Author Report for: Yang RNo contact information in database for Yang R
He Z, Chen Y, Huo D, Gao J, Xu Y, Yang R, Yang Y, Yu G Ref: Environ Pollut, :121250, 2023 : PubMed ESTHER: He_2023_Environ.Pollut__121250 PubMedSearch: He 2023 Environ.Pollut 121250 PubMedID: 36813104 Abstract Global water bodies are now at risk from inevitable cyanobacterial blooms and their production of multiple cyanotoxins, in particular cylindrospermopsin (CYN). However, research on the CYN toxicity and its molecular mechanisms is still limited, whilst the responses of aquatic species against CYN are uncovered. By integrating behavioral observations, chemical detections and transcriptome analysis, this study demonstrated that CYN exerted multi-organ toxicity to model species, Daphnia magna. The present study confirmed that CYN could cause protein inhibition by undermining total protein contents, and altered the gene expression related to proteolysis. Meantime, CYN induced oxidative stress by increasing reactive oxidative species (ROS) level, decreasing the glutathione (GSH) concentration, and interfered with protoheme formation process molecularly. Neurotoxicity led by CYN was solidly determined by abnormal swimming patterns, reduced acetylcholinesterase (AChE), and downward expression of muscarinic acetylcholine receptor (CHRM). Importantly, for the first time, this research determined CYN directly interfered with energy metabolism in cladocerans. CYN distinctively reduced filtration and ingestion rate by targeting on heart and thoracic limbs, which declined the energy intake, and could be further displayed by the reduction of motional strength and the trypsin concentration. These phenotypic alterations were supported by transcriptomic profile, including the down-regulation of oxidative phosphorylation and ATP synthesis. Moreover, CYN was speculated to trigger the self-defense responses of D. magna, known as "abandon-ship" by moderating lipid metabolism and distribution. This study, overall, comprehensively demonstrated the CYN toxicity and the responses of D. magna against it, which is of great significance to the advancements of CYN toxicity knowledge. Title: Discovery and mechanism-guided engineering of BHET hydrolases for improved PET recycling and upcycling Li A, Sheng Y, Cui H, Wang M, Wu L, Song Y, Yang R, Li X, Huang H Ref: Nat Commun, 14:4169, 2023 : PubMed ESTHER: Li_2023_Nat.Commun_14_4169 PubMedSearch: Li 2023 Nat.Commun 14 4169 PubMedID: 37443360 Gene_locus related to this paper: 9flao-ChryBHETase, bacsu-pnbae Abstract Although considerable research achievements have been made to address the plastic crisis using enzymes, their applications are limited due to incomplete degradation and low efficiency. Herein, we report the identification and subsequent engineering of BHETases, which have the potential to improve the efficiency of PET recycling and upcycling. Two BHETases (ChryBHETase and BsEst) are identified from the environment via enzyme mining. Subsequently, mechanism-guided barrier engineering is employed to yield two robust and thermostable deltaBHETases with up to 3.5-fold enhanced k(cat)/K(M) than wild-type, followed by atomic resolution understanding. Coupling deltaBHETase into a two-enzyme system overcomes the challenge of heterogeneous product formation and results in up to 7.0-fold improved TPA production than seven state-of-the-art PET hydrolases, under the conditions used here. Finally, we employ a deltaBHETase-joined tandem chemical-enzymatic approach to valorize 21 commercial post-consumed plastics into virgin PET and an example chemical (p-phthaloyl chloride) for achieving the closed-loop PET recycling and open-loop PET upcycling. Title: Broad-Specificity Screening of Pyrethroids Enabled by the Catalytic Function of Human Serum Albumin on Coumarin Hydrolysis Liang Z, Sun Y, Zeng H, Qin H, Yang R, Qu L, Zhang K, Li Z Ref: Analytical Chemistry, :, 2023 : PubMed ESTHER: Liang_2023_Anal.Chem__ PubMedSearch: Liang 2023 Anal.Chem PubMedID: 36952638 Abstract Sensing systems based on cholinesterase and carboxylesterase coupled with different transduction technologies have emerged for pesticide screening owing to their simple operation, fast response, and suitability for on-site analysis. However, the broad spectrum and specificity screening of pyrethroids over organophosphates and carbamates remains an unmet challenge for current enzymatic sensors. Human serum albumin (HSA), a multifunctional protein, can promote various chemical transformations and show a high affinity for pyrethroids, which offer a route for specific and broad-spectrum pyrethroid screening. Herein, for the first time, we evaluated the catalytic hydrolysis function of human serum albumin (HSA) on the coumarin lactone bond and revealed that HSA can act as an enzyme to catalyze the hydrolysis of the coumarin lactone bond. Molecular docking and chemical modifications indicate that lysine 199 and tyrosine 411 serve as the catalytic general base and contribute to most of the catalytic activity. Utilizing this enzymatic activity, a broad specific ratiometric fluorescence pyrethroids sensing system was developed. The binding energetics and binding constants of pesticides and HSA show that pyrethroids bind to HSA more easily than organophosphates and carbamates, which is responsible for the specificity of the sensing system. This study provides a general sensor platform and strategy for screening pesticides and reveals the catalytic activity of HSA on the hydrolysis of the coumarin lactone bond, which may open innovative horizons for the chemical sensing and biomedical applications of HSA. Title: Acute thermal stress increased enzyme activity and muscle energy distribution of yellowfin tuna Liu H, Yang R, Fu Z, Yu G, Li M, Dai S, Ma Z, Zong H Ref: PLoS ONE, 18:e0289606, 2023 : PubMed ESTHER: Liu_2023_PLoS.One_18_e0289606 PubMedSearch: Liu 2023 PLoS.One 18 e0289606 PubMedID: 37796965 Abstract Heat is a powerful stressor for fish living in natural and artificial environments. Understanding the effects of heat stress on the physiological processes of fish is essential for better aquaculture and fisheries management. In this experiment, a heating rod was used to increase the temperature at 2 degreesC/h to study the changes of energy allocation (CEA) and energy metabolity-related enzyme activities, including pepsin, trypsin, amylase, lipase, acid phosphatase, lactate dehydrogenase, alanine aminotransferase, glutamic oxalic aminotransferase and energy reserve (Ea), energy expenditure (ETS), in juvenile yellowfin tuna cells under acute temperature stress. The results showed that the Ea of juvenile yellowfin tuna muscles in response to high temperature (34 degreesC) was significantly lower than that of the control (28 degreesC), and it also increased ETS. At 6 h, CEA decreased slightly in the high-temperature group, but, the difference in CEA between 24 h and 0 h decreased. After heat stress for 6 h, the activities of acid phosphatase (ACP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and glutamic oxalacetic transaminase (AST) increased, indicating that the metabolic rate was accelerated. After heat stress for 24 h, the activity of ALT decreased, indicating that with time elapsed, the activities of some protein metabolizing enzymes increased, and some decreased. In this study, digestive enzymes, trypsin and lipase increased gradually. After heat stress, Ea and Ec change significantly. Yellowfin tuna muscles use lipids in response to sharp temperature increases at high temperatures, red muscles respond to temperature changes by increasing energy in the early stages, but not nearly as much, and white muscles reduce lipids. Title: Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma Chen X, Liu Q, Chen Y, Wang L, Yang R, Zhang W, Pan X, Zhang S, Chen C and Ren X <3 more author(s)> Chen X, Liu Q, Chen Y, Wang L, Yang R, Zhang W, Pan X, Zhang S, Chen C, Wu T, Xia J, Cheng B, Ren X (- 3) Ref: Mol Metab, :101600, 2022 : PubMed ESTHER: Chen_2022_Mol.Metab__101600 PubMedSearch: Chen 2022 Mol.Metab 101600 PubMedID: 36113774 Abstract OBJECTIVE: Oral squamous cell carcinoma (OSCC) is characterized by high recurrence and metastasis and places a heavy burden on societies worldwide. Cancer cells thrive in a changing microenvironment by reprogramming lipidomic metabolic processes to provide nutrients and energy, activate oncogenic signaling pathways, and manage redox homeostasis to avoid lipotoxicity. The mechanism by which OSCC cells maintain lipid homeostasis during malignant progression is unclear. METHODS: The altered expression of fatty acid (FA) metabolism genes in OSCC, compared with that in normal tissues, and in OSCC patients with or without recurrence or metastasis were determined using public data from the TCGA and GEO databases. Immunohistochemistry was performed to examine the carboxylesterase 2 (CES2) protein level in our own cohort. CCK-8 and Transwell assays and an in vivo xenograft model were used to evaluate the biological functions of CES2. Mass spectrometry and RNA sequencing were performed to determine the lipidome and transcriptome alterations induced by CES2. Mitochondrial mass, mtDNA content, mitochondrial membrane potential, ROS levels, and oxygen consumption and apoptosis rates were evaluated to determine the effects of CES2 on mitochondrial function in OSCC. RESULTS: CES2 was downregulated in OSCC patients, especially those with recurrence or metastasis. CES2(high) OSCC patients showed better overall survival than CES2(low) OSCC patients. Restoring CES2 expression reduced OSCC cell viability and suppressed their migration and invasion in vitro, and it inhibited OSCC tumor growth in vivo. CES2 reprogrammed lipid metabolism in OSCC cells by hydrolyzing neutral lipid diacylglycerols (DGs) to release free fatty acids and reduce the membrane structure lipid phospholipids (PLs) synthesis. Free FAs were converted to acyl-carnitines (CARs) and transferred to mitochondria for oxidation, which induced reactive oxygen species (ROS) accumulation, mitochondrial damage, and apoptosis activation. Furthermore, the reduction in signaling lipids, e.g., DGs, PLs and substrates, suppressed PI3K/AKT/MYC signaling pathways. Restoring MYC rescued the diminished cell viability, suppressed migratory and invasive abilities, damaged mitochondria and reduced apoptosis rate induced by CES2. CONCLUSIONS: We demonstrated that CES2 downregulation plays an important role in OSCC by maintaining lipid homeostasis and reducing lipotoxicity during tumor progression and may provide a potential therapeutic target for OSCC. Title: Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment Wang Y, Wu X, Yang K, Liu Q, Jiang B, Yang R, Xiao P, He C Ref: Front Pharmacol, 13:952876, 2022 : PubMed ESTHER: Wang_2022_Front.Pharmacol_13_952876 PubMedSearch: Wang 2022 Front.Pharmacol 13 952876 PubMedID: 36034803 Abstract Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mgkg-1, p < 0.05; SB 60 mgkg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1beta, IL-6, and TNF-alpha, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark. Title: IrO(2) clusters loaded on dendritic mesoporous silica nanospheres with superior peroxidase-like activity for sensitive detection of acetylcholinesterase and its inhibitors Xiao W, Cai S, Wu T, Fu Z, Liu X, Wang C, Zhang W, Yang R Ref: J Colloid Interface Sci, 635:481, 2022 : PubMed ESTHER: Xiao_2022_J.Colloid.Interface.Sci_635_481 PubMedSearch: Xiao 2022 J.Colloid.Interface.Sci 635 481 PubMedID: 36599245 Abstract Nanomaterials-based enzyme mimics (nanozymes), by simulating enzyme catalysis, have shown potential in numerous biocatalytic applications, but nanozymes face significant challenges of catalytic activity and reusability that may restrict their practical uses. Herein, we report facile fabrication of surface-clean IrO(2) clusters supported on dendritic mesoporous silica nanospheres (DMSNs), which exhibit superior peroxidase-like activity, high thermal/long-term stability, and good recyclability. The IrO(2) clusters (1.4s+/-s0.2snm in size) are obtained by the laser ablation without any ligands and possess negative surface charge, which are efficiently loaded on the amino-functionalized DMSNs by electrostatic adsorption. Owing to morphological and structural advantages, the resulted DMSN/IrO(2) heterostructure displays outstanding peroxidase-like catalytic performance. Compared with horseradish peroxidase, it shows comparable affinities but higher reaction rate (2.95sxs10(-7)sM.s(-1)) towards H(2)O(2), resulting from rapid electron transfer during the catalysis. This value is also larger than those of mesoporous silicas supported metal or metal oxides nanoparticles/clusters in the previous studies. Benefitting from excellent peroxidase-catalysis of the DMSN/IrO(2), the colorimetric assays are further successfully established for the detection of acetylcholine esterase and its inhibitor, showing high sensitivity and selectivity. The work provides novel design of supported nanozymes for biosensing. Title: A Proof-of-Concept Inhibitor of Endothelial Lipase Suppresses Triple-Negative Breast Cancer Cells by Hijacking the Mitochondrial Function Yang R, Han S, Clayton J, Haghighatian M, Tsai CC, Yao Y, Li P, Shen J, Zhou Q Ref: Cancers (Basel), 14:3763, 2022 : PubMed ESTHER: Yang_2022_Cancers.(Basel)_14_3763 PubMedSearch: Yang 2022 Cancers.(Basel) 14 3763 PubMedID: 35954428 Gene_locus related to this paper: human-LIPG Inhibitor(s) related to this paper: Cynaroside Abstract Triple-negative breast cancer (TNBC) cells reprogram their metabolism to provide metabolic flexibility for tumor cell growth and survival in the tumor microenvironment. While our previous findings indicated that endothelial lipase (EL/LIPG) is a hallmark of TNBC, the precise mechanism through which LIPG instigates TNBC metabolism remains undefined. Here, we report that the expression of LIPG is associated with long non-coding RNA DANCR and positively correlates with gene signatures of mitochondrial metabolism-oxidative phosphorylation (OXPHOS). DANCR binds to LIPG, enabling tumor cells to maintain LIPG protein stability and OXPHOS. As one mechanism of LIPG in the regulation of tumor cell oxidative metabolism, LIPG mediates histone deacetylase 6 (HDAC6) and histone acetylation, which contribute to changes in IL-6 and fatty acid synthesis gene expression. Finally, aided by a relaxed docking approach, we discovered a new LIPG inhibitor, cynaroside, that effectively suppressed the enzyme activity and DANCR in TNBC cells. Treatment with cynaroside inhibited the OXPHOS phenotype of TNBC cells, which severely impaired tumor formation. Taken together, our study provides mechanistic insights into the LIPG modulation of mitochondrial metabolism in TNBC and a proof-of-concept that targeting LIPG is a promising new therapeutic strategy for the treatment of TNBC. Title: A Novel Lipase from Lasiodiplodia theobromae Efficiently Hydrolyses C8-C10 Methyl Esters for the Preparation of Medium-Chain Triglycerides' Precursors Ng AMJ, Yang R, Zhang H, Xue B, Yew WS, Nguyen GKT Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Ng_2021_Int.J.Mol.Sci_22_10339 PubMedSearch: Ng 2021 Int.J.Mol.Sci 22 10339 PubMedID: 34638680 Gene_locus related to this paper: 9pezi-a0a5n5dna6 Abstract Medium-chain triglycerides (MCTs) are an emerging choice to treat neurodegenerative disorders such as Alzheimer's disease. They are triesters of glycerol and three medium-chain fatty acids, such as capric (C8) and caprylic (C10) acids. The availability of C8-C10 methyl esters (C8-C10 ME) from vegetable oil processes has presented an opportunity to use methyl esters as raw materials for the synthesis of MCTs. However, there are few reports on enzymes that can efficiently hydrolyse C8-C10 ME to industrial specifications. Here, we report the discovery and identification of a novel lipase from Lasiodiplodia theobromae fungus (LTL1), which hydrolyses C8-C10 ME efficiently. LTL1 can perform hydrolysis over pH ranges from 3.0 to 9.0 and maintain thermotolerance up to 70 degreesC. It has high selectivity for monoesters over triesters and displays higher activity over commercially available lipases for C8-C10 ME to achieve 96.17% hydrolysis within 31 h. Structural analysis by protein X-ray crystallography revealed LTL1's well-conserved lipase core domain, together with a partially resolved N-terminal subdomain and an inserted loop, which may suggest its hydrolytic preference for monoesters. In conclusion, our results suggest that LTL1 provides a tractable route towards to production of C8-C10 fatty acids from methyl esters for the synthesis of MCTs. Title: Optimization of fermentation conditions for the production of recombinant feruloyl esterase from Burkholderia pyrrocinia B1213 Fan G, Zhu Y, Fu Z, Sun B, Teng C, Yang R, Li X Ref: 3 Biotech, 10:216, 2020 : PubMed ESTHER: Fan_2020_3.Biotech_10_216 PubMedSearch: Fan 2020 3.Biotech 10 216 PubMedID: 32355590 Gene_locus related to this paper: 9burk-BpFae Abstract Statistical experimental designs were used to optimize conditions for recombinant Burkholderia pyrrocinia feruloyl esterase (BpFae) production in bacteria under lactose induction. After optimization by single factor design, Plackett-Burman design, steepest ascent design and the response surface method, the optimal conditions for BpFae production were: 6 g/L lactose, pH 5.5, pre-induced period 5 h, 23 degreesC, shaker rotational speed of 240 rpm, medium volume of 50 mL/250 mL, inoculum size 0.2% (v/v), and a post-induced period of 32 h in a Luria-Bertani culture. The produced BpFae activity was 7.43 U/mL, which is 2.92 times higher than that obtained under optimal conditions using IPTG as the inducer. BpFae activity was 4.82 U/mL in