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Epigenetic modification in liver fibrosis:Promising therapeutic direction with significant challenges ahead

Acta Pharmaceutica Sinica B 2024年第3期14卷 1009-1029页

作者： Runping Liu Yajing Li Qi Zheng Mingning Ding Huiping Zhou Xiaojiaoyang Li School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 102400China School of Life Sciences Beijing University of Chinese MedicineBeijing 102400China Department of microbiology and Immunology Virginia Commonwealth UniversityRichmondVA 22460USA

Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver ***’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver ***,current treatment options are limited,highlighting the urgent need for the development of new *** a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver *** the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still *** review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic *** potential cooperation of different epigenetic modifications in promoting fibrogenesis was also ***,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were *** summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

关键词： Liver fibrosis Epigenetics regulation DNA methylation Histone acetylation Histone methylation mRNA methylation Non-coding RNA Drug development

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Multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants

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Science China(Life Sciences) 2024年第1期67卷 83-95页

作者： Guangshan Xie Lin Zhu Siwen Liu Cun Li Xin Diao Yanhao Zhang Xiuli Su Yuanyuan Song Guodong Cao Li Zhong Pui Wang Xiaojuan Liu Bobo Wing-Yee Mok Shusheng Zhang Dong-Yan Jin Jie Zhou Honglin Chen Zongwei Cai State Key Laboratory of Environmental and Biological Analysis Hong Kong Baptist UniversityHong Kong SARChina State Key Laboratory for Emerging Infectious Diseases and Department of MicrobiologyLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina College of Chemistry Zhengzhou UniversityZhengzhou 450001China School of Biomedical Sciences The University of Hong KongHong Kong SARChina HKBU Shenzhen Institute of research and Continuing Education Shenzhen 518000China

SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and *** high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide *** markers for evaluating the pathogenicity of new variants are therefore *** comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels,six key molecules on the polyamine biosynthesis pathway including putrescine,SAM,dc-SAM,ODC1,SAMS,and SAMDC were found to be differentially upregulated and associated with pathogenicity of *** validate our discovery,human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 *** ODC1 as a proof-ofconcept,differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system(RAS)and positively associated with ACE2 *** experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern(VOCs)and was found to be correlated with each VOCs’pathogenic ***,the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid *** work,therefore,presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.

关键词： SARS-CoV-2 multi-omics attenuated variant predictive pathogenic marker polyamine biosynthesis

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The infection kinetics and transmission potential of two Guaico Culex viruses in Culex quinquefasciatus mosquitoes

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Virologica Sinica 2024年第2期39卷 228-234页

作者： Ru-Yi Chen Teng Zhao Jing-Jing Guo Feng Zhu Na-Na Zhang Xiao-Feng Li Hai-Tao Liu Fei Wang Yong-Qiang Deng Cheng-Feng Qin College of Bioscience and Bioengineering Jiangxi Agricultural UniversityNanchang330045China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMSBeijing100071China School of Life Sciences Southwest Forestry UniversityKunming650224China

Guaico Culex virus(GCXV)is a newly identified segmented Jingmenvirus from Culex *** in Central and South *** genome of GCXV is composed of four or five single-stranded positive RNA ***,the infection kinetics and transmission capability of GCXV in mosquitoes remain *** this study,we used reverse genetics to rescue two GCXVs(4S and 5S)that contained four and five RNA segments,respectively,in C6/36 *** in vitro characterization revealed that the two GCXVs exhibited comparable replication kinetics,protein expression and viral ***,GCXV RNAs were detected in the bodies,salivary glands,midguts and ovaries of Culex quinquefasciatus at 4–10 days after oral *** addition,two GCXVs can colonize *** eggs,resulting in positive rates of 15%–35%for the second gonotrophic *** conclusion,our results demonstrated that GCXVs with four or five RNA segments can be detected in *** eggs during the first and second gonotrophic cycles after oral infection.

