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Liver Research 2023年第3期7卷 165-176页

作者： Yuhua Gao Jun Lin Chuan Ye Siqi Guo Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking Universityand the Key Laboratory of Molecular Cardiovascular Science(Peking University)Ministry of EducationBeijingChina Center of Basic Medical Research Institute of Medical Innovation and ResearchThird HospitalPeking UniversityBeijingChina Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijingChina

Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic *** the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological ***,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA *** of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.

关键词： Bile acids(BAs) Gut microbiota Metabolic dysfunction-associated steatotic liver disease(MASLD) Metabolic dysfunction-associated steatohepatitis(MASH) Hepatocellular carcinoma(HCC) Farnesoid X receptor(FXR) G protein-coupled bile acid receptor 1(TGR5)

A DTX/MATE-Type Transporter Facilitates Abscisic Acid Efflux and Modulates ABA Sensitivity and Drought Tolerance in Arabidopsis

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molecular Plant 2014年第10期7卷 1522-1532页

作者： Haiwen Zhang Huifen Zhu Yajun Pan Yuexuan Yu Sheng Luan Legong Li College of Life sciences Capital Normal University Beijing 100048 China Department of Plant and microbial Biology University of California Berkeley CA 94720 USA Institute of Plant molecular Biology School of Life Sciences Nanjing University Nanjing 210093 China

Abscisic acid （ABA） regulates numerous physiological and developmental processes in plants. Recent studies identify intracellular ABA receptors, implicating the transport of ABA across cell membranes as crucial for ABA sensing and response. Here, we report that a DTX/Multidrug and Toxic Compound Extrusion （MATE） family member in Arabidopsis thaliana, AtDTX50, functions as an ABA efflux transporter. When expressed heterologously in both an Escherichia coli strain and Xenopus oocyte cells, AtDTX50 was found to facilitate ABA efflux. Furthermore, dtx50 mutant mesophyll cells preloaded with ABA released less ABA compared with the wild-type （WT）. The AtDTX50 gene was expressed mainly in the vascular tissues and guard ceils and its expression was strongly up-regulated by exogenous ABA. The AtDTX50：：GFP fusion protein was localized predominantly to the plasma membrane. The dtx50 mutant plants were observed to be more sensitive to ABA in growth inhibition. In addition, compared with the WT, dtx50 mutant plants were more tolerant to drought with lower stomatal conductance, consistent with its function as an ABA efflux carrier in guard cells.

关键词： hormone biology molecular transport Arabidopsis.

Investigation of temporal and spatial heterogeneities of the immune responses to Bordetella pertussis infection in the lung and spleen of mice via analysis and modeling of dynamic microarray gene expression data

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Infectious Disease Modelling 2019年第1期4卷 215-226页

作者： Nan Deng Juan C.Ramirez Michelle Carey Hongyu Miao Cesar A.Arias Andrew P.Rice Hulin Wu Department of Biostatistics and Data science School of Public HealthThe University of Texas Health Science Center at HoustonHoustonTXUSA Facultad de Ingeniería de Sistemas Universidad Antonio NariňoBogotáColombia school of Mathematics and Statistics University College DublinDublinIreland Center for Antimicrobial Resistance and microbial Genomics(CARMiG) UTHealth McGovern Medical SchoolUSA Divicon of Infectious Diseases and Department of Microbiology and molecular Genetics UTHealth McGovern Medical SchoolUSA Center for Infectious Diseases UTHealth School of Public HealthUSA molecular Genetics and Antimicrobial Resistance Unit and International Center for microbial Genomics Universidad El BosqueBogotaColombia Department of molecular Virology&Microbiology Baylor College of MedicineHoustonTXUSA

Bordetella pertussis(***)is the causative agent of pertussis,also referenced as whooping *** pertussis has been appropriately controlled by routine immunization of infants,it has experienced a resurgence since the beginning of the 21st *** that elucidating the immune response to pertussis is a crucial factor to improve therapeutic and preventive treatments,we re-analyzed a time course microarray dataset of *** infection by applying a newly developed dynamic data analysis *** results indicate that the immune response to *** is highly dynamic and heterologous across different organs during ***1 and Th17 cells,which are two critical types of T helper cell populations in the immune response to ***,and follicular T helper cells(TFHs),which are also essential for generating antibodies,might be generated at different time points and distinct locations after *** phenomenon may indicate that different lymphoid organs may have their unique functions during *** findings provide a better understanding of the basic immunology of bacterial infection,which may provide valuable insights for the improvement of pertussis vaccine design in the future.

