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DNA methylation clocks for estimating biological age in Chinese cohorts

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Protein & cell 2024年第8期15卷 575-593页

作者： Zikai Zheng Jiaming Li Tianzi Liu Yanling Fan Qiao-Cheng Zhai Muzhao Xiong Qiao-Ran Wang Xiaoyan Sun Qi-Wen Zheng Shanshan Che Beier jiang Quan Zheng Cui Wang Lixiao Liu Jiale Ping Si Wang Dan-Dan Gao Jinlin Ye Kuan Yang Yuesheng Zuo Shuai Ma Yun-GuiYang Jig Qu Feng Zhang Peilin Jia Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China Division of Orthopaedics Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China The Joint Innovation center for Engineering in Medicine Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center International Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China Aging Biomarker Consortium Beijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China nstitute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China National Genomics Data center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG ***,a systematic comparison between DNA methylation data and other omics datasets has not yet been ***,available DNAm age predictors are based on datasets with limited ethnic *** address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm ***,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological *** clocks were further employed to predict factors influencing aging *** DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age *** findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

关键词： DNA methylation aging clock aging age prediction

Lipidomic remodeling during mammalian preimplantation embryonic development

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Life Metabolism 2024年第2期3卷 3-5页

作者： Qingran Kong Shaorong Gao Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouZhejiang 325035China Clinical and Translational research center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

The dynamic changes in lipids during early embryonic development in mammals have not yet been comprehensively investi*** a recent paper published in Nature cell Biology,Zhang et *** the dynamic lipid landscapes during preimplantation embryonic development in mice and *** highlight the crucial role of lipid unsaturation in regulating embryogenesis.

关键词： Lipid al. lipids

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Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging

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Protein & cell 2024年第8期15卷 612-632页

作者： Qinchao Hu Bin Zhang Yaobin Jing Shuai Ma Lei Hu jingyi Li Yandong Zheng Zijuan Xin Jianmin Peng Si Wang Bin Cheng Jing Qu Weiqi zhang Guang-Hui Liu Songlin Wang State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhou 510060China Salivary Gland Disease center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Beijing Laboratory of Oral Health and Beijing Stomatological HospitalCapital Medical UniversityBeijing 100050China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China Advanced Innovation center for Human Brain Protection and National Clinical research center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuan Wu HospitalCapital Medical UniversityBeijing 100053China Intemational center for Aging and Cancer Hainan Medical UniversityHaikou 571199China Aging Biomarker Consortium Beijing 100101China

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory ***,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still ***,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were *** cells were identified as the most affected cell types by aging in the *** analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal *** decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation *** work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.

关键词： single-nucleus RNA-sequencing primate gingiva aging YAP

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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Mesenchymal stem cell-derived exosomes: Versatile nanomaterials for skin wound treatment

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Nano research 2024年第4期17卷 2836-2856页

作者： Yuzhen Xiao Hexi Li Junhui Zhang Songyun Yang Chunsen Zhang Yizhou Huang Xin Tang Huiqi Xie Department of Orthopedic Surgery and Orthopedic research Institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu 610041China West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610041China Sports Medicine center West China HospitalSichuan UniversityChengdu 610041China

Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine ***,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized membranous vesicles containing diverse bioactive *** the potent ability of modulating skin cell behaviors,MSC-derived exosomes(MSC-Exos)are regarded as a promising nanomaterial for regenerative wound *** hostile conditions,MSC-Exos are efficient in protecting skin cells from severe damage and restoring their *** to recent studies,MSC-Exos possess remarkable pro-healing effects in a variety of skin wounds,typically resulting in increased wound closure,inhibited scar tissue formation,and better restoration of skin *** further enhance the therapeutic potential of MSC-Exos,the development of applicable pretreatment strategies and the optimization of exosome delivery are under intensive ***,we summarize current research progress of MSC-Exos for skin wound treatment,with an emphasis on the biological effects of these nanovesicles,the repair mechanisms,and future challenges in clinical translation.