关键词： Guaico Culex virus(GCXV) Jingmenvirus Culex quinquefasciatus Vertical transmission

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Fight or flee,a vital choice for Clostridioides difficile

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mLife 2024年第1期3卷 14-20页

作者： Ji Zeng Sshuying Fang Jinquan Guo Min Dong Guo-Bao Tian Liang Tao School of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhouChina Department of Brest Surgery Panyu Central Hospital.GuangzhouChina Department of microbiology Harvard Medical SchoolBostonMassachusettsUSA Department of Urology Boston Children's HospitalHarvard Medical SchoolBostonMassachusettsUSA Department of microbiology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina Advanced Medical Technology Center The First Affiliated HospitalZhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina Key Laboratory of Tropical Diseases Control(Sun Yat-sen University) Ministry of EducationGuangzhouChina School of Medicine Xizang Minzu UniversityXianyangChina Center for Infectious Disease research Westlake Laboratory of Life Sciences and BiomedicineWestlake UniversityHangzhouChina research Center for Industries of the Future School of Life SciencesWestlake UniversityHangzhouChina

Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every *** symptoms range from mild diarrhea to life-threatening damage to the *** and recurrence of *** infection(CDl)are mediated by the metabolically dormant spores,while the virulence of *** is mainly due to the two large clostridial toxins,TcdA and *** toxins or forming spores are two different strategies for *** to cope with harsh environmental *** is of great significance to understand the molecular mechanisms for *** to skew to either of the cellular ***,we summarize the current understanding of the regulation and connections between toxin production and sporulation in *** and further discuss the potential solutions for yet-to-be-answered questions.

关键词： C.difficile sporulation TcdA TcdB toxin production

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Natural variation of an autophagy-family gene among rice subspecies affects grain size and weight

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The Crop Journal 2024年第1期12卷 121-132页

作者： Shiying Huang Peng Wang Caijing Li Qingwen Zhou Tao Huang Yicong Cai Qin Cheng Hui Wang Qi Zhong Zhihao Chen Liping Chen Haohua He Jianmin Bian Key Laboratory of Crop Physiology Ecology and Genetic BreedingMinistry of Education.Jiangxi Agricultural UniversityNanchang 330045JiangxiChina Weill Cornell Medical Immunology and Microbiology1300 York AvenueBox 62New YorkNY 10065USA

Elucidating the genetic basis of natural variation in grain size and weight among rice varieties can help breeders develop high-yielding *** identified a novel gene,GW3a(Grain Weight 3a)(LOC_Os03g27350),that affects rice grain size and ***3a mutants showed higher total starch content and dry matter accumulation than the wild type(WT),Nipponbare,suggesting that GW3a negatively regulates grain size and ***,our study found that GW3a interacted with OsATG8 by cleaving it,suggesting that GW3a may be involved in the assembly of autophagosomes and starch degradation in *** haplotype analysis of GW3a showed functional differences between indica and japonica *** together,we conclude that GW3a is expressed in the autophagosome pathway regulating starch metabolism in rice,affecting yield-related traits,such as grain size,grain weight and thousand grain weight(TGW).Our findings also shed new light on autophagy-mediated yield trait regulation,proposing a possible strategy for the genetic improvement of high-yield germplasm in rice.

关键词： Grain size GW3a Autophagy Starch content

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Structure， properties， bioactivities and structure-activity relationships of polysaccharides from Nostoc flagelliforme grown under three different culture conditions

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Food Science and Human Wellness 2024年

作者： Yanru Li Shigang Shen Longfei Wang Mengyuan Li Yan Zhang Shiru Jia Ruiying Zhu Peipei Han State Key Laboratory of Food Nutrition and Safety， Key Laboratory of Industrial Fermentation microbiology， Ministry of Education， College of Biotechnology， Tianjin University of Science and Technology

