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Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells

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Asian Journal of Andrology 2024年第2期26卷 165-174页

作者： Hai-Wei Feng Yu Zhao Yan-Ling Gao Dong-Teng Liu Li-Jun Huo key laboratory of Agricultural Animal genetics Breeding and ReproductionEducation Ministry of ChinaCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China shenzhen key laboratory of Fertility Regulation Reproductive Medicine CenterThe University of Hong Kong-Shenzhen HospitalShenzhen 518053China Maternal-Fetal medicine Institute Department of Obstetrics and GynaecologyShenzhen Baoan Women's and Children's HospitalJinan UniversityShenzhen 518100China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various *** mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial *** has been implicated in meiosis regulation,but its precise role is currently *** this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in *** found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the ***,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition *** loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB *** dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron ***,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) *** together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关键词： ClpX homologous chromosome meiosis mitochondrial recombination synapsis

BET inhibitors enhance the anti-cancer effect of etoposide by suppressing the MRN-ATM axis in the DNA damage response

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Genes & Diseases 2024年第1期11卷 19-22页

作者： Zhenhai Li Wenchao Xu Feng Chen Jun Zhang Wei-Guo Zhu Guangdong key laboratory of Genome Instability and Human Disease Prevention Department of Biochemistry and Molecular BiologyShenzhen University School of MedicineShenzhenGuangdong 518055China School of Pharmaceutical Sciences Shenzhen University Health Science CenterShenzhenGuangdong 518055China Base for International Science and Technology Cooperation:Carson Cancer Stem Cell Vaccines R&D Center International Cancer CenterShenzhen University Health Science CenterShenzhenGuangdong 518055China shenzhen Bay laboratory Shenzhen University School of MedicineShenzhenGuangdong 518055China Marshall laboratory of Biomedical Engineering Shenzhen University School of MedicineShenzhenGuangdong 518055China

Etoposide is widely used for cancer chemotherapy in the ***,long-term etoposide treatment can lead to adverse effects or drug *** improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer ***,we showed BRD4,one of the main targets of BET inhibitors,was involved in DNA damage response(DDR)via the homologous recombination(HR)repair pathway.

关键词： etoposide damage cancer

Ancient mitochondrial genome depicts sheep maternal dispersal and migration in Eastern Asia

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Journal of genetics and Genomics 2024年第1期51卷 87-95页

作者： Liu Yang Xing Zhang Yaning Hu Piao Zhu Hua Li Zhenyu Peng Hai Xiang Xinying Zhou Xingbo Zhao National Engineering laboratory for Animal Breeding Key Laboratory of AnimalGeneticsBreeding and ReproductionMinistry of Agriculture and Rural AffairsCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Guangdong Provincial key laboratory of Animal molecular Design and Precise Breeding School of Life Science and EngineeringFoshan UniversityFoshanGuangdong 528225China State key laboratory of Agricultural Genomics BGI-ShenzhenShenzhenGuangdong 518083China key laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

Sheep have been one of the most important groups of animals since ancient ***,the knowledge of their migration routes and genetic relationships is still poorly *** investigate sheep maternal migration histories alongside Eurasian communications routes,in this study,we obtain mitochondrial genomes(mitogenomes)from 17 sheep remains in 6 Chinese sites and 1 Uzbekistan site dated 4429–3100 years before present(BP).By obtaining the mitogenomes from the sheep(4429–3556 BP)found in the Tongtian Cave site in Xinjiang,Altai region of northwest China,our results support the emergence of haplogroup C sheep in Xinjiang as early as 4429–3556 *** combined phylogenetic analyses with extant ancient and modern sheep mitogenomes suggest that the Uzbekistan-Altai region may have been a migration hub for early sheep in eastern *** least two migration events have taken place for sheep crossing Eurasia to China,one passing by Uzbekistan and Northwest China to the middle and lower reaches of the Yellow River at approximately 4000 BP and another following the Altai region to middle Inner Mongolia from 4429 BP to 2500 ***,this study provides further evidence for early sheep utilization and migration patterns in Eastern Asia.