a 5 L fermenter under the abovementioned optimal conditions. BpFae produced a small amount of ethyl acetate but had no effect on the synthesis of other important esters in Baijiu. The results underpin further investigations into BpFae characterization and potential applications. Title: Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways Ji X, Li N, Ma M, Rao K, Yang R, Wang Z Ref: Environ Pollut, 264:114747, 2020 : PubMed ESTHER: Ji_2020_Environ.Pollut_264_114747 PubMedSearch: Ji 2020 Environ.Pollut 264 114747 PubMedID: 32559878 Inhibitor(s) related to this paper: Tri-M-cresyl-phosphate, Tri-o-cresylphosphate Abstract Tricresyl phosphates (TCPs), as representative aromatic organophosphate flame retardants (OPFRs), have received much attention due to their potential neurotoxicity and endocrine-disrupting effects. However, the role of estrogen receptor alpha (ERalpha) and G protein-coupled estrogen receptor (GPER) in their estrogen disrupting effects remains poorly understood. Therefore, in this study, three TCP isomers, tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) and tri-p-cresyl phosphate (TpCP), were examined for their activities on ERalpha by using two-hybrid yeast assay, and action on GPER by using Boyden chamber assay, cAMP production assay, calcium mobilization assay and molecular docking analysis. The results showed that three TCP isomers were found to act as ERalpha antagonists. Conversely, they had agonistic activity on GPER to promote GPER-mediated cell migration of MCF7 cells and SKBR3 cells. Both ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP had different mode of action, it only triggered GPER-mediated calcium mobilization, as evidenced by using the specific GPER inhibitor (G15) and GPER overexpressing experiments. Molecular docking further revealed that the way of interaction of TmCP and TpCP with GPER was different from that of ToCP with GPER, and higher activity of ToCP in activating GPER-mediated pathways might be associated with the alkyl substitution at the ortho position of the aromatic ring. Our results, for the first time, found a new target, GPER, for TCPs exerting their estrogen-disrupting effects, and demonstrated complex estrogen-disrupting effects of three TCP isomers involved their opposite activities toward ERalpha and GPER. Title: Single and combined effects of carbamazepine and copper on nervous and antioxidant systems of zebrafish (Danio rerio) Jia D, Li X, Du S, Xu N, Zhang W, Yang R, Zhang Y, He Y Ref: Environ Toxicol, :, 2020 : PubMed ESTHER: Jia_2020_Environ.Toxicol__ PubMedSearch: Jia 2020 Environ.Toxicol PubMedID: 32485069 Abstract Various pollutants co-exist in the aquatic environment such as carbamazepine (CBZ) and copper (Cu), which can cause complex effects on inhabiting organisms. The toxic impacts of the single substance have been studied extensively. However, the studies about their combined adverse impacts are not enough. In the present study, zebrafish were exposed to environmental relevant concentrations of CBZ (1, 10, and 100 mug/L), Cu (0.5, 5, and 10 mug/L) and the mixtures (1 mug/L CBZ + 0.5 mug/L Cu, 10 mug/L CBZ + 5 mug/L Cu, 100 mug/L CBZ + 10 mug/L Cu) for 45 days, the effects on nervous and antioxidant systems of zebrafish were investigated. The results demonstrated that, in comparison with single exposure group, the combined presence of CBZ and Cu exacerbated the effect of antioxidant system (the ability of inhibition of hydroxyl radicals (IHR), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)) but not nervous system (Acetylcholinesterase [AChE]). The qPCR results supported the changes of corresponding enzymes activities. Hepatic histopathological analysis verified the results of biomarkers. Our work illustrated that the toxicity of mixed pollutants is very complicated, which cannot simply be inferred from the toxicity of single pollutant, and calls for more co-exposure experiments to better understanding of the co-effects of pollutants on aquatic organisms. Title: Thiol-suppressed I(2)-etching of AuNRs: acetylcholinesterase-mediated colorimetric detection of organophosphorus pesticides Qing Z, Li Y, Luo G, Hu J, Zou Z, Lei Y, Liu J, Yang R Ref: Mikrochim Acta, 187:497, 2020 : PubMed ESTHER: Qing_2020_Mikrochim.Acta_187_497 PubMedSearch: Qing 2020 Mikrochim.Acta 187 497 PubMedID: 32803418 Abstract For the first time it is demonstrated that sulfhydryl compounds can suppress longitudinal etching of gold nanorods via consuming oxidizers, which provides a new signaling mechanism for colorimetric sensing. As a proof of concept, a colorimetric assay is developed for detecting organophosphorus pesticides, which are most widely used in modern agriculture to improve food production but with high toxicity to animals and the ecological environment. Triazophos was selected as a model organophosphorus pesticide. In the absence of triazophos, the active acetylcholinesterase can catalyze the conversion of acetylthiocholine iodide to thiocholine whose thiol group can suppress the I(2)-induced etching of gold nanorods. When triazophos is present, the activity of AchE is inhibited, and I(2)-induced etching of gold nanorods results in triazophos concentration-dependent color change from brown to blue, pink, and red. The aspect ratio of gold nanorods reduced with gradually blue-shifted longitudinal absorption. There was a linear detection range from 0 to 117 nM (R(2) = 0.9908), the detection limit was 4.69 nM, and a good application potential was demonstrated by the assay of real water samples. This method will not only contribute to public monitoring of organophosphorus pesticides but also has verified a new signaling mechanism which will open up a new path to develop colorimetric detection methods. It has been first found that sulfhydryl compounds can suppress longitudinal etching of gold nanorods (AuNRs) via consuming oxidizers, which provides a new signaling mechanism for colorimetric sensing. As a proof of concept, a colorimetric assay is developed for sensitively detecting organophosphorus pesticides (OPs). It will not only contribute to public monitoring of OPs but also has verified a new signaling mechanism which will open up a new path to develop multicolor colorimetric methods. 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: Identification of Reversible Small Molecule Inhibitors of Endothelial Lipase (EL) That Demonstrate HDL-C Increase In Vivo Tora G, Kim SH, Pi Z, Johnson JA, Jiang J, Phillips M, Lloyd J, Abell LM, Lu H and Finlay HJ <17 more author(s)> Tora G, Kim SH, Pi Z, Johnson JA, Jiang J, Phillips M, Lloyd J, Abell LM, Lu H, Locke G, Adam LP, Taylor DS, Yin X, Behnia K, Zhao L, Yang R, Basso M, Caporuscio C, Chen AY, Liu E, Kirshgessner T, Onorato JM, Ryan C, Traeger SC, Gordon D, Wexler RR, Finlay HJ (- 17) Ref: Journal of Medicinal Chemistry, 63:1660, 2020 : PubMed ESTHER: Tora_2020_J.Med.Chem_63_1660 PubMedSearch: Tora 2020 J.Med.Chem 63 1660 PubMedID: 31990537 Abstract Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting in reduction in plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained plasma high-density lipoprotein cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery of a series of oxadiazole ketones, which upon optimization, led to the identification of compound 12. Compound 12 was evaluated in a mouse pharmacodynamics (PD) model and demonstrated a 56% increase in plasma HDL-C. In a mouse reverse cholesterol transport study, compound 12 stimulated cholesterol efflux by 53% demonstrating HDL-C functionality. Title: miR-2382-5p Regulates Lipid Metabolism by Targeting NDRG2 in Mammary Epithelial Cells of Dairy Cattle Xia L, Zhao Z, Yang R, Jiang P, Liu Y, Yu H, Bai Z, Mi J, Yu X, Fang X Ref: DNA & Cell Biology, :, 2020 : PubMed ESTHER: Xia_2020_DNA.Cell.Biol__ PubMedSearch: Xia 2020 DNA.Cell.Biol PubMedID: 33124928 Abstract microRNA is a class of single-stranded RNA molecules of about 22-24 nucleotides in length, which regulate a variety of biological processes, including lipid metabolism and triglyceride synthesis at transcriptional and translational levels by degrading target mRNAs or interfering with the protein production. In this study, the effect of miR-2382-5p on triglyceride levels was examined in bovine mammary epithelial cells (BMECs), and the results showed that miR-2382-5p could decrease the content of triglyceride. Furthermore, miR-2382-5p regulated the expression of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma co-activator 1beta (PPARGC1B), hormone-sensitive lipase (HSL), and peroxisome proliferator-activated receptor gamma (PPARgamma), which are known to increase triglyceride decomposition in lipid metabolism. Luciferase reporter assay and quantitative real-time PCR (qPCR) validated that miR-2382-5p downregulated the mRNA expression of target gene N-myc downstream-regulated gene 2 (NDRG2) by specifically recognizing