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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

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

Unveiling the distinctive traits of functional rye centromeres:minisatellites,retrotransposons,and R-loop formation

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Science China(Life Sciences) 2024年第9期67卷 1989-2002页

作者： Chang Liu Shulan Fu Congyang Yi Yang Liu Yuhong Huang Xianrui Guo Kaibiao Zhang Qian Liu James A.Birchler Fangpu Han State Key laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Key laboratory for Plant genetics and Breeding Sichuan Agricultural UniversityChengdu 611130China division of Biological Science University of MissouriColumbia 65211-7400USA

Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle *** their conserved functionality,centromeric DNA sequences exhibit rapid evolution,presenting diverse sizes and compositions across *** functional significance of rye centromeric DNA sequences,particularly in centromere identity,remains *** this study,we comprehensively characterized the sequence composition and organization of rye *** findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs)and interspersed *** systematically classified LTR-RTs into five categories,highlighting the prevalence of younger CRS1,CRS2,and CRS3 of CRSs(centromeric retrotransposons of Secale cereale)were primarily located in the core centromeres and exhibited a higher association with CENH3 *** minisatellites,mainly derived from retrotransposons,along with CRSs,played a pivotal role in establishing functional centromeres in ***,we observed the formation of R-loops at specific regions of CRS1,CRS2,and CRS3,with both rye pericentromeres and centromeres exhibiting enrichment in ***,these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres,suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere *** work provides insights into the DNA sequence composition,distribution,and potential function of R-loops in rye *** knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres,offering implications for the development of synthetic centromeres in future plant modifications and beyond.

关键词： centromere LTR-RTs minisatellite rye R-loop

Combining QTL Mapping and Multi-Omics Identify Candidate Genes for Nutritional Quality Traits during Grain Filling Stage in Maize

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1441-1453页

作者： Pengcheng Li Tianze Zhu Yunyun Wang Shuangyi Yin Xinjie Zhu Minggang Ji Wenye Rui Houmiao Wang Zefeng Yang Chenwu Xu Jiangsu Key laboratory of Crop genetics and Physiology Key Laboratory of Plant Functional Genomics of the Ministry of EducationJiangsu Key Laboratory of Crop Genomics and Molecular BreedingAgricultural College of Yangzhou UniversityYangzhou225009China Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops Yangzhou UniversityYangzhou225009China

The nutritional composition and overall quality of maize kernels are largely determined by the key chemical com-ponents:protein,oil,and ***,the genetic basis underlying these nutritional quality traits during grainﬁlling remains poorly *** this study,the concentrations of protein,oil,and starch were studied in 204 recombinant inbred lines resulting from a cross between DH1M and T877 at four different stages *** the traits exhibited considerable phenotypic *** the grain-ﬁlling stage,the levels of protein and starch content generally increased,whereas oil content decreased,with signiﬁcant changes observed between 30 and 40 days after *** trait locus(QTL)mapping was conducted and a total of 32 QTLs,comprising 14,12,and 6 QTLs for grain protein,oil,and starch content were detected,*** QTLs were consistently detectable across different time *** integrating QTL analysis,glo-bal gene expression proﬁling,and comparative genomics,we identiﬁed 157,86,and 54 differentially expressed genes harboring nonsynonymous substitutions between the parental lines for grain protein,oil,and starch con-tent,*** gene function annotation prioritized 15 candidate genes potentially involved in reg-ulating grain quality traits,including those encoding transcription factors(NAC,MADS-box,bZIP,and MYB),cell wall invertase,cellulose-synthase-like protein,cell division cycle protein,trehalase,auxin-responsive factor,and phloem protein *** study offers signiﬁcant insights into the genetic architecture of maize kernel nutritional quality and identiﬁes promising QTLs and candidate genes,which are crucial for the genetic enhance-ment of these traits in maize breeding programs.

