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Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI Key laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Key laboratory of Reproduction and genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

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Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

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Animal Models and Experimental Medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai NHC Key laboratory of human Disease Comparative Medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient *** better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor *** exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and *** believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient *** characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid *** study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research

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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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A booming field of large animal model research

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Zoological Research 2024年第2期45卷 311-313页

作者： Xiao-Jiang Li Liangxue Lai Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State Key laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhouGuangdong 510632China CAS Key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China

Animal models are integral to the study of fundamental biological processes and the etiology of human *** animal models,especially those involving mice,have yielded abundant and significant insights,greatly enhancing ... 详细信息

关键词： mechanisms insight field

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PCAF-mediated acetylation of METTL3 impairs mRNA translation efficiency in response to oxidative stress

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Science China(Life Sciences) 2024年第10期67卷 2157-2168页

作者： Cheng Liu Miao Yu Mengyuan Wang Siyuan Yang Yenan Fu Lei Zhang Chaoyang Zhu Hongquan Zhang Program for Cancer and cell Biology Department of Human AnatomyHistology and EmbryologySchool of Basic Medical SciencesPeking University International Cancer Instituteand State Key Laboratory of Molecular OncologyPeking University Health Science CenterBeijing 100191China Department of General Surgery and Urological Surgery Huaihe HospitalHenan UniversityKaifeng 100084China Department of human Anatomy Histologyand EmbryologyShenzhen University School of MedicineShenzhen 518055China

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase ***3 enhances RNA translation independently of its catalytic ***,the underlying mechanism is still ***,we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by *** the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at ***,acetylation of METTL3 blocks its interaction with EIF3H,a subunit of the translation initiation factor,thereby reducing mRNA translation ***,acetylation of METTL3 responds to oxidative ***,oxidative stress enhances the interaction of PCAF with METTL3,increases METTL3 acetylation,and suppresses the interaction of METTL3 with EIF3H,thereby decreasing the translation efficiency of ribosomes and inhibiting cell ***,we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.

关键词： METTL3 acetylation PCAF m^(6)A oxidative stress translation SIRT3

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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen cell therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

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RETINOBLASTOMA RELATED 1 switches mitosis to meiosis in rice

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Plant Communications 2024年第6期5卷 193-212页

作者： Yongjie Miao Hanli You Huixin Liu Yangzi Zhao Jiangzhe Zhao Yafei Li Yi Shen Ding Tang Baohui Liu Kewei Zhang Zhukuan Cheng Guangdong Provincial Key laboratory of Plant Adaptation and Molecular Design Innovative Center of Molecular Genetics and EvolutionSchool of Life SciencesGuangzhou UniversityGuangzhou 510006China Jiangsu Key laboratory of Crop Genomics and Molecular Breeding/Zhongshan Biological Breeding laboratory/Key laboratory of Plant Functional Genomics of the Ministry of Education Agricultural College of Yangzhou UniversityYangzhou 225009China State Key laboratory of Plant Genomics Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Zhejiang Provincial Key laboratory of Biotechnology on Specialty Economic Plants Department of BiologyCollege of Life SciencesZhejiang Normal UniversityJinhua 321004China Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops/Jiangsu Key laboratory of Crop genetics and Physiology Yangzhou UniversityYangzhou 225009China

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing ***,the mechanisms that regulate this process in plants remain largely ***,we find that the rice(Oryza sativa L.)protein RETINOBLASTOMA RELATED 1(RBR1)is essential to the transition from mitosis to *** of RBR1 function results in hyper-proliferative sporogenous-celllike cells(SCLs)in the anther locules during early stages of reproductive *** hyperproliferative SCLs are unable to initiate meiosis,eventually stagnating and degrading at late developmental stages to form pollen-free *** results suggest that RBR1 acts as a gatekeeper of entry into ***,cytokinin content is significantly increased in rbr1 mutants,whereas the expression of type-B response factors,particularly LEPTO1,is significantly *** the known close association of cytokinins with cell proliferation,these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin *** a genetic strategy,the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been *** summary,we reveal a unique role of RBR1 in the initiation of meiosis;our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

关键词： RETINOBLASTOMA RELATED1 meiosis initiation cytokinin rice

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Zinc lactate alleviates oxidative stress by modulating crosstalk between constitutive androstane receptor signaling pathway and gut microbiota profile in weaned piglets

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Animal Nutrition 2024年第1期16卷 23-33页