and binding to its 3'-untranslated region (UTR). Meanwhile, overexpression of NDRG2 led to increased triglyceride and cholesterol production in BMECs. In summary, this study suggested that miR-2382-5p regulated lipid metabolism by targeting NDRG2, which might be a potential target for molecular manipulation of milk fat composition to produce healthy milk. This study also provided basic data for further understanding lipid metabolism in dairy cattle. Title: Identification of substituted benzothiazole sulfones as potent and selective inhibitors of endothelial lipase Kim SH, Johnson JA, Jiang J, Parkhurst B, Phillips M, Pi Z, Qiao JX, Tora G, Ye Chen A and Finlay HJ <16 more author(s)> Kim SH, Johnson JA, Jiang J, Parkhurst B, Phillips M, Pi Z, Qiao JX, Tora G, Ye Chen A, Liu E, Yin X, Yang R, Zhao L, Taylor DS, Basso M, Behnia K, Onorato J, Chen XQ, Abell LM, Lu H, Locke G, Caporuscio C, Adam LP, Gordon D, Wexler RR, Finlay HJ (- 16) Ref: Bioorganic & Medicinal Chemistry Lett, 29:1918, 2019 : PubMed ESTHER: Kim_2019_Bioorg.Med.Chem.Lett_29_1918 PubMedSearch: Kim 2019 Bioorg.Med.Chem.Lett 29 1918 PubMedID: 31176700 Gene_locus related to this paper: human-LIPG Inhibitor(s) related to this paper: SCHEMBL15589912, LIPG-inhib-Compound32 Abstract A low level of high density lipoprotein (HDL) is an independent risk factor for cardiovascular disease. HDL reduces inflammation and plays a central role in reverse cholesterol transport, where cholesterol is removed from peripheral tissues and atherosclerotic plaque. One approach to increase plasma HDL is through inhibition of endothelial lipase (EL). EL hydrolyzes phospholipids in HDL resulting in reduction of plasma HDL. A series of benzothiazole sulfone amides was optimized for EL inhibition potency, lipase selectivity and improved pharmacokinetic profile leading to the identification of Compound 32. Compound 32 was evaluated in a mouse pharmacodynamic model and found to show no effect on HDL cholesterol level despite achieving targeted plasma exposure (Ctrough>15 fold over mouse plasma EL IC50 over 4days). Title: Screening of acetylcholinesterase inhibitors and characterizing of phytochemical constituents from Dichocarpum auriculatum (Franch.) W.T. Wang & P. K. Hsiao through UPLC-MS combined with an acetylcholinesterase inhibition assay in vitro Li P, Liu S, Liu Q, Shen J, Yang R, Jiang B, He C, Xiao P Ref: J Ethnopharmacol, 245:112185, 2019 : PubMed ESTHER: Li_2019_J.Ethnopharmacol_245_112185 PubMedSearch: Li 2019 J.Ethnopharmacol 245 112185 PubMedID: 31446073 Inhibitor(s) related to this paper: Palmatine Abstract ETHNOPHARMACOLOGICAL RELEVANCE: The genus Dichocarpum is endemic to East Asia, and many of them are traditionally used folk medicine in China. Dichocarpum auriculatum (Franch.) W. T. Wang et P. K. Hsiao has the effect of clearing away heat, removing toxicity, and relieving swelling in southwestern China. Intriguingly, its root and whole herb also used as remedy for the neurological disease epilepsy. However, there are not any scientific reports on the phytochemistry and pharmacological activities of D. auriculatum. AIM OF STUDY: Traditional and folk medicinal knowledge would be useful for finding new pharmaceutical resources. There are many evidences over the years reported that an interaction probably exists between epilepsy and Alzheimer's disease (AD). The aim of the study was to investigate the potential AChE inhibitors and the phytochemical profiles of the specie D. auriculatum. MATERIALS AND METHODS: The AChE inhibitory activity of plant extracts of D. auriculatum and other 6 species from different regions of the genus Dichocarpum were evaluated in vitro assays and the UPLC-Q-TOF-MS technique was used to analyze the chemical constituents. Moreover, UPLC-ESI-MS/MS was used to determine the distribution of 12 standard compounds in samples. RESULTS: As a preferred source of potential acetylcholinesterase inhibitors of the genus Dichocarpum, D. auriculatum has been further investigated. The screening results show that the ability of root extracts from D. auriculatum (IC50=0.15mg.mL(-)(1)) to inhibit AChE was better than other samples, it is consistent with traditional medicinal records. The phytochemical constituents of D. auriculatum was surveyed firstly by UPLC-Q-TOF-MS analysis, and 36 compounds, including 14 alkaloids, 16 flavonoids, 6 others, were identified tentatively. Further experiments showed that five compounds (columbamine, palmatine, dauricine, jatrorrhizine and berberine) from D. auriculatum were confirmed the potential inhibition of AChE activity in vitro (IC50: 0.24-6.37muM) and UPLC-ESI-MS/MS results showed that the content of most active compounds in roots was much higher than in aerial parts. Palmatine (IC50=0.34muM) and columbamine (IC50=0.24muM) showed prominent AChE inhibitory activity among the tested compounds. CONCLUSIONS: This is the first report about the evaluation of AChE inhibitory activity and phytochemical profiles of D. auriculatum, led to the identification of 36 compounds including alkaloids and flavonoids, and five alkaloids exhibited a significant AChE inhibitory activity and had the potential as AChE inhibitors. This study provided scientific experimental basis for the traditional efficacy of neurological disease of the plant. Title: Asatone and Isoasatone A Against Spodoptera litura Fab. by Acting on Cytochrome P450 Monoxygenases and Glutathione Transferases Ling R, Yang R, Li P, Zhang X, Shen T, Li X, Yang Q, Sun L, Yan J Ref: Molecules, 24:, 2019 : PubMed ESTHER: Ling_2019_Molecules_24_ PubMedSearch: Ling 2019 Molecules 24 PubMedID: 31683670 Abstract Asatone and isoasatone A from Asarum ichangense Cheng were determined to be defensive compounds to some insects in a previous investigation. However, the anti-insect activity mechanisms to caterpillar are still unclear. The compounds asatone and isoasatone A from A. ichangense were induced by Spodoptera litura. The anti-insect activity of asatone and isoasatone A to S. litura was further tested by weight growth rate of the insect through a diet experiment. Isoasatone A showed a more significant inhibitory effect on S. litura than asatone on the second day. The concentration of asatone was higher than isoasatone A in the second instar larvae of S. litura after 12 h on the feeding test diet. Both compounds caused mid-gut structural deformation and tissue decay as determined by mid-gut histopathology of S. litura. Furthermore, some detoxification enzyme activity were measured by relative expression levels of genes using a qPCR detecting system. Asatone inhibited the gene expression of the cytochrome P450 monooxygenases (P450s) CYP6AB14. Isoasatone A inhibited the relative expression levels of CYP321B1, CYP321A7, CYP6B47, CYP6AB14, and CYP9A39. Asatone increased the relative gene expression of the glutathione transferases (GSTs) SIGSTe1 and SIGSTo1, in contrast, isoasatone A decreased the relative gene expression of SIGSTe1 by about 33 fold. Neither compound showed an effect on acetylcholinesterase SIAce1 and SIAce2. The mechanism of anti-insect activity by both compounds could be explained by the inhibition of enzymes P450s and GSTs. The results provide new insights into the function of unique secondary metabolites asatone and isoasatone A in genus Asarum, and a new understanding of why A. ichangense is largely free of insect pests. Title: Benzothiazole-based compounds as potent endothelial lipase inhibitors Meng W, Adam LP, Behnia K, Zhao L, Yang R, Kopcho LM, Locke GA, Taylor DS, Yin X and Finlay H <1 more author(s)> Meng W, Adam LP, Behnia K, Zhao L, Yang R, Kopcho LM, Locke GA, Taylor DS, Yin X, Wexler RR, Finlay H (- 1) Ref: Bioorganic & Medicinal Chemistry Lett, :126673, 2019 : PubMed ESTHER: Meng_2019_Bioorg.Med.Chem.Lett__126673 PubMedSearch: Meng 2019 Bioorg.Med.Chem.Lett 126673 PubMedID: 31519373 Gene_locus related to this paper: human-LIPG Inhibitor(s) related to this paper: LIPG-inhib-Compound8i, LIPG-inhib-Compound32 Abstract A series of benzothiazoles with a cyano group was synthesized and evaluated as endothelial lipase (EL) inhibitors for the potential treatment of cardiovascular diseases. Efforts to reduce molecular weight and polarity in the series led to improved physicochemical properties of these compounds, as well as selectivity for EL over hepatic lipase (HL). As a benchmark compound, 8i demonstrated potent EL activity, an acceptable absorption, distribution, metabolism and elimination (ADME) profile and pharmacokinetic (PK) exposure which allowed further evaluation in preclinical animal efficacy studies. Title: Aryl-phosphorus-containing flame retardants induce oxidative stress, the p53-dependent DNA damage response and mitochondrial impairment in A549 cells Yuan S, Han Y, Ma M, Rao K, Wang Z, Yang R, Liu Y, Zhou X Ref: Environ Pollut, 250:58, 2019 : PubMed ESTHER: Yuan_2019_Environ.Pollut_250_58 