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Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy

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science China(Life sciences) 2024年第6期67卷 1155-1169页

作者： Shuai Yuan Xudong Zhang Jiabing Zhan Rong Xie Jiahui Fan Beibei Dai Yanru Zhao Zhongwei Yin Qian Liu Dao Wen Wang Huaping Li Chen Chen Division of Cardiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of genetics and Molecular Mechanisms of Cardiological Disorders Wuhan 430030China department of Forensic Medicine Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in ***-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing *** knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in *** of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to *** knockdown attenuated these ***,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate ***-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL *** findings uncover the critical role of CFIRL,a fibroblast-associated lnc RNA,in heart failure by facilitating crosstalk between fibroblasts and *** knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.

关键词： lncRNA fibroblast fibrosis dilated cardiomyopathy heart failure

Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-κB and MAPK signaling pathway in mice

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Journal of Environmental sciences 2024年第3期137卷 553-566页

作者： Xingpei Fan Xiaoyan Li Jiaxin Li Yuxia Zhang Xiangjuan Wei Hailong Hu Boya Zhang Haining Du Meimei Zhao Ruijiao Zhu Daqian Yang Yuri Oh Ning Gu School of Life science and technology Harbin Institute of TechnologyHarbin 150001China State Key Laboratory of Urban Water Resource and Environment Harbin Institute of TechnologyHarbin 150006China department of Medicine Renal Electrolyte and Hypertension DivisionDepartment of GeneticsPerelman School of MedicineUniversity of PennsylvaniaPhiladelphia 19104USA Faculty of Education Wakayama UniversityWakayama 640-8441Japan

Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread ***,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at ***,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling *** PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor *** activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and *** activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin *** parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγ***,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were *** treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in *** on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.

关键词： Nanoplastics Resveratrol Hyperglycemia Lipid metabolism Infammatory response Reactive oxygen species(ROS)

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic

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Asian Journal of Andrology 2024年第1期26卷 41-45页

作者： Shun Bai Ming-Zhen Li Yang-Yang Wan Xue-Chun Hu Yi-Xun Liu Xian-Hong Tong Tong-Hang Guo Lu Zong Ran Liu Yuan-Qi Zhao Ping Xiang Bo Xu Xiao-Hua Jiang department of Gynecology and Obstetrics Reproductive and Genetic HospitalThe First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China NHC Key Laboratory of Male Reproduction and genetics Guangdong Provincial Reproductive Science Institute(Guangdong Provincial Fertility Hospital)Guangzhou 510600China department of Urology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Wannan Medical College Wuhu 241002China

Genetic risk factors have been shown to contribute to the development of sexual ***,the role of methylenetetrahydrofolate reductase(MTHFR)gene variants in the risk of erectile dysfunction(ED)remains *** this study,we recruited 1254 participants who underwent ED assessed by the International Index of Erectile *** MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction(PCR).No significant difference in the genotypic frequency of the MTHFR C677T polymorphism(CC,CT,and TT)was observed between men from the ED and non-ED *** addition,on binary logistic regression analysis,both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T ***,a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED(P=O.02).The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis,even after adjusting for potential confounders(odds ratio[OR]=2.46,95%confidence interval[CI]:1.15-5.50,P=0.02).These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe *** of MTHFR gene polymorphisms may provide complementary information for ED patients during routineclinicaldiagnosis.

关键词： erectile dysfunction gene variant genetic risk factors methylenetetrahydrofolate reductase sexual function

Regulation of aging by NELF-A and RNA polymerase Ⅱ elongation

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Neural Regeneration Research 2024年第7期19卷 1415-1416页

作者： Chin-Tong Ong Zhen-Kai Ngian Temasek Life sciences Laboratory and department of Biological sciences National University of SingaporeSingaporeSingapore department of genetics Harvard Medical SchoolBostonMAUSA Institute of Molecular and Cell Biology Agency for ScienceTechnology and ResearchSingaporeSingapore

Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and *** in different animal models have l... 详细信息

关键词： aging twelve integrity

Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease:current knowledge and new insights

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Frontiers of Medicine 2024年第1期18卷 31-45页

作者： Yaonan Song Haoran Wei Zhitong Zhou Huiqing Wang Weijian Hang Junfang Wu Dao Wen Wang Division of Cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of genetics and Molecular Mechanisms of Cardiological Disorders Wuhan430030China

Phenylacetylglutamine(PAGln)is an amino acid derivate that comes from the amino acid *** are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular *** this review,we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of *** summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases,such as heart failure,coronary heart disease/atherosclerosis,and cardiac *** underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic ***,other possible mechanisms such as inflammatory response and oxidative stress could also be induced by ***,since PAGln is produced across different organs including the intestine,liver,and kidney,the cross-talk among multiple organs focused on the function of this uremic toxic ***,the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

关键词： PAGln cardiovascular disease gut microbiota uremic metabolite biomarker

lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression

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Frontiers of Medicine 2024年第3期18卷 484-498页

作者： Xiang Nie Jiahui Fan Yanwen Wang Rong Xie Chen Chen Huaping Li Dao Wen Wang Division of Cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of genetics and Molecular Mechanisms of Cardiological Disorders Wuhan430030China

lncRNA ZNF593 antisense(ZNF593-AS)transcripts have been implicated in heart failure through the regulation of myocardial *** decreased transcriptional activity of ZNF593-AS has also been detected in cardiac ***,the function of ZNF593-AS in cardiac hypertrophy remains ***,we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine(PE).In vivo,ZNF593-AS aggravated pressure overload–induced cardiac hypertrophy in knockout *** contrast,cardiomyocyte-specific transgenic mice(ZNF593-AS MHC-Tg)exhibited attenuated TAC-induced cardiac *** vitro,vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy,whereas GapmeR-induced inhibition aggravated hypertrophic *** using RNA-seq and gene set enrichment analyses,we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2(Mfn2)is a direct target of ***593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial ***,it represents a promising therapeutic target for combating pathological cardiac remodeling.

