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simplifyEnrichment:A Bioconductor Package for Clustering and Visualizing Functional Enrichment Results

Genomics, Proteomics & Bioinformatics 2023年第1期21卷 190-202页

作者： Zuguang Gu Daniel Hübschmann Molecular Precision Oncology Program National Center for Tumor Diseases(NCT)HeidelbergD-69120 HeidelbergGermany Heidelberg Institute of Stem Cell Technology and Experimental Medicine(HI-STEM) D-69120 HeidelbergGermany German Cancer Consortium(DKTK) D-69120 HeidelbergGermany Department of Pediatric Immunology Hematology and OncologyUniversity Hospital HeidelbergD-69120 HeidelbergGermany

Functional enrichment analysis or gene set enrichment analysis is a basic bioinformatics method that evaluates the biological importance of a list of genes of ***,it may produce a long list of significant terms with highly redundant information that is difficult to *** tools to simplify enrichment results by clustering them into groups either still produce redundancy between clusters or do not retain consistent term similarities within *** propose a new method named binary cut for clustering similarity matrices of functional *** comprehensive benchmarks on both simulated and real-world datasets,we demonstrated that binary cut could efficiently cluster functional terms into groups where terms showed consistent similarities within groups and were mutually exclusive between *** compared binary cut clustering on the similarity matrices obtained from different similarity measures and found that semantic similarity worked well with binary cut,while similarity matrices based on gene overlap showed less consistent *** implemented the binary cut algorithm in the R package simplifyEnrichment,which additionally provides functionalities for visualizing,summarizing,and comparing the *** simplifyEnrichment package and the documentation are available at https://***/packages/simplifyEnrichment/.

关键词： Functional enrichment Simplify enrichment Clustering R/Bioconductor Software Visualization

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Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts

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Bioactive Materials 2023年第10期28卷 206-226页

作者： Yun Jiang Ling-Ling Zhang Fan Zhang Wei Bi Peng Zhang Xiu-Jian Yu Sen-Le Rao Shi-Hui Wang Qiang Li Chen Ding Ying Jin Zhong-Min Liu Huang-Tian Yang Translational Medical Center for Stem Cell Therapy&Institute for Heart Failure and Regenerative Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200092China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of Sciences(CAS)CASShanghai200031PR China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development School of Life SciencesInstitute of Biomedical SciencesHuman Phenome InstituteZhongshan HospitalFudan UniversityShanghai200433China Institute for Stem Cell and Regeneration CASBeijing100101PR China

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts;however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.

关键词： Induced human pluripotent stem cells Cardiac lineage cells Extracellular matrix patch Cardiomyocyte regeneration Infarcted heart repair

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Identification and Analysis of Factors of Delay in Road Construction Projects 1st

Identification and Analysis of Factors of Delay in Road Cons...

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1st Indian Geotechnical and Geoenvironmental engineering Conference, IGGEC 2021

作者： Shukla, Bishnu Kant Bansal, Vaishnavi Varadharajan, S. Bharti, Gaurav Shenoy, Aparupa Singh, Udit Kumar Kirthanashri, S.V. Department of Civil Engineering JSS Academy of Technical Education Noida201301 India Amity Institute of Molecular Medicine and Stem Cell Research Noida201301 India

ISBN: (纸本)9789811947384

Delays are frequent in any civil engineering projects including the road projects. Project delays can result in cost overrun, time overruns, quality issues, etc. In this study, a national highway road project has been considered. A total of probable 90 delay factors were recognized and were characterized into nine foremost categories. A questionnaire was prepared, and it was filled by 101 respondents. Relative importance index technique has been used for the analysis of questionnaire data. The top and base 15 delay factors were recognized. The top five delay factors were found to be: consequence of sub-surface circumstances (rock, water table, soil, etc.), design related clashes/faults, provide the furnished site to the contractor, scarcity of skilled labour, resource allocation related delay, etc. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

关键词： Roads and streets

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Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer’s disease-like mouse model

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Signal Transduction and Targeted Therapy 2023年第2期8卷 813-826页

作者： Xiao-ying Sun Xiao-lin Yu Jie Zhu Ling-jie Li Lun Zhang Ya-ru Huang Dong-qun Liu Mei Ji Xun Sun Ling-xiao Zhang Wei-wei Zhou Dongming Zhang Jianwei Jiao Rui-tian Liu State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemistry and Chemical Engineering University of Chinese Academy of ScienceBeijing 100049China Innovation Academy for Green Manufacture Institute Chinese Academy of SciencesBeijing 100190China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China

Passive immunotherapy is one of the most promising interventions for Alzheimer’s disease(AD).However,almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal ***,we showed that Aβ-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aβ,antibody,and ***,anti-Aβantibodies without Fc fragment,or with blockage of CR3 or FcγRIIb,did not exert these adverse ***,Aβ-targeting antibodies,but not their Fab fragments,significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment,whereas the memory impairments in mice were gradually rescued *** the recovery rate of synapses in humans is much lower than that in mice,our findings may clarify the variances in the preclinical and clinical studies assessing AD ***,Aβ-targeting antibodies lack of Fc fragment,or with reduced Fc effector function,may not induce microglial synaptic pruning,providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.

关键词： Aβ Alzheimer inflammation

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Metal-phenolic networks modified polyurethane as periosteum for bone regeneration

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Chinese Chemical Letters 2022年第3期33卷 1623-1626页

作者： Qingyi Zhang Kai Huang Jie Tan Xiongxin Lei Liping Huang Yuting Song Qianjin Li Chenyu Zou Huiqi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Treatment of bone defects still poses a great challenge in orthopedic clinics, and the vital role of periosteum in such processes has attracted widespread attention. However, studies focusing on the oxidative stress micro-environment with an artificial periosteum at the site of defect have been scarce. The intrinsic anti-oxidative properties and therapeutic potential for bone defects of metal-phenolic networks(MPNs)have provided a potential solution to this. Herein, we have developed a protocatechualdehyde + zinc ion(PCA+Zn^(Ⅱ)) MPN coating on a thermoplastic polyurethane membrane with a one-pot method to fabricate a new-type of periosteum with meritorious biocompatibility and abilities of modulating oxidative stress condition and promoting osteogenesis and mineralization for better bone regeneration, which has shown to be a promising strategy for constructing artificial periosteum with various MPNs.

关键词： Metal-phenolic networks Surface modification Periosteum Oxidative stress Mineralization

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Progress in clinical trials of stem cell therapy for cerebral palsy

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Neural Regeneration Research 2021年第7期16卷 1377-1382页

作者： Zhong-Yue Lv Ying Li Jing Liu Stem Cell Clinical Research Center National Joint Engineering LaboratoryRegenerative Medicine CenterThe First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cell and Precision Medicine DalianLiaoning ProvinceChina

Cerebral palsy is the most common disease in children associated with lifelong disability in many *** research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral *** cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem *** this review, we summarize the design schemes and results of these clinical *** findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical ***, we also assess the safety and efficacy of these clinical *** anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.

关键词： adverse events brain cell transplantation central nervous system cerebral palsy clinical trials plasticity regeneration stem cell

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Fabrication and Characterization of Willemite Scaffolds Using Corn Stalk as a Novel Bio Template for Bone Tissue engineering Applications

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Journal of Bionic engineering 2023年第1期20卷 16-29页

作者： Zahra Yahay Seyed Mehdi Mirhadi Fariborz Tavangarian Department of Cellular Biotechnology Cell Science Research CenterRoyan Institute for BiotechnologyACECRIsfahan81593-58686Iran Department of Materials Engineering Shahreza BranchIslamic Azad UniversityShahrezaIsfahan86145-311Iran Mechanical Engineering Program School of ScienceEngineering and TechnologyPennsylvania State UniversityHarrisburgMiddletownPA17057USA

In this paper,we used Corn Stalk(CS)as a renewable and economical bio template to fabricate willemite scaffolds with the potential application in skull bone *** was used as a sacrificial template to synthesize the *** scaffolds with the chemical formula of Zn2SiO4 and pore size in the range of 3 to 10µm could be successfully synthesized by soaking CS in the willemite solution for 24 h and sintering at 950°C for 5 *** porosity of the samples was controlled by the soaking time(between 12 and 48 h)in the willemite solution from 5 to 35%,*** properties of these scaffolds showed a good approximation with cranial bone *** addition,cytotoxicity assays(MTT)were performed on Human Bone Marrow Stromal cells(HBMSc)and A172 human glioblastoma cell lines by direct and indirect culture methods to estimate their toxicity for bone and nerve cells,*** Phosphatase(ALP)activity and DAPI/Phalloidin cell staining were also performed to investigate the efficiency of the scaffolds for bone tissue engineering *** results showed that the scaffolds had good biocompatibility with both HBMSC and A172 cells,noticeable improvement on ALP activity,and great apatite formation ability in Simulated Body Fluid(SBF).All the evidence ascertained that willemite scaffolds made by corn stalks could be a useful candidate for bone tissue engineering applications.