PubMedSearch: Yuan 2019 Environ.Pollut 250 58 PubMedID: 30981936 Inhibitor(s) related to this paper: Diphenyl-phosphate, Diphenyl-methyl-phosphate, EHDPP Abstract Aryl phosphorus-containing flame retardants (aryl-PFRs) have been frequently detected with increasingly used worldwide as one of alternatives for brominated flame retardants. However, information on their adverse effects on human health and ecosystem is insufficient, with limited study on their molecular mode of action insvitro. In this study, the cytotoxicity, DNA damage, mitochondrial impairment and the involved molecular mechanisms of certain frequently detectable aryl-PFRs, including 2-ethylhexyldiphenyl phosphate (EHDPP), methyl diphenyl phosphate (MDPP), bisphenol-A bis (diphenyl phosphate) (BDP), isodecyl diphenyl phosphate (IDPP), cresyl diphenyl phosphate (CDP) and the structurally similar and widely used organophosphorus pesticide chlorpyrifos (CPF), were evaluated in A549 cells using high-content screening (HCS) system. Aryl-PFRs showed different lethal concentration 50 (LC50) values ranging from 97.94 to 546.85 microM in A549 cells using CCK-8 assay. EHDPP, IDPP, CDP, MDPP and CPF demonstrated an ability to induce DNA damage, evidenced by increased DNA content and S phase-reducing cell cycle arrest effect using fluorophore dye cocktail assay. Additionally, the selected aryl-PFRs induced mitochondrial impairment by the increasing mitochondrial mass and decreasing mitochondrial membrane potential. Moreover, BDP, MDPP, and CDP, which contain short alkyl chains showed their potential oxidative stress with intracellular ROS and mitochondrial superoxide overproduction from an initially relatively low concentration. Additionally, based on the promotion of firefly luminescence in p53-transfected A549 cells, p53 activation was found to be involved in aryl-PFRs-induced DNA damage. Further real-time PCR results showed that all selected aryl-PFRs triggered p53/p21/gadd45beta-, and p53/p21/mdm2-mediated cell cycle pathways, and the p53/bax mediated apoptosis pathway to induce DNA damage and cytotoxic effects. These results suggest that aryl-PFRs (e.g., BDP, MDPP, CDP) cause oxidative stress-mediated DNA damage and mitochondrial impairment, and p53-dependent pathway was involved in the aryl-PFRs-induced DNA damage and cell cycle arrest. In conclusion, this study improves the understanding of PFRs-induced adverse outcomes and the involved molecular mechanism. Title: PK/PD Disconnect Observed with a Reversible Endothelial Lipase Inhibitor Hangeland JJ, Abell LM, Adam LP, Jiang J, Friends TJ, Haque LE, Neels J, Onorato JM, Chen AYA and Lawrence RM <10 more author(s)> Hangeland JJ, Abell LM, Adam LP, Jiang J, Friends TJ, Haque LE, Neels J, Onorato JM, Chen AYA, Taylor DS, Yin X, Harrity TW, Basso MD, Yang R, Sleph PG, Gordon DA, Huang CS, Wexler RR, Finlay HJ, Lawrence RM (- 10) Ref: ACS Med Chem Lett, 9:673, 2018 : PubMed ESTHER: Hangeland_2018_ACS.Med.Chem.Lett_9_673 PubMedSearch: Hangeland 2018 ACS.Med.Chem.Lett 9 673 PubMedID: 30034599 Gene_locus related to this paper: human-LIPG Abstract Screening of a small set of nonselective lipase inhibitors against endothelial lipase (EL) identified a potent and reversible inhibitor, N-(3-(3,4-dichlorophenyl)propyl)-3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-c arboxamide (5; EL IC50 = 61 nM, ELHDL IC50 = 454 nM). Deck mining identified a related hit, N-(3-(3,4-dichlorophenyl)propyl)-4-hydroxy-1-methyl-5-oxo-2,5-dihydro-1H-pyrrole- 3-carboxamide (6a; EL IC50 = 41 nM, ELHDL IC50 = 1760 nM). Both compounds were selective against lipoprotein lipase (LPL) but nonselective versus hepatic lipase (HL). Optimization of compound 6a for EL inhibition using HDL as substrate led to N-(4-(3,4-dichlorophenyl)butan-2-yl)-1-ethyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrro le-3-carboxamide (7c; EL IC50 = 148 nM, ELHDL IC50 = 218 nM) having improved PK over compound 6a, providing a tool molecule to test for the ability to increase HDL-cholesterol (HDL-C) levels in vivo using a reversible EL inhibitor. Compound 7c did not increase HDL-C in vivo despite achieving plasma exposures targeted on the basis of enzyme activity and protein binding demonstrating the need to develop more physiologically relevant in vitro assays to guide compound progression for in vivo evaluation. Title: Sulfonylated Benzothiazoles as Inhibitors of Endothelial Lipase Johnson JA, Tora G, Pi Z, Phillips M, Yin X, Yang R, Zhao L, Chen AY, Taylor DS and Finlay HJ <13 more author(s)> Johnson JA, Tora G, Pi Z, Phillips M, Yin X, Yang R, Zhao L, Chen AY, Taylor DS, Basso M, Rose A, Behnia K, Onorato J, Chen XQ, Abell LM, Lu H, Locke G, Caporuscio C, Galella M, Adam LP, Gordon D, Wexler RR, Finlay HJ (- 13) Ref: ACS Med Chem Lett, 9:1263, 2018 : PubMed ESTHER: Johnson_2018_ACS.Med.Chem.Lett_9_1263 PubMedSearch: Johnson 2018 ACS.Med.Chem.Lett 9 1263 PubMedID: 30613337 Gene_locus related to this paper: human-LIPG Abstract Endothelial lipase (EL) selectively metabolizes high density lipoprotein (HDL) particles. Inhibition of EL has been shown to increase HDL concentration in preclinical animal models and was targeted as a potential treatment of atherosclerosis. We describe the introduction of an alpha-sulfone moiety to a benzothiazole series of EL inhibitors resulting in increased potency versus EL. Optimization for selectivity versus hepatic lipase and pharmacokinetic properties resulted in the discovery of 24, which showed good in vitro potency and bioavailability but, unexpectedly, did not increase HDL in the mouse pharmacodynamic model at the target plasma exposure. Title: Identification of the bovine HSL gene expression profiles and its association with fatty acid composition and fat deposition traits Fang X, Zhao Z, Jiang P, Yu H, Xiao H, Yang R Ref: Meat Sci, 131:107, 2017 : PubMed ESTHER: Fang_2017_Meat.Sci_131_107 PubMedSearch: Fang 2017 Meat.Sci 131 107 PubMedID: 28501436 Abstract Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of hydrolysing a variety of esters and is considered to be a candidate gene affecting fat deposition traits. Gene expression profiles of HSL were analysed in various adipose tissues of cattle, and the effect of HSL on lipid metabolism genes was analysed by a PCR array. Novel polymorphisms were identified within the HSL regulatory domain by sequencing, and the relationship between HSL variants and fat deposition traits was analysed. HSL mRNA was highly expressed in the subcutaneous and visceral fat of cattle. CPT1B/CPT1C and other lipocatabolic genes were upregulated, and lipogenesis-related genes (FASN, LPL and ACOT12) were downregulated by HSL overexpression in BFFs. Five novel variants in the HSL functional domain were significantly associated with fat deposition traits, including FCR, LBT, MFW and fatty acid composition. HSL plays a pivotal role in the regulation of lipolysis and fatty acid biosynthesis in beef cattle. Title: Discovery of Multitarget-Directed Ligands against Alzheimer's Disease through Systematic Prediction of Chemical-Protein Interactions Fang J, Li Y, Liu R, Pang X, Li C, Yang R, He Y, Lian W, Liu AL, Du GH Ref: J Chem Inf Model, 55:149, 2015 : PubMed ESTHER: Fang_2015_J.Chem.Inf.Model_55_149 PubMedSearch: Fang 2015 J.Chem.Inf.Model 55 149 PubMedID: 25531792 Inhibitor(s) related to this paper: DL0410 Abstract To determine chemical-protein interactions (CPI) is costly, time-consuming, and labor-intensive. In silico prediction of CPI can facilitate the target identification and drug discovery. Although many in silico target prediction tools have been developed, few of them could predict active molecules against multitarget for a single disease. In this investigation, naive Bayesian (NB) and recursive partitioning (RP) algorithms were applied to construct classifiers for predicting the active molecules against 25 key targets toward Alzheimer's disease (AD) using the multitarget-quantitative structure-activity relationships (mt-QSAR) method. Each molecule was initially represented with two kinds of fingerprint descriptors (ECFP6 and MACCS). One hundred classifiers were constructed, and their performance was evaluated and verified with internally 5-fold cross-validation and external test set validation. The range of the area under the receiver operating characteristic curve (ROC) for the test sets was from 0.741 to 1.0, with an average of 0.965. In addition, the important fragments for multitarget against AD given by NB classifiers were also analyzed. Finally, the validated models were employed to systematically predict the potential targets for six approved anti-AD drugs and 19 known active compounds related to AD. The prediction results were confirmed by reported bioactivity data and our in vitro experimental validation, resulting in several multitarget-directed ligands (MTDLs) against AD, including seven acetylcholinesterase (AChE) inhibitors ranging from 0.442 to 72.26 muM and four histamine receptor 3 (H3R) antagonists ranging from 0.308 to 58.6 muM. To be exciting, the best MTDL DL0410 was identified as an dual cholinesterase inhibitor with IC50 values of 0.442 muM (AChE) and 3.57 muM (BCHE) as well as a H3R antagonist with an IC50 of 0.308 muM. This investigation is the first report using mt-QASR approach to predict chemical-protein interaction for a single disease and discovering highly potent MTDLs. This protocol may be useful for in silico multitarget prediction of other diseases. Title: Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera Sun Z, Harris HM, McCann A, Guo C, Argimon S, Zhang W, Yang X, Jeffery IB, Cooney JC and O'Toole PW <21 more author(s)> Sun Z, Harris HM, McCann A, Guo C, Argimon S, Zhang W, Yang X, Jeffery IB, Cooney JC, Kagawa TF, Liu W, Song Y, Salvetti E, Wrobel A, Rasinkangas P, Parkhill J, Rea MC, O'Sullivan O, Ritari J, Douillard FP, Paul Ross R, Yang R, Briner AE, Felis GE, de Vos WM, Barrangou R, Klaenhammer TR, Caufield PW, Cui Y, Zhang H, O'Toole PW (- 21) Ref: Nat Commun, 6:8322, 2015 : PubMed ESTHER: Sun_2015_Nat.Commun_6_8322 PubMedSearch: Sun 2015 Nat.Commun 6 8322 PubMedID: 26415554 Gene_locus related to this paper: 9laco-a0a0r1hz65, 9laco-a0a0r1j1t4, 9laco-a0a0r1j3p0, 9laco-a0a0r1k3i0, 9laco-a0a0r1k563, 9laco-a0a0r1kgb3, 9laco-a0a0r1kji2, 9laco-a0a0r1kwq5, 9laco-a0a0r1l700, 9laco-a0a0r1p6l8, 9laco-a0a0r1q939, 9laco-a0a0r1qv39, 9laco-a0a0r1wj75, laccl-a0a0r2bne3, 9laco-a0a0r2dnk9, 9laco-a0a0r2ds70, 9laco-a0a0r2k127, 9laco-a0a0r2lee7, 9laco-a0a0r2lqt2, 9laco-a0a0r2m354, 9laco-a0a0r2n9f2, 9laco-a0a0r2nrk2, lacze-a0a0r1ekw6, 9laco-a0a0r1ju11, 9laco-a0a0r1k516, 9laco-a0a0r1leq9, 9laco-a0a0r1lul8, 9laco-a0a0r1lzg4, 9laco-a0a0r1mhp8, 9laco-a0a0r1mjt1, 9laco-a0a0r1nv21, 9laco-a0a0r1q1p6, 9laco-a0a0r1qm41, 9laco-a0a0r1qs58, 9laco-a0a0r1rgu0, 9laco-a0a0r1tg12, 9laco-a0a0r1u777, 9laco-a0a0r1ufv3, 9laco-a0a0r1ul77, 9laco-a0a0r1vad0, 9laco-a0a0r1w3f4, 9laco-a0a0r1w9r8, 9laco-a0a0r1wpq2, 9laco-a0a0r1x2g3, 9laco-a0a0r2abe6, 9laco-a0a0r2b6w1, 9laco-a0a0r2b8g1, 9laco-a0a0r2ch10, 9laco-a0a0r2cld6, 9laco-a0a0r2cv38, 9laco-a0a0r2d3x3, 9laco-a0a0r2dct2, 9laco-a0a0r2flt3, 9laco-a0a0r2frk5, 9laco-a0a0r2guq4, 9firm-a0a0r2h5m0, weivi-a0a0r2h8r4, 9lact-a0a0r2hnx4, 9lact-a0a0r2jkt6, 9lact-a0a0r2jmz1, 9laco-a0a0r2jwg5, 9laco-a0a0r2jxu0, 9laco-a0a0r2jxw0, lacam-a0a0r2kgt3, 9laco-a0a0r2kx86, 9laco-a0a0r2mxi6, 9laco-a0a0r1vln2, 9laco-a0a0r2ca25, 9laco-a0a0r1zjs2, weipa-c5rbw8 Abstract Lactobacilli are a diverse group of species that occupy diverse nutrient-rich niches associated with humans, animals, plants and food. They are used widely in biotechnology and food preservation, and are being explored as therapeutics. Exploiting lactobacilli has been complicated by metabolic diversity, unclear species identity and uncertain relationships between them and other commercially important lactic acid bacteria. The capacity for biotransformations catalysed by lactobacilli is an untapped biotechnology resource. Here we report the genome sequences of 213 Lactobacillus strains and associated genera, and their encoded genetic catalogue for modifying carbohydrates and proteins. In addition, we describe broad and diverse presence of novel CRISPR-Cas immune systems in lactobacilli that may be exploited for genome editing. We rationalize the phylogenomic distribution of host interaction factors and bacteriocins that affect their natural and industrial environments, and mechanisms to withstand stress during technological processes. We present a robust phylogenomic framework of existing species and for classifying new species. Title: Biodegradation and Mineralization of Polystyrene by Plastic-Eating Mealworms: Part 1. Chemical and Physical Characterization and Isotopic Tests Yang Y, Yang J, Wu WM, Zhao J, Song Y, Gao L, Yang R, Jiang L Ref: Environ Sci Technol, 49:12080, 2015 : PubMed ESTHER: Yang_2015_Environ.Sci.Technol_49_12080 PubMedSearch: Yang 2015 Environ.Sci.Technol 49 12080 PubMedID: 26390034 Abstract Polystyrene (PS) is generally considered to be durable and resistant to biodegradation. Mealworms (the larvae of Tenebrio molitor Linnaeus) from different sources chew and eat Styrofoam, a common PS product. The Styrofoam was efficiently degraded in the larval gut within a retention time of less than 24 h. Fed with Styrofoam as the sole diet, the larvae lived as well as those fed with a normal diet (bran) over a period of 1 month. The analysis of fecula egested from Styrofoam-feeding larvae, using gel permeation chromatography (GPC), solid-state (13)C cross-polarization/magic angle spinning nuclear magnetic resonance (CP/MAS NMR) spectroscopy, and thermogravimetric Fourier transform infrared (TG-FTIR) spectroscopy, substantiated that cleavage/depolymerization of long-chain PS molecules and the formation of depolymerized metabolites occurred in the larval gut. Within a 16 day test period, 47.7% of the ingested Styrofoam carbon was converted into CO2 and the residue (ca. 49.2%) was egested as fecula with a limited fraction incorporated into biomass (ca. 0.5%). Tests with alpha (13)C- or beta (13)C-labeled PS confirmed that the (13)C-labeled PS was mineralized to (13)CO2 and incorporated into lipids. The discovery of the rapid biodegradation of PS in the larval gut reveals a new fate for plastic waste in the environment. Title: Lysophosphatidylcholine synthesis by lipase-catalyzed ethanolysis Yang G, Yang R, Hu J Ref: J Oleo Sci, 64:443, 2015 : PubMed ESTHER: Yang_2015_J.Oleo.Sci_64_443 PubMedSearch: Yang 2015 J.Oleo.Sci 64 443 PubMedID: 25766935 Abstract Lysophosphatidylcholine (LPC) is amphiphilic substance, and possesses excellent physiological functions. In this study, LPC was prepared through ethanolysis of phosphatidylcholine (PC) in n-hexane or solvent free media catalyzed by Novozym 435 (from Candida antarctica), Lipozyme TLIM (from Thermomcyces lanuginosus) and Lipozyme RMIM (from Rhizomucor miehei). The results showed that three immobilized lipases from Candida Antarctica, Thermomcyces lanuginosus and Rhizomucor miehei could catalyze ethanolysis of PC efficiently. In n-hexane, the LPC conversions of ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TLIM and Lipozyme RMIM could reach to 98.5 +/- 1.6%, 94.6 +/- 1.4% and 93.7 +/- 1.8%, respectively. In solvent free media, the highest LPC conversions of ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TL IM and Lipozyme RM IM were 97.7 +/- 1.7%, 93.5 +/- 1.2% and 93.8 +/- 1.9%, respectively. The catalytic efficiencies of the three lipases were in the order of Novozyme 435 > Lipozyme TLIM > Lipozyme RMIM. Furthermore, their catalytic efficiencies in n-hexane were better than those in solvent free media. Title: Iterative type I polyketide synthases involved in enediyne natural product biosynthesis Chen X, Ji R, Jiang X, Yang R, Liu F, Xin Y Ref: IUBMB Life, 66:587, 2014 : PubMed ESTHER: Chen_2014_IUBMB.Life_66_587 PubMedSearch: Chen 2014 IUBMB.Life 66 587 PubMedID: 25278375 Abstract Enediyne natural products are potent antibiotics structurally characterized by an enediyne core containing two acetylenic groups conjugated to a double bond in a 9- or 10-membered carbocycle. The biosynthetic gene clusters for enediynes encode a novel iterative type I polyketide synthase (PKSE), which is generally believed to initiate the biosynthetic process of enediyne cores. This review article will cover research efforts made since its discovery to elucidate the role of the PKSE in enediyne core biosynthesis. Topics covered include the unique domain architecture, identification, and characterization of turnover products, and interaction with partner thioesterase protein. Title: Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation Fang J, Wu P, Yang R, Gao L, Li C, Wang D, Wu S, Liu AL, Du GH Ref: Acta Pharm Sin B, 4:430, 2014 : PubMed ESTHER: Fang_2014_Acta.Pharm.Sin.B_4_430 PubMedSearch: Fang 2014 Acta.Pharm.Sin.B 4 430 PubMedID: 26579414 Abstract In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (DeltaE ele+DeltaG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds. Title: Identification of tanshinone IIA as a natural monoacylglycerol lipase inhibitor by combined in silico and in vitro approach Yang R, Lu Y, Liu J Ref: Med Chem Commun, 5:1528, 2014 : PubMed ESTHER: Yang_2014_Med.Chem.Commun_5_1528 PubMedSearch: Yang 2014 Med.Chem.Commun 5 1528 Inhibitor(s) related to this paper: Tanshinone-IIA Abstract Monoacylglycerol lipase (MAGL) was proposed as a novel target for the treatment of Alzheimer's disease (AD). In this paper, in silico screening of a focused library was implemented to dock natural products against MAGL to evaluate the calculated binding affinities of ligands with the receptor. Five hits were experimentally tested to determine their inhibitory effects on MAGL in vitro. Finally, tanshinone IIA (1) was