 28 PubMedID: 28855441 Abstract BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. CONCLUSIONS: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice. Title: Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease Lan JS, Hou JW, Liu Y, Ding Y, Zhang Y, Li L, Zhang T Ref: J Enzyme Inhib Med Chem, 32:776, 2017 : PubMed ESTHER: Lan_2017_J.Enzyme.Inhib.Med.Chem_32_776 PubMedSearch: Lan 2017 J.Enzyme.Inhib.Med.Chem 32 776 PubMedID: 28585866 Abstract A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Abeta (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC50, 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 muM for eqBuChE and 4.4 muM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Abeta (1-42) aggregation (64.7% at 20 muM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases. Title: Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-alpha and IL-1beta in an Abeta25-35-induced Rat Model of Alzheimer's Disease Li L, Xu S, Liu L, Feng R, Gong Y, Zhao X, Li J, Cai J, Feng N and Peng Y <2 more author(s)> Li L, Xu S, Liu L, Feng R, Gong Y, Zhao X, Li J, Cai J, Feng N, Wang L, Wang X, Peng Y (- 2) Ref: J Alzheimers Dis, 56:1403, 2017 : PubMed ESTHER: Li_2017_J.Alzheimers.Dis_56_1403 PubMedSearch: Li 2017 J.Alzheimers.Dis 56 1403 PubMedID: 28157092 Abstract The dyshomeostasis of transition metal ions, accumulation of amyloid-beta (Abeta) senile plaques and neuroinflammatory response found in the brain of patients with Alzheimer's disease (AD) have been suggested to be involved in AD pathogenesis. Novel compounds capable of targeting metal-Abeta species and neuroinflammation would be valuable. AD-35 is such a patented small-molecule compound derived from innovative modification of the chemical structure of donepezil. This compound could moderately inhibit acetylcholinesterase and metal-induced Abeta aggregation in vitro and showed disassembly of Abeta aggregates. The effects of AD-35 on cognitive impairments and neuroinflammatory changes caused by intracerebroventricular injection of Abeta25-35 were studied in rats. Compared to sham group, Abeta25-35 injection significantly led to learning and memory deficits, astrocyte activation, and pro-inflammatory cytokines releases (TNF-alpha and IL-1beta). Further studies indicated that the phosphorylation of extracellular signal-regulated kinase was involved in astrocyte activation and pro-inflammatory cytokines production. Oral administration of AD-35 could markedly attenuate Abeta25-35 injection-induced astrocyte activation, pro-inflammatory cytokines TNF-alpha and IL-1beta release, and memory deficits. On the contrary, donepezil only showed inhibition of IL-1beta production, but failed to block astrocyte activation and TNF-alpha production. These results showed that AD-35 would be a novel multi-mechanism drug for the prevention and/or treatment of AD. Title: Retrograde Synaptic Inhibition Is Mediated by alpha-Neurexin Binding to the alpha2delta Subunits of N-Type Calcium Channels Tong XJ, Lopez-Soto EJ, Li L, Liu H, Nedelcu D, Lipscombe D, Hu Z, Kaplan JM Ref: Neuron, 95:326, 2017 : PubMed ESTHER: Tong_2017_Neuron_95_326 PubMedSearch: Tong 2017 Neuron 95 326 PubMedID: 28669545 Abstract The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/alpha2delta), decreasing UNC-36 abundance at pre-synaptic elements. Retrograde inhibition is mediated by a soluble form of NRX-1's ectodomain, which is released from the post-synaptic membrane by the SUP-17/ADAM10 protease. Mammalian Neurexin-1alpha binds alpha2delta-3 and decreases CaV2.2 current in transfected cells, whereas Neurexin-1alpha has no effect on CaV2.2 reconstituted with alpha2delta-1 and alpha2delta-2. Collectively, these results suggest that alpha-Neurexin binding to alpha2delta is a conserved mechanism for regulating synaptic transmission. Title: Hepatotoxicity induced by radix Sophorae tonkinensis in mice and increased serum cholinesterase as a potential supplemental biomarker for liver injury Wang L, Lu J, Sun W, Gu Y, Zhang C, Jin R, Li L, Zhang Z, Tian X Ref: Exp Toxicol Pathol, 69:193, 2017 : PubMed ESTHER: Wang_2017_Exp.Toxicol.Pathol_69_193 PubMedSearch: Wang 2017 Exp.Toxicol.Pathol 69 193 PubMedID: 28126209 Abstract Radix Sophorae tonkinensis (S. tonkinensis) is used in Chinese folk medicine to treat sore throats, viral hepatitis, and jaundice. However, little is known about the hepatotoxicity induced by it. This study is to investigate hepatotoxicity induced by radix S. tonkinensis and a potential supplemental biomarker for liver injury through acute toxicity, accumulative toxicity, tolerance test, and sub-chronic toxicity. The contents of cytisine (CYT), matrine (MT), and oxymatrine (OMT) in radix S. tonkinensis extracts were determined simultaneously by the method we developed. In the acute toxicity study, mice were scheduled for single oral gavage at doses of 0, 2.4, 3.2, 4.2, 5.6, 7.5g/kg of radix S. tonkinensis extracts respectively. Another three groups of mice received radix S. tonkinensis extracts orally in single doses of 0, 4.3, 5.6g/kg, while the two groups of the hepatic injury model were induced by intraperitoneal injection with 0.1% and 0.2% carbon tetrachloride (CCl4). Mortality rate, analysis of serum biochemistry, and histopathological examination were used to assess the acute toxicity. In the accumulative toxicity study, mice were treated radix S. tonkinensis extracts orally by the method of dose escalation for 20days respectively. Accumulative toxicity was assessed by mortality rate. In the tolerance test, half of the mice of test group in the accumulative toxicity were administered the dose of 4.3g/kg radix S. tonkinensis extracts, and the rest of the mice in the test group were assigned to receive the dose of 5.6g/kg radix S. tonkinensis extracts. In the sub-chronic toxicity study, mice were treated with daily doses of 0, 0.25, 1.0, 2.5g/kg radix S. tonkinensis extracts for 90days. Assessments of body weights, serum biochemical analysis, and histopathological examination were performed. An enzyme-inhibition assay for butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) of CYT, MT, and OMT was also carried out. The contents of CYT, MT, and OMT in radix S. tonkinensis extracts were 5.63mg/g, 27.63mg/g, and 16.20mg/g respectively. In the acute toxicity study, LD50 of radix S. tonkinensis extracts was 4.3g/kg. No mice were found dead in the accumulative toxicity study. In the acute toxicity and tolerance test, increased ALT, AST, and CHE levels were observed in a dose-response manner, while the severity of histological changes in liver was shown in a dose-dependent mode. In the sub-chronic toxicity, though there was a decline trend of ALT and AST levels found in 0.25g/kg, 1.0g/kg, and 2.5g/kg radix S. tonkinensis extracts as compared to control, which might be related to weight loss, the severity of histopathological changes in the liver and the increased serum CHE level was shown in a dose-response manner. MT, OMT, and CYT showed inhibitory effects on BuChE and AChE in the enzyme-inhibition assay. The results of this study indicate that radix S. tonkinensis should have hepatotoxicity, and increased serum CHE is a potential supplemental biomarker for liver injury. Title: [Metabolomics study of tris(2-chloroethyl) phosphate induced hepaotoxicity and nephrotoxicity in Sprague-Dawley rats] Yang WQ, Zhao F, Li L, Fang YJ Ref: Zhonghua Yu Fang Yi Xue Za Zhi, 51:1041, 2017 : PubMed ESTHER: Yang_2017_Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi_51_1041 PubMedSearch: Yang 2017 Zhonghua.Yu.Fang.Yi.Xue.Za.Zhi 51 1041 PubMedID: 29136753 Abstract Objective: To discuss the potential toxic target organ and the toxic effects and mechanisms of tris (2-chloroethyl) phosphate (TCEP) on SD rats. Methods: 40 female SD rats weaning from milk for 21 days, weighted (50+/-2.3)g were selected as subjects and marked by the weight. They were randomly divided into 4 groups, namely control group, 50 (L), 100 (M) and 250 (H) mg.kg(-1).d(-1) dose of TCEP group. Each group has 10 rats, and administrated the corresponding dose of drug or vehicle by mouth, quaque die for 60 days. All rats were sacrificed after the last administration. The livers and kidneys were dyed by HE for pathological observation; and the blood samples were collected to analyze the biochemical index. H(1)-Nuclear Magnetic Resonance ((1)H-NMR)-based metabolomics methods coupling with histopathogy examination were used to investigate the toxic effects of TCEP. Results: Inflammatory cell infiltration and hepatic necrosis were observed in the liver of TCEP-treated rats. Inflammatory cells invaded and calcification/ossification foci were also found in renal of TCEP-treated rats and tumor hyperplasia were existed in renal tubule in H group. The level of HDL-C in the L, M and H group were separately (1.7+/-0.09) , (1.5+/-0.07) and (1.3+/-0.1) micromol/L, which were all significantly lower than that of control group ( (1.9+/-0.2) micromol/L) (P<0.05) . The activity of cholinesterase (CHE) in the L, M and H group were separately (918+/-14.8) , (828+/-28.6) and (674+/-36.5) U/L, which were all significantly lower than that of control group ((1056+/-28.8) micromol/L) (P<0.05). Moreover, The level of creatinine (CRE) in the L, M and H group were separately (29.8+/-4.6) , (28.9+/-5.3) and (25.8+/-6.2) micromol/L, which were all significantly lower than that of control group ((30.2+/-3.9) micromol/L) (P<0.05). In the H group, the enzyme activities of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP) and the contents of total bilirubin (TBIL), glucose (GLU) and uric acid (UA) were all significantly higher than the results in control group. The results of (1)H-NMR metabolomics showed that the contents of lactate, glycine, high-density lipoprotein, low-density lipoprotein and phosphatidylcholine in blood of rats would decrease by TCEP exposure, while N-acetylglycoprotein, acetate, alanine, glucose, lipids, lipoproteins and fatty acids would increase. Conclusion: TCEP caused disorders in endogenous energy metabolism, leading to the pathological changes of inflammatory cells infiltration and necrosis in liver and kidney, caused enzyme activity changes of ALT, ALP and the content changes of other liver and kidney injury-related markers. Title: Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib Yeo A, Li L, Warren L, Aponte J, Fraser D, King K, Johansson K, Barnes A, Macphee C and Waterworth D <6 more author(s)> Yeo A, Li L, Warren L, Aponte J, Fraser D, King K, Johansson K, Barnes A, Macphee C, Davies R, Chissoe S, Tarka E, O'Donoghue ML, White HD, Wallentin L, Waterworth D (- 6) Ref: PLoS ONE, 12:e0182115, 2017 : PubMed ESTHER: Yeo_2017_PLoS.One_12_e0182115 PubMedSearch: Yeo 2017 PLoS.One 12 e0182115 PubMedID: 28753643 Gene_locus related to this paper: human-PLA2G7 Inhibitor(s) related to this paper: Darapladib Abstract Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY) and one in acute coronary syndrome (SOLID-TIMI 52). No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%). We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants) using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction) as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1) and identified three novel loci (TOMM5, FRMD5 and LPL) using the GWAS-significance threshold P<=5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2) within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores) and one common locus (minor allele frequency 0.24) with genotype by treatment interaction effect passing the GWAS-significance threshold. This locus conferred risk in placebo subjects, hazard ratio (HR) 1.22 with 95% confidence interval (CI) 1.11-1.33, but was protective in darapladib subjects, HR 0.79 (95% CI 0.71-0.88). No major loci for tolerability were found. Thus, genetic analysis confirmed and extended the influence of lipoprotein loci on Lp-PLA2 levels, identified some novel null alleles in the PLA2G7 gene, and only identified one potentially efficacious subgroup within these two large clinical trials. Title: Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice Zhang SJ, Xu TT, Li L, Xu YM, Qu ZL, Wang XC, Huang SQ, Luo Y, Luo NC and Wang Q <3 more author(s)> Zhang SJ, Xu TT, Li L, Xu YM, Qu ZL, Wang XC, Huang SQ, Luo Y, Luo NC, Lu P, Shi YF, Yang X, Wang Q (- 3) Ref: Oncotarget, 8:49338, 2017 : PubMed ESTHER: Zhang_2017_Oncotarget_8_49338 PubMedSearch: Zhang 2017 Oncotarget 8 49338 PubMedID: 28521305 Abstract The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time. BSYZ decreases the activity of acetylcholinesterase (AChE), and increases the activity of choline acetyltransferase (ChAT) and the concentration of acetylcholine (Ach) in both hippocampus and cortex. In addition, western blot results (Bcl-2, Bax and Caspase-3) and TUNEL staining show that BSYZ prevents neuron from apoptosis, and elevates the expression of neurotrophic factors, including nerve growth factor (NGF), postsynapticdensity 95 (PSD95) and synaptophysin (SYN), in both hippocampus and cortex. BSYZ also increases the protein expression of SIRT1 and alleviates ER stress-associated proteins (PERK, IRE-1alpha, eIF-2alpha, BIP, PDI and CHOP). These results indicate that the neuroprotective mechanism of BSYZ might be related with SIRT1/ER stress pathway. Title: Adipose triglyceride lipase (Atgl) mediates the antibiotic jinggangmycin-stimulated reproduction in the brown planthopper, Nilaparvata lugens Stal Jiang YP, Li L, Liu ZY, You LL, Wu Y, Xu B, Ge LQ, Song QS, Wu JC Ref: Sci Rep, 6:18984, 2016 : PubMed ESTHER: Jiang_2016_Sci.Rep_6_18984 PubMedSearch: Jiang 2016 Sci.Rep 6 18984 PubMedID: 26739506 Abstract The antibiotic jinggangmycin (JGM) is an agrochemical product widely used in China for controlling rice sheath blight, Rhizoctonia solani. Unexpectedly, it stimulates reproduction in the brown planthopper (BPH), Nilaparvata lugens (Stal). However, the underlying molecular mechanisms of the stimulation are unclear. The present investigation demonstrates that adipose triglyceride lipase (Atgl) is one of the enzymes involved in the JGM-stimulated reproduction in BPH. Silence of Atgl in JGM-treated (JGM + dsAtgl) females eliminated JGM-stimulated fecundity of BPH females. In addition, Atgl knockdown significantly reduced the protein and glycerin contents in the ovaries and fat bodies of JGM + dsAtgl females required for reproduction. We conclude that Atgl is one of the key enzymes responsible for JGM-stimulated reproduction in BPH. Title: Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction Kong Q, Min X, Sun R, Gao J, Liang R, Li L, Chu X Ref: Oncol Lett, 12:1783, 2016 : PubMed ESTHER: Kong_2016_Oncol.Lett_12_1783 PubMedSearch: Kong 2016 Oncol.Lett 12 1783 PubMedID: 27588125 Abstract The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment. Title: Ces3/TGH Deficiency Attenuates Steatohepatitis Lian J, Wei E, Groenendyk J, Das SK, Hermansson M, Li L, Watts R, Thiesen A, Oudit GY and Lehner R <1 more author(s)> Lian J, Wei E, Groenendyk J, Das SK, Hermansson M, Li L, Watts R, Thiesen A, Oudit GY, Michalak M, Lehner R (- 1) Ref: Sci Rep, 6:25747, 2016 : PubMed ESTHER: Lian_2016_Sci.Rep_6_25747 PubMedSearch: Lian 2016 Sci.Rep 6 25747 PubMedID: 27181051 Gene_locus related to this paper: mouse-Ces1d Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in developed countries. NAFLD describes a wide range of liver pathologies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is distinguished from simple steatosis by inflammation, cell death and fibrosis. In this study we found that mice lacking triacylglycerol hydrolase (TGH, also known as carboxylesterase 3 or carboxylesterase 1d) are protected from high-fat diet (HFD) - induced hepatic steatosis via decreased lipogenesis, increased fatty acid oxidation and improved hepatic insulin sensitivity. To examine the effect of the loss of TGH function on the more severe NAFLD form NASH, we ablated Tgh expression in two independent NASH mouse models, Pemt(-/-) mice fed HFD and Ldlr(-/-) mice fed high-fat, high-cholesterol Western-type diet (WTD). TGH deficiency reduced liver inflammation, oxidative stress and fibrosis in Pemt(-/-) mice. TGH deficiency also decreased NASH in Ldlr(-/-) mice. Collectively, these findings indicate that TGH deficiency attenuated both simple hepatic steatosis and irreversible NASH. Title: Preparation of Diacylglycerol-enriched Rice Bran Oil by Lipase-catalyzed Deacidification in Packed-bed Reactors by Continuous Dehydration Lu Y, Zou X, Han W, Jiang Y, Jin Q, Li L, Xu X, Wang X Ref: J Oleo Sci, 65:151, 2016 : PubMed ESTHER: Lu_2016_J.Oleo.Sci_65_151 PubMedSearch: Lu 2016 J.Oleo.Sci 65 151 PubMedID: 26833284 Abstract Diacylglycerol-enriched rice bran oil (RBO-DAG) was produced by deacidification of high-acid rice bran oil (RBO) with glycerol (Gly) using Lipozyme RM IM by continuous dehydration by combination of two enzyme columns (column 1 and 3, used for deacidification) with one molecular sieves column (column 2, used for dehydration). The conditions for three columns were respectively optimized. Response surface methodology (RSM) was used to optimize the conditions of column 1. The content of DAG and conversion of free fatty acid (FFA) were used as indicators and the effects of the enzyme load (8-12 g), flow rate (0.3-0.6 mL/min), substrate molar ratio (4-6) and reaction temperature (55-75 degC) were investigated. The content of DAG and conversion of FFA were significantly correlated to the flow rate and substrate molar ratio. Most desirable conditions of the reaction with respect to the maximal DAG content and FFA conversion was attained under the residence time of 40 min, substrate molar ratio of 5.52 (Gly: RBO) and temperature of 66 degC. The conditions for column 2 were investigated by varying molecular sieves load and flow rate, and the maximal dehydration rate of 85.22% was obtained under the optimal conditions. For column 3, the optimum conditions were obtained as: flow rate, 0.2mL/min; temperature, 65 degC, and the content of DAG and FFA were 38.99% and 3.04%, respectively under these conditions. The catalytic activity of the lipase was stable in twelve continuous operations with 83.22% of its original ability, demonstrating its potential in the continuous packed-bed reactors (PBRs) system. These results showed that packed-bed reactors combined with continuous deacidification and dehydration in one system had great value in industrial production for high-acid RBO with the improved conversion rate. Title: A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y and Chen Z <10 more author(s)> Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y, Bian Z, Hacker A, Yeo A, Parish S, Hill MR, Chissoe S, Peto R, Cardon L, Collins R, Li L, Chen Z (- 10) Ref: Int J Epidemiol, 45:1588, 2016 : PubMed ESTHER: Millwood_2016_Int.J.Epidemiol_45_1588 PubMedSearch: Millwood 2016 Int.J.Epidemiol 45 1588 PubMedID: 27301456 Gene_locus related to this paper: human-PLA2G7 Abstract BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning. Title: Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo Wu Q, Yan W, Liu C, Li L, Yu L, Zhao S, Li G Ref: Environ Pollut, 213:793, 2016 : PubMed ESTHER: Wu_2016_Environ.Pollut_213_793 PubMedSearch: Wu 2016 Environ.Pollut 213 793 PubMedID: 27038211 Abstract Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnalpha7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. a1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons. Title: Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System Xu QQ, Xu YJ, Yang C, Tang Y, Li L, Cai HB, Hou BN, Chen HF, Wang Q and Zhang SJ <1 more author(s)> Xu QQ, Xu YJ, Yang C, Tang Y, Li L, Cai HB, Hou BN, Chen HF, Wang Q, Shi XG, Zhang SJ (- 1) Ref: Biomed Res Int, 2016:9852536, 2016 : PubMed ESTHER: Xu_2016_Biomed.Res.Int_2016_9852536 PubMedSearch: Xu 2016 Biomed.Res.Int 2016 9852536 PubMedID: 27556046 Inhibitor(s) related to this paper: Tanshinone-IIA Abstract Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction. 