关键词： Sheep Ancient DNA Eastern Asia Mitochondrial genome Migration Altai

A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys

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Neuroscience Bulletin 2024年第1期40卷 90-102页

作者： Yefei Chen Jingyi Wang Jing Liu Jianbang Lin Yunping Lin Jinyao Nie Qi Yue Chunshan Deng Xiaofei Qi Yuantao Li Ji Dai Zhonghua Lu Department of Anesthesiology Shenzhen Maternity and Child Healthcare HospitalThe First School of Clinical MedicineSouthern Medical UniversityShenzhen 518027China shenzhen Technological Research Center for Primate Translational medicine Shenzhen Key Laboratory for Molecular Biology of Neural DevelopmentShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China CAS key laboratory of Brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Guangdong Provincial key laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Biomedical Research Institute Hubei University of MedicineShiyan 442000China Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Retrograde adeno-associated viruses(AAVs)are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural ***,few retro-grade AAV capsids have been shown to offer access to cor-tical projection neurons across different species and enable the manipulation of neural function in non-human primates(NHPs).Here,we report the development of a novel retro-grade AAV capsid,AAV-DJ8R,which efficiently labeled cortical projection neurons after local administration into the striatum of mice and *** addition,intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral ***,AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque *** data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

关键词： Retrograde AAV Capsid variant Cortical projection neuron Optogenetics Monkey

Genome-wide association study identifies 12 new genetic loci associated with growth traits in pigs

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Journal of Integrative Agriculture 2024年第1期23卷 217-227页

作者： Mu Zeng Binhu Wang Lei Liu Yalan Yang Zhonglin Tang Guangdong Provincial key laboratory of Animal molecular Design and Precise Breeding/key laboratory of Animal molecular Design and Precise Breeding of Guangdong Higher Education Institutes School of Life Science and EngineeringFoshan UniversityFoshan 528231China Kunpeng Institute of Modern Agriculture at Foshan Agricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesFoshan 528200China shenzhen Branch Guangdong Laboratory of Lingnan Modern Agriculture/Key Laboratory of Livestock and Poultry Multi-omics of Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China

Growth traits are among the most important economic traits in pigs and are regulated by polygenes with complex regulatory *** the major indicators of growth performance,the backfat thickness(BFT),loin eye area(LEA),and days to 100 kg(D100)traits are commonly used to the genetics improvement in ***,the available genetic markers for these traits are *** uncover novel loci and candidate genes associated with growth performance,we collected the phenotypic information of BFT,LEA,and D100 in 1,186 pigs and genotyped all these individuals using the Neogen GGP porcine 80K *** performed a genome-wide association study(GWAS)using 4 statistical models,including mixed linear models(MLM),fixed and random model circulating probability unification(FarmCPU),settlement of MLM under progressively exclusive relationships(SUPER),Bayesian-information and linkage-disequilibrium Iteratively nested keyway(Blink),and identified 5,3,and 6 high-confidence single nucleotide polymorphisms(SNPs)associated with BFT,LEA,and D100,*** annotation and quantitative trait locus(QTL)mapping analysis suggested that6 genes(SKAP2,SATB1,PDE7B,PPP1R16B,WNT3,and WNT9B)were potentially associated with growth performance in *** analysis suggested that the expression of Src Kinase Associated Phosphoprotein 2(SKAP2)was higher in prenatal muscles than in postnatal muscles,and the expression of Phosphodiesterase 7B(PDE7B)continuously increased during the prenatal stages and gradually decreased after birth,implying their potential roles in prenatal skeletal muscle ***,this study provides new candidate loci and genes for the genetic improvement of pigs.

关键词： GWAS pig growth trait QTL mapping skeletal muscle

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

Aryl hydrocarbon receptor:Linking environment to aging process in elderly patients with asthma

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Chinese Medical Journal 2024年第4期137卷 382-393页

作者： Tianrui Yang Rongjun Wan Wei Tu Sai Nithin Avvaru Peisong Gao Division of Allergy and Clinical Immunology Department of MedicineJohns Hopkins University School of MedicineBaltimoreMD 21224USA Department of Geriatric medicine The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650032China Department of Respiratory medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China The State key laboratory of Respiratory Disease for Allergy Shenzhen Key Laboratory of Allergy and ImmunologyShenzhen University School of MedicineShenzhenGuangdong 518055China

Aging is a significant risk factor for various diseases,including asthma,and it often leads to poorer clinical outcomes,particularly in elderly *** is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage,resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic *** effects of aging affect not only the elderly but also those of younger ages,posing significant challenges to global ***,understanding the molecular mechanisms associated with aging in different diseases is *** intriguing factor is the aryl hydrocarbon receptor(AhR),which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging ***,we review the literature on several major hallmarks of aging,including mitochondrial dysfunction,cellular senescence,autophagy,mitophagy,epigenetic alterations,and microbiome ***,we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures,particularly in relation to the immune ***,we explore how aging hallmarks affect clinical characteristics,inflammatory features,exacerbations,and the treatment of *** is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

关键词： Aging Environment Reactive oxygen species Senescence Aryl hydrocarbon receptor Asthma

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