The physicochemical properties， structural characteristics， antioxidant， radioprotective and lipid-lowering activities， as well as the underlying structure-activity relationships of polysaccharides extracted from Nostoc flagelliforme grown under normal （WL-EPS-1）， salt stress （NaCl-EPS-1） and mixotrophic culture conditions （Glu-EPS-1） were studied. The results demonstrated that WL-EPS-1， NaCl-EPS-1 and Glu-EPS-1 were heteropolysaccharides comprising different proportions of monosaccharides and uronic acid， with different average molecular weights of 0.99 × 103， 1.09 × 103and 1.18 × 103kDa， respectively. Their intrinsic viscosity values were significantly different， at 24.72 dL/g， 29.98 dL/g and 41.06 dL/g， respectively. The functional groups of polysaccharides were not greatly affected， but the chemical composition， triple-helix structure， chain length and surface morphology were significantly influenced by culture conditions. In vitro bioactivity assays showed that the antioxidant activity generally increased in the order of WL-EPS-1 < NaCl-EPS-1 < Glu-EPS-1， while NaCl-EPS-1 had the best radioprotective effect， and Glu-EPS-1 had the best lipid-lowering effect. In addition， the structure-activity relationship of the polysaccharides was analyzed by Partial Least Squares （PLS）， which revealed that the most important factors affecting the antioxidant， radioprotective and lipid-lowering activities of polysaccharides were viscosity and molecular weight. This study provides a strategy for obtaining high-bioactivity polysaccharides by appropriate regulation of culture conditions， as well as opening new directions for the molecular modification of polysaccharides.

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Asymmetric reduction of conjugated C=C bonds by immobilized fusion of old yellow enzyme and glucose dehydrogenase

Green Synthesis and Catalysis

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Green Synthesis and Catalysis 2024年第2期5卷 80-87页

作者： Yongxing Li Pengqian Luan Lele Dong Jianqiao Liu Luying Jiang Jing Bai Fufeng Liu Yanjun Jiang School of Chemical Engineering and Technology Hebei University of TechnologyTianjin 300130China College of Food Science and Biology Hebei University of Science&Technology26 Yuxiang StreetYuhua DistrictShijiazhuang 050018China Key Laboratory of Industrial Fermentation microbiology of Ministry of Education Tianjin Key Laboratory of Industrial MicrobiologyCollege of BiotechnologyTianjin University of Science&TechnologyTianjin 300457China

Asymmetric reduction of the conjugated C=C bonds by the old yellow enzymes(OYEs)presents a promising field in the synthesis of chiral ***,few natural OYEs have been applied in large-scale applications due to the requirement of costly NADPH and low operational ***,a stable and efficient fusion of YqjM from Bacillus subtilis and glucose dehydrogenase(GDH)from Bacillus megaterium was constructed to stereoselectively reduce the conjugated C=C bonds in a self-sufficient continuous *** effects of the enzyme order and different linkers on the fusions were investigated by structural analysis and all-atom molecular dynamics *** best fusion YqjM_G_GDH gave 98% conversion of 100 mmol/L 2-methylcyclopentenone with an excellent ee value(>99%)in 3 h,while the mixture of individual enzymes only obtained 68% conversion after more than 8 *** improved substrate conversion of YqjM_G_GDH fusion was probably attributed to the increased flexibility of each fused enzyme and the shortening of the diffusion distance of NADPH regenerated.A one-pot process was designed to purify and immobilize the fusion on the Ni2t-nitrilotriacetic acid functionalized magnetic mesoporous silica *** resulting immobilized biocatalyst not only catalyzed the asymmetric reduction of various α,β-unsaturated ketones(20 mmol/L)continuously with only 50μmol/L NADPt to initiate the whole process,but also retained more than 82%of the initial activity after seven cycles,serving as a good candidate for the industrial applications.