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: Characterization of hepatic enzyme activity in older adults with dementia: potential impact on personalizing pharmacotherapy Campbell NL, Skaar TC, Perkins AJ, Gao S, Li L, Khan BA, Boustani MA Ref: Clin Interv Aging, 10:269, 2015 : PubMed ESTHER: Campbell_2015_Clin.Interv.Aging_10_269 PubMedSearch: Campbell 2015 Clin.Interv.Aging 10 269 PubMedID: 25609939 Abstract OBJECTIVE: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs). MATERIALS AND Title: Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis He T, Hu J, Yan G, Li L, Zhang D, Zhang Q, Chen B, Huang Y Ref: Clinical Science (Lond), 129:49, 2015 : PubMed ESTHER: He_2015_Clin.Sci.(Lond)_129_49 PubMedSearch: He 2015 Clin.Sci.(Lond) 129 49 PubMedID: 25700221 Abstract The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis. Title: In vitro acaricidal activity of 1,8-cineole against Sarcoptes scabiei var. cuniculi and regulating effects on enzyme activity Hu Z, Chen Z, Yin Z, Jia R, Song X, Li L, Zou Y, Liang X, He C and Shi F <5 more author(s)> Hu Z, Chen Z, Yin Z, Jia R, Song X, Li L, Zou Y, Liang X, He C, Yin L, Lv C, Zhao L, Su G, Ye G, Shi F (- 5) Ref: Parasitol Res, 114:2959, 2015 : PubMed ESTHER: Hu_2015_Parasitol.Res_114_2959 PubMedSearch: Hu 2015 Parasitol.Res 114 2959 PubMedID: 25924796 Abstract 1,8-Cineole found in many essential oils is a monoterpene and acts as a repellent against Sarcoptes scabiei var. cuniculi. In the present study, the acaricidal activity of 1,8-cineole against S. scabiei var. cuniculi was evaluated and the acaricidal mechanism was also investigated by assaying enzyme activities. The results showed that the lethal concentration of 50 % (LC50) value (95 % confidence limit (CL)) and the lethal time of 50 % (LT50) value (95 % CL) of 1,8-cineole were 2.77 mg/mL and 3.606 h, respectively. The pathological changes under transmission electron microscopy showed that the morphology of the mitochondria was abnormal, the cell nuclear membrane was damaged, and the nuclear chromatin was dissoluted. The activities of superoxide dismutase (SOD), glutathione-s-transferases (GSTs), monoamine oxidase (MAO), nitric oxide synthase (NOS), and acetylcholinesterase (AChE) were significantly changed after treatment with 1,8-cineole for 4, 8, 12, and 24 h. SOD and GSTs are associated with the protection mechanism of scabies mites. And, the activities of SOD and GSTs were increased as compared with the control group. MAO, AChE, and NOS are associated with the nervous system of scabies mites. The activity of MAO was increased whereas the AChE was suppressed. The activity of NOS was suppressed in the high-dose group whereas increased in the middle-dose group and low-dose group. These results indicated that the mechanism of 1,8-cineole mainly attributed to the changes of these enzyme activities related to the nervous system of scabies mites. Title: The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-Induced Astrocyte-Related Inflammation Kong H, Yin F, He F, Omran A, Li L, Wu T, Wang Y, Peng J Ref: Journal of Molecular Neuroscience, 57:28, 2015 : PubMed ESTHER: Kong_2015_J.Mol.Neurosci_57_28 PubMedSearch: Kong 2015 J.Mol.Neurosci 57 28 PubMedID: 25957996 Abstract Astrocyte activation, associated with the release of pro-inflammatory cytokines interleukin 1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), is a hallmark of multiple brain diseases, including mesial temporal lobe epilepsy. In recent years, several microRNAs have emerged as important controllers of Toll-like receptor (TLR) signaling. In this study, we investigated the effect of miR-132, miR-146a, and miR-155 on myeloid-related protein-8 (MRP8) induced astrocyte-related inflammation. Using quantitative polymerase chain reaction (qPCR) and western blot, we found clear upregulation of TLR4 and downstream inflammatory cytokines, along with dysregulation of miR-132, miR-146a, and miR-155 in in vitro astrocytes after exposing them to different concentrations of MRP8. In addition, we focused on the effect of miR-132 on astrocyte-related inflammation induced by MRP8 via lentiviral infection then evaluated the expression of its possible target genes: acetylcholinesterase (AChE) and interleukin-1 receptor-associated kinase (IRAK4). Our results show that miR-132 is a negative feedback regulator of IL-1beta and IL-6, but not TNF-alpha, by targeting IRAK4. Together, our findings demonstrate the novel role of TLR4-related microRNAs, especially miR-132, in the regulation of MRP8-induced astrocyte activation and highlight the importance of miR-132 in the modulation of innate immune response induced by endogenous ligands in neurological diseases. Title: Esterification degree of fructose laurate exerted by Candida antarctica lipase B in organic solvents Li L, Ji F, Wang J, Li Y, Bao Y Ref: Enzyme Microb Technol, 69:46, 2015 : PubMed ESTHER: Li_2015_Enzyme.Microb.Technol_69_46 PubMedSearch: Li 2015 Enzyme.Microb.Technol 69 46 PubMedID: 25640724 Abstract Sugar esters of fatty acids have many applications as biocompatible and biodegradable emulsifiers, which are determined by their degrees of esterification (DE). Direct esterification of fructose with lauric acid in organic media used commercial immobilized Candida antarctica lipase B (CALB) was investigated for DE. Significant difference of DE was observed between 2-methyl-2-butanol (2M2B) and methyl ethyl ketone (MEK), as di-ester/mono-ester molar ratio of 1.05:1 in 2M2B and 2.79:1 in MEK. Fourier transform infrared (FTIR) spectra showed that the secondary structure of the enzyme binding mono-ester presented distinct difference in 2M2B and MEK. Contents of beta-turn and antiparallel beta-sheet of CALB in 2M2B were 26.9% and 16.2%, respectively, but 19.1% and 13.2% in MEK. To understand the relationship between the conformational changes and differences of DE, mono-ester and fatty acid were directly employed for synthesis of di-ester. The maximum initial velocity of di-ester synthesis in MEK was 0.59mmolg(enzyme)(-1)h(-1), which was 2.19-fold as greater as that in 2M2B, indicating that CALB conformation in MEK was preferred for the synthesis of di-ester. These results demonstrated that the conformation of CALB binding mono-ester affected by organic solvents essentially determined DE. Title: Bioaccumulation, subcellular distribution, and acute effects of chromium in Japanese medaka (Oryzias latipes) Li L, Chen H, Bi R, Xie L Ref: Environ Toxicol Chem, 34:2611, 2015 : PubMed ESTHER: Li_2015_Environ.Toxicol.Chem_34_2611 PubMedSearch: Li 2015 Environ.Toxicol.Chem 34 2611 PubMedID: 26096885 Abstract Chromium (Cr) is an essential element but is toxic to aquatic organisms at elevated concentrations. In the present study, adult Japanese medaka (Oryzias latipes) were exposed to a sublethal hexavalent chromium (Cr(VI)) concentration via dissolved and dietary exposures for 6 d. Various measurements of Cr were made: bioaccumulation in different tissues, subcellular distribution in the liver, effects on antioxidants and acetylcholinesterase (AChE), and Cr-induced lipid peroxidation. The results showed that bioaccumulation increased dramatically in all tested tissues from dissolved exposure but only significantly in the intestine from dietary treatment, implying that dissolved exposure may be predominant for Cr accumulation in medaka. Subcellular distribution revealed that Cr accumulated in the liver was mainly (46%) associated with the heat-stable protein fraction. Among the antioxidants examined, catalase (CAT) responded to dissolved Cr exposure in most tissues whereas superoxide dismutase (SOD) was less responsive. Malondialdehyde concentrations were significantly elevated in most tissues examined in the dissolved Cr-exposed fish, but were only elevated in the liver and intestine in the dietary Cr-exposed fish. The AChE activity in the brain was stimulated by 49% in the dissolved Cr-exposed fish. Reductions in condition factor and gonadosomatic index were also observed. These data help in an understanding of Cr tissue distribution and the acute effects of Cr in Japanese medaka. Environ Toxicol Chem 2015;34:2611-2617. (c) 2015 SETAC. Title: The chronic effects of lignin-derived bisphenol and bisphenol A in Japanese medaka Oryzias latipes Li D, Chen Q, Cao J, Chen H, Li L, Cedergreen N, Xie H, Xie L Ref: Aquat Toxicol, 170:199, 2015 : PubMed ESTHER: Li_2015_Aquat.Toxicol_170_199 PubMedSearch: Li 2015 Aquat.Toxicol 170 199 PubMedID: 26674368 Abstract One of the ultimate goals of green chemistry is to produce greener and more environmentally friendly chemicals to replace the existing toxic chemicals. In this study, Japanese medaka were exposed to 1.5mg/L of bisphenol A or lignin-derived bisphenol for 60 days, and the expressions of various biochemical markers, effects on reproduction, and histopathology were evaluated. The results showed that concentrations of liver vitellogenin of LD-BP exposed males were approximately 125% higher compared to the control males. Total number of eggs from the BPA and LD-BP exposed fish was approximately 47% (p<0.001) and 25% (p<0.05) less than the control fish, respectively. Total number of brood was lower from the BPA (46%, p<0.05) and LD-BP (17%, p<0.05) exposed fish than that of the control fish. Relative to the control fish, catalase and glutathione-S-transferase were significantly affected by the two chemicals in all tested tissues. BPA and LD-BP caused lipid peroxidation in all the tested tissues. Furthermore, acetylcholinesterase and alpha-glucosidase activity were significantly inhibited. Histopathological analysis showed that both the testis and ovary were mildly damaged by both chemicals. LD-BP affected medaka slightly more severe than BPA except on the reproduction, which was most likely due to different uptake, translocation, binding to targets and metabolism. Our results demonstrated that chronic exposure to both chemicals caused several adverse effects to medaka. Further research on the toxicity of LD-BP to other aquatic organisms is needed before substitution of traditional BPA with LD-BP can be recommended. Title: Efficient mono-acylation of fructose by lipase-catalyzed esterification in ionic liquid co-solvents Li L, Ji F, Wang J, Jiang B, Li Y, Bao Y Ref: Carbohydr Res, 416:51, 2015 : PubMed ESTHER: Li_2015_Carbohydr.Res_416_51 PubMedSearch: Li 2015 Carbohydr.Res 416 51 PubMedID: 26343327 Abstract Fructose monoesters are eco-friendly nonionic surfactants in various applications. Selective preparation of mono-acylated fructose is challenging due to the multiple hydroxyl sites available for acylation both chemically and enzymatically. Ionic liquids (ILs) have profound impacts not only on the reaction media but also on the catalytic properties of enzymes in the acylation process. In this study, utilizing an IL co-solvent system, selective synthesis of mono-acylated fructose with lauric acid catalyzed by immobilized Candida antarctica lipase B (CALB) was investigated. The imidazolium-based ILs selected as co-solvents with 2-methyl-2-butanol (2M2B) markedly improved the ratios of monolauroyl fructose in the presence of 60% [BMIM][TfO] (v/v) and 20% [BMIM][BF4] (v/v), in which the mono-acylated fructose was 85% and 78% respectively. Based on a Ping-Pong Bi-Bi model, a kinetic equation was fitted, by which the kinetic parameters revealed that the affinity between fructose and acyl-enzyme intermediate was enhanced. The inhibition effect of fructose on free enzyme was weakened in the presence of IL co-solvents. The conformation of CALB binding substrates also changed in the co-solvent system as demonstrated by Fourier transform infrared spectra. These results demonstrated that the variation of CALB kinetic characteristics was a crucial factor for the selectivity of mono-acylation in ILs/2M2B co-solvents. Title: Purification and Characterization of a Lipase with High Thermostability and Polar Organic Solvent-Tolerance from Aspergillus niger AN0512 Liu G, Hu S, Li L, Hou Y Ref: Lipids, 50:1155, 2015 : PubMed ESTHER: Liu_2015_Lipids_50_1155 PubMedSearch: Liu 2015 Lipids 50 1155 PubMedID: 26216145 Abstract An extracellular lipase (EC 3.1.1.3, AN0512Lip) from Aspergillus niger AN0512 was purified and its characteristics were investigated. After the process of ammonium sulfate precipitation followed by ion-exchange chromatography and gel filtration, the purified lipase was achieved with 203.6-fold purification and 22.1 % recovery. AN0512Lip exhibited the highest activity at 50 degrees C and pH 5.0. It was thermostable and pH-stable, as indicated by that more than 50 % activity retained at 60 degrees C for 20 h and more than 90 % activity retained at pH 3.0 for 20 h, respectively. AN0512Lip activity was stimulated by some divalent metal ions (especially Cu(2+), Ca(2+)), while greatly suppressed by EDTA, indicating that AN0512Lip was a metal-activated enzyme. Moreover, AN0512Lip exhibited high tolerance for various polar organic solvents with log P < 0.8, and the highest lipase activity (476 % of its original activity) was achieved after addition of 90 % (V/V) isopropanol to the reaction mixture. AN0512Lip also displayed 3-regiospecificity and great affinity for the long-chain fatty ester. The preliminary test showed that AN0512Lip was a candidate for enriching EPA and DHA in fish oil. All the unique properties, such as thermostability, Cu(2+)-dependent, 3-regiospecificity, and polar organic solvent-tolerance, indicated that AN0512Lip could have potential applications in the food industry, even in organic synthesis and the pharmaceutical industry. Title: Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P and Ye J <6 more author(s)> Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P, Zhang X, Gu Y, Xu Y, Wang Z, Li Z, Zhang H, Ye J (- 6) Ref: Hepatology, 61:870, 2015 : PubMed ESTHER: Wang_2015_Hepatology_61_870 PubMedSearch: Wang 2015 Hepatology 61 870 PubMedID: 25179419 Abstract Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. Title: The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y and He Y <14 more author(s)> Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y, Chen M, Xu Y, Jin H, Xiao X, Hu G, Bao F, Hu Y, Wan P, Li L, Deng X, Kuang T, Xiang C, Zhu JK, Oliver MJ, He Y (- 14) Ref: Proc Natl Acad Sci U S A, 112:5833, 2015 : PubMed ESTHER: Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833 PubMedSearch: Xiao 2015 Proc.Natl.Acad.Sci.U.S.A 112 5833 PubMedID: 25902549 Gene_locus related to this paper: 9lami-a0a2z7c6k4, 9lami-a0a2z7bgj4 Abstract "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes. 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: Molecular cloning and characterization of a thermostable lipase from deep-sea thermophile Geobacillus sp. EPT9 Zhu Y, Li H, Ni H, Xiao A, Li L, Cai H Ref: World J Microbiol Biotechnol, 31:295, 2015 : PubMed ESTHER: Zhu_2015_World.J.Microbiol.Biotechnol_31_295 PubMedSearch: Zhu 2015 World.J.Microbiol.Biotechnol 31 295 PubMedID: 25388475 Abstract A gene (1,254 bp) encoding a lipase was identified from a deep-sea hydrothermal field thermophile Geobacillus sp. EPT9. The open reading frame of this gene encoded 417 amino acid residues. The gene was cloned, overexpressed in Escherichia coli, and the target protein was purified to homogeneity. The purified recombinant enzyme presented a molecular mass of 44.8 kDa. When p-nitrophenyl palmitate was used as a substrate, the recombinant lipase was optimally active at 55 degrees C and pH 8.5. The recombinant enzyme retained 44 % residual activity after incubation at 80 degrees C for 1 h, which indicated that Geobacillus sp. EPT9 lipase was thermostable. Homology modeling of strain EPT9 lipase was developed with the lipase from Bacillus sp. L2 as a template. The core structure exhibits an alpha/beta-hydrolase fold and the typical catalytic triad might consist of Ser142, Asp346, and His387. The enzymatic activity of EPT9 lipase was inhibited by addition of phenylmethylsulfonyl fluoride, indicating that it contains serine residue, which plays an important role in the catalytic mechanism. Title: Effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver Gao F, Liu Y, Li L, Li M, Zhang C, Ao C, Hou X Ref: Anim Reprod Sci, 147:99, 2014 : PubMed ESTHER: Gao_2014_Anim.Reprod.Sci_147_99 PubMedSearch: Gao 2014 Anim.Reprod.Sci 147 99 PubMedID: 24852270 Abstract This study investigated the effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver. Eighteen ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.175MJMEkgBW(-0.75)d(-1), n=6), Restricted Group 2 (RG2, 0.33MJMEkgBW(-0.75)d(-1), n=6) and a Control Group (CG, ad libitum, 0.67MJMEkgBW(-0.75)d(-1), n=6). Fetuses were recovered at slaughter on d 140. Fetuses in the RG1 group exhibited decreased (P<0.05) liver weight, total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD), cholinesterase (CHE), total protein (TP), globulin (GLB), and alanine transaminase (ALT). In addition, intermediate changes were found in the RG2 fetuses, including decreased liver weight, T-AOC and CHE (P<0.05). In contrast, increases in fetal hepatic collagen fibers and reticular fibers, glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOs), monoamine oxidase (MAO), albumin (ALB)/GLB, aspartate transaminase (AST), and AST/ALT were found in the RG1 fetuses (P<0.05). The RG2 fetuses had increased fetal hepatic collagen fibers, NOs and MAO (P<0.05) relative to the control fetuses. These results indicate that impaired fetal hepatic growth, fibrosis, antioxidant imbalance and dysfunction were associated with maternal undernutrition. Title: Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture Han Z, Li L, Wang L, Degos V, Maze M, Su H Ref: Journal of Neurochemistry, 131:498, 2014 : PubMed ESTHER: Han_2014_J.Neurochem_131_498 PubMedSearch: Han 2014 J.Neurochem 131 498 PubMedID: 25040630 Abstract Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of alpha-7 nicotinic acetylcholine receptor (alpha-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA 568487 (PHA, alpha-7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (alpha-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Behavior was tested 3 days after pMCAO. Neuronal injury, CD68(+) , M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of nuclear factor kappa b in microglia/macrophages, oxidative and anti-oxidant gene expression were quantified. Compared to saline-treated mice, PHA-treated mice performed better in behavioral tests, had fewer apoptotic neurons (NeuN(+) TUNEL(+) ), fewer CD68(+) and M1 macrophages, and more M2 macrophages. PHA increased anti-oxidant gene expression and decreased oxidative stress and phosphorylation of nuclear factor kappa b p65. Methyllycaconitine had the opposite effects. Our data indicate that alpha-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture. Bone fracture at the acute stage of stroke exacerbates neuroinflammation, oxidative stress, and brain injury, and our study has shown that the alpha-7 nAchR agonist, PHA (PHA 568487), attenuates neuroinflammation, oxidative stress, and brain injury in mice with stroke and bone fracture. Hence, PHA could provide an opportunity to develop a new strategy to reduce brain injury in patients suffering from stroke and bone fracture. Title: Lid closure mechanism of Yarrowia lipolytica lipase in methanol investigated by molecular dynamics simulation Jiang Y, Li L, Zhang H, Feng W, Tan T Ref: J Chem Inf Model, 54:2033, 2014 : PubMed ESTHER: Jiang_2014_J.Chem.Inf.Model_54_2033 PubMedSearch: Jiang 2014 J.Chem.Inf.Model 54 2033 PubMedID: 24954406 Abstract In nonaqueous organic solvents, lipases can catalyze esterification reactions, which increase their application value. Yarrowia lipolytica Lipase (Lip2) possesses potential values in medicine and industrial production. In order to investigate its lid closure mechanism in methanol we performed