successfully identified as a natural MAGL inhibitor in a concentration dependent manner with an IC50 value of 48 M. Considering being used as long-term treatment of cardiovascular diseases in China, tanshinone IIA has the potential to be developed as a good candidate for the treatment of AD and other MAGL-associated diseases. Title: Predictions of BCHE Inhibitors Using Support Vector Machine and Naive Bayesian Classification Techniques in Drug Discovery Fang J, Yang R, Gao L, Zhou D, Yang S, Liu AL, Du GH Ref: J Chem Inf Model, 53:3009, 2013 : PubMed ESTHER: Fang_2013_J.Chem.Inf.Model_53_3009 PubMedSearch: Fang 2013 J.Chem.Inf.Model 53 3009 PubMedID: 24144102 Inhibitor(s) related to this paper: DL0410 Abstract Butyrylcholinesterase (BCHE, EC 3.1.1.8) is an important pharmacological target for Alzheimer's disease (AD) treatment. However, the currently available BCHE inhibitor screening assays are expensive, labor-intensive, and compound-dependent. It is necessary to develop robust in silico methods to predict the activities of BCHE inhibitors for the lead identification. In this investigation, support vector machine (SVM) models and naive Bayesian models were built to discriminate BCHE inhibitors (BCHEIs) from the noninhibitors. Each molecule was initially represented in 1870 structural descriptors (1235 from ADRIANA.Code, 334 from MOE, and 301 from Discovery studio). Correlation analysis and stepwise variable selection method were applied to figure out activity-related descriptors for prediction models. Additionally, structural fingerprint descriptors were added to improve the predictive ability of models, which were measured by cross-validation, a test set validation with 1001 compounds and an external test set validation with 317 diverse chemicals. The best two models gave Matthews correlation coefficient of 0.9551 and 0.9550 for the test set and 0.9132 and 0.9221 for the external test set. To demonstrate the practical applicability of the models in virtual screening, we screened an in-house data set with 3601 compounds, and 30 compounds were selected for further bioactivity assay. The assay results showed that 10 out of 30 compounds exerted significant BCHE inhibitory activities with IC50 values ranging from 0.32 to 22.22 muM, at which three new scaffolds as BCHE inhibitors were identified for the first time. To our best knowledge, this is the first report on BCHE inhibitors using machine learning approaches. The models generated from SVM and naive Bayesian approaches successfully predicted BCHE inhibitors. The study proved the feasibility of a new method for predicting bioactivities of ligands and discovering novel lead compounds. Title: Whole-Genome Sequencing of Lactobacillus shenzhenensis Strain LY-73T Lin Z, Liu Z, Yang R, Zou Y, Wan D, Chen J, Guo M, Zhao J, Fang C, Liu F Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Lin_2013_Genome.Announc_1_e00972 PubMedSearch: Lin 2013 Genome.Announc 1 e00972 PubMedID: 24265500 Gene_locus related to this paper: 9laco-u4tvs6, 9laco-u4ti93 Abstract Lactobacillus shenzhenensis strain LY-73(T) is a novel species which was first isolated from fermented goods. Here, we report the draft genome sequence of Lactobacillus shenzhenensis LY-73(T). Title: The Reference Genome of the Halophytic Plant Eutrema salsugineum Yang R, Jarvis DE, Chen H, Beilstein MA, Grimwood J, Jenkins J, Shu S, Prochnik S, Xin M and Wang X <5 more author(s)> Yang R, Jarvis DE, Chen H, Beilstein MA, Grimwood J, Jenkins J, Shu S, Prochnik S, Xin M, Ma C, Schmutz J, Wing RA, Mitchell-Olds T, Schumaker KS, Wang X (- 5) Ref: Front Plant Sci, 4:46, 2013 : PubMed ESTHER: Yang_2013_Front.Plant.Sci_4_46 PubMedSearch: Yang 2013 Front.Plant.Sci 4 46 PubMedID: 23518688 Gene_locus related to this paper: theha-e4mxu0, thesl-v4nk72, eutsa-v4l4z1, eutsa-v4kk46, eutsa-v4mej3, eutsa-v4ns11, eutsa-v4mg02, eutsa-v4mqm9, eutsa-v4k1y6, eutsa-v4lad0, eutsa-v4nr92, eutsa-v4kqc3, eutsa-v4l0s2, eutsa-v4lip3, eutsa-v4kkg2, eutsa-v4kvd3, eutsa-v4m9g4, eutsa-v4lqg2, eutsa-v4lp36, eutsa-v4km66, eutsa-v4nhr8, eutsa-v4kqx9, eutsa-v4lv73 Abstract Halophytes are plants that can naturally tolerate high concentrations of salt in the soil, and their tolerance to salt stress may occur through various evolutionary and molecular mechanisms. Eutrema salsugineum is a halophytic species in the Brassicaceae that can naturally tolerate multiple types of abiotic stresses that typically limit crop productivity, including extreme salinity and cold. It has been widely used as a laboratorial model for stress biology research in plants. Here, we present the reference genome sequence (241 Mb) of E. salsugineum at 8x coverage sequenced using the traditional Sanger sequencing-based approach with comparison to its close relative Arabidopsis thaliana. The E. salsugineum genome contains 26,531 protein-coding genes and 51.4% of its genome is composed of repetitive sequences that mostly reside in pericentromeric regions. Comparative analyses of the genome structures, protein-coding genes, microRNAs, stress-related pathways, and estimated translation efficiency of proteins between E. salsugineum and A. thaliana suggest that halophyte adaptation to environmental stresses may occur via a global network adjustment of multiple regulatory mechanisms. The E. salsugineum genome provides a resource to identify naturally occurring genetic alterations contributing to the adaptation of halophytic plants to salinity and that might be bioengineered in related crop species. Title: Effect of bis(7)-tacrine on cognition in rats with chronic cerebral ischemia Shu XJ, Liu W, Zhang L, Yang R, Yi HL, Li CL, Ye YJ, Ai YX Ref: Neuroscience Letters, 512:103, 2012 : PubMed ESTHER: Shu_2012_Neurosci.Lett_512_103 PubMedSearch: Shu 2012 Neurosci.Lett 512 103 PubMedID: 22330749 Inhibitor(s) related to this paper: Bis7-tacrine Abstract Bis(7)-tacrine (B7T), a novel dimeric acetyl cholinesterase (AChE) inhibitor, has multiple neuroprotective activities against neuronal damage. However, its therapeutic effects in chronic cerebral ischemia remain unknown. In the present study, adult male Sprague-Dawley rats were subjected with permanent ligation of the bilateral common carotid arteries to investigate the roles of B7T on cognitive function, neuronal apoptosis and neurogenesis in the hippocampus. Results from spatial navigation test showed that chronic cerebral ischemia impaired spatial learning, B7T treatment shorten escape latency of ischemia rats as compared with saline-treated rats. Probe trial test indicated that spatial memory deficit of chronic cerebral ischemic animals was reversed by B7T treatment. Immunohistochemical results showed that B7T reduced neuronal apoptosis in the hippocampal CA1 region as compared with ischemia rats, and B7T treatment increased neurogenesis in the hippocampus. These findings suggest that B7T may exert its neuroprotective effects by inhibiting apoptosis and promoting neurogenesis in 2VO rats. Title: Complete genome sequence of Bordetella pertussis CS, a Chinese pertussis vaccine strain Zhang S, Xu Y, Zhou Z, Wang S, Yang R, Wang J, Wang L Ref: Journal of Bacteriology, 193:4017, 2011 : PubMed ESTHER: Zhang_2011_J.Bacteriol_193_4017 PubMedSearch: Zhang 2011 J.Bacteriol 193 4017 PubMedID: 21622744 Gene_locus related to this paper: borpe-CATD2 Abstract Bordetella pertussis is the causative agent of pertussis. Here, we report the genome sequence of Bordetella pertussis strain CS, isolated from an infant patient in Beijing and widely used as a vaccine strain for production of an acellular pertussis vaccine in China. Title: Draft genome sequences of Yersinia pestis isolates from natural foci of endemic plague in China Eppinger M, Guo Z, Sebastian Y, Song Y, Lindler LE, Yang R, Ravel J Ref: Journal of Bacteriology, 191:7628, 2009 : PubMed ESTHER: Eppinger_2009_J.Bacteriol_191_7628 PubMedSearch: Eppinger 2009 J.Bacteriol 191 7628 PubMedID: 19820101 Gene_locus related to this paper: yerpe-BIOH, yerpe-dlhh, yerpe-PIP, yerpe-PLDB, yerpe-PTRB, yerpe-Y0507, yerpe-y3224, yerpe-YPLA, yerpe-YPO0180, yerpe-YPO0667, yerpe-YPO0773, yerpe-YPO0986, yerpe-YPO1501, yerpe-YPO1997, yerpe-YPO2526, yerpe-YPO2814 Abstract To gain insights into the evolutionary origin, emergence, and pathogenicity of the etiologic agent of plague, we have sequenced the genomes of four Yersinia pestis strains isolated from the zoonotic rodent reservoir in foci of endemic plague in China. These resources enable in-depth studies of Y. pestis sequence variations and detailed whole-genome comparisons of very closely related genomes from the supposed site of the origin and the emergence of global pandemics of plague. Title: An organophosphorus hapten used in the preparation of monoclonal antibody and as an active immunization vaccine in the detoxication of soman poisoning Jia P, Wang Y, Yu M, Wu J, Yang R, Zhao Y, Zhou L Ref: Toxicol Lett, 187:45, 2009 : PubMed ESTHER: Jia_2009_Toxicol.Lett_187_45 PubMedSearch: Jia 2009 Toxicol.Lett 187 45 PubMedID: 19429243 Abstract Soman is an organophosphorus neurotoxin which inhibits the activity of acetylcholinesterase (AChE). The goal of this work was to find out whether antibodies against an organophosphorus hapten could protect mice from soman toxicity. An organophosphorus hapten P6 was synthesized. Its chemical conjugates with limulus polyphemus hemocyanin and bovine serum albumin were used as immune antigen (P6-LPH) and detection antigen (P6-BSA), respectively. Eight hybridoma cell lines secreting monoclonal antibodies (Mabs) were established. The binding reactivities of Mabs with P6 and soman were determined by competitive inhibition enzyme immunoassay (CIEIA). All antibodies recognized P6 and four of them (2C10, 3G1, 3B9 and 3C11) combined with soman. The IC(50) was 10(-6.5) to 10(-5.3)mol/l for P6 and 10(-5) to 10(-3.5)mol/l for soman. Furthermore, Mab 3G1 reduced the inhibition of AChE activity by soman in vitro. When soman was pre-incubated with Mabs before being injected into mice, soman potency was reduced, indicating that Mabs could protect mice from soman toxicity. In an active immunization regimen, mice immunized with P6-LPH and challenged with 0.15mg/kg soman injected subcutaneously, had fewer signs of intoxication and a higher survival rate compared with control mice. These results demonstrate that the anti-soman antibodies have proper characteristics as scavengers in the detoxication of soman poisoning. Title: A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D and Yu J <16 more author(s)> Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D, Li M, Song Y, Zhu X, Sun H, Feng T, Guo Z, Ju A, Ge J, Dong Y, Sun W, Jiang Y, Yan J, Yang H, Wang X, Gao GF, Yang R, Yu J (- 16) Ref: PLoS ONE, 2:e315, 2007 : PubMed ESTHER: Chen_2007_PLoS.ONE_2_E315 PubMedSearch: Chen 2007 PLoS.ONE 2 E315 PubMedID: 17375201 Gene_locus related to this paper: strsu-a4vws4, strsu-q302y4, strsy-a4vus4, strsy-a4vwf6 Abstract BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections. Title: Effect of antioxidant capacity on blood lipid metabolism and lipoprotein lipase activity of rats fed a high-fat diet Yang R, Le G, Li A, Zheng J, Shi Y Ref: Nutrition, 22:1185, 2006 : PubMed ESTHER: Yang_2006_Nutrition_22_1185 PubMedSearch: Yang 2006 Nutrition 22 1185 PubMedID: 17095404 Abstract OBJECTIVE: The present study explored the effect of antioxidant capacity on blood lipid metabolism and lipoprotein lipase (LPL) activity of rats fed with a high-fat diet (HFD). Furthermore, the relation of the atherosclerotic index (AI) and LPL activity to total antioxidant capacity (TAC) was studied. Title: Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans Song Y, Tong Z, Wang J, Wang L, Guo Z, Han Y, Zhang J, Pei D, Zhou D and Yang R <16 more author(s)> Song Y, Tong Z, Wang J, Wang L, Guo Z, Han Y, Zhang J, Pei D, Zhou D, Qin H, Pang X, Zhai J, Li M, Cui B, Qi Z, Jin L, Dai R, Chen F, Li S, Ye C, Du Z, Lin W, Yu J, Yang H, Huang P, Yang R (- 16) Ref: DNA Research, 11:179, 2004 : PubMed ESTHER: Song_2004_DNA.Res_11_179 PubMedSearch: Song 2004 DNA.Res 11 179 PubMedID: 15368893 Gene_locus related to this paper: yerpe-BIOH, yerpe-IRP1, yerpe-PIP, yerpe-PLDB, yerpe-PTRB, yerpe-q8zey9, yerpe-Y0644, yerpe-y1616, yerpe-y3224, yerpe-YPLA, yerpe-YPO0180, yerpe-YPO0667, yerpe-YPO0773, yerpe-YPO0776, yerpe-YPO0986, yerpe-YPO1501, yerpe-YPO1997, yerpe-YPO2002, yerpe-YPO2336, yerpe-YPO2526, yerpe-YPO2638, yerpe-YPO2814 Abstract Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity. Title: Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus Zhou D, Tong Z, Song Y, Han Y, Pei D, Pang X, Zhai J, Li M, Cui B and Yang R <7 more author(s)> Zhou D, Tong Z, Song Y, Han Y, Pei D, Pang X, Zhai J, Li M, Cui B, Qi Z, Jin L, Dai R, Du Z, Wang J, Guo Z, Huang P, Yang R (- 7) Ref: Journal of Bacteriology, 186:5147, 2004 : PubMed ESTHER: Zhou_2004_J.Bacteriol_186_5147 PubMedSearch: Zhou 2004 J.Bacteriol 186 5147 PubMedID: 15262951 Gene_locus related to this paper: yerpe-YPLA Abstract Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine. Title: NTP technical report on the toxicity studies of Pesticide/Fertilizer Mixtures Administered in Drinking Water to F344/N Rats and B6C3F1 Mice Yang R Ref: Toxic Rep Ser, 36:1, 1993 : PubMed ESTHER: Yang_1993_Toxic.Rep.Ser_36_1 PubMedSearch: Yang 1993 Toxic.Rep.Ser 36 1 PubMedID: 12209188 Abstract Toxicity studies were performed with pesticide and fertilizer mixtures representative of groundwater contamination found in California and Iowa. The California mixture was composed of aldicarb, atrazine, 1,2-dibromo-3-chloropropane, 1,2- dichloropropane, ethylene dibromide, simazine, and ammonium nitrate. The Iowa mixture contained alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate. The mixtures were administered in drinking water (with 512 ppm propylene glycol) to F344/N rats and B6C3F1 mice of each sex at concentrations ranging from 0.1x to 100x, where 1x represented the median concentrations of the individual chemicals found in studies of groundwater contamination from normal agricultural activities. This report focuses primarily on 26-week toxicity studies describing histopathology, clinical pathology, neurobehavior/neuropathology, and reproductive system effects. The genetic toxicity of the mixtures was assessed by determining the frequency of micronuclei in peripheral blood of mice and evaluating micronuclei and sister chromatid exchanges in splenocytes from female mice and male rats. Additional studies with these mixtures that are briefly reviewed in this report include teratology studies with Sprague-Dawley rats and continuous breeding studies with CD-1 Swiss mice. In 26-week drinking water studies of the California and the Iowa mixtures, all rats (10 per sex and group) survived to the end of the studies, and there were no significant effects on body weight gains. Water consumption was not affected by the pesticide/fertilizer contaminants, and there were no clinical signs of toxicity or neurobehavioral effects as measured by a functional observational battery, motor activity evaluations, thermal sensitivity evaluations, and startle response. There were no clear adverse effects noted in clinical pathology (including serum cholinesterase activity), organ weight, reproductive system, or histopathologic evaluations, although absolute and relative liver weights were marginally increased with increasing exposure concentration in both male and female rats consuming the Iowa mixture. In 26-week drinking water studies in mice, one male receiving the California mixture at 100x died during the study, and one control female and one female in the 100x group in the Iowa mixture study also died early. It could not be determined if the death of either of the mice in the 100x groups was related to consumption of the pesticide/fertilizer mixtures. Water consumption and body weight gains were not affected in these studies, and no signs of toxicity were noted in clinical observations or in neurobehavioral assessments. No clear adverse effects were noted in clinical pathology, reproductive system, organ weight, or histopathologic evaluations of exposed mice. The pesticide/fertilizer mixtures, when tested over a concentration range similar to that used in the 26-week studies, were found to have no effects in teratology studies or in a continuous breeding assay examining reproductive and developmental toxicity. The California and Iowa pesticide mixtures were tested for induction of micronuclei in peripheral blood erythrocytes of female mice. Results of tests with the California mixture were negative. Significant increases in micronucleated normochromatic erythrocytes were seen at the two-highest concentrations (10x and 100x) of the Iowa mixture, but the increases were within the normal range of micronuclei in historical control animals. Splenocytes of male rats and female mice exposed to these mixtures were examined for micronucleus and sister chromatid exchange frequencies. Sister chromatid exchange frequencies were marginally increased in rats and mice receiving the California mixture, but neither species exhibited increased frequencies of micronucleated splenocytes. None of these changes were considered to have biological importance. In summary, studies of potential toxicity associated with the consumption of mixtures of pesticides and a fertilizer representative of groundwater contamination in agriculturative of groundwater contamination in agricultural areas of Iowa and California failed to demonstrate any significant adverse effects in rats or mice receiving the mixtures in drinking water at concentrations as high as 100 times the median concentrations of the individual chemicals determined by groundwater surveys. | |||||||
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