关键词： Maize protein oil starch QTL mapping candidate genes

Association between Exposure of Rare Earth Elements and Outcomes of In Vitro Fertilization-Embryo Transfer in Beijing

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Biomedical and Environmental Sciences 2024年第8期37卷 876-886页

作者： Yutong Wang Jing Li Shirong Xu Shengli Lin Zhenchen Hou Linlin Wang Yali Huang Yue Sun Wei Guo Lailai Yan Ying Wang Chan Tian State Key laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Department of Medical genetics Peking UniversityBeijing 100191China National Clinical Research Center for Obstetrics and gynecology Peking University Third HospitalBeijing 100191China Key laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Central laboratory of School of Public Health Peking UniversityBeijing 100191China School of Basic Medical Sciences Peking UniversityBeijing 100191China

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from *** A total of 141 couples were *** and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann–Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,*** models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET *** Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization ***,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical *** Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy *** is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive ***,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

关键词： Rare earth elements In vitro fertilization Pregnancy outcomes Mixture exposure analysis

The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa

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Asian Journal of Andrology 2024年第1期26卷 107-111页

作者： Liu Liu Jing Yang Wen-Jing Zhang Yi-Ling Zhou Gui-Jun Zhao Ya Huang Shu-Yan Tang Obstetrics and gynecology Hospital Fudan UniversityShanghai 200011China Shanghai Key laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China State Key laboratory of Genetic Engineering and Collaborative Innovation Center for genetics and Development Department of Computational BiologySchool of Life SciencesFudan UniversityShanghai 200436China Shanghai Towako Hospital Shanghai 200131China Shanghai Institute of Medical genetics Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200040China

Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to *** several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately ***,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated *** analysis revealed a novel homozygous c.520A>G(***174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and *** algorithms predicted this variant to be a damaging *** with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental *** investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy *** analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the *** findings reveal a candidate causative gene for vacuolated spermatozoa.

关键词： AMZ2 male infertility sperm quality teratozoospermia

CCDC181 is required for sperm flagellum biogenesis and male fertility in mice

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Zoological Research 2024年第5期45卷 1061-1072页

作者： Xiang-Jun Zhang Xiao-Ning Hou Jian-Teng Zhou Bao-Lu Shi Jing-Wei Ye Meng-Lei Yang Xiao-Hua Jiang Bo Xu Li-Min Wu Qing-Hua Shi division of Reproduction and genetics First Affiliated Hospital of University of Science and Technology of China(USTC)Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceInstitute of Health and MedicineHefei Comprehensive National Science CenterUniversity of Science and Technology of ChinaHefeiAnhui 230001China

The structural integrity of the sperm flagellum is essential for proper sperm *** defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully ***181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile *** this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain *** this study,Ccdc181 knockout mice were *** absence of CCDC181 led to defective sperm head shaping and flagellum ***,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm *** findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

关键词： Male infertility CCDC181 MMAF Spermiogenesis Flagellum biogenesis

Dominant negative effect as a novel mechanism of SPAST gene mutation in a large family with hereditary spastic paraplegia

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Genes & Diseases 2024年第5期11卷 74-77页

作者： Ke Deng Haibo Ruan Feifei Yu Zhenle Pei Congjian Xu Shuo Zhang Shanghai Ji Ai genetics&IVF Institute Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200000China Shanghai Key laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200000China The First People’s Hospital of Wenling WenlingZhejiang 317500China Rushan Hospital of Traditional Chinese Medicine RushanShandong 264599China Department of Obstetrics and gynecology Fudan UniversityShanghai 200000China.

Hereditary spastic paraplegia(HSP)is a group of disorders with genetic heterogeneity,lower-extremity weakness,and spasticity are the most common signs and *** is the most frequently disease-causing *** is a microtubule-severing enzyme encoded by SPAST that cleaves long microtubules into short fragments by interacting with other proteins or *** spastic paraplegia type 4(SPG4),which is autosomal dominant,is the clinical subtype associated with SPAST ***4 accounts for up to one-third of all HSP cases and usually presents with isolated lower extremity spasticity,with or without bladder or sensory dysfunction.1 The main cause of SPG4 is believed to be spastin haploinsufficiency,which results from mutations in the SPAST gene.

关键词： bladder insufficiency clinical

High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke P.Lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and molecular genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal division and division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid *** adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the *** demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating