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Both 20S and 19S proteasome components are essential for meiosis in male mice

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Zoological Research 2025年第01期 27-40页

作者： Ting-Ting Han Li-Ying Wang Qiu-Xing Zhou Wei Wei Yan-Jie Ma Ying-Hong Chen Wei Li Zhen-Yu Ju Chao Liu Key Laboratory of regenerative medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Guangzhou Women and Children's Medical Center Guangzhou Medical University

The proteasome, an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles, performs both shared and distinct ***, a highly complex developmental process, relies on proteasome activity at multiple stages to regulate protein turnover. In this study, we selected the20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis. Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models, we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell *** further clarify their functional significance, we specifically knocked out Psma1 and Psmd2 in germ *** of either PSMA1 or PSMD2 led to disrupted spermatogenesis, characterized by the complete absence of sperm in the epididymis. Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation. Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1, a key regulator of mitosis-to-meiosis transition, leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation. This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.

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Epigenetics disruptions enabled by porphyrin-derived metal-organic frameworks disarm resistances to sonocatalytic ROS anti-tumor actions

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Fundamental Research 2025年第1期5卷 296-306页

作者： Yan Zhang Dou Du Chao Fang Xin Yu Yujia Fang Xinyu Liu Di Ou Haohao Yin Hui Liu Taixia Wang Lu Lu Xiaolong Li Kun Zhang Central Laboratory Ultrasound Research and Education InstituteShanghai Tenth People's HospitalTongji University School of MedicineTongji UniversityShanghai 200072China department of Medical Oncology Shanghai Pulmonary HospitalThoracic Cancer InstituteTongji University School of MedicineTongji UniversityShanghai 200433China

Post-transcriptional epigenetic modifications provide numerous implications for tumor progression,metastasis and recurrence,which also pose resistances to reactive oxygen species(ROS)-based ***,we proposed an epigenetic deubiquitination disruption strategy to disarm the ubiquitination-deubiquitination balance-induced resistances to ROS production and ROS-based anti-tumor action for potentiating sonodynamic treatment(SDT)*** end it,porphyrin-derived metal-organic framework(MOF)sonocatalytic nanoplatforms were developed to load deubiquitination inhibitors(i.e.,Auranofin).Ultrasound-triggered Auranofin release from PCN224@Au has been validated to blockade the deubiquitinating process and drive proteasome-mediated target protein *** epigenetic deubiquitination disruption not only synergized with MOF-mediated sonocatalytic ROS production,but also inactivate deubiquitinating enzymes,blockade the deubiquitination process and further remove these resistances,both of which mutually behaved as reciprocal impetuses to significantly magnify SDT outcomes against liver *** a deubiquitination-engineered disruption approach finds an unprecedented pathway to disarm deubiquitination-induced resistances to SDT and other ROS-based anti-tumor means,which also enlightens us to establish other post-transcriptional epigenetic modification disruption strategies to re-program the tumor microenvironment and elevate the anti-tumor efficiency of various treatment methods(e.g.,immunotherapy).

关键词： Epigenetics engineering Ubiquitylation modulation Sonocatalysis Reactive oxygen species resistance Anti-tumor action

Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation

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Science China Life Sciences 2025年

作者： Xinyu Cui Yu Dong Qiang Zhan Yixin Huang Qianshu Zhu Zihao Zhang Guang Yang Liping Wang Shijun Shen Jia Zhao Zhiyi Lin Jiatong Sun Zhongqu Su Yihan Xiao Chuyu Zhang Yuwei Liang Lu Shen Lichen Ji Xuguang Zhang Jiqing Yin Hong Wang Zhiyang Chen Zhenyu Ju Cizhong Jiang Rongrong Le Shaorong Gao Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Life Sciences and Technology Tongji University Key Laboratory of regenerative medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University Shandong Key Laboratory of Animal Bioengineering and Disease Prevention College of Animal Science and Technology Shandong Agricultural University department of Joint Surgery Shanghai East Hospital Tongji University School of Medicine Shanghai institute of Nutrition and Health Chinese Academy of Sciences

Inflammation is a driving force of hematopoietic stem cells(HSCs) aging, causing irreversible exhaustion of functional HSCs. However, the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood. Here, we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal, leading to depletion of HSCs. Meanwhile, the central regulator nuclear factor kappa B(NF-κB) mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs, with precocious activation of myeloid lineage genes. Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation. Mechanistically, enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation. Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.

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Exploration of evolutionary mechanisms shaping KZFP and retrotransposon interactions

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Science Bulletin 2025年第3期70卷 328-332页

作者： Qian Wu Junqin Xu Jiaxin Zeng Yixuan Wang Peng Yang Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Clinical Research Center for Anesthesiology and Perioperative MedicineTranslational Research Institute of Brain and Brain-Like IntelligenceShanghai Fourth People’s HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China institute for regenerative medicine State Key Laboratory of Cardiology and Medical Innovation CenterShanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Retrotransposon expansion has profoundly reshaped genomes[1],[2].As crucial defense mechanisms that counteract retrotransposons in humans,members of the Krüppel-associated box(KRAB)zinc finger(ZF)protein(KZFP)family ... 详细信息

关键词： shaped expansion mechanisms

Current status of nanofat in the management of knee osteoarthritis:A systematic review

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World Journal of Orthopedics 2025年第1期16卷 68-78页

