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How do lateral septum projections to the ventral CA1 influence sociability?

Neural Regeneration Research 2024年第8期19卷 1789-1801页

作者： Dan Wang Di Zhao Wentao Wang Fengai Hu Minghu Cui Jing Liu Fantao Meng Cuilan Liu Changyun Qiu Dunjiang Liu Zhicheng Xu Yameng Wang Yu Zhang Wei Li Chen Li Department of Rehabilitation Medicine Binzhou Medical University HospitalBinzhouShandong ProvinceChina Medical Research Center Binzhou Medical University HospitalBinzhouShandong ProvinceChina institute for metabolic&Neuropsychiatric Disorders Binzhou Medical University HospitalBinzhouShandong ProvinceChina Department of Psychology Binzhou Medical University HospitalBinzhouShandong ProvinceChina College of Nursing Binzhou Medical UniversityBinzhouShandong ProvinceChina

Social dysfunction is a risk factor for several neuropsychiatric *** studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social *** r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea *** this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence *** res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these ***,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in *** findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty *** findings provide new insights rega rding the neural circuits that regulate sociability.

关键词： chemogenetics GABA receptor GABAergic neurons glutamatergic neurons lateral septum neural excitability neural projection social novelty social preference ventral CA1

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Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile Biotechnology(Shanghai)Co.Ltd. Shanghai 201315China institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Laboratory of Animal Nutritional Physiology and metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle ***,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains *** propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging *** investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total ***,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle ***,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/*** butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and *** a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle *** findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

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Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

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Chinese Medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China metabolic Epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight changediseases)=1.21,95%CI:1.11-1.31,P<0.001),whereas subjects with weight gain≥5 kg had 11%(HR_(Cancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,P<0.001).For the change of weight status,both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death(HR_(Overweight to normal)=1.18,95%CI:1.09-1.27;HR_(Becoming underweight)=1.35,95%CI:1.25-1.46)and cancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality Cancer Stroke Heart diseases Body mass index

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评价散寒化湿颗粒与奈玛特韦-利托那韦对照治疗轻型/中型新型冠状病毒感染有效性和安全性的随机、开放、多中心临床研究

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Science Bulletin 2024年第12期69卷 1954-1963页

作者：邹晓辉常康范国辉郑欢伟神和正唐亮杨映映王业明赵林华吕红周昕沈小明陈利强仝小林曹彬 National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesLaboratory of Clinical Microbiology and Infectious DiseasesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Clinical Research and Data Management Center of Respiratory MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Shijiazhuang Hospital of Traditional Chinese Medicine Shijiazhuang 050051China Linyi Traditional Chinese Medicine Hospital Linyi 276000China Wuxi Traditional Chinese Medicine Hospital Wuxi 214071China National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Traditional Chinese Medicine for Pulmonary DiseasesCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China institute of metabolic diseases Guang’anmen Hospital of ChinaAcademy of Chinese Medical SciencesBeijing 100053China Taicang Traditional Chinese Medicine Hospital Taicang 215400China The First Hospital of Qiqihar Qiqihar 161005China The Second Affiliated Hospital of Jiaxing University Jiaxing 314000China Huizhou First Hospital Huizhou 516003China National Center for Integrated Traditional Chinese Medicine and Western Medicine China-Japan Friendship HospitalBeijing 100029China

Sanhan Huashi granules(SHG)demonstrated therapeutic effects against coronavirus disease 2019(COVID-19)in observational *** order to compare the effectiveness and safety of SHG and nirmatrelvir–ritonavir in treating adults with mild-to-moderate COVID-19,we conducted a randomized,activecontrolled,open-label,multi-center trial conducted between February and July in *** patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir–ritonavir group.A total of 400participants were randomized,among which 200 participants ultimately received SHG and 198 received nirmatrelvir–*** primary outcome was time to sustained clinical recovery through day *** significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir–ritonavir(6.0(95%CI,5.0 to 6.0)vs.8.0(95%CI,6.0 to 9.0)d;P=0.001),particularly for individual symptoms including fever,sore throat,cough and *** participants in either group died and incidence of severe COVID-19 showed no difference between two *** who received nirmatrelvir–ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG(46.4%(95%CI,39.1 to 53.7)vs.65.6%(95%CI,58.3 to 72.4);P<0.001).Most adverse events were mild in both *** summary,SHG was superior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19,despite a lower virus clearance rate observed after 5 d of treatment(Chinese Clinical Trial Registry Identifier:Chi CTR2300067872).

关键词： Traditional Chinese medicine COVID-19 Nirmatrelvir-Ritonavir Sustained clinical recovery

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Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

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Science China(Life Sciences) 2024年第5期67卷 1035-1050页

作者： Yaling Wang Jingwen Chen Xueying Huang Bangguo Wu Peng Dai Feng Zhang Jinsong Li Lingbo Wang State Key Laboratory of Genetic Engineering Shanghai Key Laboratory of Metabolic Remodeling and HealthInstitute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(Shanghai institute for Biomedical and Pharmaceutical Technologies) School of PharmacyFudan UniversityShanghai 200433China Shanghai Key Laboratoryof Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchoolof Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced *** enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for ***,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona *** further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO *** ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar *** study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.