关键词： lncRNA ZNF593-AS cardiac hypertrophy Mfn2 oxidative phosphorylation

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

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Biomedical and Environmental sciences 2024年第5期37卷 445-456页

作者： HU Wei Qiong ZHOU Wei Guang ZHOU Guang Wei LIAO Jia Xi SHI Jia Xing XIE FengYang LI Shou Heng WANG Yong FENG Xian Hong GU Xiu Li CHEN Bi Feng department of Biological science and technology School of ChemistryChemical Engineering and Life SciencesWuhan University of TechnologyWuhan 430070HubeiChina Institute of WUT-AMU Wuhan University of TechnologyWuhan 430070HubeiChina department of Clinical Laboratory Wuhan Xinzhou District People’s HospitalWuhan 430499HubeiChina department of Reproductive genetics Wuhan Huake Reproductive HospitalWuhan 430013HubeiChina

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than ***,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer *** A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were *** of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger ***-four eligible studies were included in the *** After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese *** meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese *** The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

关键词： LEPR gene rs1137101 Digestive system cancers Genetic susceptibility Meta-analysis

Filamentation and inhibition of prokaryotic CTP synthase with ligands

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mLife 2024年第2期3卷 240-250页

作者： Chenjun Guo Zixuan Wang Ji‐Long Liu School of Life science and technology ShanghaiTech UniversityShanghaiChina department of Physiology Anatomy and GeneticsUniversity of OxfordOxfordUK Shanghai Clinical Research and Trial Center ShanghaiChina

Cytidine triphosphate synthase(CTPS)plays a pivotal role in the de novo synthesis of cytidine triphosphate(CTP),a fundamental building block for RNA and DNA that is essential for *** is capable of directly binding to all four nucleotide triphosphates:adenine triphosphate,uridine triphosphate,CTP,and guanidine ***,CTPS can form cytoophidia in vivo and metabolic filaments in vitro,undergoing regulation at multiple *** is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic *** cryo-electron microscopy,we determined the structure of Escherichia coli CTPS(ecCTPS)filament in complex with CTP,nicotinamide adenine dinucleotide(NADH),and the covalent inhibitor 6-diazo-5-oxo-L-norleucine(DON),achieving a resolution of *** constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis,providing an evolutionary perspective on CTPS filament *** computational analysis revealed a solvent-accessible ammonia tunnel upon DON *** comparative structural analysis,we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic *** biochemical assays and structural analysis,we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on *** results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

关键词： CTP synthase Cryo-electron microscopy cytoophidium metabolic filament species specific inhibition

Endomembrane-biased dimerization of ABCG16 and ABCG25 transporters determines their substrate selectivity in ABA-regulated plant growth and stress responses

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Molecular Plant 2024年第3期17卷 478-495页

作者： Yeling Zhou Yuzhu Wang Dong Zhang Jiansheng Liang institute of Plant and Food science Department of BiologySchool of Life SciencesSouthern University of Science and Technology(SUSTech)Shenzhen 518055China Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes Southern University of Science and Technology(SUSTech)Shenzhen 518055China jiangsu Key Laboratory of Crop genetics and Physiology/Co-lnnovation Center for Modern Production technology of Grain Crops Key Laboratory of Plant Functional Genomics of the Ministry of EducationYangzhou UniversityYangzhou 225009China

ATP-binding cassette(ABC)transporters are integral membrane proteins that have evolved diverse func-tions fulfilled via the transport of various *** Arabidopsis,the G subfamily of ABC proteins is particularly abundant and participates in multiple signaling pathways during plant development and stress *** this study,we revealed that two Arabidopsis ABCG transporters,ABCG16 and ABCG25,engage in ABA-mediated stress responses and early plant growth through endomembrane-specific dimerization-coupled transport of ABA and ABA-glucosyl ester(ABA-GE),*** first revealed that ABCG16 contributes to osmotic stress tolerance via ABA *** specifically,ABCG16 induces cellular ABA efflux in both yeast and plant *** FRET analysis,we showed that ABCG16 forms oblig-atory homodimers for ABA export activity and that the plasma membrane-resident ABCG16 homodimers specifically respond to ABA,undergoing notable conformational ***,we demonstrated that ABCG16 heterodimerizes with ABCG25 at the endoplasmic reticulum(ER)membrane and facilitates the ER entry of ABA-GE in both Arabidopsis and tobacco *** specific responsiveness of the ABCG16-ABCG25 heterodimer to ABA-GE and the superior growth of their double mutant support an inhib-itory role of these twoABCGs in early seedling establishment via regulation of ABA-GE translocation across the ER *** endomembrane-specific analysis of the FRET signals derived from the homo-or heterodimerized ABcG complexes allowed us to link endomembrane-biased dimerization to the transloca-tion of distinct substrates by ABcG transporters,providing a prototypic framework for understanding the omnipotence of ABcG transporters in plant development and stress responses.

关键词： abscisic acid ABCG transporter dimerization endomembrane substrate selectivity