关键词： pertussis organs microarray

Variations in diversity, composition,and species interactions of soil microbial community in response to increased N deposition and precipitation intensity in a temperate grassland

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Ecological Processes 2023年 495-506页

作者： Shuyan Cui Yushan Xiao Yu Zhou Pengfeng Wu Liqiang Cui Guo Zheng College of Life science Shenyang Normal University school of Environmental science and Engineering Yancheng Institute of Technology

Background Global climate change has resulted in precipitation regimes exhibiting an increasing trend in rainfall intensity but a reduction in frequency. In addition, nitrogen(N) deposition occurs simultaneously in arid and semi-arid regions. microbial biomass, diversity, composition, and species interactions are key determinants of ecological functions. We examined the effects of changes in precipitation intensity and N addition on the soil bacterial and fungal communities in a semi-arid grassland in Inner Mongolia, *** The microbial biomass(bacterial PLFAs and fungal PLFAs) was determined through phospholipid fatty acid(PLFA) analysis, and microbial diversity(Shannon index and evenness index) was determined with high-throughput sequencing(16S and ITS). Species interactions were determined using a molecular ecological network analysis. The relationships between microbial community(bacterial community and fungal community) and environmental variables were examined by Mantel *** We found that N addition decreased fungal PLFA under moderate, high, and extreme precipitation intensity treatments and increased fungal community complexity under the high precipitation intensity treatment. Furthermore, N addition increased bacterial diversity under moderate and high precipitation intensity treatments. N addition caused greater environmental stress to the fungal community, which was dominated by deterministic *** The effects of N deposition on soil bacterial and fungal communities were altered by precipitation intensity. The changes in soil bacterial and fungal communities were different, implying that composition and functional traits adapt differently to projected global changes at a regional scale.

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Microbe social skill:the cell-to-cell communication between microorganisms

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science Bulletin 2017年第7期62卷 516-524页

作者： Xi Zhao Xiong Liu Xin Xu Yu V.Fu State Key Laboratory of microbial Resources Institute of MicrobiologyChinese Academy of Sciences Savaid Medical school University of Chinese Academy of Sciences

Although microbes primarily are single-cell organisms,they are not isolated *** use various means to communicate with one *** on the communication,microbes establish a social interaction with their neighbors in a specific ecological niche,and cooperative behaviors are normally performed to provide benefits on the population and species *** the microbiome era,in order to better understand the behaviors of microbes,deep understanding of the social communication between microbes hence becomes a key to interpret microbe *** we summarize the molecular mechanisms that underlie the cell-to-cell communication in prokaryotic and eukaryotic microorganisms,the recent discoveries and novel technologies in understanding the interspecies and interkingdom communication,and discuss new concepts of the sociomicrobiology.

关键词：微生物利用细胞间通讯社会交往通信新技术生物行为单细胞生物分子机制细胞通讯

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Engineering Broad-Spectrum Bacterial Blight Resistance by Simultaneously Disrupting Variable TALE-Binding Elements of Multiple Susceptibility Genes in Rice

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molecular Plant 2019年第11期12卷 1434-1446页

作者： Zhengyin Xu Xiameng Xu Qiang Gong Ziyang Li Ying Li Sai Wang Yangyang Yang Wenxiu Ma Longyu Liu Bo Zhu Lifang Zou Gongyou Chen school of Agriculture and Biology/State Key Laboratory of microbial Metabolism Shanghai Jiao Tong UniversityShanghai 200240China