作者： Naveen Jeyaraman Sandeep Shrivastava VR Ravi Arulkumar Nallakumarasamy Madhan Jeyaraman department of Orthopaedics Datta Meghe Institute of Higher Education and ResearchWardha 442004MaharashtraIndia department of regenerative medicine Mother Cell Regenerative CentreTiruchirappalli 620017Tamil NaduIndia department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennai 600077Tamil NaduIndia

BACKGROUND Osteoarthritis(OA)is a prevalent joint disorder requiring innovative treatment *** To evaluate the use of nanofat,a specialized form of adipose tissue-derived cells,in the treatment of OA,by examining its efficacy,safety profile,mechanisms of action,comparative effectiveness,and long-term *** A comprehensive review of preclinical studies,clinical trials,and in vitro investigations was *** included studies provided insights into the potential role of nanofat in OA treatment,addressing its efficacy,safety profile,mechanisms of action,comparative effectiveness,and long-term *** Clinical studies consistently reported the efficacy of nanofat in providing pain relief and functional improvement in patients with *** adverse events were limited to the injection site,such as localized pain and inflammation,and resolved within a few days to *** adverse events were rare,and no significant long-term complications were ***,nanofat was found to enhance chondrocyte proliferation,reduce inflammation,and promote angiogenesis,thereby contributing to its therapeutic *** Nanofat therapy holds promise as a therapeutic option for managing OA,providing pain relief,functional improvement,and potential tissue *** safety profile of nanofat treatment appears favorable,but long-term data are still *** protocols,larger randomized controlled trials,longer follow-up periods,and cost-effectiveness evaluations are warranted to establish optimal protocols,comparative effectiveness,and long-term *** current limitations,nanofat therapy demonstrates translational potential and should be considered in clinical practice for OA treatment,with careful patient selection and monitoring.

关键词： Osteoarthritis Nanofat Adipose tissue Cartilage Knee

Optimized inner ear organoids for efficient hair cell generation and ototoxicity response modeling

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Science China Life Sciences 2025年

作者： Xuanhe Qin Liping Fu Chunying Li Xilin Tan Xiaolei Yin institute for regenerative medicine State Key Laboratory of Cardiology and Medical Innovation CenterShanghai East HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

Hair cells in the mammalian cochlea are highly vulnerable to damage from drug toxicity,noise exposure,aging,and genetic mutations,with no capacity for *** in hair cell protection research has been limited by the scarcity of cochlear tissue and suitable in vitro ***,we present a novel one-step,self-organizing inner ear organoid system optimized with small molecules,which bypasses the need for multi-step expansion and forced differentiation *** approach efficiently generates hair cells and supporting cells that recapitulate the molecular,cellular,and structural characteristics of the inner ***-cell RNA sequencing revealed the diversity and fidelity of cell populations within the *** this platform,we validated the protective effects of candidate compounds against hair cell damage,highlighting its potential as a powerful tool for drug discovery and mechanistic studies of hair cell protection.

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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Neural Regeneration Research 2025年第3期20卷 821-835页

作者： Jing Wang Bing Zhang Lanfang Li Xiaomei Tang Jinyu Zeng Yige Song Chao Xu Kai Zhao Guoqiang Liu Youming Lu Xinyan Li Kai Shu department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina department of Neurosurgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina department of Pathophysiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina institute for Brain Research Wuhan Center of Brain ScienceHuazhong University of Science and TechnologyWuhanHubei ProvinceChina department of Graduate Student Chongqing Medical UniversityChongqingChina department of Basic medicine School of Medical ScienceHubei University for NationalitiesEnshiHubei ProvinceChina department of Anatomy School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive ***,the mechanism underlying this neurogenesis impairment remains *** this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain *** results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and *** with repetitive traumatic brain injuryalso showed deficits in spatial memory ***,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was *** inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological *** findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

关键词： complement C1 dendrite dentate gyrus hippocampus neural stem cell neurogenesis neuroinflammation neurological function neuron traumatic brain injury

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and regenerative medicine&department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

Single-cell technologies: current and near future

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Science China(Life Sciences) 2025年第1期68卷 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi KeyLaboratory of Spine and Spinal CordInjury Repairand Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchoolofLifeSciencesandTechnologyTongji UniversityShanghai 200082China Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Translational Medical Center for Stem Cell Therapy and institute for regenerative medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200082China Research institute of Intelligent Computing Zhejiang LabHangzhou 311121China Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of Chinese medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Key Laboratory of Advanced Theory and Application in Statistics and Data Science(MOE) School of StatisticsEast China Normal UniversityShanghai 200062China

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity,tissue organization,and overall organism function(Sun et al.,2024).In 2009,single-cell RNA sequencing(scRNA-seq)was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology,single-cell approaches have expanded to encompass other omics,such as genomics,epigenomics,proteomics,and ***,multimodal technologies including spatially resolved transcriptomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening at the single-cell level further advanced our ability to comprehensively understand cellular ***-cell methods provide deeper insights into disease mechanisms across various conditions,including cancer,developmental disorders,and aging-associated *** this issue,we focus on topics related to single-cell methods,covering the following four aspects:(i)single-cell multi-omic sequencing technology;(ii)single-cell spatial technology;(iii)singlecell CRISPR screening technology;(iv)applications of single-cell technology.

关键词： expanded enable insight

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