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Unraveling brain aging through the lens of oral microbiota

Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina institute for stem cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing institute for stem cell and regenerative medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for stem cells School of Life Sciences and TechnologyTongji University Translational Medical Center for stem cell Therapy and institute for regenerative medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab Shanghai Research institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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From stem cells to red blood cells:how far away from the clinical application?

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Science China(Life Sciences) 2014年第6期57卷 581-585页

作者： XIE XiaoYan LI YanHua PEI XueTao stem cell and regenerative medicine Lab Beijing Institute of Transfusion Medicine South China Research Center for stem cell and regenerative medicine

The generation of red blood cells(RBCs)from stem cells provides a solution for deficiencies in blood ***,primary hematopoietic stem cells,embryonic stem cells and induced pluripotent stem cells have shown the potential to produce fully mature ***,we discuss the advantages,induction protocols,progress and possible clinical applications of stem cells in RBC production.

关键词： stem cells red blood cells differentiation clinical application

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CAPE promotes the expansion of human umbilical cord blood-derived hematopoietic stem and progenitor cells in vitro

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Science China(Life Sciences) 2014年第2期57卷 188-194页

作者： LIU YiMing ZHANG BoWen ZHANG Jing WANG SiHan YAO HaiLei HE LiJuan CHEN Lin YUE Wen LI YanHua PEI XueTao stem cell and regenerative medicine Lab Beijing Institute of Transfusion Medicine

Due to the low number of collectable stem cells from single umbilical cord blood(UCB)unit,their initial uses were limited to pediatric *** applications of UCB hematopoietic stem and progenitor cells(HSPCs)would become feasible if there were a culture method that can effectively expand HSPCs while maintaining their self-renewal *** recent years,numerous attempts have been made to expand human UCB HSPCs in *** this study,we report that caffeic acid phenethyl ester(CAPE),a small molecule from honeybee extract,can promote in vitro expansion of *** with CAPE increased the percentage of HSPCs in cultured mononuclear ***,culture of CD34+HSPCs with CAPE resulted in a significant increase in total colony-forming units and high proliferative potential colony-forming ***-forming unit-erythroid was the mostly affected colony type,which increased more than 3.7-fold in 1μg mL 1CAPE treatment group when compared to the *** appears to induce HSPC expansion by upregulating the expression of SCF and HIF1-α.Our data suggest that CAPE may become a potent medium supplement for in vitro HSPC expansion.

关键词： hematopoietic stem and progenitor cells caffeic acid phenethyl ester expansion

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Advances in cell lineage reprogramming

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Science China(Life Sciences) 2013年第3期56卷 228-233页

作者： ZHOU JunNian YUE Wen PEI XueTao stem cell and regenerative medicine Lab Beijing Institute of Transfusion Medicine

As a milestone breakthrough of stem cell and regenerative medicine in recent years, somatic cell reprogramming has opened up new applications of regenerative medicine by breaking through the ethical shackles of embryonic stern cells. However, induced pluripo- tent stem （iPS） cells are prepared with a complicated protocol that results in a low reprogramming rate. To obtain differentiated target cells, iPS cells and embryonic stem cells still need to be induced using step-by-step procedures. The safety of induced target cells from iPS cells is currently a further concerning matter. More broadly conceived is lineage reprogramming that has been investigated since 1987. Adult stem cell plasticity, which triggered interest in stem cell research at the end of the last century, can also be included in the scope of lineage reprogramming. With the promotion of iPS cell research, lineage reprogramming is now considered as one of the most promising fields in regenerative medicine, will hopefully lead to customized, personalized therapeutic options for patients in the future.

关键词： regenerative medicine lineage reprogramming transdifferentiation dedifferentiation transdetemination

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Synergistic engineering of CRISPR-Cas nucleases enables robust mammalian genome editing

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The Innovation 2022年第4期3卷 74-82页

作者： Yangcan Chen Yanping Hu Xinge Wang Shengqiu Luo Ning Yang Yi Chen Zhikun Li Qi Zhou Wei Li State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China institute for stem cell and regenerative medicine Chinese Academy of SciencesBeijing 100101China bejing institute for stem cell and regenerative medicine Beijing 100101China

The naturally occurring prokaryotic CRISPR-Cas systems provide valuable resources for the development of new genome-editing ***,the majority of prokaryotic Cas nucleases exhibit poor editing efficiency in mammalian cells,which significantly limits their ***,we have developed a method termed Improving Editing Activity by Synergistic Engineering(MIDAS).This method exerts a synergistic effect to improve mammalian genome-editing efficiency of a wide range of CRISPR-Cas systems by enhancing the interactions of Cas nuclease with the protospacer adjacent motif(PAM)and the single-stranded DNA(ssDNA)substrate in the catalytic pocket *** robustly and significantly increased the gene-editing efficiency of Cas12i,Cas12b,and CasX in human ***,a Cas12i variant,Cas12iMax,exhibited robust activity with a very broad PAM range(NTNN,NNTN,NAAN,and NCAN)and higher efficiency than the current widely used Cas nucleases.A high-fidelity version of Cas12iMax(Cas12iHiFi)has been further engineered to minimize off-target *** work provides an expandable and efficacious method for engineering Cas nucleases for robust mammalian genome editing.