关键词： Enzyme fusion Old yellowenzymes Asymmetricreduction C=C bond Cofactor regeneration Immobilization

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Insights into the Impact of Bifidobacterium bifidum， B. breve， and B. longum on the Immune Response Against Salmonella Infection in Neonatal Rats

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Food Science and Human Wellness 2024年

作者： Chunxiu Lin Yugui Lin Min Guo Rui Xiao Shunhe Wang Yonghua Zhou Jianxin Zhao Hao Zhang Wei Chen Gang Wang State Key Laboratory of Food Science and Resources， Jiangnan University School of Food Science and Technology， Jiangnan University microbiology Laboratory， Zhongshan Bo'ai Hospital， Southern Medical University Key Laboratory of National Health Commission on Parasitic Disease Control and Prevention， Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology， Jiangsu Institute of Parasitic Diseases National Engineering research Center for Functional Food， Jiangnan University (Yangzhou) Institute of Food Biotechnology， Jiangnan University Wuxi Translational Medicine research Center and Jiangsu Translational Medicine research Institute Wuxi Branch

Infants exhibit diminished susceptibility to external infections， a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract. Nonetheless， a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages. In this study， the impact of early intervention with Bifidobacterium bifidum (B. bifidum)， B. breve， and B. longum on neonatal rats infected with Salmonella enterica serovar Typhimurium (S. typhimurium) SL1344 were compared. The study encompasses various immunity levels， including gut immunity， central immunity (thymus)， peripheral immunity (spleen)， and brain immunity. Following Salmonella infection， significant alterations in neonatal rats were observed in growth and developmental levels， immune markers， cytokine levels， balance of T lymphocyte subpopulations， intestinal barrier function， and blood-brain barrier integrity. Compared with B. breve and B. longum， B. bifidum demonstrated more pronounced efficacy in regulating these physiological processes. By conducting multi-level analyses of gut microbiota， bifidobacterial community， colonic content metabolomics， and serum metabolomics， the significance of B. bifidum's role is underscored， and the immune-enhancing function of messenger metabolites is unveiled. Among these metabolites， γ-L-Glutamyl-L-glutamic acid and Orotic acid were found to be shared by all three species， while Hippuric acid and 1a，1b-dihomo Prostaglandin F2α were unique to B. bifidum， and DL-Arginine was specific to B. longum. Overall， this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections， emphasizing the significant role of B. bifidum.

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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler Christina Schneider Markus Casper Frank Lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical microbiology and Hygiene Saarland UniversityHomburg 66421Germany Department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of Metabolic Liver Diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUND Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

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Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway

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Plant Communications 2024年第8期5卷 172-188页

作者： Hu-Jiao Lan Jie Ran Wen-Xu Wang Lei Zhang Ni-Ni Wu Ya-Ting Zhao Min-Jun Huang Min Ni Fen Liu Ninghui Cheng Paul A.Nakata Jianwei Pan Steven A.Whitham Barbara J.Baker Jian-Zhong Liu Zhejiang Provincial Key Laboratory of Biotechnology on Specialty Economic Plants Zhejiang Normal UniversityJinhua 321004China Institute of Plant Genetics and Developmental Biology College of Chemistry and Life SciencesZhejiang Normal UniversityJinhua 321004China College of Life Sciences Lanzhou UniversityLanzhou 730000China Department of Plant Pathology and microbiology Iowa State UniversityAmesIA 50011USA Department of Plant and Microbial Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA Plant Gene Expression Center U.S.Department of Agriculture-Agricultural Research ServiceAlbanyCA 94706USA Lushan Botanical Garden Chinese Academy of SciencesJiujiang 332000China U.S.Department of Agriculture-Agricultural research Service Children’s Nutrition Research CenterDepartment of PediatricsBaylor College of MedicineHoustonTX 77030USA

The crosstalk between clathrin-mediated endocytosis(CME)and the autophagy pathway has been reported in mammals;however,the interconnection of CME with autophagy has not been established in ***,we report that the Arabidopsis CLATHRIN LIGHT CHAIN(CLC)subunit 2 and 3 double mutant,clc2-1 clc3-1,phenocopies Arabidopsis AUTOPHAGY-RELATED GENE(ATG)mutants in both autoimmunity and nutrient ***,the autophagy pathway is significantly compromised in the clc2-1 clc3-1 ***,multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific *** expected,both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation,and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 ***,simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum,supporting the functional relevance of the CLC2-ATG8h/8i *** conclusion,our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.

关键词： autophagy clathrin light chain immunity clathrin-mediated endocytosis senescence cell death

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