molecular dynamics (MD) simulations of the open conformation of Lip2 in methanol and hexane, respectively. Simulation results indicated that Lip2 undergoes a greater conformational change in methanol. Principle component analysis showed Lip2 has "double-domain" and "torsion" motion modes in hexane and methanol. By analyzing B-factor and dynamical cross-correlation, region Ser274-Asn288, region Thr106-His126, and region Asp61-Asp67 were found to interact with the lid region (Thr88-Leu105). Furthermore, local restricted MD simulations showed that closure mechanism of Lip2 is "double-lid movement" which is also observed in Pseudomonas aeruginosa Lipase (PAL), and we detected two interaction propagation pathways in Lip2 driven by the interaction between Ser274-Asn288 and methanol. Title: Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates Kong XD, Yuan S, Li L, Chen S, Xu JH, Zhou J Ref: Proc Natl Acad Sci U S A, 111:15717, 2014 : PubMed ESTHER: Kong_2014_Proc.Natl.Acad.Sci.U.S.A_111_15717 PubMedSearch: Kong 2014 Proc.Natl.Acad.Sci.U.S.A 111 15717 PubMedID: 25331869 Gene_locus related to this paper: bacme-g9bex6 Inhibitor(s) related to this paper: 2-Phenoxyacetamide, (R)-3-[1]naphthyloxy-propane-1,2-diol Abstract Optically pure epoxides are essential chiral precursors for the production of (S)-propranolol, (S)-alprenolol, and other beta-adrenergic receptor blocking drugs. Although the enzymatic production of these bulky epoxides has proven difficult, here we report a method to effectively improve the activity of BmEH, an epoxide hydrolase from Bacillus megaterium ECU1001 toward alpha-naphthyl glycidyl ether, the precursor of (S)-propranolol, by eliminating the steric hindrance near the potential product-release site. Using X-ray crystallography, mass spectrum, and molecular dynamics calculations, we have identified an active tunnel for substrate access and product release of this enzyme. The crystal structures revealed that there is an independent product-release site in BmEH that was not included in other reported epoxide hydrolase structures. By alanine scanning, two mutants, F128A and M145A, targeted to expand the potential product-release site displayed 42 and 25 times higher activities toward alpha-naphthyl glycidyl ether than the wild-type enzyme, respectively. These results show great promise for structure-based rational design in improving the catalytic efficiency of industrial enzymes for bulky substrates. Title: Theoretical and Experimental Studies on Activity of Yarrowia lipolytica Lipase in Methanol/Water Mixtures Li L, Jiang Y, Zhang H, Feng W, Chen B, Tan T Ref: J Phys Chem B, 118:1976, 2014 : PubMed ESTHER: Li_2014_J.Phys.Chem.B_118_1976 PubMedSearch: Li 2014 J.Phys.Chem.B 118 1976 PubMedID: 24520949 Abstract Methanol is regularly used as a substrate for biodiesel synthesis. Excess methanol can however inhibit the lipase activity. In the present work, the activity and conformational changes of Yarrowia lipolytica lipase (LIP2) at different concentrations of methanol were investigated by measuring fluorescence, UV-vis spectra, and molecular dynamics simulations. The lipase tended to expand at higher concentrations of methanol, and the methanol molecules were able to enter into the LIP2, leading to microenvironment changes around the aromatic amino acids. More hydrophobic groups were exposed to the solvents at high methanol concentrations, and the original hydrophobic interaction in the protein was destroyed, thus resulting in the tertiary structure change of the lipase. Title: Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis Li L, Li N, Pang W, Zhang X, Hammock BD, Ai D, Zhu Y Ref: PLoS ONE, 9:e94092, 2014 : PubMed ESTHER: Li_2014_PLoS.One_9_e94092 PubMedSearch: Li 2014 PLoS.One 9 e94092 PubMedID: 24718617 Abstract Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; manipulation of their levels is a potentially useful pharmacological strategy. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to form the corresponding diols, thus altering and reducing the activity of these oxylipins. To better understand the phenotypic impact of sEH disruption, we compared the effect of EPHX2 gene knockout (EPHX2-/-) and sEH inhibition in mouse models. Measurement of plasma oxylipin profiles confirmed that the ratio of EETs/DHETs was increased in EPHX2-/- and sEH-inhibited mice. However, plasma concentrations of 9, 11, 15, 19-HETE were elevated in EPHX2-/- but not sEH-inhibited mice. Next, we investigated the role of this difference in cardiac dysfunction induced by Angiotensin II (AngII). Both EPHX2 gene deletion and inhibition protected against AngII-induced cardiac hypertrophy. Interestingly, cardiac dysfunction was attenuated by sEH inhibition rather than gene deletion. Histochemical staining revealed that compared with pharmacological inhibition, EPHX2 deletion aggravated AngII-induced myocardial fibrosis; the mRNA levels of fibrotic-related genes were increased. Furthermore, cardiac inflammatory response was greater in EPHX2-/- than sEH-inhibited mice with AngII treatment, as evidenced by increased macrophage infiltration and expression of MCP-1 and IL-6. In vitro, AngII-upregulated MCP-1 and IL-6 expression was significantly attenuated by sEH inhibition but promoted by EPHX2 deletion in cardiofibroblasts. Thus, compared with pharmacological inhibition of sEH, EPHX2 deletion caused the shift in arachidonic acid metabolism, which may led to pathological cardiac remodeling, especially cardiac fibrosis. Title: Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1; q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male Li L, Chen H, Yin C, Yang C, Wang B, Zheng S, Zhang J, Fan W Ref: Gene, 547:43, 2014 : PubMed ESTHER: Li_2014_Gene_547_43 PubMedSearch: Li 2014 Gene 547 43 PubMedID: 24937803 Abstract It is widely accepted that the incidence of chromosomal aberration is 10-15.2% in the azoospermic male; however, the exact genetic damages are currently unknown for more than 40% of azoospermia. To elucidate the causative gene defects, we used the next generation sequencing (NGS) to map the breakpoints of a chromosome insertion from an azoospermic male who carries a balanced, maternally inherited karyotype 46, XY, inv ins (18,7) (q22.1; q36.2q21.11). The analysis revealed that the breakage in chromosome 7 disrupts two genes, dipeptidyl aminopeptidase-like protein 6 (DPP6) and contactin-associated protein-like 2 (CACNA2D1), the former participates in regulation of voltage-gated potassium channels, and the latter is one of the components in voltage-gated calcium channels. The deletion and duplication were not identified equal or beyond 100 kb, but 4 homologous DNA elements were verified proximal to the breakpoints. One of the proband's sisters inherited the same aberrant karyotype and experienced recurrent miscarriages and consecutive fetus death, while in contrast, another sister with a normal karyotype experienced normal labor and gave birth to healthy babies. The insertional translocation is confirmed with FISH and the Y-chromosome microdeletions were excluded by genetic testing. This is the first report describing chromosome insertion inv ins (18,7) and attributes DPP6 and CACNA2D1 to azoospermia. Title: Sensitive detection of acetylcholine based on a novel boronate intramolecular charge transfer fluorescence probe Liu C, Shen Y, Yin P, Li L, Liu M, Zhang Y, Li H, Yao S Ref: Analytical Biochemistry, 465C:172, 2014 : PubMed ESTHER: Liu_2014_Anal.Biochem_465C_172 PubMedSearch: Liu 2014 Anal.Biochem 465C 172 PubMedID: 25132563 Abstract A highly sensitive and selective fluorescence method for the detection of acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was developed. This strategy involves the reaction of ACh with acetylcholinesterase (AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl-1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining ACh in a wide concentration range with a low detection limit of 2.7nM (signal/noise=3). Compared with other fluorescent probes based on the mechanism of nonspecific oxidation, this reported boronate probe has the advantage of no interference from other biologically relevant reactive oxygen species (ROS) on the detection of ACh. This study provides a new method for the detection of ACh with high selectivity and sensitivity. Title: Structural and functional characterization of a novel alpha/beta hydrolase from cariogenic pathogen Streptococcus mutans Wang Z, Li L, Su XD Ref: Proteins, 82:695, 2014 : PubMed ESTHER: Wang_2014_Proteins_82_695 PubMedSearch: Wang 2014 Proteins 82 695 PubMedID: 24115105 Gene_locus related to this paper: strmu-SMU.1393C Abstract The protein Smu.1393c from Streptococcus mutans is annotated as a putative alpha/beta hydrolase, but it has low sequence identity to the structure-known alpha/beta hydrolases. Here we present the crystal structure of Smu.1393c at 2.0 A resolution. Smu.1393c has a fully open alkaline substrate pocket, whose conformation is unique among other similar hydrolase structures. Three residues, Ser101, His251, and Glu125, were identified as the active center of Smu.1393c. By screening a series of artificial hydrolase substrates, we demonstrated Smu.1393c had low carboxylesterase activity towards short-chain carboxyl esters, which provided a clue for exploring the in vivo function of Smu.1393c. Proteins 2014; 82:695-700. (c) 2013 Wiley Periodicals, Inc. Title: Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1 Wang X, Wang Q, Zhang W, Wang Y, Li L, Wen T, Zhang T, Zhang Y, Xu J and Li J <9 more author(s)> Wang X, Wang Q, Zhang W, Wang Y, Li L, Wen T, Zhang T, Zhang Y, Xu J, Hu J, Li S, Liu L, Liu J, Jiang W, Tian J, Li Y, Schuler D, Wang L, Li J (- 9) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Wang_2014_Genome.Announc_2_e00171 PubMedSearch: Wang 2014 Genome.Announc 2 e00171 PubMedID: 24625872 Gene_locus related to this paper: maggm-v6ezc0 Abstract We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and "domestication" by accelerated evolution of the strain upon repeated passaging. Title: Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone attenuates lipopolysaccharide-induced inflammation by activating the unfolded protein response Zhang J, Gong F, Li L, Zhao M, Song J Ref: Biomed Rep, 2:233, 2014 : PubMed ESTHER: Zhang_2014_Biomed.Rep_2_233 PubMedSearch: Zhang 2014 Biomed.Rep 2 233 PubMedID: 24649102 Abstract N-3-oxododecanoyl homoserine lactone (3-oxo-C12-HSL), a quorum-sensing signal molecule produced by Pseudomonas aeruginosa (P. aeruginosa), is involved in the expression of bacterial virulence factors and in the modulation of host immune responses by directly disrupting nuclear factor-kappaB (NF-kappaB) signaling and inducing cell apoptosis. The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress may suppress inflammatory responses in the later phase by blocking NF-kappaB activation. It was recently demonstrated that 3-oxo-C12-HSL may induce UPR in human aortic endothelial cells (HAECs). Therefore, 3-oxo-C12-HSL may also inhibit NF-kappaB activation and suppress inflammatory responses by activating UPR. However, the possible underlying mechanism has not been fully elucidated. Accordingly, we investigated the effects of 3-oxo-C12-HSL on cellular viability, UPR activation, lipopolysaccharide (LPS)-induced NF-kappaB activation and inflammatory response in the RAW264.7 mouse macrophage cell line. Treatment with 6.25 muM 3-oxo-C12-HSL was not found to affect the viability of RAW264.7 cells. However, pretreating RAW264.7 cells with 6.25 muM 3-oxo-C12-HSL effectively triggered UPR and increased the expression of UPR target genes, such as CCAAT/enhancer-binding protein beta (C/EBP beta) and CCAAT/enhancer-binding protein-homologous protein (CHOP). The expression of C/EBP beta and CHOP was found to be inversely correlated with LPS-induced NF-kappaB activation. 3-Oxo-C12-HSL pretreatment was also shown to inhibit LPS-stimulated proinflammatory cytokine production. Hence, 3-oxo-C12-HSL may attenuate LPS-induced inflammation via UPR-mediated NF-kappaB inhibition without affecting cell viability. This may be another mechanism through which P. aeruginosa evades the host immune system and maintains a persistent infection. Title: Medication adherence and tolerability of Alzheimer's disease medications: study protocol for a randomized controlled trial Campbell NL, Dexter P, Perkins AJ, Gao S, Li L, Skaar TC, Frame A, Hendrie HC, Callahan CM, Boustani MA Ref: Trials, 14:125, 2013 : PubMed ESTHER: Campbell_2013_Trials_14_125 PubMedSearch: Campbell 2013 Trials 14 125 PubMedID: 23782591 Abstract BACKGROUND: The class of acetylcholinesterase inhibitors (ChEI), including donepezil, rivastigmine, and galantamine, have similar efficacy profiles in patients with mild to moderate Alzheimer's disease (AD). However, few studies have evaluated adherence to these agents. We sought to prospectively capture the rates and reasons for nonadherence to ChEI and determine factors influencing tolerability and adherence. METHODS/DESIGN: We designed a pragmatic randomized clinical trial to evaluate the adherence to ChEIs among older adults with AD. Participants include AD patients receiving care within memory care practices in the greater Indianapolis area. Participants will be followed at 6-week intervals up to 18 weeks to measure the primary outcome of ChEI discontinuation and adherence rates and secondary outcomes of behavioral and psychological symptoms of dementia. The primary outcome will be assessed through two methods, a telephone interview of an informal caregiver and electronic medical record data captured from each healthcare system through a regional health information exchange. The secondary outcome will be measured by the Healthy Aging Brain Care Monitor and the Neuropsychiatric Inventory. In addition, the trial will conduct an exploratory evaluation of the pharmacogenomic signatures for the efficacy and the adverse effect responses to ChEIs. We hypothesized that patient-specific factors, including pharmacogenomics and pharmacokinetic characteristics, may influence the study outcomes. DISCUSSION: This pragmatic trial will engage a diverse population from multiple memory care practices to evaluate the adherence to and tolerability of ChEIs in a real world setting. Engaging participants from multiple healthcare systems connected through a health information exchange will capture valuable clinical and non-clinical influences on the patterns of utilization and tolerability of a class of medications with a high rate of discontinuation. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686. Title: [Effects of cornel iridoid glycoside on activity of cholinesterases in vitro] Chu SJ, Zhang L, Liu G, Zhou WX, Li L Ref: Zhongguo Zhong Yao Za Zhi, 38:1331, 2013 : PubMed ESTHER: Chu_2013_Zhongguo.Zhong.Yao.Za.Zhi_38_1331 PubMedSearch: Chu 2013 Zhongguo.Zhong.Yao.Za.Zhi 38 1331 PubMedID: 23944063 Abstract The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BCHE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BCHE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BCHE in vitro, which may be one of the mechanisms of CIG to treat AD. Title: Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H and Cai W <5 more author(s)> Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H, Li S, Zhou T, Yang Z, Yang X, Gao G, Cai W (- 5) Ref: Mol Cell Endocrinol, 377:123, 2013 : PubMed ESTHER: Dai_2013_Mol.Cell.Endocrinol_377_123 PubMedSearch: Dai 2013 Mol.Cell.Endocrinol 377 123 PubMedID: 23850519 Abstract Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Title: Endoplasmic reticulum-localized hepatic lipase decreases triacylglycerol storage and VLDL secretion Erickson B, Selvan SP, Ko KW, Kelly K, Quiroga AD, Li L, Nelson R, King-Jones K, Jacobs RL, Lehner R Ref: Biochimica & Biophysica Acta, 1831:1113, 2013 : PubMed ESTHER: Erickson_2013_Biochim.Biophys.Acta_1831_1113 PubMedSearch: Erickson 2013 Biochim.Biophys.Acta 1831 1113 PubMedID: 23376223 Abstract Hepatic triacylglycerol levels are governed through synthesis, degradation and export of this lipid. Here we demonstrate that enforced expression of hepatic lipase in the endoplasmic reticulum in McArdle RH7777 hepatocytes resulted in a significant decrease in the incorporation of fatty acids into cellular triacylglycerol and cholesteryl ester accompanied by attenuation of secretion of apolipoprotein B-containing lipoproteins. Hepatic lipase-mediated depletion of intracellular lipid storage increased the expression of peroxisome proliferator-activated receptor alpha and its target genes and augmented oxidation of fatty acids. These data show that 1) hepatic lipase is active in the endoplasmic reticulum and 2) intracellular hepatic lipase modulates cellular lipid metabolism and lipoprotein secretion. Title: Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method Gu S, Lu Y, Ding Y, Li L, Zhang F, Wu Q Ref: Anal Chim Acta, 796:68, 2013 : PubMed ESTHER: Gu_2013_Anal.Chim.Acta_796_68 PubMedSearch: Gu 2013 Anal.Chim.Acta 796 68 PubMedID: 24016585 Abstract A simple but robust droplet-based microfluidic system was developed for dose-response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose-response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC50 (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6min, and the total consumption of reagents was less than 5muL. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active. Title: Chemical Analog-to-Digital Signal Conversion Based on Robust Threshold Chemistry and Its Evaluation in the Context of Microfluidics-Based Quantitative Assays Huynh T, Sun B, Li L, Nichols KP, Koyner JL, Ismagilov RF Ref: J Am Chem Soc, 135:14775, 2013 : PubMed ESTHER: Huynh_2013_J.Am.Chem.Soc_135_14775 PubMedSearch: Huynh 2013 J.Am.Chem.Soc 135 14775 PubMedID: 24060606 Abstract In this article, we describe a nonlinear threshold chemistry based on enzymatic inhibition and demonstrate how it can be coupled with microfluidics to convert a chemical concentration (analog input) into patterns of ON or OFF reaction outcomes (chemical digital readout). Quantification of small changes in concentration is needed in a number of assays, such as that for cystatin C, where a 1.5-fold increase in concentration may indicate the presence of acute kidney injury or progression of chronic kidney disease. We developed an analog-to-digital chemical signal conversion that gives visual readout and applied it to an assay for cystatin C as a model target. The threshold chemistry is based on enzymatic inhibition and gives sharper responses with tighter inhibition. The chemistry described here uses acetylcholinesterase (AChE) and produces an unambiguous color change when the input is above a predetermined threshold concentration. An input gives a pattern of ON/OFF responses when subjected to a monotonic sequence of threshold concentrations, revealing the input concentration at the point of transition from OFF to ON outcomes. We demonstrated that this threshold chemistry can detect a 1.30-fold increase in concentration at 22 degrees C and that it is robust to experimental fluctuations: it provided the same output despite changes in temperature (22-34 degrees C) and readout time (10-fold range). We applied this threshold chemistry to diagnostics by coupling it with a traditional sandwich immunoassay for serum cystatin C. Because one quantitative measurement comprises several assays, each with its own threshold concentration, we used a microfluidic SlipChip device to process 12 assays in parallel, detecting a 1.5-fold increase (from 0.64 (49 nM) to 0.96 mg/L (74 nM)) of cystatin C in serum. We also demonstrated applicability to analysis of patient serum samples and the ability to image results using a cell phone camera. This work indicates that combining developments in nonlinear chemistries with microfluidics may lead to development of user-friendly diagnostic assays with simple readouts. Title: Dynamics of fecal microbial communities in children with diarrhea of unknown etiology and genomic analysis of associated Streptococcus lutetiensis Jin D, Chen C, Li L, Lu S, Li Z, Zhou Z, Jing H, Xu Y, Du P and Xu J <8 more author(s)> Jin D, Chen C, Li L, Lu S, Li Z, Zhou Z, Jing H, Xu Y, Du P, Wang H, Xiong Y, Zheng H, Bai X, Sun H, Wang L, Ye C, Gottschalk M, Xu J (- 8) Ref: BMC Microbiol, 13:141, 2013 : PubMed ESTHER: Jin_2013_BMC.Microbiol_13_141 PubMedSearch: Jin 2013 BMC.Microbiol 13 141 PubMedID: 23782707 Abstract BACKGROUND: The sequences of the 16S rRNA genes extracted from fecal samples provide insights into the dynamics of fecal microflora. This potentially gives valuable etiological information for patients whose conditions have been ascribed to unknown pathogens, which cannot be accomplished using routine culture methods. We studied 33 children with diarrhea who were admitted to the Children's Hospital in Shanxi Province during 2006. Title: [Effects of Shenwu capsule on learning-memory ability and cholinergic function of brain in AD-like rat model induced by chronic infusion of sodium azide by minipump] Zhang L, Zhang RY, Li YL, Ye CF, Li L Ref: Zhongguo Zhong Yao Za Zhi, 38:1300, 2013 : PubMed ESTHER: Zhang_2013_Zhongguo.Zhong.Yao.Za.Zhi_38_1300 PubMedSearch: Zhang 2013 Zhongguo.Zhong.Yao.Za.Zhi 38 1300 PubMedID: 23944056 Abstract Because of the proposed importance of mitochondrial cytochrome C oxidase (COX) decrease in Alzheimer's disease (AD) , the protective effect of Shenwu capsule on mitochondrial deficiency model rats and its pharmacological mechanism were investigated in present study. Rats were administered with azide at 1 mg . kg-1 . h-1 subcutaneously via an Alzet minipump for 30 days. Tweny-four hours after the operation, the rats were administered intragastrically by Shenwu capsule with the dose of 0. 