作者： Wenjie Tang Xuan Xiang Houfu Wang Wentao Zhou Liuqin He Yulong Yin Tiejun Li College of Animal Science and Technology Hunan Agricultural University Sichuan Academy of Animal Sciences Animal Breeding and Genetics Key Laboratory of Sichuan Province Livestock and Poultry Biological Products Key laboratory of Sichuan Province Sichuan Animtech Feed Co. Ltd Hunan Provincial Key laboratory of Animal Nutritional Physiology and Metabolic Process CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production Institute of Subtropical Agriculture Chinese Academy of Sciences College of Advanced Agricultural Science University of Chinese Academy of Sciences Hunan Provincial Key laboratory of Animal Intestinal Function and Regulation Laboratory of Animal Nutrition and Human Health College of Life Sciences Hunan Normal University

This study aimed to determine the regulatory mechanism of dietary zinc lactate (ZL) supplementation on intestinal oxidative stress damage in a paraquat (PQ)-induced piglet model. Twenty-eight piglets (mean body weight 9.51±0.23 kg) weaned at 28 d of age were randomly divided into control, ZL, PQ, and ZL+PQ groups (n=7 in each group). The ZL-supplemented diet had little effect on growth performance under normal physiological conditions. However, under PQ challenge, ZL supplementation significantly improved average daily gain (P<0.05) and reduced the frequency of diarrhea. ZL improved intestinal morphology and ultrastructure by significantly increasing the expression level of the jejunal tight junction protein, zonula occludens-1(ZO-1) (P<0.05), and intestinal zinc transport and absorption in PQ-induced piglets, which reduced intestinal permeability. ZL supplementation also enhanced the expression of antioxidant and antiinflammatory factor-related genes and decreased inflammatory cytokine expression and secretion in PQinduced piglets. Furthermore, ZL treatment significantly inhibited the activation of constitutive androstane receptor (CAR) signaling (P<0.01) in PQ-induced piglets and altered the structure of the gut microbiota, especially by significantly increasing the abundance of beneficial gut microbes, including UCG＿002, Ruminococcus, Rikenellaceae＿RC9＿gut＿group, Christensenellaceae＿R＿7＿group, Treponema, unclassified＿Christensenellaceae, and unclassified＿Erysipelotrichaceae (P <0.05). These data reveal that pre-administration of ZL to piglets can suppress intestinal oxidative stress by improving antioxidant and anti-inflammatory capacity and regulating the crosstalk between CAR signaling and gut microbiota.

关键词： Zinc lactate Intestinal barrier Oxidative stress Inflammation Constitutive androstane receptor Gut microbiota

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Transcriptomic and epigenomic landscapes of muscle growth during the postnatal period of broilers

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Journal of Animal Science and Biotechnology 2024年第5期15卷 1851-1865页

作者： Shuang Gu Qiang Huang Yuchen Jie Congjiao Sun Chaoliang Wen Ning Yang State Key laboratory of Animal Biotech Breeding and Frontier Science Center for Molecular Design Breeding China Agricultural UniversityBeijing 100193China National Engineering laboratory for Animal Breeding and Key laboratory of Animal genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsDepartment of Animal Genetics and BreedingCollege of Animal Science and Technology China Agricultural UniversityBeijing 100193China. Sanya Institute of China Agricultural University Hainan 572025China

Background Broilers stand out as one of the fastest-growing livestock globally,making a substantial contribution to animal meat ***,the molecular and epigenetic mechanisms underlying the rapid growth and development of broiler chickens are still *** study aims to explore muscle development patterns and regulatory networks during the postnatal rapid growth phase of fast-growing *** measured the growth performance of Cornish(CC)and White Plymouth Rock(RR)over a 42-d *** muscle samples from both CC and RR were randomly collected at day 21 after hatching(D21)and D42 for RNA-seq and ATAC-seq library *** The consistent increase in body weight and pectoral muscle weight across both breeds was observed as they matured,with CC outpacing RR in terms of weight at each stage of *** expression analysis identified 398 and 1,129 genes in the two dimensions of breeds and ages,respectively.A total of 75,149 ATAC-seq peaks were annotated in promoter,exon,intron and intergenic regions,with a higher number of peaks in the promoter and intronic *** age-biased genes and breed-biased genes of RNA-seq were combined with the ATAC-seq data for subsequent *** results spotlighted the upregulation of ACTC1 and FDPS at D21,which were primarily associated with muscle structure development by gene cluster ***,a noteworthy upregulation of MUSTN1,FOS and TGFB3 was spotted in broiler chickens at D42,which were involved in cell differentiation and muscle regeneration after injury,suggesting a regulatory role of muscle growth and *** This work provided a regulatory network of postnatal broiler chickens and revealed ACTC1 and MUSTN1 as the key responsible for muscle development and *** findings highlight that rapid growth in broiler chickens triggers ongoing muscle damage and subsequent *** findings provide a foundation for future research to i

关键词： ATAC-seq Broiler Pectoral muscle development Rapid growth RNA-seq

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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of human Glioblastoma cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(Pcells(Pcell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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