关键词： disease modeling infertility multiple morphological abnormalities of the flagella(MMAF) induction of STOP-codons(iSTOP CRISPR-STOP) sperm motility

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Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

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World Journal of Hepatology 2024年第5期16卷 703-715页

作者： Li Xu Yu-Hong Fan Xiao-Jing Zhang Lan Bai State Key Laboratory of New Targets Discovery and Drug Development for Major diseases Gannan Innovation and Translational Medicine Research InstituteGannan Medical UniversityGanzhou 341000China School of Basic Medical Sciences Wuhan UniversityWuhan 430060China

Non-alcoholic fatty liver disease(NAFLD)poses a significant health challenge in modern societies due to shifts in lifestyle and dietary *** complexity stems from genetic predisposition,environmental influences,and metabolic *** processes govern various cellular functions such as transcription,chromatin structure,and cell *** NAFLD,these epigenetic tendencies,especially the process of histone methylation,are intricately intertwined with fat accumulation in the *** methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to *** early-stage NAFLD is reversible,its progression to severe stages becomes almost ***,early detection and intervention in NAFLD are crucial,and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

关键词： Non-alcoholic fatty liver disease Mechanism Histone methylation Methyltransferases Demethytrasferases Epigenetic modification Adipogenesis

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Unraveling the complex roles of macrophages in obese adipose tissue:an overview

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Frontiers of Medicine 2024年第2期18卷 205-236页

作者： Chang Peng Jun Chen Rui Wu Haowen Jiang Jia Li Hangzhou institute for Advanced Study University of Chinese Academy of SciencesHangzhou310000China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China Department of Prosthodontics Shanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghai200011China

Macrophages,a heterogeneous population of innate immune cells,exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic *** activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects,inducing insulin resistance through increased inflammation,impaired thermogenesis,and adipose tissue ***,adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis,facilitating the clearance of dead adipocytes,and promoting mitochondrial *** the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic ***,the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell *** this review,we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity,as well as explore the potential of drug delivery systems targeting macrophages,aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.

关键词： obesity inflammation adipose tissue macrophages adipose tissue homeostasis

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Prevalence and characteristics of MAFLD in Chinese adults aged 40 years or older:A community-based study

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Hepatobiliary & Pancreatic diseases International 2022年第2期21卷 154-161页

作者： Jing Zeng Li Qin Qian Jin Rui-Xu Yang Guang Ning Qing Su Zhen Yang Jian-Gao Fan Department of Gastroenterology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Endocrinology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of endocrine and metabolic diseases Shanghai Institute of Endocrinology and MetabolismShanghai Clinical Center for Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P metabolic disorders than those in the MAFLD + NAFLD + group(all P metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.

关键词： Nonalcoholic fatty liver disease metabolic dysfunction-associated fatty liver disease Prevalence Oral glucose tolerance test

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Association between metabolic Dysfunction-associated Fatty Liver Disease and Cognitive Impairment

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1034-1041页

作者： Qiang Yu Ruixin He Haowen Jiang Ji Wu Zhifeng Xi Kang He Yongbo Liu Tao Zhou Mingxuan Feng Ping Wan Hexin Yan Qiang Xia Department of Liver Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Depart-ment of endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShang-hai Jiaotong University School of MedicineShanghaiChina Shanghai National Clinical Research Center for metabolic diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR ChinaShang-hai National Center for Translational MedicineRuijin HospitalShanghai Jiaotong University School of MedicineShang-haiChina State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of Anesthesiology and Critical Care Medicine Renji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina.

Background and Aims:metabolic dysfunction-associated fatty liver disease(MAFLD)is a newly proposed term based on modified *** nonalcoholic fatty liver disease(NAFLD)has been well-documented as a multisystem dis-ease,research on the correlation of MAFLD and extra-hepatic diseases is *** study aimed to clarify the association of MAFLD,as well as NAFLD status with cognitive ***:A total of 5,662 participants 20-59 years of age who underwent cognitive tests and liver ultrasonography in the Third National Health and Nutrition Examination Survey were included in the *** function was evalu-ated using three computer-administered tests,the serial dig-it learning test(SDLT),the simple reaction time test(SRTT)and the symbol digit substitution test(SDST).Results:Par-ticipants with MAFLD had significantly poorer performance on the SRTT[odds ratio(OR)1.47,95%confidence interval(CI):1.14-1.89)].MAFLD with moderate-severe liver stea-tosis was associated with higher risks of scoring low in the SDLT(OR 1.37,95%CI:1.04-1.82)and SRTT(OR 1.55,95%CI:1.19-2.02).NAFLD combined with metabolic dys-function,instead of NAFLD without metabolic disorders,was associated an increased risk of a low SRTT score(OR 1.44,95%CI:1.10-1.82).MAFLD patients had a high probability of fibrosis,prediabetes,and diabetes and were also signifi-cantly associated with increased risks based on the SDST or SRTT ***:MAFLD was significantly associ-ated with increased risk of cognitive impairment,especially among MAFLD patients with a high degree of liver fibrosis,moderate-severe steatosis,or hyperglycemia.

关键词： NHANES metabolic dysfunction-associated fatty liver disease Nonalcoholic fatty liver disease Cognitive dysfunction

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Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling Wang Xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo Wang Shanghai Key Laboratory of metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful *** deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental ***,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is ***,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are *** Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF *** find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO *** analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in *** finally show that intracytoplasmic sperm injection overcomes Ccdc38-related *** study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling

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