45, 0. 9 and 1. 8 g . kg-1 . d-1 for one month. Then learning-memory ability was determined by the watermaze test and passive avoidance tests. The activity of choline-acetyl-transfertase(ChAT) and acetylcholinesterase (AChE) in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. M-cholinergic receptor binding ability (M-binding) was assayed by radio binding. Chronic infusion of sodium azide via minipump induced learning-memory deficiency of rats. Both ChAT activity and M-binding decreased in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. As the result, the cholinergic function of the brain decreased in model rats. Shenwu capsule significantly improved learning and memory ability and the mechanism may be related with the improved cholinergic function in model brain: ChAT activity and M-binding significantly increased in Shenwu treated groups compared with model group; and the increased activity of AChE in hippocampus returned to normal. Mitochondria, especially mitochondrial cytochrome C oxidase, may play the key role in the early event of AD. Chronic, partial in vivo inhibition of mitochondrial cytochrome C oxidase in rats provides a suitable model mimicking several aspects of AD. Shenwu capsule indicate effectiveness in AD-like mitochondrial deficiency model rats, so it would be applied in the treatment of AD. Title: Hopeahainol A attenuates memory deficits by targeting beta-amyloid in APP/PS1 transgenic mice Zhu X, Ye L, Ge H, Chen L, Jiang N, Qian L, Li L, Liu R, Ji S and Xu Y <5 more author(s)> Zhu X, Ye L, Ge H, Chen L, Jiang N, Qian L, Li L, Liu R, Ji S, Zhang S, Jin J, Guan D, Fang W, Tan R, Xu Y (- 5) Ref: Aging Cell, 12:85, 2013 : PubMed ESTHER: Zhu_2013_Aging.Cell_12_85 PubMedSearch: Zhu 2013 Aging.Cell 12 85 PubMedID: 23107435 Inhibitor(s) related to this paper: Hopeahainol-A Abstract Increasing evidence demonstrates that amyloid beta (Abeta) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Abeta is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H(2) O(2) -treated PC12 cells. In this study, we reported that HopA might bind to Abeta(1-42) directly and inhibit the Abeta(1-42) aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Abeta(1-42) and Abeta-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD. Title: Draft genome sequence of Rahnella aquatilis strain HX2, a plant growth-promoting rhizobacterium isolated from vineyard soil in Beijing, China Guo Y, Jiao Z, Li L, Wu D, Crowley DE, Wang Y, Wu W Ref: Journal of Bacteriology, 194:6646, 2012 : PubMed ESTHER: Guo_2012_J.Bacteriol_194_6646 PubMedSearch: Guo 2012 J.Bacteriol 194 6646 PubMedID: 23144397 Gene_locus related to this paper: rahaq-h8nn14, rahac-h2iui7, rahaq-h8nx59 Abstract Rahnella aquatilis strain HX2 is a plant growth-promoting, disease-suppressive rhizobacterium that was isolated from a vineyard soil in Beijing, China. Here, we report the genome sequence of this strain, which provides a valuable resource for future research examining the mechanisms of traits associated with plant growth promotion and biocontrol. Title: Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice Hager L, Li L, Pun H, Liu L, Hossain MA, Maguire GF, Naples M, Baker C, Magomedova L and Ng DS <4 more author(s)> Hager L, Li L, Pun H, Liu L, Hossain MA, Maguire GF, Naples M, Baker C, Magomedova L, Tam J, Adeli K, Cummins CL, Connelly PW, Ng DS (- 4) Ref: Journal of Biological Chemistry, 287:20755, 2012 : PubMed ESTHER: Hager_2012_J.Biol.Chem_287_20755 PubMedSearch: Hager 2012 J.Biol.Chem 287 20755 PubMedID: 22500017 Abstract We recently reported that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor knock-out background, are hypersensitive to insulin and resistant to high fat diet-induced insulin resistance (IR) and obesity. We demonstrated that chow-fed Ldlr-/-xLcat+/+ mice have elevated hepatic endoplasmic reticulum (ER) stress, which promotes IR, compared with wild-type controls, and this effect is normalized in Ldlr-/-xLcat-/- mice. In the present study, we tested the hypothesis that hepatic ER cholesterol metabolism differentially regulates ER stress using these models. We observed that the Ldlr-/-xLcat+/+ mice accumulate excess hepatic total and ER cholesterol primarily attributed to increased reuptake of biliary cholesterol as we observed reduced biliary cholesterol in conjunction with decreased hepatic Abcg5/g8 mRNA, increased Npc1l1 mRNA, and decreased Hmgr mRNA and nuclear SREBP2 protein. Intestinal NPC1L1 protein was induced. Expression of these genes was reversed in the Ldlr-/-xLcat-/- mice, accounting for the normalization of total and ER cholesterol and ER stress. Upon feeding a 2% high cholesterol diet (HCD), Ldlr-/-xLcat-/- mice accumulated a similar amount of total hepatic cholesterol compared with the Ldlr-/-xLcat+/+ mice, but the hepatic ER cholesterol levels remained low in conjunction with being protected from HCD-induced ER stress and IR. Hepatic ER stress correlates strongly with hepatic ER free cholesterol but poorly with hepatic tissue free cholesterol. The unexpectedly low ER cholesterol seen in HCD-fed Ldlr-/-xLcat-/- mice was attributable to a coordinated marked up-regulation of ACAT2 and suppressed SREBP2 processing. Thus, factors influencing the accumulation of ER cholesterol may be important for the development of hepatic insulin resistance. Title: [Wolman disease with novel mutation of LIPA gene in a Chinese infant] Huang YL, Sheng HY, Zhao XY, Yu JK, Li L, Liu HS, Gu CM, He DM, Liu L Ref: Zhonghua Er Ke Za Zhi, 50:601, 2012 : PubMed ESTHER: Huang_2012_Zhonghua.Er.Ke.Za.Zhi_50_601 PubMedSearch: Huang 2012 Zhonghua.Er.Ke.Za.Zhi 50 601 PubMedID: 23158738 Gene_locus related to this paper: human-LIPA Abstract OBJECTIVE To explore the clinical characteristics of Wolman disease and diagnostic methods using enzymatic and molecular analysis METHOD Lysosomal acid lipase activity was measured using 4-methylumbelliferyl oleate in the leukocytes of an infant suspected of Wolman disease and LIPA gene mutational analysis was performed by PCR and direct sequencing in the proband and his parents After the diagnosis was confirmed the clinical biochemical radiological and histopathological findings in this case of Wolman disease were retrospectively reviewed RESULT The sixteen-day-old boy was failing to thrive with progressive vomiting abdominal distention and hepatosplenomegaly Abdominal X-ray revealed adrenal calcifications which were confirmed on abdominal CT scan Xanthomatosis were observed on enlarged liver spleen and lymph nodes during abdominal surgery Liver and lymph node biopsy showed foamy histiocytes The lysosomal acid lipase activity in leukocytes was 3.5 nmol/(mg.h control 35.5 105.8 nmol/(mg.h Serum chitotriosidase activity was 315.8 nmol/(ml.h control Title: Ces3/TGH deficiency improves dyslipidemia and reduces atherosclerosis in Ldlr(-/-) mice Lian J, Quiroga AD, Li L, Lehner R Ref: Circulation Research, 111:982, 2012 : PubMed ESTHER: Lian_2012_Circ.Res_111_982 PubMedSearch: Lian 2012 Circ.Res 111 982 PubMedID: 22872154 Gene_locus related to this paper: mouse-Ces1d Abstract RATIONALE: Carboxylesterase 3/triacylglycerol hydrolase (TGH) has been shown to participate in hepatic very low-density lipoprotein (VLDL) assembly. Deficiency of TGH in mice lowers plasma lipids and atherogenic lipoproteins without inducing hepatic steatosis. OBJECTIVE: To investigate the contribution of TGH to atherosclerotic lesion development in mice that lack low-density lipoprotein receptor (LDLR). METHODS AND Title: Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice Lian J, Wei E, Wang SP, Quiroga AD, Li L, Pardo AD, van der Veen J, Sipione S, Mitchell GA and Di Pardo A <1 more author(s)> Lian J, Wei E, Wang SP, Quiroga AD, Li L, Pardo AD, van der Veen J, Sipione S, Mitchell GA, Lehner R, Di Pardo A (- 1) Ref: Hepatology, 56:2154, 2012 : PubMed ESTHER: Lian_2012_Hepatology_56_2154 PubMedSearch: Lian 2012 Hepatology 56 2154 PubMedID: 22707181 Abstract Carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) participates in hepatic very low-density lipoprotein (VLDL) assembly and in adipose tissue basal lipolysis. Global ablation of Ces3/Tgh expression decreases serum triacylglycerol (TG) and nonesterified fatty acid levels and improves insulin sensitivity. To understand the tissue-specific role of Ces3/TGH in lipid and glucose homeostasis, we generated mice with a liver-specific deletion of Ces3/Tgh expression (L-TGH knockout [KO]). Elimination of hepatic Ces3/Tgh expression dramatically decreased plasma VLDL TG and VLDL cholesterol concentrations but only moderately increased liver TG levels in mice fed a standard chow diet. Significantly reduced plasma TG and cholesterol without hepatic steatosis were also observed in L-TGH KO mice challenged with a high-fat, high-cholesterol diet. L-TGH KO mice presented with increased plasma ketone bodies and hepatic fatty acid oxidation. Intrahepatic TG in L-TGH KO mice was stored in significantly smaller lipid droplets. Augmented hepatic TG levels in chow-fed L-TGH KO mice did not affect glucose tolerance or glucose production from hepatocytes, but impaired insulin tolerance was observed in female mice. CONCLUSION: Our data suggest that ablation of hepatic Ces3/Tgh expression decreases plasma lipid levels without causing severe hepatic steatosis. Title: Complete genome sequence of Paenibacillus mucilaginosus 3016, a bacterium functional as microbial fertilizer Ma M, Wang Z, Li L, Jiang X, Guan D, Cao F, Chen H, Wang X, Shen D and Li J <1 more author(s)> Ma M, Wang Z, Li L, Jiang X, Guan D, Cao F, Chen H, Wang X, Shen D, Du B, Li J (- 1) Ref: Journal of Bacteriology, 194:2777, 2012 : PubMed ESTHER: Ma_2012_J.Bacteriol_194_2777 PubMedSearch: Ma 2012 J.Bacteriol 194 2777 PubMedID: 22535950 Gene_locus related to this paper: paemk-f8fjj7, paemk-f8fd43, paemk-f8fl06, 9bacl-h6ntc5 Abstract Paenibacillus mucilaginosus is a ubiquitous functional bacterium in microbial fertilizer. Here we report the complete sequence of P. mucilaginosus 3016. Multiple sets of functional genes have been found in the genome. To the best of our knowledge, this is the first announcement about the complete genome sequence of a P. mucilaginosus strain. Title: Deficiency of carboxylesterase 1/esterase-x results in obesity, hepatic steatosis, and hyperlipidemia Quiroga AD, Li L, Trotzmuller M, Nelson R, Proctor SD, Kofeler H, Lehner R Ref: Hepatology, 56:2188, 2012 : PubMed ESTHER: Quiroga_2012_Hepatology_56_2188 PubMedSearch: Quiroga 2012 Hepatology 56 2188 PubMedID: 22806626 Gene_locus related to this paper: mouse-Ces1g Abstract Increased lipogenesis, together with hyperlipidemia and increased fat deposition, contribute to obesity and associated metabolic disorders including nonalcoholic fatty liver disease. Here we show that carboxylesterase 1/esterase-x (Ces1/Es-x) plays a regulatory role in hepatic fat metabolism in the mouse. We demonstrate that Ces1/Es-x knockout mice present with increased hepatic lipogenesis and with oversecretion of apolipoprotein B (apoB)-containing lipoproteins (hepatic very-low density lipoproteins), which leads to hyperlipidemia and increased fat deposition in peripheral tissues. Consequently, Ces1/Es-x knockout mice develop obesity, fatty liver, hyperinsulinemia, and insulin insensitivity on chow diet without change in food intake and present with decreased energy expenditure. Ces1/Es-x deficiency prevents the release of polyunsaturated fatty acids from triacylglycerol stores, leading to an up-regulation of sterol regulatory element binding protein 1c-mediated lipogenesis, which can be reversed with dietary omega-3 fatty acids. Conclusion: These studies support a role for Ces1/Es-x in the partitioning of regulatory fatty acids and concomitant control of hepatic lipid biosynthesis, secretion, and deposition. Title: Lipase-catalyzed preparation of diacylglycerol-enriched oil from high-acid rice bran oil in solvent-free system Song Z, Liu Y, Jin Q, Li L, Wang X, Huang J, Liu R Ref: Appl Biochem Biotechnol, 168:364, 2012 : PubMed ESTHER: Song_2012_Appl.Biochem.Biotechnol_168_364 PubMedSearch: Song 2012 Appl.Biochem.Biotechnol 168 364 PubMedID: 22948601 Abstract The ability of immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) to catalyze the reaction of high-acid rice bran oil (RBO) and monoglyceride (MG) for diacylglycerol-enriched rice bran oil (RBO-DG) preparation was investigated. The effects of substrate ratio, reaction temperature, time, and enzyme load on the respective content of free fatty acid (FFA) and DG in the final RBO-DG products was investigated. Enzyme screening on the reaction was also investigated. Response surface methodology (RSM) was used to optimize the effects of the reaction temperature (50-70 degreeC), the enzyme load (2-6 %; relative to the weight of total substrates), and the reaction time (4-8 h) on the respective content of FFA and DG. Validation of the RSM model was verified by the good agreement between the experimental and the predicted values. The optimum preparation conditions were as follows: MG/RBO, 0.25; temperature, 56 degreeC; enzyme load, 4.77 %; and reaction time, 5.75 h. Under the suggested conditions, the respective content of FFA and DG was 0.28 and 27.98 %, respectively. Repeated reaction tests indicated that Lipozyme RM IM could be used nine times under the optimum conditions with 90 % of its original catalytic activity still retained. Title: Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, beta-amyloid aggregation and Ca(2+) overload Wang Y, Wang F, Yu JP, Jiang FC, Guan XL, Wang CM, Li L, Cao H, Li MX, Chen JG Ref: Bioorganic & Medicinal Chemistry, 20:6513, 2012 : PubMed ESTHER: Wang_2012_Bioorg.Med.Chem_20_6513 PubMedSearch: Wang 2012 Bioorg.Med.Chem 20 6513 PubMedID: 23000296 Abstract In this study, a series of multipotent phenylthiazole-tacrine hybrids (7a-7e, 8, and 9a-9m) were synthesized and biologically evaluated. Screening results showed that phenylthiazole-tacrine hybrids were potent cholinesterase inhibitors with pIC(50) (-logIC(50)) value ranging from 5.78+/-0.05 to 7.14+/-0.01 for acetylcholinesterase (AChE), and from 5.75+/-0.03 to 10.35+/-0.15 for butyrylcholinesterase (BCHE). The second series of phenylthiazole-tacrine hybrids (9a-9m) could efficiently prevent Abeta(1-42) self-aggregation. The structure-activity relationship revealed that their inhibitory potency relied on the type of middle linker and substitutions at 4'-position of 4-phenyl-2-aminothiazole. In addition, 7a and 7c also displayed the Ca(2+) overload blockade effect in the primary cultured cortical neurons. Consequently, these compounds emerged as promising molecules for the therapy of Alzheimer's disease. Title: Draft genome sequence of Alicyclobacillus hesperidum strain URH17-3-68 Wang P, Li L, Chen X, Jiang N, Liu G, Chen L, Xu J, Song H, Chen Z, Ma Y Ref: Journal of Bacteriology, 194:6348, 2012 : PubMed ESTHER: Wang_2012_J.Bacteriol_194_6348 PubMedSearch: Wang 2012 J.Bacteriol 194 6348 PubMedID: 23105079 Gene_locus related to this paper: 9bacl-h2esd6, 9bacl-j9e7t9 Abstract Alicyclobacillus hesperidum is a thermoacidophilic bacterium. We isolated strain URH17-3-68 from hot spring sludge in Tengchong, Yunnan province, China. Its extracellular products include heat- and acid-stable enzymes which are important for industrial applications. Here we report the draft genome of this strain. Title: Multifunctional mercapto-tacrine derivatives for treatment of age-related neurodegenerative diseases Wang Y, Guan XL, Wu PF, Wang CM, Cao H, Li L, Guo XJ, Wang F, Xie N and Chen JG <1 more author(s)> Wang Y, Guan XL, Wu PF, Wang CM, Cao H, Li L, Guo XJ, Wang F, Xie N, Jiang FC, Chen JG (- 1) Ref: Journal of Medicinal Chemistry, 55:3588, 2012 : PubMed ESTHER: Wang_2012_J.Med.Chem_55_3588 PubMedSearch: Wang 2012 J.Med.Chem 55 3588 PubMedID: 22420827 Abstract Cooperating mercapto groups with tacrine in a single molecular, novel multifunctional compounds have been designed and synthesized. These mercapto-tacrine derivatives displayed a synergistic pharmacological profile of long-term potentiation enhancement, cholinesterase inhibition, neuroprotection, and less hepatotoxicity, emerging as promising molecules for the therapy of age-related neurodegenerative diseases. Title: The oyster genome reveals stress adaptation and complexity of shell formation Zhang G, Fang X, Guo X, Li L, Luo R, Xu F, Yang P, Zhang L, Wang X and Yin Y <66 more author(s)> Zhang G, Fang X, Guo X, Li L, Luo R, Xu F, Yang P, Zhang L, Wang X, Qi H, Xiong Z, Que H, Xie Y, Holland PW, Paps J, Zhu Y, Wu F, Chen Y, Wang J, Peng C, Meng J, Yang L, Liu J, Wen B, Zhang N, Huang Z, Zhu Q, Feng Y, Mount A, Hedgecock D, Xu Z, Liu Y, Domazet-Loso T, Du Y, Sun X, Zhang S, Liu B, Cheng P, Jiang X, Li J, Fan D, Wang W, Fu W, Wang T, Wang B, Zhang J, Peng Z, Li Y, Li N, Chen M, He Y, Tan F, Song X, Zheng Q, Huang R, Yang H, Du X, Chen L, Yang M, Gaffney PM, Wang S, Luo L, She Z, Ming Y, Huang W, Huang B, Zhang Y, Qu T, Ni P, Miao G, Wang Q, Steinberg CE, Wang H, Qian L, Liu X, Yin Y (- 66) Ref: Nature, 490:49, 2012 : PubMed ESTHER: Zhang_2012_Nature_490_49 PubMedSearch: Zhang 2012 Nature 490 49 PubMedID: 22992520 Gene_locus related to this paper: cragi-k1qzk7, cragi-k1rad0, cragi-k1p6v9, cragi-k1pa46, cragi-k1pga2, cragi-k1pp63, cragi-k1pwa8, cragi-k1q0b1.1, cragi-k1q0b1.2, cragi-k1q1h2, cragi-k1q2z6, cragi-k1qaj8, cragi-k1qaw5, cragi-k1qhl5, cragi-k1qly1, cragi-k1qqb1.1, cragi-k1qqb1.2, cragi-k1qs61, cragi-k1qs99, cragi-k1qwl6, cragi-k1r068, cragi-k1r0n3.1, cragi-k1r0n3.2, cragi-k1r0r4, cragi-k1r1i9, cragi-k1r8q9, cragi-k1rgi1, cragi-k1rig4, cragi-k1s0a7.1, cragi-k1s0a7.2, cragi-k1s0a7.3, cragi-k1q6q0, cragi-k1rru1, cragi-k1qfi4, cragi-k1qvm5, cragi-k1qq58, cragi-k1qdc0, cragi-k1r754, cragi-k1pje5, cragi-k1qca6, cragi-k1qdt5, cragi-k1qkz7, cragi-k1rgd2, cragi-k1puh6, cragi-k1raz4, cragi-k1qqj4, cragi-k1rbs1 Abstract The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. Title: miR-122 inhibits viral replication and cell proliferation in hepatitis B virus-related hepatocellular carcinoma and targets NDRG3 Fan CG, Wang CM, Tian C, Wang Y, Li L, Sun WS, Li RF, Liu YG Ref: Oncol Rep, 26:1281, 2011 : PubMed ESTHER: Fan_2011_Oncol.Rep_26_1281 PubMedSearch: Fan 2011 Oncol.Rep 26 1281 PubMedID: 21725618 Abstract microRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory functions that participate in diverse biological pathways. miR-122, a liver-specific miRNA, has been found to be down-regulated in hepatocellular carcinoma (HCC) and HCC-derived cell lines. In this study, miR-122 was down-regulated in the hepatitis B virus (HBV)-related HCC cell line HepG2.2.15 compared to HepG2. NDRG3, a member of the N-myc downstream-regulated gene (NDRG) family, was up-regulated in HepG2.2.15 and was identified as a target gene of miR-122. An inverse correlation between the expression of miR-122 and the NDRG3 protein was noted in HBV-related HCC specimens. The transfection of the miR-122 expression vector into the HepG2.2.15 cell line repressed the transcription and expression of NDRG3, which subsequently reversed the malignant phenotype of the cells. The replication of HBV, expression of viral antigens and proliferation of cells were significantly inhibited by restoration of miR-122. The data demonstrate that miR-122 plays an important role in HBV-related hepatocarcinogenesis by targeting NDRG3. Thus, miR-122 and NDRG3 represent key diagnostic markers and potential therapeutic targets for HBV-related HCC. Title: [Clinical features and treatment of dementia with Lewy bodies] Li L, Wang JT, Zhang ZX, Cui RX, Yuan J Ref: Zhonghua Yi Xue Za Zhi, 91:1617, 2011 : PubMed ESTHER: Li_2011_Zhonghua.Yi.Xue.Za.Zhi_91_1617 PubMedSearch: Li 2011 Zhonghua.Yi.Xue.Za.Zhi 91 1617 PubMedID: 21914395 Abstract OBJECTIVE: To investigate the clinical, neuropsychological, neuroimaging features and treatment of dementia with Lewy bodies (DLB). METHODS: The clinical, neuropsychological, neuroimaging and therapeutic features of 33 DLB patients were retrospectively analyzed. RESULTS: There were 25 males and 8 females. The mean course from onset to diagnosis was 3.3 years. Sleep disorder, depression, anxiety and constipation were present at 1 - 10 years prior to DLB onset in 10 patients. Memory impairment (52%) and parkinsonism (21%) were initial symptoms. The mean duration from memory impairment to presence of parkinsonism was 17 months. Pattern of extrapyramidal signs showed bilateral, symmetry and axial muscles bias as postural instability and facial impassivity, tremor was less in DLB. Hallucination (70%), sleep disorder (63%), apathy (56%) and delusion (52%) were the major behavioral and psychological symptoms. Hallucination occurred within a mean of 15 months after presence of initial symptoms. Cognition impairment progressed rapidly in half of patients. Neuropsychological tests of mild patients revealed visuospatial dysfunction and relatively preservation of memory. Severe impairment of all domains of cognition was noticed in moderate-severe patients. MRI (magnetic resonance imaging) revealed the preservation of hippocampal structures. And PET (positron emission tomography) showed hypometabolism of occipital lobe. Cholinesterase inhibitors could improve cognitive impairment and behavioral symptoms in a large majority of patients. CONCLUSION: Neuronal dysfunction may be present at an early stage of DLB. Early presence of hallucination, a high prevalence of sleep disorders, axial rigidity and hypometabolism of occipital lobe on PET may help to distinguish DLB from other types of dementia. Title: Putative EPHX1 enzyme activity is related with risk of lung and upper aerodigestive tract cancers: a comprehensive meta-analysis Li X, Hu Z, Qu X, Zhu J, Li L, Ring BZ, Su L Ref: PLoS ONE, 6:e14749, 2011 : PubMed ESTHER: Li_2011_PLoS.One_6_e14749 PubMedSearch: Li 2011 PLoS.One 6 e14749 PubMedID: 21445251 Abstract BACKGROUND: EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking. Two functional polymorphisms in the EPHX1 gene, Tyr113His and His139Arg can alter the enzyme activity, suggesting their possible association with carcinogenesis risk, particularly of some tobacco-related cancers. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive systematic review and meta-analysis was performed of available studies on these two polymorphisms and cancer risk published up to November 2010, consisting of 84 studies (31144 cases and 42439 controls) for Tyr113His and 77 studies (28496 cases and 38506 controls) for His139Arg primarily focused on lung cancer, upper aerodigestive tract (UADT) cancers (including oral, pharynx, larynx and esophagus cancers), colorectal cancer or adenoma, bladder cancer and breast cancer. Results showed that Y113H low activity allele (H) was significantly associated with decreased risk of lung cancer (OR = 0.88, 95%CI = 0.80-0.96) and UADT cancers (OR = 0.86, 95%CI = 0.77-0.97) and H139R high activity allele (R) with increased risk of lung cancer (OR = 1.18, 95%CI = 1.04-1.33) but not of UADT cancers (OR = 1.05, 95%CI = 0.93-1.17). Pooled analysis of lung and UADT cancers revealed that low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R showed decreased risk of these cancers (OR = 0.83, 95%CI = 0.75-0.93) whereas high EPHX1 activity increased risk of the cancers (OR = 1.20, 95%CI = 0.98-1.46). Furthermore, modest difference for the risk of lung and UADT cancers was found between cigarette smokers and nonsmokers both in single SNP analyses (low activity allele H: OR = 0.77/0.85 for smokers/nonsmokers; high activity allele R: OR = 1.20/1.09 for smokers/nonsmokers) and in combined double SNP analyses (putative low activity: OR = 0.73/0.88 for smokers/nonsmokers; putative high activity: OR = 1.02/0.93 for smokers/ nonsmokers). CONCLUSIONS/SIGNIFICANCE: Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas putative high EPHX1 activity may have a harmful effect. Moreover, cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk. Title: Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population Li L, Qi L, Lv N, Gao Q, Cheng Y, Wei Y, Ye J, Yan X, Dang A Ref: Ann Hum Genet, 75:605, 2011 : PubMed ESTHER: Li_2011_Ann.Hum.Genet_75_605 PubMedSearch: Li 2011 Ann.Hum.Genet 75 605 PubMedID: 21834908 Gene_locus related to this paper: human-PLA2G7 Abstract The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI. Title: Complete genome sequence of Paenibacillus polymyxa SC2, a strain of plant growth-promoting Rhizobacterium with broad-spectrum antimicrobial activity Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H and Du B <7 more author(s)> Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H, Feng R, Wang X, Ge Y, Yao L, Bing X, Yang X, Li J, Du B (- 7) Ref: Journal of Bacteriology, 193:311, 2011 : PubMed ESTHER: Ma_2011_J.Bacteriol_193_311 PubMedSearch: Ma 2011 J.Bacteriol 193 311 PubMedID: 21037012 Gene_locus related to this paper: paep6-e0rmc7, paeps-e3e5s8, paeps-e3ebx3, paeps-e3e602 Abstract Paenibacillus polymyxa SC2 is an important plant growth-promoting rhizobacterium (PGPR). Here, we report the complete genome sequence of P. polymyxa SC2. Multiple sets of functional genes have been found in the genome. As far as we know, this is the first complete genome sequence of Paenibacillus polymyxa. Title: Increased fat mass and insulin resistance in mice lacking pancreatic lipase-related protein 1 Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L and Fei J <2 more author(s)> Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L, Sun X, Wang Z, Fei J (- 2) Ref: J Nutr Biochem, 22:691, 2011 : PubMed ESTHER: Ren_2011_J.Nutr.Biochem_22_691 PubMedSearch: Ren 2011 J.Nutr.Biochem 22 691 PubMedID: 21115337 Gene_locus related to this paper: human-PNLIPRP1, mouse-1plrp Abstract Pancreatic triglyceride lipase (PTL) and its cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase-related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. The lipase activity of PLRP2 has been confirmed, whereas no known triglyceride lipase activity has been detected with PLRP1 up to now. To explore the biological functions of PLRP1 in vivo, we generated Plrp1 knockout (KO) mice in our laboratory. Here we show that the Plrp1 KO mice displayed mature-onset obesity with increased fat mass, impaired glucose clearance and the resultant insulin resistance. When fed on high-fat (HF) diet, the Plrp1 KO mice exhibited an increased weight gain, fat mass and severe insulin resistance compared with wild-type mice. Pancreatic juice extracted from Plrp1 KO mice had greater ability to hydrolyze triglyceride than that from the wild-type littermates. We propose that PLRP1 may function as a metabolic inhibitor in vivo of PLT-colipase-mediated dietary triglyceride digestion and provides potential anti-obesity targets for developing new drugs. Title: Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase Shen LL, Liu H, Peng J, Gan L, Lu L, Zhang Q, Li L, He F, Jiang Y Ref: Mol Biol Rep, 38:553, 2011 : PubMed ESTHER: Shen_2011_Mol.Biol.Rep_38_553 PubMedSearch: Shen 2011 Mol.Biol.Rep 38 553 PubMedID: 20373033 Abstract The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid. Title: The genome sequence of the leaf-cutter ant Atta cephalotes reveals insights into its obligate symbiotic lifestyle Suen G, Teiling C, Li L, Holt C, Abouheif E, Bornberg-Bauer E, Bouffard P, Caldera EJ, Cash E and Currie CR <39 more author(s)> Suen G, Teiling C, Li L, Holt C, Abouheif E, Bornberg-Bauer E, Bouffard P, Caldera EJ, Cash E, Cavanaugh A, Denas O, Elhaik E, Fave MJ, Gadau J, Gibson JD, Graur D, Grubbs KJ, Hagen DE, Harkins TT, Helmkampf M, Hu H, Johnson BR, Kim J, Marsh SE, Moeller JA, Munoz-Torres MC, Murphy MC, Naughton MC, Nigam S, Overson R, Rajakumar R, Reese JT, Scott JJ, Smith CR, Tao S, Tsutsui ND, Viljakainen L, Wissler L, Yandell MD, Zimmer F, Taylor J, Slater SC, Clifton SW, Warren WC, Elsik CG, Smith CD, Weinstock GM, Gerardo NM, Currie CR (- 39) Ref: PLoS Genet, 7:e1002007, 2011 : PubMed ESTHER: Suen_2011_PLoS.Genet_7_e1002007 PubMedSearch: Suen 2011 PLoS.Genet 7 e1002007 PubMedID: 21347285 Gene_locus related to this paper: acrec-f4w848, acrec-f4wah1, acrec-f4wai9, acrec-f4wda7, acrec-f4wfh7, acrec-f4wk54, acrec-f4wng2, acrec-f4wpb7, acrec-f4wpb8, acrec-f4wpb9, acrec-f4x2j7, acrec-f4x3l5, acrec-f4x6y6, acrec-f4x7w5, acrec-f4x7w6, acrec-f4x378, acrec-f4x808, attce-h9hc46, solin-e9ige7, attce-w4wts9, attce-w4x506, attce-w4vya2, attce-w4vyi5, attce-w4wib4, attce-w4wkj3, attce-w4x3s7, attce-w4x3u4, attce-w4wu92, attce-w4w1m9, attce-w4x2m8, attce-w4w776, attce-w4x1t1, attce-a0a158nl98, attce-a0a158nmi0, attce-a0a158nqx5, attce-a0a158nr47.2, attce-a0a158ns84, attce-a0a158nvq4, attce-a0a158nij4, attce-a0a158nhg2, attce-a0a158nhn7, attce-a0a158nbh6, attce-a0a158ne04, attce-a0a158nyf0 Abstract Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host-microbe symbioses. Title: Elevated adipose triglyceride lipase in newly diagnosed type 2 diabetes mellitus with hypertension Xu S, Yang G, Yang M, Li S, Liu H, Li L Ref: American Journal of Medicine Sci, 342:452, 2011 : PubMed ESTHER: Xu_2011_Am.J.Med.Sci_342_452 PubMedSearch: Xu 2011 Am.J.Med.Sci 342 452 PubMedID: 21709540 Abstract INTRODUCTION: Adipose triglyceride lipase (ATGL) is a recently identified triacylglycerol lipase responsible for adiposity lipolysis. Its pathophysiologic role in humans remains unknown. MATERIAL AND METHODS: In this study, the authors investigated the levels of plasma ATGL among patients with type 2 diabetes mellitus (T2DM), patients with T2DM and hypertension and control subjects. They also assessed the association between plasma ATGL and body composition and metabolic parameters. RESULTS AND CONCLUSIONS: Plasma ATGL levels significantly increased in patients with T2DM and hypertension compared with those with T2DM (78.3 +/- 23.4 versus 65.1 +/- 22.8 mug/L, P < 0.01). No gender differences were found among plasma ATGL levels. Furthermore, they found that the plasma ATGL level was positively correlated with total cholesterol (r = 0.17, P < 0.05) and high-density lipoprotein C (r = 0.16, P < 0.05) in simple regression analysis of pooled data, whereas, in multiple stepwise regression analysis, diastolic blood pressure, total cholesterol and homeostasis model assessment of insulin resistance were independently related factors with plasma ATGL levels (Y = -13.662 + 0.343 x waist + 0.268 x diastolic blood pressure + 0.053 x 2hPin + 0.966 x homeostasis model assessment of insulin resistance). This work indicates the potential link of ATGL with the pathogenesis of insulin resistance and T2DM. Title: Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation Yang J, Wang L, Ji X, Feng Y, Li X, Zou C, Xu J, Ren Y, Mi Q and Zhang KQ <16 more author(s)> Yang J, Wang L, Ji X, Feng Y, Li X, Zou C, Xu J, Ren Y, Mi Q, Wu J, Liu S, Liu Y, Huang X, Wang H, Niu X, Li J, Liang L, Luo Y, Ji K, Zhou W, Yu Z, Li G, Li L, Qiao M, Feng L, Zhang KQ (- 16) Ref: PLoS Pathog, 7:e1002179, 2011 : PubMed ESTHER: Yang_2011_PLoS.Pathog_7_E1002179 PubMedSearch: Yang 2011 PLoS.Pathog 7 E1002179 PubMedID: 21909256 Gene_locus related to this paper: artoa-g1wyr4, artoa-g1x1a7, artoa-g1x3f4, artoa-g1x3h6, artoa-g1x9s5, artoa-g1x9z4, artoa-g1xcb5, artoa-g1xhl6, artoa-g1xjb3, artoa-g1xjy0, artoa-g1xkw3, artoa-g1xnf2, artoa-g1xnf8, artoa-g1xqd4, artoa-g1xqt1, artoa-g1xte8, artoa-g1xu91, artoa-g1xv59, artoa-g1x382, artoa-g1x3q3, artoa-g1wxl5, artoa-g1xj75, artoa-g1xd25, artoa-g1wzu7, artoa-g1xt42, artoa-g1xhm8, artoa-g1wy43 Abstract Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions. Title: GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity Cheng S, Li L, He S, Liu J, Sun Y, He M, Grasing K, Premont RT, Suo WZ Ref: Journal of Biological Chemistry, 285:41541, 2010 : PubMed ESTHER: Cheng_2010_J.Biol.Chem_285_41541 PubMedSearch: Cheng 2010 J.Biol.Chem 285 41541 PubMedID: 21041302 Inhibitor(s) related to this paper: Methoctramine Abstract Membrane G protein-coupled receptor kinase 5 (GRK5) deficiency is linked to Alzheimer disease, yet its precise roles in the disease pathogenesis remain to be delineated. We have previously demonstrated that GRK5 deficiency selectively impairs desensitization of presynaptic M2 autoreceptors, which causes presynaptic M2 hyperactivity and inhibits acetylcholine release. Here we report that inactivation of one copy of Grk5 gene in transgenic mice overexpressing beta-amyloid precursor protein (APP) carrying Swedish mutations (Tg2576 or APPsw) resulted in significantly increased beta-amyloid (Abeta) accumulation, including increased Abeta(+) plaque burdens and soluble Abeta in brain lysates and interstitial fluid (ISF). In addition, secreted beta-APP fragment (sAPPbeta) also increased, whereas full-length APP level did not change, suggesting an alteration in favor of beta-amyloidogenic APP processing in these animals. Reversely, perfusion of methoctramine, a selective M2 antagonist, fully corrected the difference between the control and GRK5-deficient APPsw mice for ISF Abeta. In contrast, a cholinesterase inhibitor, eserine, although significantly decreasing the ISF Abeta in both control and GRK5-deficient APPsw mice, failed to correct the difference between them. However, combining eserine with methoctramine additively reduced the ISF Abeta further in both animals. Altogether, these findings indicate that GRK5 deficiency accelerates beta-amyloidogenic APP processing and Abeta accumulation in APPsw mice via impaired cholinergic activity and that presynaptic M2 hyperactivity is the specific target for eliminating the pathologic impact of GRK5 deficiency. Moreover, a combination of an M2 antagonist and a cholinesterase inhibitor may reach the maximal disease-modifying effect for both amyloid pathology and cholinergic dysfunction. Title: Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M and Yu Z <1 more author(s)> He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M, Wang S, Yu Z (- 1) Ref: Journal of Bacteriology, 192:4074, 2010 : PubMed ESTHER: He_2010_J.Bacteriol_192_4074 PubMedSearch: He 2010 J.Bacteriol 192 4074 PubMedID: 20525827 Gene_locus related to this paper: bacan-BA3703, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1677, bacce-BC1788, bacce-BC2141, bacce-BC2171, bacce-BC2456, bacce-BC2458, bacce-BC3133, bacce-BC4102, bacce-BC4854, bacce-BC4862, bacce-BC5130, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells Li L, Dong X, Leong MC, Zhou W, Yang Z, Chen F, Bao Y, Jia W, Hu R Ref: Int J Mol Med, 26:483, 2010 : PubMed ESTHER: Li_2010_Int.J.Mol.Med_26_483 PubMedSearch: Li 2010 Int.J.Mol.Med 26 483 PubMedID: 20818486 Gene_locus related to this paper: human-f172a Abstract The family with sequence similarity 172, member A (FAM172A) is a hypothetical protein. We recently cloned the FAM172A gene from normal human aortic tissues. In a previous study we also showed that the FAM172A gene was up-regulated by high glucose levels in macrophages. In the present study, we further identified the FAM172A protein at the level of translation and studied the effects of high glucose levels on its expression in human aortic smooth muscle cells. The FAM172A gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2. The cloned sequence shows an open reading frame of 1251 nucleotides encoding a protein of 416 amino acids. We further expressed the recombinant FAM172A protein and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A protein was identified for the first time at the translation level by Western blot analysis. Western blotting also demonstrated that the FAM172A protein could be detected in human aortic endothelial, human aortic smooth muscle cells and THP-1-derived macrophages, the highest expression being observed in the human aortic smooth muscle cells. By a combination of bioinformatics and confocal laser scanning microscopy, we found that the FAM172A protein in HEK293 cells, was mainly located in the nucleus, and that there was an Arb2 conserved domain in the FAM172A protein sequence. We also presented evidence that the FAM172 protein expression in human aortic smooth muscle cells was up-regulated by high glucose levels in a concentration-dependent and time-course manner. We speculated that as a novel protein, FAM172A could be involved in the pathogenesis of high glucose-induced vascular damage. Title: Enantioselective cytotoxicity of isocarbophos is mediated by oxidative stress-induced JNK activation in human hepatocytes Liu H, Liu J, Xu L, Zhou S, Li L, Liu W Ref: Toxicology, 276:115, 2010 : PubMed ESTHER: Liu_2010_Toxicology_276_115 PubMedSearch: Liu 2010 Toxicology 276 115 PubMedID: 20688129 Inhibitor(s) related to this paper: Isocarbophos Abstract Recent studies have shown the enantioselectivity of chiral pesticides in environmental fate, aquatic toxicity, endocrine disruption and cytotoxicity. Thus it is of significance to investigate the molecular mechanisms of chiral pesticides enantioselectivity in cytotoxicity. In the present study, we used Hep G2 cells as in vitro model to assay cytotoxicity of enantiomers of isocarbophos (ICP), a widely used chiral organophosphorus pesticide. The results of cell viability assay and cytoflow assay indicated an obvious enantioselective hepatocyte toxicity of ICP: (-)-ICP was about two times more toxic than (+)-ICP in Hep G2 cells. We found that (-)-ICP, but not (+)-ICP, up-regulated Bax protein expression and down-regulated Bcl-2 expression levels, which resulted in an increase in Bax/Bcl-2 ratio with the apoptosis co-ordination. Although (-)-ICP enantioselectively activated both ERK and JNK, only the specific inhibitor for JNK could completely reverse (-)-ICP-induced apoptosis of Hep G2 cells. It suggests that (-)-ICP-induced hepatocyte toxicity was more dominantly through the sustained activation of JNK pathway, but only partially via ERK cascade. Furthermore, (-)-ICP induced ROS production, while (+)-ICP had no effect on ROS generation. The antioxidant MnTBAP attenuated (-)-ICP-induced activation of JNK and ERK, indicating that the outcome from challenge with (-)-ICP enantiomer depends on the oxidative stress-induced activation of a series of signaling cascades that promote hepatocyte apoptosis. In conclusion, (-)-ICP enantioselectively causes the change of Bax/Bcl-2 ratio, triggers the generation of intracellular ROS and sequentially induces sustainable activation of JNK, which in turn, results in a decrease in cell viability and an increase in cell apoptosis. Our observations provide further insight into enantiomers toxicity pathway which is able to differentiate between enantiomer activities at molecular level. Title: Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium Ma LJ, van der Does HC, Borkovich KA, Coleman JJ, Daboussi MJ, Di Pietro A, Dufresne M, Freitag M, Grabherr M and Rep M <53 more author(s)> Ma LJ, van der Does HC, Borkovich KA, Coleman JJ, Daboussi MJ, Di Pietro A, Dufresne M, Freitag M, Grabherr M, Henrissat B, Houterman PM, Kang S, Shim WB, Woloshuk C, Xie X, Xu JR, Antoniw J, Baker SE, Bluhm BH, Breakspear A, Brown DW, Butchko RA, Chapman S, Coulson R, Coutinho PM, Danchin EG, Diener A, Gale LR, Gardiner DM, Goff S, Hammond-Kosack KE, Hilburn K, Hua-Van A, Jonkers W, Kazan K, Kodira CD, Koehrsen M, Kumar L, Lee YH, Li L, Manners JM, Miranda-Saavedra D, Mukherjee M, Park G, Park J, Park SY, Proctor RH, Regev A, Ruiz-Roldan MC, Sain D, Sakthikumar S, Sykes S, Schwartz DC, Turgeon BG, Wapinski I, Yoder O, Young S, Zeng Q, Zhou S, Galagan J, Cuomo CA, Kistler HC, Rep M (- 53) Ref: Nature, 464:367, 2010 : PubMed ESTHER: Ma_2010_Nature_464_367 PubMedSearch: Ma 2010 Nature 464 367 PubMedID: 20237561 Gene_locus related to this paper: fusox-a0a1d3s5h0, gibf5-fus2, fusof-f9f2k2, fusof-f9f3l6, fusof-f9f6t8, fusof-f9f6v2, fusof-f9f132, fusof-f9f781, fusof-f9fd72, fusof-f9fd90, fusof-f9fem0, fusof-f9fhk2, fusof-f9fj19, fusof-f9fj20, fusof-f9fki8, fusof-f9fmx2, fusof-f9fnt4, fusof-f9fpy4, fusof-f9fvs6, fusof-f9fwu0, fusof-f9fxz4, fusof-f9fzy5, fusof-f9g2a2, fusof-f9g3b1, fusof-f9g5h7, fusof-f9g6e6, fusof-f9g6y7, fusof-f9g7b0, fusof-f9g797, fusof-f9g972, fusof-f9ga50, fusof-f9gck4, fusof-f9gd15, gibze-a8w610, gibze-b1pdn0, gibze-i1r9e6, gibze-i1rda9, gibze-i1rdk7, gibze-i1rec8, gibze-i1rgs0, gibze-i1rgy0, gibze-i1rh52, gibze-i1rhi8, gibze-i1rig9, gibze-i1rip5, gibze-i1rpg6, gibze-i1rsg2, gibze-i1rv36, gibze-i1rxm5, gibze-i1rxp8, gibze-i1rxv5, gibze-i1s1u3, gibze-i1s3j9, gibze-i1s6l7, gibze-i1s8i8, gibze-i1s9x4, gibze-q4huy1, gibze-i1rg17, fuso4-j9mvr9, fuso4-j9ngs6, fuso4-j9niq8, fuso4-j9nqm2, gibze-i1rb76, gibze-i1s1m7, gibze-i1s3z6, gibze-i1rd78, gibze-i1rgl9, gibze-i1rjp7, gibze-i1s1q6, gibze-i1ri35, gibze-i1rf76, gibze-i1rhp3, fusc1-n4uj11, fusc4-n1s9p6, gibf5-s0dqr2, gibm7-w7n1b5, fusof-f9g6q0, gibm7-w7n497, fusox-x0bme4, gibm7-w7mcf8, gibm7-w7mak5, fusox-x0a2c5, gibm7-w7mum7, fusox-w9iyc7, gibm7-w7maw6, gibm7-w7msi0, gibm7-w7luf0, gibm7-w7msa3, gibm7-w7mna8, gibm7-w7n8b7, gibm7-w7n564, fusox-w9jpi0, gibm7-w7ngc3, gibm7-w7m4v6, gibm7-w7m4v2, gibm7-w7lt61, gibm7-w7mly6, gibm7-w7ncn3, fusox-w9ibd7, fusof-f9fnm6, gibm7-w7n526, gibza-a0a016pda4, gibza-a0a016pl96, gibm7-w7muq1, fusof-f9gfd3, gibm7-w7mt52, gibze-i1rjb5, gibf5-s0ehu3, fusox-w9hvf0, gibze-i1rkc4, gibm7-w7mv30, gibze-a0a1c3ylb1, fuso4-a0a0c4diy4, gibm7-w7n4n0, gibze-gra11, gibze-fsl2, gibf5-fub4, gibf5-fub5, gibf5-fus5, gibm7-dlh1 Abstract Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective. Title: Enantioselective interaction with acetylcholinesterase of an organophosphate insecticide fenamiphos Wang C, Zhang N, Li L, Zhang Q, Zhao M, Liu W Ref: Chirality, 22:612, 2010 : PubMed ESTHER: Wang_2010_Chirality_22_612 PubMedSearch: Wang 2010 Chirality 22 612 PubMedID: 19899158 Inhibitor(s) related to this paper: Fenamiphos Abstract Enantioselectivity in the environmental behavior and ecotoxicity of chiral pesticide is widely observed. However, the investigation of the enantioselective mechanisms remains limited. In this study, we used fenamiphos (FAP), an organophosphorus insecticide, to study enantioselectivity in toxicity to arthropods and the inhibition potential towards acetylcholinesterase (AChE) in the rat pheochromocytoma 12 (PC 12) cell line. Furthermore, we carried out molecular docking to help explain the mechanisms of enantioselective toxicity of FAP. The two enantiomers of FAP were successfully separated and identified as R-(+)-FAP and S-(-)-FAP. Toxicological assays revealed that R-(+)-FAP was 2.4-fold more toxic than S-(-)-FAP to Daphnia magna and approximately threefold more to PC12 cells. Based on molecular docking results, dynamic simulation shows that strong hydrophobic interactions and a key hydrogen bond can only exist between R-(+)-FAP and AChE, which helps explain the preference of R-(+) binding to AChE over that of the S-(-)-enantiomer, and supports our biological results. Our present study considers the impact of stereochemistry on ecotoxicological effects and, ultimately, on development of environmentally safe, insecticidally efficient pesticides. Title: Comparative genomic characterization of Actinobacillus pleuropneumoniae Xu Z, Chen X, Li L, Li T, Wang S, Chen H, Zhou R Ref: Journal of Bacteriology, 192:5625, 2010 : PubMed ESTHER: Xu_2010_J.Bacteriol_192_5625 PubMedSearch: Xu 2010 J.Bacteriol 192 5625 PubMedID: 20802045 Gene_locus related to this paper: actp2-a3mzf9, actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2 Abstract The Gram-negative bacterium Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumoniae, a lethal respiratory infectious disease causing great economic losses in the swine industry worldwide. In order to better interpret the genetic background of serotypic diversity, nine genomes of A. pleuropneumoniae reference strains of serovars 1, 2, 4, 6, 9, 10, 11, 12, and 13 were sequenced by using rapid high-throughput approach. Based on 12 genomes of corresponding serovar reference strains including three publicly available complete genomes (serovars 3, 5b, and 7) of this bacterium, we performed a comprehensive analysis of comparative genomics and first reported a global genomic characterization for this pathogen. Clustering of 26,012 predicted protein-coding genes showed that the pan genome of A. pleuropneumoniae consists of 3,303 gene clusters, which contain 1,709 core genome genes, 822 distributed genes, and 772 strain-specific genes. The genome components involved in the biogenesis of capsular polysaccharide and lipopolysaccharide O antigen relative to serovar diversity were compared, and their genetic diversity was depicted. Our findings shed more light on genomic features associated with serovar diversity of A. pleuropneumoniae and provide broader insight into both pathogenesis research and clinical/epidemiological application against the severe disease caused by this swine pathogen. Title: Preparation of a crosslinked bioimprinted lipase for enrichment of polyunsaturated fatty acids from fish processing waste Yan J, Li L, Tang Q, Jiang M, Jiang S Ref: Appl Biochem Biotechnol, 162:757, 2010 : PubMed ESTHER: Yan_2010_Appl.Biochem.Biotechnol_162_757 PubMedSearch: Yan 2010 Appl.Biochem.Biotechnol 162 757 PubMedID: 20101527 Abstract Geotrichum sp. lipase modified with a combined method composed of crosslinking and bioimprinting was employed to selectively hydrolyze waste fish oil for enrichment of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in glycerides. Crosslinked polymerization by monomer (polyethylene glycol 400 dimethyl acrylate), crosslinker (trimethylolpropane trimethylacrylate), and photoinitiator (benzoin methyl ether) coupled to bioimprinting using palmitic acid as imprint molecule, resulted in much more effective enzyme preparation used in aqueous hydrolysis reaction. Since the crosslinked polymerization modification maintained bioimprinted property and gave good dispersion of enzyme in reaction mixture, the crosslinked bioimprinted enzyme exhibited higher hydrolysis temperature, enhanced specific activity, shorter hydrolysis time, and better operational stability compared to free lipase. Crude fish oil was treated at 45 degrees C with this crosslinked bioimprinted lipase for 8 h, and 46% hydrolysis degree resulted in the production of glycerides containing 41% of EPA and DHA (EPA+DHA), achieving 85.7% recovery of initial EPA and DHA. The results suggested that bioimprinted enzymes did not lose their induced property in aqueous environment when prepared according to the described crosslinking-bioimprinting method. It could also be seen that the crosslinked bioimprinted lipase was effective in producing glycerides that contained a higher concentration of polyunsaturated fatty acid with better yield. Title: Cloning, characterization, and expression of a novel secretory lipase-like gene from Clonorchis sinensis Hu F, Chen W, Li L, Lu Y, Song W, Kuang Y, Zhang F Ref: Parasitol Res, 105:1661, 2009 : PubMed ESTHER: Hu_2009_Parasitol.Res_105_1661 PubMedSearch: Hu 2009 Parasitol.Res 105 1661 PubMedID: 19756752 Gene_locus related to this paper: closi-c3v6k8 Abstract A secretory lipase-like gene was isolated from total cDNA of adult Clonorchis sinensis. The gene has an open reading frame of 1,218 bp long and encodes for a protein of 406 amino acids including a putative signal peptide of 20 amino acids. The deduced amino acid sequence including signal peptide has 42-45% identity with lipase of other species and two typical enzymic active sites that contain consensus sequence (Gly-X-Ser-X-Gly) of lipase. The cDNA encoding this protein was subcloned into pET-28a (+) expression vector and expressed in Escherichia coli. The expressed fusion protein has a molecular mass of about 45 kDa. Prediction of signal peptide and Western blot analysis indicated that the secretory lipase-like protein is an excretory-secretory product of C. sinensis. Immunostaining revealed that the secretory lipase-like protein was localized in the tegument of the adult worm and metacercaria. These results provide basis for further studies on the nutrition taking and invasion of C. sinensis mediated by the secretory lipase-like protein. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo Li L, Yang G, Shi S, Yang M, Liu H, Boden G Ref: Cytokine, 45:12, 2009 : PubMed ESTHER: Li_2009_Cytokine_45_12 PubMedSearch: Li 2009 Cytokine 45 12 PubMedID: 19026557 Abstract Inflammatory cytokines have been linked to obesity-related insulin resistance. To investigate the effect of TNF-alpha, an inflammatory cytokine, on insulin action, C57BL/6J mice were treated with TNF-alpha for 7 days after which we examined the in vivo effects of TNF-alpha on glucose tolerance and insulin sensitivity with IV glucose tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, we analyzed the in vivo effect of TNF-alpha on several metabolism-related genes and adipocytokines implicated in the development of insulin resistance. TNF-alpha treatment resulted in markedly increased fasting blood glucose, insulin and free fatty acids (FFA) levels and reduced glucose tolerance. During the clamps, the rates insulin-stimulated whole body (G(Rd)) and skeletal muscle glucose uptake (MGU) and insulin's ability to suppress hepatic glucose production (HGP) were decreased in TNF-alpha treated animals, indicating insulin resistance. In addition, both PPARgamma and ATGL mRNA expression in adipose tissues as well as ATGL protein levels in plasma were downregulated. Moreover, adipose mRNA expression and plasma protein levels of adiponectin and visfatin were significantly down-regulated. We conclude that the alterations of PPARgamma, ATGL, adiponectin and visfatin may contribute to the development of insulin resistance mediated by TNF-alpha. Title: Carbazole-degradative IncP-7 plasmid pCAR1.2 is structurally unstable in Pseudomonas fluorescens Pf0-1, which accumulates catechol, the intermediate of the carbazole degradation pathway Takahashi Y, Shintani M, Li L, Yamane H, Nojiri H Ref: Applied Environmental Microbiology, 75:3920, 2009 : PubMed ESTHER: Takahashi_2009_Appl.Environ.Microbiol_75_3920 PubMedSearch: Takahashi 2009 Appl.Environ.Microbiol 75 3920 PubMedID: 19376894 Gene_locus related to this paper: psest-bpdF Abstract We determined the effect of the host on the function and structure of the nearly identical IncP-7 carbazole-degradative plasmids pCAR1.1 and pCAR1.2. We constructed Pseudomonas aeruginosa PAO1(pCAR1.2) and P. fluorescens Pf0-1Km(pCAR1.2) and compared their growth on carbazole- and succinate-containing media with that of P. putida KT2440(pCAR1.1). We also assessed the stability of the genetic structures of the plasmids in each of the three hosts. Pf0-1Km(pCAR1.2) showed dramatically delayed growth when carbazole was supplied as the sole carbon source, while the three strains grew at nearly the same rate on succinate. Among the carbazole-grown Pf0-1Km(pCAR1.2) cells, two types of deficient strains appeared and dominated the population; such dominance was not observed in the other two strains or for succinate-grown Pf0-1Km(pCAR1.2). Genetic analysis showed that the two deficient strains possessed pCAR1.2 derivatives in which the carbazole-degradative car operon was deleted or its regulatory gene, antR, was deleted by homologous recombination between insertion sequences. From genomic information and quantitative reverse transcription-PCR analyses of the genes involved in carbazole mineralization by Pf0-1Km(pCAR1.2), we found that the cat genes on the chromosome of Pf0-1Km, which are necessary for the degradation of catechol (a toxic intermediate in the carbazole catabolic pathway), were not induced in the presence of carbazole. The resulting accumulation of catechol may have enabled the strain that lost its carbazole-degrading ability to have overall higher fitness than the wild-type strain. These results suggest that the functions of the chromosomal genes contributed to the selection of plasmid derivatives with altered structures. Title: Cloning of a novel pyrethroid-hydrolyzing carboxylesterase gene from Sphingobium sp. strain JZ-1 and characterization of the gene product Wang BZ, Guo P, Hang BJ, Li L, He J, Li SP Ref: Applied Environmental Microbiology, 75:5496, 2009 : PubMed ESTHER: Wang_2009_Appl.Environ.Microbiol_75_5496 PubMedSearch: Wang 2009 Appl.Environ.Microbiol 75 5496 PubMedID: 19581484 Gene_locus related to this paper: sphwj-c0la90 Abstract A novel esterase gene, pytH, encoding a pyrethroid-hydrolyzing carboxylesterase was cloned from Sphingobium sp. strain JZ-1. The gene contained an open reading frame of 840 bp. Sequence identity searches revealed that the deduced enzyme shared the highest similarity with many alpha/beta-hydrolase fold proteins (20 to 24% identities). PytH was expressed in Escherichia coli BL21 and purified using Ni-nitrilotriacetic acid affinity chromatography. It was a monomeric structure with a molecular mass of approximately 31 kDa and a pI of 4.85. PytH was able to transform p-nitrophenyl esters of short-chain fatty acids and a wide range of pyrethroid pesticides, and isomer selectivity was not observed. No cofactors were required for enzyme activity. Title: Separation and toxicity of salithion enantiomers Zhou S, Lin K, Li L, Jin M, Ye J, Liu W Ref: Chirality, 21:922, 2009 : PubMed ESTHER: Zhou_2009_Chirality_21_922 PubMedSearch: Zhou 2009 Chirality 21 922 PubMedID: 19161220 Inhibitor(s) related to this paper: Salithion Abstract Enantioseletive toxicities of chiral pesticides have become an environmental concern recently. In this study, we evaluated the enantiomeric separation of salithion on a suite of commercial chiral columns and assessed the toxicity of enantiomers toward butyrylcholinesterase and Daphnia magna. Satisfactory separations of salithion enantiomers could be achieved on all tested columns, that is, Chiralcel OD, Chiralcel OJ, and Chiralpak AD column. However, the Chiralpak AD column offered the best separation and was chosen to prepare micro-scale of pure salithion enantiomers for subsequent bioassays. The first and second enantiomers eluted on the Chiralpak AD column were further confirmed to be (-)-S-salithion and (+)-R-salithion, respectively. The half inhibition concentrations to butyrylcholinesterase of racemate, (+)-R-salithion, and (-)-S-salithion were 33.09, 2.92, and 15.60 mg/l, respectively, showing (+)-R-enantiomer being about 5.0 times more potent than its (-)-S-form. However, the median lethal concentrations (96 h) of racemate, (+)-R-salithion, and (-)-S-salithion toward D. magna were 3.54, 1.10, and 0.36 microg/l, respectively, suggesting that (-)-S-salithion was about 3.0 times more toxic than (+)-R-form. Racemic salithion was less toxic than either of the enantiomers in both bioassays, suggesting that antagonistic interactions might occur between the enantiomers during the toxication action. This work reveals that the toxicity of salithion toward butyrylcholinesterase and D. magna is enantioselective, and this factor should be taken into consideration in the environmental risk assessment of salithion. Title: [Effects of tumor necrosis factor-alpha induced insulin resistance on adipose triglyceride lipase in mice] Cheng YL, Li L, Yang GY, Shi SC, Chen Y, Zhu W, Sun X Ref: Zhonghua Yi Xue Za Zhi, 88:2417, 2008 : PubMed ESTHER: Cheng_2008_Zhonghua.Yi.Xue.Za.Zhi_88_2417 PubMedSearch: Cheng 2008 Zhonghua.Yi.Xue.Za.Zhi 88 2417 PubMedID: 19087720 Abstract OBJECTIVE: To investigate the effects of tumor necrosis factor (TNF)-alpha induced insulin resistance (IR) on glucose and lipid metabolism and adipose triglyceride lipase (ATGL). Title: Characterization of the saframycin A gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner Li L, Deng W, Song J, Ding W, Zhao QF, Peng C, Song WW, Tang GL, Liu W Ref: Journal of Bacteriology, 190:251, 2008 : PubMed ESTHER: Li_2008_J.Bacteriol_190_251 PubMedSearch: Li 2008 J.Bacteriol 190 251 PubMedID: 17981978 Abstract Saframycin A (SFM-A), produced by Streptomyces lavendulae NRRL 11002, belongs to the tetrahydroisoquinoline family of antibiotics, and its core is structurally similar to the core of ecteinascidin 743, which is a highly potent antitumor drug isolated from a marine tunicate. In this study, the biosynthetic gene cluster for SFM-A was cloned and localized to a 62-kb contiguous DNA region. Sequence analysis revealed 30 genes that constitute the SFM-A gene cluster, encoding an unusual nonribosomal peptide synthetase (NRPS) system and tailoring enzymes and regulatory and resistance proteins. The results of substrate prediction and in vitro characterization of the adenylation specificities of this NRPS system support the hypothesis that the last module acts in an iterative manner to form a tetrapeptidyl intermediate and that the colinearity rule does not apply. Although this mechanism is different from those proposed for the SFM-A analogs SFM-Mx1 and safracin B (SAC-B), based on the high similarity of these systems, it is likely they share a common mechanism of biosynthesis as we describe here. Construction of the biosynthetic pathway of SFM-Y3, an aminated SFM-A, was achieved in the SAC-B producer (Pseudomonas fluorescens). These findings not only shed new insight on tetrahydroisoquinoline biosynthesis but also demonstrate the feasibility of engineering microorganisms to generate structurally more complex and biologically more active analogs by combinatorial biosynthesis. Title: Single and joint acute toxicity of isocarbophos enantiomers to Daphnia magna Lin K, Liu W, Li L, Gan J Ref: Journal of Agricultural and Food Chemistry, 56:4273, 2008 : PubMed ESTHER: Lin_2008_J.Agric.Food.Chem_56_4273 PubMedSearch: Lin 2008 J.Agric.Food.Chem 56 4273 PubMedID: 18489111 Inhibitor(s) related to this paper: Isocarbophos Abstract Although enantioselectivity in the toxicity of chiral pesticides has received considerable attention over recent years, how coexisting enantiomers interact with each other during their toxic action remains unknown. In this study, we attempted to resolve the enantiomers of a chiral