Xanthomonas oryzae ***(Xoo),the causal agent of bacterial blight of rice,employs the transcription activator-like effectors(TALEs)to induce the expression of the OsSWEET family of putative sugar transporter genes,which function in conferring disease susceptibility(S)in rice *** engineer broadspectrum bacterial blight resistance,we used CRISPR/Cas9-mediated gene editing to disrupt the TALEbinding elements(EBEs)of two S genes,OsSWEETH and OsSWEET14,in rice ***,which harbors the recessive resistance allele of Xa25/*** engineered rice line MS14K exhibited broadspectrum resistance to most Xoo strains with a few exceptions,suggesting that the compatible strains may contain new *** identified two PthXo2-like TALEs,Tal5LN18 and Tal7PX061,as major virulence factors in the compatible Xoo strains LN18 and PX061,respectively,and found that Xoo encodes at least five types of PthXo2-like *** that PthXo2/PthXo2.1 target OsSlVEETf3 for transcriptional activation,the genomes of 3000 rice varieties were analyzed for EBE variationsin the OsSWEET13 promoter,and 10Xa25-like haplotypes were *** found that Tal5LN18 and Tal7PX〇6i bind slightly different EBE sequences in the OsSWEET13 promoter to activate its ***/Cas9 technology was then used to generate InDels in the EBE of the OsSWEET13 promoter in MS14K to creat a new germplasm with three edited OsSWEET EBEs and broad-spectrum resistance against all Xoo strains ***,our findings illustrate how to disarm TALE-S co-evolved loci to generate broad-spectrum resistance through the loss of effector-triggered susceptibility in plants.

关键词： Xanthomonas oryzae pv.oryzae TALE susceptible gene ETS RLS

Transcriptome-guided identification of a four-component system, SbrH1-R, that modulates milbemycin biosynthesis by influencing gene cluster expression, precursor supply, and antibiotic efflux

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Synthetic and Systems Biotechnology 2022年第2期7卷 705-717页

作者： Lan Ye Yanyan Zhang Shanshan Li Hairong He Guomin Ai Xiangjing Wang Wensheng Xiang school of Life science Northeast Agricultural UniversityNo.59 Mucai StreetXiangfang DistrictHarbin150030China State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing100193China State Key Laboratory of microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijingChina College of Pharmacy Henan University of Chinese MedicineZhengzhou 450046HenanChina

Streptomyces can produce numerous antibiotics and many other bioactive ***,the molecular mechanisms of transcriptional regulators in control of antibiotic production by influencing the expression of biosynthetic gene clusters(BGCs)have been extensively ***,for regulators that affect both antibiotic production and cell growth,the way to influence antibiotic production may be diverse,but related studies are ***,based on time-course transcriptome analysis,a four-component system,SbrH1-R,consisting of the two-component system SbrKR(SBI_03479/3478)and two hypothetical proteins SbrH1(SBI_03481)and SbrH2(SBI_03480)potentially related with the biosynthesis of milbemycins was identified in Streptomyces bingchenggensis *** of sbrH1-R resulted in weakened cell growth but a 110%increase of milbemycin production compared with that in *** transcriptome analyses of the sbrH1-R mutant and BC-101-4 revealed that SbrH1-R not only indirectly represses milbemycin BGC expression,but also inhibits milbemycin production by modulating expression levels of genes related to precursor supply and antibiotic *** genetic experiments identified several new targets,including five precursor supply-associated reactions/pathways(e.g.,the reaction from pyruvate to acetyl-CoA,the reaction from acetyl-CoA to citrate,the fatty acidβ-oxidation process,and the branched chain amino acid and phenylalanine acid degradation pathways)and a milbemycin exporter system(MilEX2)that can be engineered for milbemycin *** results shed new light on the understanding of regulation of milbemycin biosynthesis and provide useful targets for future metabolic engineering of the native host to improve milbemycin production.