关键词： editing engineering mammalian

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Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

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World Journal of Methodology 2025年第1期15卷 72-79页

作者： Serdar Kabatas ErdinçCivelek Eyüp Can Savrunlu Umut Karaaslan Özlem Yıldız Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Pediatric Allergy-Immunology Institute of Health Sciences Marmara UniversityIstanbul 34865Türkiye Center for stem cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye Department of Child and Adolescent Psychiatry University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Child and Adolescent Psychiatry Kocaeli University Faculty of MedicineKocaeli 41001Türkiye Center for regenerative medicine and stem cell Research&Manufacturing Liv HospitalIstanbul 34340Türkiye Department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for stem cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted *** recent studies,neuroinflammation and immune dysregulation have come to the forefront in its *** are studies suggesting that stem cell therapy may be effective in the treatment of *** To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell *** A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with *** The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor *** serious side effects were encountered during the 2-year *** The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

关键词： Autism spectrum disorder Neurorehabilitation stem cell transplantation Wharton jelly mesenchymal stem cells Inflammation

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Optimizing bone marrow harvesting sites for enhanced mesenchymal stem cell yield and efficacy in knee osteoarthritis treatment

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World Journal of Methodology 2025年第2期15卷 92-107页

作者： Arulkumar Nallakumarasamy Sandeep Shrivastava Ravi Velamoor Rangarajan Naveen Jeyaraman Avinash Gandi Devadas Swaminathan Ramasubramanian 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 Government Medical CollegeOmandurar Government EstateChennai 600002Tamil NaduIndia Department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennai 600077Tamil NaduIndia

Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment *** therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in *** the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal *** paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA *** iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced *** integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic ***,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical *** directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting ***,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.

关键词： Knee Osteoarthritis Mesenchymal stem cells Bone marrow harvest regenerative medicine

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Current approaches to reduce or eliminate mitochondrial DNA mutations

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Science China(Life Sciences) 2016年第5期59卷 532-535页

作者： Liang Yang Tingfang Mei Xiaobing Lin Haite Tang Yi Wu Rui Wang Jinglei Liu Zahir Shah Xingguo Liu Key Laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Mitochondrial DNA （mtDNA） mutations have been impli- cated in a broad range of disorders which severely affect human health （Wallace, 1999）. Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA （nDNA）. Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions （60%-90%） before respiratory activity is affected （Schon et al., 2012）. It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell （iPSC） modeling. These various methods have their own advantages and limitations.

关键词：线粒体DNA突变基因突变 mtDNA突变线粒体疾病人类健康核DNA 多能干细胞病理变化

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Computer-aided engineering of CRISPR-Cas proteins for enhanced human genome editing

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Science China(Life Sciences) 2023年第4期66卷 883-886页

作者： Yangcan Chen Yanping Hu Shengqiu Luo Xinge Wang Bangwei Mao Yi Chen Jing Xu Zhikun Li Qi Zhou Wei Li State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China institute for stem cell and regenerative medicine Chinese Academy of SciencesBeijing 100101China bejing institute for stem cell and regenerative medicine Beijing 100101China

Dear *** remarkably diversified CRISPR-Cas systems in nature have provided unlimited valuable resources to develop genome editing tools that are revolutionizing the fields of biotechnology and ***,due to their microbial origin,the activity of most naturally occurring CRISPR-Cas nucleases is relatively poor in mammalian cells(Ran et al.,2015).Thus,improving the mammalian genome editing efficiency becomes the priority for harnessing more CRISPRCas systems for widespread *** protein engineering serves as a powerful approach to enhance the catalytic activity of ***,this approach largely relies on proteinic three-dimension(3D)structure information as guide for *** fact is that of the large numbers of the CRISPR-Cas systems discovered in recent years,only a small number of them with the 3D structures were *** bypass this limitation,here,we report an efficient and simple strategy for rational engineering of Cas nucleases without the need of 3D structure information and successfully optimized nucleases from Cas9 and Cas12 families.

关键词： rational editor editing

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