关键词： exosomes mesenchymal stem cells diabetic wounds burn wounds scar wound healing

Human iP SC-derived mesenchymal stem cells relieve high blood pressure in spontaneously hypertensive rats via splenic nerve activated choline acetyltransferase-positive cells

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Science China Life Sciences 2024年

作者： Zhen Zhang Weijun Huang Xiaoran Zhang Zhecun Wang Manting Xie Bingbing Xie Yiling Wang Xiaoyong Chen Andy Peng Xiang Qiuling Xiang center for stem cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education Sun Yat-sen University Department of Physiology Zhongshan School of Medicine Sun Yat-sen University Department of Vascular Surgery the First Affiliated Hospital Sun Yat-sen University

Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells（MSCs） has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cellderived mesenchymal stem cells（hiPSC-MSCs） are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSCMSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats（SHRs）. cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation（SND）, underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine（NE）, which increased the number of choline acetyltransferase-positive（ChAT+） cells in the spleen and peripheral blood. Consequently, the acetylcholine（ACh） produced by elevated ChAT+cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT+cells. The co

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Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science center for stem cell research Tongji UniversityShanghai 200092China Clinical and Translation research center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

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Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate:immune mechanisms of recurrent early pregnancy loss

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National Science Review 2024年第06期 129-145页

作者： Wentong Jia Liyang Ma Xin Yu Feiyang Wang Qian Yang Xiaoye Wang Mengjie Fan Yan Gu Ran Meng Jian Wang Yuxia Li Rong Li Xuan Shao Yan-Ling Wang State Key Laboratory of stem cell and Reproductive Biology Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of Sciences Beijing Institute for stem cell and Regenerative Medicine University of the Chinese Academy of Sciences NHC Key Lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drug and Devices Shanghai Institute for Biomedical and Pharmaceutical Technologies National Clinical center for Obstetrics and Gynecology Peking University Third Hospital Department of Family Planning The Second Hospital of Tianjin Medical University Department of Prenatal Screening Haidian Maternal and Child Health Hospital

Decidual natural killer（dNK） cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss（RPL） at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG（NOD/Shi-scid/IL-2Rγnull） mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients（dNK-RPL）remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+dNK *** studies revealed that CD56+CD39+dNK subset facilitates early differentiation of mouse trophoblast stem cells（m TSCs） towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor（M-CSF）. Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

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Comparison of Treatment Efficacy of Different Number of Botulinum Toxin Type A Injection Sites for Crow's Feet Lines: A Single-center Retrospective Clinical Study in Vietnam

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International Journal of Dermatology and Venereology 2024年第3期7卷 131-136页

作者： Nguyen Quang M. Le Thi M. Duong Phuc H. Vu Thai H. Le Huu D. Department of stem cell research and Application National Hospital of Dermatology and Venereology Hanoi 100000 Viet Nam Department of Healthcare Activity Direction National Hospital of Dermatology and Venereology Hanoi 100000 Viet Nam Department of Dermatology Hanoi Medical University Hanoi 100000 Viet Nam

Objective: Botulinum toxin type A is frequently used to treat crow's feet lines. However, the optimal dose and injection sites are still controversial. The objective of this study was to compare the efficacy of different botulinum toxin type A injection patterns for the treatment of crow's feet. Methods: This single-center, retrospective, clinical study was conducted at the National Hospital of Dermatology and Venereology from July 2020 to December 2020. Data on 60 patients with crow's feet were collected and divided into 2 groups (3- or 4-point intramuscular injection) according to the intramuscular injection technique the patients received. The treatment efficacy was assessed based on the changes in the Crow's Feet Grading Scale score at 1, 4, and 16 weeks after treatment. Repeated measures analysis of variance was used for the assessment of changes in scores over time between the two groups. Results: After treatment, the average Crow's Feet Grading Scale score was significantly decreased compared with the pretreatment score at all timepoints (1, 4, and 16 weeks) in both states (dynamic: For 3-point intramuscular injection technique, 1 week: 1.90 ± 0.71 vs. 2.97 ± 0.56; 4 weeks: 1.87 ± 0.68 vs. 2.97 ± 0.56; 16 weeks: 2.60 ± 0.67 vs. 2.97 ± 0.56. For 4-point intramuscular injection technique, 1 week: 1.73 ± 0.83 vs. 3.03 ± 0.49; 4 weeks: 1.73 ± 0.74 vs. 3.03 ± 0.49; 16 weeks: 2.57 ± 0.68 vs. 3.03 ± 0.49, all P < 0.001. and static: For 3-point intramuscular injection technique, 1 week: 1.20 ± 0.89 vs. 2.20 ± 0.85; 4 weeks: 1.20 ± 0.89 vs. 2.20 ± 0.85; 16 weeks: 1.87 ± 0.97 vs. 2.20 ± 0.85; For 4-point intramuscular injection technique, 1 week: 1.50 ± 0.86 vs. 2.30 ± 0.84; 4 weeks: 1.33 ± 0.84 vs. 2.30 ± 0.84; 16 weeks: 1.87 ± 0.97 vs. 2.30 ± 0.84. All P < 0.001). The average subjective patient-rated satisfaction scores after treatment were significantly higher in the 4-point injection group than in the 3-point injection group (P = 0.028). The adverse events were pos

关键词： botulinum toxin type A crow's feet lines dose injection site