关键词： Milbemycins Streptomyces bingchenggensis SbrH1-R Precursor supply Milbemycin exporter Overproduction

A Quantitative Assay for Measuring of Bovine Immunodeficiency Virus Using a Luciferase-based Indicator Cell Line

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Virologica Sinica 2010年第2期25卷 137-144页

作者： Xue YAO Hong-yan GUO Chang LIU Xuan XU Jian-sen DU Hao-yue LIANG Yun-qi GENG Wen-tao QIAO Key Laboratory of molecular Microbiology and Technology Ministry of Education Key Laboratory of microbial Functional Genomics （Tianjin） Nankai University Tianjin 300071 China school of Medicine Nankai University Tianjin 300071 China

In order to quantitate the bovine immunodeficiency virus (BIV) infection in vitro, a BIV indicator cell line (BIVL) was established by transfecting baby hamster kidney cells with reporter plasmids containing the firefly luciferase gene driven by a BIV long terminal repeat promoter. The BIV activates promoter activity of the LTR to express luciferase upon infection. BIV infection could therefore by quantified by detection of luciferase activity. Compared to standard assays used to detect BIV infection, the BIVL-based assay is 10 times more sensitive than the the CPE-based assay, and has similar sensitivity with the viral capsid protein Western blot assay. BIV indicator cell line could detect BIV infection specifically. Luciferase activity of BIV infected BIVL cells showed a time dependent manner, and 60 h post infection is the optimal time to detect BIV infection. Luciferase activity of BIVL cells correlates with the BIV capsid protein expression. Moreover, a linear relationship was found between MOI and the activated intensity of luciferase expression. In brief, the BIV indicator cell line is an easy, robust and quantitive method for monitoring BIV infection.

关键词：萤火虫荧光素酶基因牛免疫缺陷病毒定量检测细胞株感染细胞蛋白免疫印迹法启动子活性基础

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High-throughput fluorescent screening of thioredoxin reductase inhibitors to inhibit Mycobacterium tuberculosis

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Chinese Chemical Letters 2024年第3期35卷 358-362页

作者： Fei Yan Xin Zhao Ruibo Li Xiuyan Han Qiulong Yan Lei Feng Xiulan Xin Jingnan Cui Xiaochi Ma Second Affiliated Hospital Dalian Medical UniversityDalian 116044China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China school of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453007China College of Bioengineering Beijing PolytechnicBeijing 100029China

Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB *** is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB *** reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and *** the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural *** screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium *** the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.

关键词： Thioredoxin reductase NIR fluorescent probe Fluorescence imaging High-throughput screening inhibitors Inhibit Mycobacterium tuberculosis

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MLK4 has negative effect on TLR4 signaling

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Cellular & molecular Immunology 2012年第1期9卷 27-33页

作者： Alim Seit-Nebi Wei Cheng Hong Xu Jiahuai Han The Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering School of Life SciencesXiamen UniversityXiamenChina Department of Immunology and microbial science The Scripps Research InstituteLa JollaCAUSA

The stimulation of Toll-like receptors (TLRs) on macrophages triggers production of proinflammatory cytokines such as tumor-necrosisfactor-a (TNF-a). The TNF production is mediated by a series of signaling events and subsequent transcriptional andpost-transcriptional activation of the TNF gene. Termination of TLR-mediated cellular signaling is also important for a properimmunoresponse, since sustained cytokine expression can result in immune disorders. Here we identified that mixed-lineage kinase(MLK) 4 is a TLR4-interacting protein. Unlike previously characterized MLK group members, MLK4 cannot act as a mitogen-activatedprotein kinase kinase kinase (MAP3K) to mediate c-Jun N-terminal kinase (JNK), p38 or extracellular signal-regulated kinase (ERK)activation. Rather, MLK4 appears to be able to inhibit lipopolysaccharide (LPS)-induced activation of the JNK or ERK pathways, butdoes not have effect on LPS-induced p38 or NF-kB activation. The LPS-induced TNF production in MLK4 knockdown andoverexpression cells were also increased and reduced, respectively. These data demonstrate that MLK4 is a negative regulator of TLR4signaling.

关键词： Kinase MLK4 TLR4