organophosphate insecticide, isocarbophos, and investigated the acute toxicity of individual enantiomers and various enantiomer mixtures. Baseline enantiomeric separation of isocarbophos was achieved on a Chiralcel OD column with the mobile phase of n-hexane/isopropanol (90/10, v/v) at a flow rate of 0.8 mL/min. The resolved enantiomers were differentiated by their responses on a circular dichroism detector. The median lethal concentrations (LC 50) of racemate, (+)-enantiomer, and (-)-enantiomer of isocarbophos toward Daphnia magna were 13.9, 7.08, and 353 microg/L, respectively, after 48 h of static exposure, displaying a 50-fold difference between the enantiomers. Toxic unit (TU) analysis was employed to evaluate the joint toxicity of isocarbophos enantiomer mixtures. The calculated TU mix for the acute toxicity (48 h test) of various binary mixtures ranged from 0.83 to 1.04, suggesting a mode of additive effect. Further evaluation of available literature data for chiral organophosphorus insecticides showed that the joint toxicity of enantiomers may be additive, synergistic, and antagonistic. Therefore, when significant enantioselectivity exists for a chiral pesticide, it is important to also evaluate the interaction of enantiomers in the joint toxicity effect when enantiomers are present in a mixture. Title: C-reactive protein enhances macrophage lipoprotein lipase expression Maingrette F, Li L, Renier G Ref: J Lipid Res, 49:1926, 2008 : PubMed ESTHER: Maingrette_2008_J.Lipid.Res_49_1926 PubMedSearch: Maingrette 2008 J.Lipid.Res 49 1926 PubMedID: 18708524 Abstract High serum levels of C-reactive protein (CRP), a strong predictor of cardiovascular events, are documented in patients with type 2 diabetes. Accumulating evidence suggests that CRP could directly promote arterial damage. To determine the role of CRP in diabetic atherosclerosis, we examined the effect of CRP on the expression of macrophage lipoprotein lipase (LPL), a proatherogenic molecule upregulated in type 2 diabetes. Treatment of human macrophages with native CRP increased, in a dose- and time-dependent manner, LPL protein expression and secretion. Modified CRP reproduced these effects. Preincubation of human macrophages with antioxidants, protein kinase C (PKC), and mitogen-activated protein kinase (MAPK) inhibitors prevented CRP-induced LPL expression. Exposure of human macrophages to CRP further increased intracellular reactive oxygen species generation, classic PKC isozymes expression, and extracellular signal-regulated protein kinase 1/2 phosphorylation. In CRP-treated J774 macrophages, increased macrophage LPL mRNA levels and enhanced binding of nuclear proteins to the activated protein-1 (AP-1)-enhancing element were observed. These effects were prevented by antioxidants, as well as by PKC, MAPK, and AP-1 inhibitors. These data show for the first time that CRP directly increases macrophage LPL expression and secretion. Given the predominant role of macrophage LPL in atherogenesis, LPL might represent a novel factor underlying the adverse effect of CRP on the diabetic vasculature. Title: Genome biology of Actinobacillus pleuropneumoniae JL03, an isolate of serotype 3 prevalent in China Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W and Chen H <16 more author(s)> Xu Z, Zhou Y, Li L, Zhou R, Xiao S, Wan Y, Zhang S, Wang K, Li W, Jin H, Kang M, Dalai B, Li T, Liu L, Cheng Y, Zhang L, Xu T, Zheng H, Pu S, Wang B, Gu W, Zhang XL, Zhu GF, Wang S, Zhao GP, Chen H (- 16) Ref: PLoS ONE, 3:e1450, 2008 : PubMed ESTHER: Xu_2008_PLoS.ONE_3_E1450 PubMedSearch: Xu 2008 PLoS.ONE 3 E1450 PubMedID: 18197260 Gene_locus related to this paper: actp2-a3n347, actp7-b3h2v1, actp7-b3h2x2, actpj-b0bpm3, actpj-b0bqd8 Abstract Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a cause of considerable world wide economic losses in the swine industry. We sequenced the complete genome of A. pleuropneumoniae, JL03, an isolate of serotype 3 prevalent in China. Its genome is a single chromosome of 2,242,062 base pairs containing 2,097 predicted protein-coding sequences, six ribosomal rRNA operons, and 63 tRNA genes. Preliminary analysis of the genomic sequence and the functions of the encoded proteins not only confirmed the present physiological and pathological knowledge but also offered new insights into the metabolic and virulence characteristics of this important pathogen. We identified a full spectrum of genes related to its characteristic chemoheterotrophic catabolism of fermentation and respiration with an incomplete TCA system for anabolism. In addition to confirming the lack of ApxI toxin, identification of a nonsense mutation in apxIVA and a 5'-proximal truncation of the flp operon deleting both its promoter and the flp1flp2tadV genes have provided convincing scenarios for the low virulence property of JL03. Comparative genomic analysis using the available sequences of other serotypes, probable strain (serotype)-specific genomic islands related to capsular polysaccharides and lipopolysaccharide O-antigen biosyntheses were identified in JL03, which provides a foundation for future research into the mechanisms of serotypic diversity of A. pleuropneumoniae. Title: Hydrolysis and soil sorption of insecticide pyraclofos Yang H, Xue B, Li L, Zhou S, Tu Y, Lin C Ref: J Environ Sci Health B, 43:219, 2008 : PubMed ESTHER: Yang_2008_J.Environ.Sci.Health.B_43_219 PubMedSearch: Yang 2008 J.Environ.Sci.Health.B 43 219 PubMedID: 18368541 Abstract The hydrolysis of the insecticide pyraclofos in buffered solutions at pH 5.0, 7.0 and 9.0, and its sorption on four soils of different physicochemical properties were investigated. The results showed that the degradation of pyraclofos in buffered solutions followed pseudo-first-order kinetics. At 40 degrees C, the rate constants for the hydrolysis of pyraclofos at pH 5.0, 7.0 and 9.0 were 0.0214, 0.1293, and 2.1656 d(-1), respectively. Pyraclofos was relatively stable under both acidic and neutral conditions, while it was readily hydrolyzed under basic conditions. The sorption of pyraclofos on four soils was well described by the Freundlich equation. The sorption constant, K(f), increased with an increase in soil organic carbon content, suggesting that organic carbon content was an important factor affecting sorption. The K(oc) values for Xiaoshan clay loam soil, Hangzhou I clay loam soil, Hangzhou II soil, and Fuyang silt loam soil were 30.4, 6.7, 5.3, and 7.1, respectively. These results suggest that the sorption of pyraclofos on the tested soils was relatively weak. Title: Current experimental therapy for Alzheimer's disease Chen S, Zhang XJ, Li L, Le WD Ref: Curr Neuropharmacol, 5:127, 2007 : PubMed ESTHER: Chen_2007_Curr.Neuropharmacol_5_127 PubMedSearch: Chen 2007 Curr.Neuropharmacol 5 127 PubMedID: 18615180 Abstract In the past decade, enormous efforts have been devoted to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been transferred into extensive experimental approaches aimed at reversing disease progression. The trend in future AD therapy has been shifted from traditional anti-acetylcholinesterase treatment to multiple mechanisms-based therapy targeting amyloid plaques formation and amyloid peptides (Abeta)-mediated cytotoxicity, and neurofibrillary tangles generation. This review will cover current experimental studies with the focus on secretases-based drug development, immunotherapy, and anti-neurofibrillary tangles intervention. The outcome of these on-going studies may provide high hope that AD can be cured in the future. Title: Adipocyte-derived lipoprotein lipase induces macrophage activation and monocyte adhesion: role of fatty acids Li L, Renier G Ref: Obesity (Silver Spring), 15:2595, 2007 : PubMed ESTHER: Li_2007_Obesity.(Silver.Spring)_15_2595 PubMedSearch: Li 2007 Obesity.(Silver.Spring) 15 2595 PubMedID: 18070750 Abstract OBJECTIVE: We evaluated the effect of adipocyte-derived lipoprotein lipase (LPL) on macrophage activation and monocyte adhesion and the role of fatty acids in these effects. RESEARCH METHODS AND PROCEDURES: 3T3-L1 adipocytes were incubated with heparin or insulin to induce LPL secretion; then adipocyte conditioned media (CM) were added to cultured J774 macrophages or human aortic endothelial cells (HAECs). Macrophage cytokine production and monocyte adhesion to HAECs were determined. Title: Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A Bai L, Li L, Xu H, Minagawa K, Yu Y, Zhang Y, Zhou X, Floss HG, Mahmud T, Deng Z Ref: Chemical Biology, 13:387, 2006 : PubMed ESTHER: Bai_2006_Chem.Biol_13_387 PubMedSearch: Bai 2006 Chem.Biol 13 387 PubMedID: 16632251 Gene_locus related to this paper: strhy-q1l2j3 Abstract A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VAL-A) biosynthesis revealed 16 structural genes, 2 regulatory genes, 5 genes related transport, transposition/integration or tellurium resistance; another 4 genes had no obvious identity. The VAL-A biosynthetic pathway was proposed, with assignment of the required genetic functions confined to the sequenced region. A cluster of eight reassembled genes was found to support VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo inactivation of the putative glycosyltransferase gene (valG) abolished the final attachment of glucose for VAL production and resulted in accumulation of the VAL-A precursor, validoxylamine, while the normal production of VAL-A could be restored by complementation with valG. The role of valG in the glycosylation of validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay. Title: Proteomic analyses of Oryza sativa mature pollen reveal novel proteins associated with pollen germination and tube growth Dai S, Li L, Chen T, Chong K, Xue Y, Wang T Ref: Proteomics, 6:2504, 2006 : PubMed ESTHER: Dai_2006_Proteomics_6_2504 PubMedSearch: Dai 2006 Proteomics 6 2504 PubMedID: 16548068 Abstract As a highly reduced organism, pollen performs specialized functions to generate and carry sperm into the ovule by its polarily growing pollen tube. Yet the molecular genetic basis of these functions is poorly understood. Here, we identified 322 unique proteins, most of which were not reported previously to be in pollen, from mature pollen of Oryza sativa L. ssp japonica using a proteomic approach, 23% of them having more than one isoform. Functional classification reveals that an overrepresentation of the proteins was related to signal transduction (10%), wall remodeling and metabolism (11%), and protein synthesis, assembly and degradation (14%), as well as carbohydrate and energy metabolism (25%). Further, 11% of the identified proteins are functionally unknown and do not contain any conserved domain associated with known activities. These analyses also identified 5 novel proteins by de novo sequencing and revealed several important proteins, mainly involved in signal transduction (such as protein kinases, receptor kinase-interacting proteins, guanosine 5'-diphosphate dissociation inhibitors, C2 domain-containing proteins, cyclophilins), protein synthesis, assembly and degradation (such as prohibitin, mitochondrial processing peptidase, putative UFD1, AAA+ ATPase), and wall remodeling and metabolism (such as reversibly glycosylated polypeptides, cellulose synthase-like OsCsLF7). The study is the first close investigation, to our knowledge, of protein complement in mature pollen, and presents useful molecular information at the protein level to further understand the mechanisms underlying pollen germination and tube growth. Title: Role of neuropeptide Y and dipeptidyl peptidase IV in regulation of Ewing's sarcoma growth Kitlinska J, Kuo L, Abe K, Pons J, Yu M, Li L, Tilan J, Toretsky J, Zukowska Z Ref: Advances in Experimental Medicine & Biology, 575:223, 2006 : PubMed ESTHER: Kitlinska_2006_Adv.Exp.Med.Biol_575_223 PubMedSearch: Kitlinska 2006 Adv.Exp.Med.Biol 575 223 PubMedID: 16700526 Title: Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M and Ausubel FM <7 more author(s)> Lee DG, Urbach JM, Wu G, Liberati NT, Feinbaum RL, Miyata S, Diggins LT, He J, Saucier M, Deziel E, Friedman L, Li L, Grills G, Montgomery K, Kucherlapati R, Rahme LG, Ausubel FM (- 7) Ref: Genome Biol, 7:R90, 2006 : PubMed ESTHER: Lee_2006_Genome.Biol_7_R90 PubMedSearch: Lee 2006 Genome.Biol 7 R90 PubMedID: 17038190 Gene_locus related to this paper: pseae-a3kt39, pseae-CPO, pseae-metx, pseae-PA0231, pseae-PA0308, pseae-PA0368, pseae-PA0480, pseae-PA0502, pseae-PA0599, pseae-PA1239, pseae-PA1291, pseae-PA1558, pseae-PA1621, pseae-PA1622, pseae-PA2086, pseae-PA2451, pseae-PA2689, pseae-PA2745, pseae-PA2764, pseae-PA2927, pseae-PA2934, pseae-PA2949, pseae-PA3053, pseae-PA3132, pseae-PA3226, pseae-PA3301, pseae-PA3324, pseae-PA3429, pseae-PA3586, pseae-PA3628, pseae-PA3695, pseae-PA3994, pseae-PA4152, pseae-PA5080, pseae-PCHF, pseae-phag, pseae-rhla, pseae-q9i252 Abstract BACKGROUND: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. RESULTS: The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. CONCLUSION: Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds. Title: Dipeptidyl peptidase IV: a molecular switch of vascular actions of neuropeptide Y Li L, Demuth HU, Zukowska Z Ref: Advances in Experimental Medicine & Biology, 575:135, 2006 : PubMed ESTHER: Li_2006_Adv.Exp.Med.Biol_575_135 PubMedSearch: Li 2006 Adv.Exp.Med.Biol 575 135 PubMedID: 16700516 Title: A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis Yu XH, Zhao TQ, Wang L, Liu ZP, Zhang CM, Chen R, Li L, Liu G, Hu WC Ref: Biochemical & Biophysical Research Communications, 341:82, 2006 : PubMed ESTHER: Yu_2006_Biochem.Biophys.Res.Commun_341_82 PubMedSearch: Yu 2006 Biochem.Biophys.Res.Commun 341 82 PubMedID: 16431216 Gene_locus related to this paper: human-LPL Abstract A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes. Title: Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE-/- and LDLR-/- mice Ko KW, Paul A, Ma K, Li L, Chan L Ref: J Lipid Res, 46:2586, 2005 : PubMed ESTHER: Ko_2005_J.Lipid.Res_46_2586 PubMedSearch: Ko 2005 J.Lipid.Res 46 2586 PubMedID: 16199802 Abstract Endothelial lipase (EL) is a determinant of high density lipoprotein-cholesterol (HDL-C) level, which is negatively correlated with atherosclerosis susceptibility. We found no difference in aortic atherosclerotic lesion areas between 26-week-old EL+/+ apolipoprotein E-deficient (apoE-/-) and EL-/- apoE-/- mice. To more firmly establish the role of EL in atherosclerosis, we extended our study to EL-/- and EL+/+ low density lipoprotein receptor-deficient (LDLR-/-) mice that were fed a Western diet. Morphometric analysis again revealed no difference in atherosclerosis lesion area between the two groups. Compared with EL+/+ mice, we found increased HDL-C in EL-/- mice with apoE-/- or LDLR-/- background but no difference in macrophage content between lesions of EL-/- and EL+/+ mice in apoE-/- or LDLR-/- background. EL inactivation had no effect on hepatic mRNAs of proteins involved in reverse cholesterol transport. A survey of lipid homeostasis in EL+/+ and EL-/- macrophages revealed that oxidized LDL-induced ABCA1 was attenuated in EL-/- macrophages. This potentially proatherogenic change may have nullified any minor protective increase of HDL in EL-/- mice. Thus, although EL modulated lipoprotein profile in mice, there was no effect of EL inactivation on atherosclerosis development in two hyperlipidemic atherosclerosis-prone mouse models. Title: The complete genome sequence of Mycobacterium avium subspecies paratuberculosis Li L, Bannantine JP, Zhang Q, Amonsin A, May BJ, Alt D, Banerji N, Kanjilal S, Kapur V Ref: Proc Natl Acad Sci U S A, 102:12344, 2005 : PubMed ESTHER: Li_2005_Proc.Natl.Acad.Sci.U.S.A_102_12344 PubMedSearch: Li 2005 Proc.Natl.Acad.Sci.U.S.A 102 12344 PubMedID: 16116077 Gene_locus related to this paper: mycpa-q73tc9, mycpa-q73vt9, mycpa-q73xs5, mycpa-q741s1 Abstract We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease. Title: [The association of S447X and Hind III polymorphism in the lipoprotein lipase gene with dyslipidemia of the metabolic syndrome in patients with essential hypertension] Liu A, Li L, Cao W, Shan S, Lu J, Guo X, Hu Y Ref: Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 22:151, 2005 : PubMed ESTHER: Liu_2005_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_22_151 PubMedSearch: Liu 2005 Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi 22 151 PubMedID: 15793775 Abstract OBJECTIVE: To assess the association of S447X mutation and Hind III polymorphism in the lipoprotein lipase gene with dyslipidemia of the metabolic syndrome in patients with essential hypertension. Title: The Genomes of Oryza sativa: a history of duplications Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S and Yang H <88 more author(s)> Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Xiao Y, Bu D, Tan J, Yang L, Ye C, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Huang X, Su Z, Tong W, Tong Z, Ye J, Wang L, Lei T, Chen C, Chen H, Huang H, Zhang F, Li N, Zhao C, Huang Y, Li L, Xi Y, Qi Q, Li W, Hu W, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wong GK, Yang H (- 88) Ref: PLoS Biol, 3:e38, 2005 : PubMed ESTHER: Yu_2005_PLoS.Biol_3_e38 PubMedSearch: Yu 2005 PLoS.Biol 3 e38 PubMedID: 15685292 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9S7P1, orysa-Q9FYP7, orysa-Q5ZBH3, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P9, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-Q949C9, orysa-cbp1, orysa-cbp3, orysa-cbpx, orysa-Q33B71, orysa-Q8GSJ3, orysa-LPL1, orysa-Q6YSZ8, orysa-Q8S5X5, orysa-Q8LIG3, orysa-Q6K7F5, orysa-Q7F1B1, orysa-Q8H4S9, orysa-Q69UB1, orysa-Q9FW17, orysa-Q337C3, orysa-Q7F959, orysa-Q84QZ6, orysa-Q84QY7, orysa-Q851E3, orysa-Q6YTH5, orysa-Q0JK71, orysa-Q8S1D9, orysa-Q5N8V4, orysa-Q0JCY4, orysa-Q8GTK2, orysa-B9EWJ8, orysa-Q8H3K6, orysa-Q6ZDG8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q6ZDG4, orysa-Q5NAI4, orysa-Q658B2, orysa-Q5JMQ8, orysa-Q5QMD9, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-Q8W0F0, orysa-pir7a, orysa-pir7b, orysa-q2qlm4, orysa-q2qm78, orysa-q2qm82, orysa-q2qn31, orysa-q2qnj4, orysa-q2qnt9, orysa-q2qur1, orysa-q2qx94, orysa-q2qyi1, orysa-q2qyj1, orysa-q2r051, orysa-q2r077, orysa-q2ram0, orysa-q2rat1, orysa-q2rbb3, orysa-Q4VWY7, orysa-q5na00, orysa-q5nbu1, orysa-Q5QLC0, orysa-q5smv5, orysa-Q5VP27, orysa-q5vrt2, orysa-q5w6c5, orysa-q5z5a3, orysa-q5z9i2, orysa-q5z417, orysa-q5z901, orysa-Q5ZAM8, orysa-Q5ZBI5, orysa-Q5ZCR3, orysa-q6atz0, orysa-q6ave2, orysa-q6f358, orysa-q6h6s1, orysa-q6h7i6, orysa-q6i5q3, orysa-q6i5u7, orysa-q6j657, orysa-q6k3d9, orysa-q6k4q2, orysa-q6k880, orysa-q6l5b6, orysa-Q6L5F5, orysa-q6l556, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zc62, orysa-q6zia4, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xej4, orysa-q7xem8, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q7XVB5, orysa-Q8L562, orysa-Q8LQS5, orysa-Q8RZ40, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8S0V0, orysa-Q8S125, orysa-Q8SAY7, orysa-Q8SAY9, orysa-Q8W3C6, orysa-Q8W3F2, orysa-Q8W3F4, orysa-Q8W3F6, orysa-Q9LHX5, orysa-q33aq0, orysa-q53lh1, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q60ew8, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j07, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q67uz1, orysa-q67v34, orysa-q67wz5, orysa-q69j38, orysa-q69k08, orysa-q69md7, orysa-q69me0, orysa-q69pf3, orysa-q69ti3, orysa-q69xr2, orysa-q69y12, orysa-q69y21, orysa-q75hy2, orysa-q75i01, orysa-Q94JD7, orysa-Q0J0A4, orysa-q651a8, orysa-q651z3, orysa-q652g4, orysa-q688m0, orysa-q688m8, orysa-q688m9, orysa-Q6H8G1, orysi-a2wn01, orysi-a2xc83, orysi-a2yh83, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-a3b9l8, orysj-b9eub8, orysj-b9eya5, orysj-b9fi05, orysj-b9fkb0, orysj-b9fn42, orysj-b9gbb7, orysj-cgep, orysj-PLA7, orysj-q0d4u5, orysj-q0djj0, orysj-q0jaf0, orysj-q5jl22, orysj-q5jlw7, orysj-q5z419, orysj-q6h7q9, orysj-q6yvk6, orysj-q6z6i1, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q338c0, orysi-b8bly4, orysj-b9gbs4, orysi-a2zb88, orysj-b9gbs1, orysi-b8b698, orysj-pla4, orysj-pla1 Abstract We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family. Title: Enhanced lipoprotein lipase secretion and foam cell formation by macrophages of patients with growth hormone deficiency: possible contribution to increased risk of atherogenesis? Serri O, Li L, Maingrette F, Jaffry N, Renier G Ref: J Clinical Endocrinology Metab, 89:979, 2004 : PubMed ESTHER: Serri_2004_J.Clin.Endocrinol.Metab_89_979 PubMedSearch: Serri 2004 J.Clin.Endocrinol.Metab 89 979 PubMedID: 14764824 Abstract GH deficiency is associated with increased prevalence of atherosclerosis, and recent data indicate a proatherogenic role for macrophage lipoprotein lipase (LPL) in the arterial wall. In this pilot study, we determined LPL expression and foam cell formation in monocyte-derived macrophages of 12 control subjects and nine patients with GH deficiency without GH replacement therapy. LPL mRNA levels, mass, and activity were increased in macrophages of patients with GH deficiency. In these subjects, macrophage LPL activity correlated with body mass index and fat mass. Incubation of patient macrophages with IGF-I for 24 h or differentiation of monocytes isolated from GH-deficient patients into macrophages in the presence of this growth factor decreased the amount of LPL mass. Compared with control cells, macrophages derived from GH-deficient patients took up and stored increased amounts of proatherogenic lipoproteins and were more easily converted to foam cells. In the supernatants of these cells, increased levels of free fatty acids and TNFalpha were also documented. These results demonstrate that macrophages of patients with GH deficiency secrete increased amounts of proatherogenic cytokines and are more susceptible to foam cell formation. These alterations may contribute to the increased cardiovascular risk in patients with GH deficiency. Title: Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients Christodoulou C, Krupp LB, Liang Z, Huang W, Melville P, Roque C, Scherl WF, Morgan T, MacAllister WS and Peyster R <4 more author(s)> Christodoulou C, Krupp LB, Liang Z, Huang W, Melville P, Roque C, Scherl WF, Morgan T, MacAllister WS, Li L, Tudorica LA, Li X, Roche P, Peyster R (- 4) Ref: Neurology, 60:1793, 2003 : PubMed ESTHER: Christodoulou_2003_Neurology_60_1793 PubMedSearch: Christodoulou 2003 Neurology 60 1793 PubMedID: 12796533 Abstract OBJECTIVE: To relate neuropsychological performance to measures of cerebral injury in persons with MS selected for cognitive impairment. Title: Reactive Oxygen Species Mediate Pyridostigmine-Induced Neuronal Apoptosis: Involvement of Muscarinic and NMDA Receptors Li L, Shou Y, Borowitz JL, Isom GE Ref: Toxicol Appl Pharmacol, 177:17, 2001 : PubMed ESTHER: Li_2001_Toxicol.Appl.Pharmacol_177_17 PubMedSearch: Li 2001 Toxicol.Appl.Pharmacol 177 17 PubMedID: 11708896 Inhibitor(s) related to this paper: Pyridostigmine Abstract Pyridostigmine bromide (PB) is a reversible cholinesterase inhibitor used for treatment of myasthenia gravis and for prophylactic protection against organophosphate nerve agent. We previously showed PB can induce apoptotic death in rat brain following systemic treatment. To study mechanisms by which PB induces brain cell death, cultured rat cerebellar granule cells were used. Cytotoxicity was determined after exposure to PB (10-1000 microM) for 24 h; a high concentration of PB (>500 microM) significantly increased lactate dehydrogenase release, which was reduced by pretreatment with the antioxidant, N-t-butyl-alpha-phenyl-nitrone (PBN). Apoptosis, as determined by TUNEL staining, was concentration dependent (10-250 microM) after a 24-h exposure and cytotoxicity was confirmed by gel electrophoresis of DNA, release of cytochrome c from mitochondria, elevation of caspase activity, and electron microscopy. The oxidant-sensitive fluorescent dye 2',7'-dichlorofluorescin diacetate was used to detect reactive oxidative species (ROS) generation. Pretreatment with PBN, superoxide dismutase, catalase, or the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) blocked PB-induced ROS generation and apoptotic cell death. Pretreatment with atropine or MK-801 blocked ROS generation and the subsequent neurotoxicity, showing that both muscarinic and NMDA receptors mediate the response. DNA extracted from PB-treated cells revealed oligonucleosomal fragmentation on gel electrophoresis and antioxidants attenuated the DNA fragmentation, providing further evidence for a link of ROS generation and apoptosis. These results indicate that muscarinic receptor-mediated ROS generation is an initiating factor in PB-induced apoptotic cell death and activation of the NMDA glutamate receptor is directly linked to the response. Title: The tethered agonist approach to mapping ion channel proteins--toward a structural model for the agonist binding site of the nicotinic acetylcholine receptor Li L, Zhong W, Zacharias N, Gibbs C, Lester HA, Dougherty DA Ref: Chemical Biology, 8:47, 2001 : PubMed ESTHER: Li_2001_Chem.Biol_8_47 PubMedSearch: Li 2001 Chem.Biol 8 47 PubMedID: 11182318 Abstract BACKGROUND: The integral membrane proteins of neurons and other excitable cells are generally resistant to high resolution structural tools. Structure-function studies, especially those enhanced by the nonsense suppression methodology for unnatural amino acid incorporation, constitute one of the most powerful probes of ion channels and related structures. The nonsense suppression methodology can also be used to incorporate functional side chains designed to deliver novel structural probes to membrane proteins. In this vein, we sought to generalize a potentially powerful tool - the tethered agonist approach - for mapping the agonist binding site of ligand-gated ion channels. Title: Muscarinic receptor-mediated pyridostigmine-induced neuronal apoptosis Li L, Gunasekar PG, Borowitz JL, Isom GE Ref: Neurotoxicology, 21:541, 2000 : PubMed ESTHER: Li_2000_Neurotoxicol_21_541 PubMedSearch: Li 2000 Neurotoxicol 21 541 PubMedID: 11022862 Inhibitor(s) related to this paper: Pyridostigmine Abstract Pyridostigmine is a reversible cholinesterase (ChE) inhibitor that is associated with neurologic dysfunction involving both central and peripheral nervous systems. To determine the neurotoxic potential of pyridostigmine, rats were sacrificed at intervals after drug administration (0.5-1.85 mg/kg, i.p., twice daily for 4 days) and brains examined histologically. ChE inhibition was used as a biomarker of pyridostigmine activity. Using the in situ terminal deoxynucleotidyl transferase nick-end labeling of DNA fragments (TUNEL) method and electron microscopy, apoptotic brain cell death was noted in cerebral cortex over a dose range of 0.5-1.85 mg/kg and at the higher dose (1.85 mg/kg), apoptosis was also noted in striatum and hippocampus. These responses were blocked by pretreatment with atropine. Rat cortical cells in culture also underwent apoptosis when exposed to pyridostigmine (250 microM for 24 hr), indicating that the pyridostigmine can initiate apoptosis, independent of peripheral mechanisms. Pretreatment of cells with atropine (10 microM) inhibited pyridostigmine-induced apoptosis, confirming the response was mediated by muscarinic receptors. Short term treatment of rats with pyridostigmine (1.85 mg/kg twice daily for 4 days) induced a prolonged apoptotic response, which was evident in rat cortex up to 30 days after the last dose. Active apoptosis persisted, despite recovery of serum ChE activity. These in vivo and in vitro observations indicate that pyridostigmine can initiate a prolonged neurodegeneration. Title: Effects of a traditional Chinese medicine, Qing Nao Yi Zhi Fang, on glutamate excitotoxicity in rat fetal cerebral neuronal cells in primary culture Zhang J, Li L, Chen X, Zhang B, Wang Y, Yamamoto K Ref: Neuroscience Letters, 290:21, 2000 : PubMed ESTHER: Zhang_2000_Neurosci.Lett_290_21 PubMedSearch: Zhang 2000 Neurosci.Lett 290 21 PubMedID: 10925165 Abstract Qing Nao Yi Zhi Fang (QNYZ), a traditional Chinese medicine, has been developed as a drug to be used for the prevention and treatment of vascular dementia. However, the mechanisms by which this drug affects vascular dementia remain unknown. We examined the effects of QNYZ serum on glutamate excitotoxicity in rat fetal cerebral neuronal cells in primary culture. Exposure of neuronal cells to glutamate leads to a decrease in the activities of cholinesterase, superoxide dismutase, and streptoavidin peroxidase, and an increase in lactate dehydrogenase release. These enzyme activities were restored to the levels in untreated cells by the addition of QNYZ serum. QNYZ serum suppressed the increased nitric oxide production induced by glutamate and prevented glutamate-mediated apoptosis. QNYZ serum also improved mitochondrial energy metabolism after glutamate exposure. These findings suggest that QNYZ has protective effects against glutamate-mediated excitotoxicity in neuronal cells during ischemic brain injury. Title: [A gene analysis of familial lipoprotein lipase deficiency in China] Shen J, Chen R, Hu W, Bingshen KE, Li L, Du Y, Liu Y Ref: Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 16:233, 1999 : PubMed ESTHER: Shen_1999_Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi_16_233 PubMedSearch: Shen 1999 Zhonghua.Yi.Xue.Yi.Chuan.Xue.Za.Zhi 16 233 PubMedID: 10431049 Abstract OBJECTIVE: To investigate the gene mutation of lipoprotein lipase(LPL) of familial LPL deficiency in China. Title: Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice Weng W, Li L, van Bennekum AM, Potter SH, Harrison EH, Blaner WS, Breslow JL, Fisher EA Ref: Biochemistry, 38:4143, 1999 : PubMed ESTHER: Weng_1999_Biochemistry_38_4143 PubMedSearch: Weng 1999 Biochemistry 38 4143 PubMedID: 10194330 Abstract Carboxyl ester lipase (CEL; EC 3.1.1.13) hydrolyzes cholesteryl esters and retinyl esters in vitro. In vivo, pancreatic CEL is thought to liberate cholesterol and retinol from their esters prior to absorption in the intestine. CEL is also a major lipase in the breast milk of many mammals, including humans and mice, and is thought to participate in the processing of triglycerides to provide energy for growth and development while the pancreas of the neonate matures. Other suggested roles for CEL include the direct facilitation of the intestinal absorption of free cholesterol and the modification of plasma lipoproteins. Mice with different CEL genotypes [wild type (WT), knockout (CELKO), heterozygote] were generated to study the functions of CEL in a physiological system. Mice grew and developed normally, independent of the CEL genotype of the pup or nursing mother. Consistent with this was the normal absorption of triglyceride in CELKO mice. The absorption of free cholesterol was also not significantly different between CELKO (87 +/- 26%, mean +/- SD) and WT littermates (76 +/- 10%). Compared to WT mice, however, CELKO mice absorbed only about 50% of the cholesterol provided as cholesteryl ester (CE). There was no evidence for the direct intestinal uptake of CE or for intestinal bacterial enzymes that hydrolyze it, suggesting that another enzyme besides CEL can hydrolyze dietary CE in mice. Surprisingly, CELKO and WT mice absorbed similar amounts of retinol provided as retinyl ester (RE). RE hydrolysis, however, was required for absorption, implying that CEL was not the responsible enzyme. The changes in plasma lipid and lipoprotein levels to diets with increasing lipid content were similar in mice of all three CEL genotypes. Overall, the data indicate that in the mouse, other enzymes besides CEL participate in the hydrolysis of dietary cholesteryl esters, retinyl esters, and triglycerides. Title: [Neurotoxicity of antibody against motoneuron on cultured rat cortical neurons] Gao Y, Li Y, Lin J, Li L, Wan X Ref: Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 20:296, 1998 : PubMed ESTHER: Gao_1998_Zhongguo.Yi.Xue.Ke.Xue.Yuan.Xue.Bao_20_296 PubMedSearch: Gao 1998 Zhongguo.Yi.Xue.Ke.Xue.Yuan.Xue.Bao 20 296 PubMedID: 11367695 Abstract OBJECTIVE In order to determine the role of antibody against motoneuron in the process of neuronal death. METHODS: Cultured rat cortical neurons growing in serum-free medium, were employed to observe the effects of antibody against motoneuron (anti-SMN) on the survival of these cultured neurons. RESULTS: (1) Exposure of the cultures in serum-free medium to anti-SMN with dilution of 1:50 results in death of 31%-41% of neurons for 24 hours incubation, 50%-67% for 48 hours and above 90% after 72 hours. The neurotoxicity induced by anti-SMN was accompanied by concentration-dependent release of lactate dehydrogenase into the culture medium. Cultures exposed to normal rat IgG as controls exhibited no such sign. (2) The cultured neurons exposed to anti-SMN (1:200) expressed markedly higher levels of immunoreactive Calbindin-D28k especially after 48 hours incubation with it. There was a reduction in the number of acetylcholinesterase-positive neurons compared to the normal control. Title: [The mechanisms of pathogenesis in Alzheimer's disease] Li L Ref: Sheng Li Ke Xue Jin Zhan, 29:345, 1998 : PubMed ESTHER: Li_1998_Sheng.Li.Ke.Xue.Jin.Zhan_29_345 PubMedSearch: Li 1998 Sheng.Li.Ke.Xue.Jin.Zhan 29 345 PubMedID: 12501666 Title: From ab initio quantum mechanics to molecular neurobiology: a cation-pi binding site in the nicotinic receptor Zhong W, Gallivan JP, Zhang Y, Li L, Lester HA, Dougherty DA Ref: Proc Natl Acad Sci U S A, 95:12088, 1998 : PubMed ESTHER: Zhong_1998_Proc.Natl.Acad.Sci.U.S.A_95_12088 PubMedSearch: Zhong 1998 Proc.Natl.Acad.Sci.U.S.A 95 12088 PubMedID: 9770444 Abstract The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that cation-pi interactions may be involved in binding the quaternary ammonium group of the agonist, acetylcholine. Here we show a compelling correlation between: (i) ab initio quantum mechanical predictions of cation-pi binding abilities and (ii) EC50 values for acetylcholine at the receptor for a series of tryptophan derivatives that were incorporated into the receptor by using the in vivo nonsense-suppression method for unnatural amino acid incorporation. Such a correlation is seen at one, and only one, of the aromatic residues-tryptophan-149 of the alpha subunit. This finding indicates that, on binding, the cationic, quaternary ammonium group of acetylcholine makes van der Waals contact with the indole side chain of alpha tryptophan-149, providing the most precise structural information to date on this receptor. Consistent with this model, a tethered quaternary ammonium group emanating from position alpha149 produces a constitutively active receptor. Title: Brain-derived neurotrophic factor fails to arrest neuromuscular disorders in the paralyse mouse mutant, a model of motoneuron disease Blondet B, Murawsky M, Houenou LJ, Li L, Ait-Ikhlef A, Yan Q, Rieger F Ref: Journal of Neurology Sci, 153:20, 1997 : PubMed ESTHER: Blondet_1997_J.Neurol.Sci_153_20 PubMedSearch: Blondet 1997 J.Neurol.Sci 153 20 PubMedID: 9455973 Abstract Several new neurotrophic factors have been recently identified and shown to prevent motoneuron death in vitro and in vivo. One such agent is brain-derived neurotrophic factor (BDNF). In this study, we tested BDNF on an animal model of early-onset motoneuron disease: the paralyse mouse mutant, characterized by a progressive skeletal muscle atrophy and the loss of 30-35% of spinal lumbar motoneurons between the first and second week post-natal. The results show that subcutaneous injections of 1 or 10 mg/kg BDNF did not have any significant effect in increasing the mean survival time of mutant mice or in preventing the loss of motor function and total body weight in paralyse mice. The weight and choline acetyltransferase activity of specific muscles and the number of motoneurons in the spinal cords were identical in BDNF-treated and placebo-injected paralyse mice. These results suggest that BDNF does not act on the disease process in paralyse mice in the conditions we used. By contrast, BDNF has previously been shown to partially prevent the loss of motor function in the wobbler mouse, a suggested model of later-onset motoneuron disease. Taken together these findings suggest that BDNF acts differently on early and late-onset motoneuron diseases. It is however possible that treatment of paralyse mice with BDNF or combinations of different neurotrophic factors prior to the phenotypical expression of the paralyse mutation may prevent the loss of motor function and motoneurons in mutant mice. Title: [An animal model of non-hereditary Alzheimer's disease and its behavioral and pathologic changes] Li L Ref: Sheng Li Ke Xue Jin Zhan, 28:325, 1997 : PubMed ESTHER: Li_1997_Sheng.Li.Ke.Xue.Jin.Zhan_28_325 PubMedSearch: Li 1997 Sheng.Li.Ke.Xue.Jin.Zhan 28 325 PubMedID: 11038683 Abstract An animal model of non-hereditary AD was built by lesioning nucleus basalis of Meynert (nbM) and to investigate the behavioral alteration by Morris water maze, the pathological changes by special staining for senile plaques(SPs), enzymatic cytochemical staining for AChE, and immunocytochemical staining for beta amyloid protein (beta AP) and tau protein. Transmission electron microscopic observation has also been made. Results showed: (1) loss of learning and memory ability; (2) occurrence of necrotic granules in cytoplasm and inclusion in axon hillock; accumulation of necrotic cell, and formation of SPs under light microscope; (3) accumulation of microtubules and formation of inclusion, increase of lysosome and edema and vacuolation of neurons and neuroterminals under electron microscopy; (4) decrease of synaptic density; (5) sharp decrease of AChE (acetylcholinesterase) positive fibers and neurons shown by immunocytochemical staining; (6) overexpression of beta AP and tau protein. Title: The paralyse mouse mutant: a new animal model of anterior horn motor neuron degeneration Houenou LJ, Blondet B, Li L, Murawsky M, Oppenheim RW, Rieger F Ref: J Neuropathol Experimental Neurology, 55:698, 1996 : PubMed ESTHER: Houenou_1996_J.Neuropathol.Exp.Neurol_55_698 PubMedSearch: Houenou 1996 J.Neuropathol.Exp.Neurol 55 698 PubMedID: 8642395 Abstract The survival and morphometric characteristics of lumbar spinal motoneurons were examined in the paralyse mouse mutant. Affected (par/par) mice can be first recognized at approximately postnatal day (PN) 7 to 8 and are characterized by their smaller-than-normal body size, a progressive generalized muscle weakness, and lack of coordination. Mutant mice die by PN16-18, when they have become almost completely paralyzed. Previously, we have shown that this mutation involves alteration of several developmental aspects of the neuromuscular system. However, whether ventral (or anterior) horn motoneurons degenerate and die during the course of the disease was unknown. We report here that at the time the mutant phenotype can be first identified (i.e. approximately PN8), lumbar motoneuron numbers in the lateral motor column of the spinal cord of paralyse mice were not significantly different from those of control littermates. In contrast, by PN14, there was a significant (30 to 35%) decrease in motoneuron numbers in mutant compared to control mice. Furthermore, motoneuron (nuclear and soma) sizes were significantly decreased in the mutants at both stages examined, i.e. PN8 and PN14. These results show that the paralyse mutation involves atrophy and subsequent death of anterior horn motoneurons. Together with the rapid progression and the severity of the disease, these results suggest that the paralyse mouse may represent a good animal model for studying early-onset human motor neuron diseases such as spinal muscular atrophy. | ||||||||||||||||||||||||||||||||||||||||||||||||||
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