关键词： Corn stalk Bio template Bioactive ceramics-Scaffolds Bone tissue engineering

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Single-cell genomics: the human biomolecular and cell atlases

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5570-5571页

作者： Yuqing Mei Jingjing Wang Guoji Guo Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative MedicineZhejiang University School of MedicineHangzhouZhejiang 310000China Liangzhu Laboratory Zhejiang UniversityHangzhouZhejiang 311121China Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cell and Regenerative MedicineHangzhouZhejiang 310058China Institute of Hematology Zhejiang UniversityHangzhouZhejiang 310000China

Recently,in a series of three papers published in Nature,the Human Biomolecular Atlas program(HuBMAP)consortium reported three multi-model single-cell and spatial atlases.1–3 Each work covered more than a million cells and mapped them to specific locations in the body,providing new standards to study human organs in both health and disease states.

关键词： states. molecular organs

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Turning “trashed” genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells

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Molecular Therapy 2025年第4期33卷 1368-1379页

作者： Wang, Yajie Jiang, Jie Shang, Kai Xu, Xiaobao Sun, Jie Bone Marrow Transplantation Center of the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China Liangzhu Laboratory Zhejiang University Hangzhou 311121 China Department of Cell Biology Zhejiang University School of Medicine Hangzhou 310058 China Institute of Hematology Zhejiang University and Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy Zhejiang Hangzhou 310058 China

Chimeric antigen receptor (CAR)-based immune cell therapy involves genetically engineering immune cells, such as T cells and natural killer (NK) cells, to express CARs that can specifically recognize target antigens. This modification enables T/NK cells to selectively eliminate tumor cells following adoptive transfer. One common approach to stably integrate CARs into the genome of T/NK cells is through retroviral or lentiviral vectors. However, these vectors mediate semi-random gene integration, posing risks such as oncogenic mutations, gene silencing, and variable CAR expression levels. Targeted integration of CAR genes into the specific genomic locus could overcome these limitations, but identifying the optimal integration sites to maximize the safety and efficacy of CAR-T/NK cell products remains a critical question. Improper integration sites may disturb the endogenous genes surrounding the integration sites, raising safety concerns. Additionally, regulatory elements at the integration sites, such as promoters, can influence the expression level of CAR genes, thus affecting the efficacy of CAR-T/NK cells. In this review, we summarized current strategies for selecting integration sites and promoters in the engineering of CAR-T/NK cells to achieve potent anti-tumor efficacy in preclinical studies. © 2025 The American Society of Gene and cell Therapy

关键词： CAR-NK CAR-T gene editing promoter site-specific integration

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A targetable pathway to eliminate TRA-1-60^(+)/TRA-1-81^(+)chemoresistant cancer cells

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Journal of Molecular cell Biology 2023年第6期15卷 25-39页

作者： Lei Tan Xiaohua Duan Pratyusha Mutyala Ting Zhou Sadaf Amin Tuo Zhang Brian Herbst Gokce Askan Tomer Itkin Zhaoying Xiang Fabrizio Michelassi Michael D.Lieberman Christine AIacobuzio-Donahue Steven DLeach Todd Evans Shuibing Chen Department of Surgery Weill Cornell MedicineNew YorkNY 10065USA Center for Energy Metabolism and Reproduction Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Center for Genomic Health Weill Cornell MedicineNew YorkNY 10065USA The SKI Stem Cell Research Facility The Center for Stem Cell Biology and Developmental Biology ProgramMemorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Genomic Resource Core Facility Weill Cornell Medical CollegeNew YorkNY 10065USA Rubenstein Center for Pancreatic Cancer Research Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Division of Regenerative Medicine Hartman Institute for Therapeutic Organ RegenerationAnsary Stem Cell InstituteDepartment of MedicineWeill Cornell MedicineNew YorkNY 10065USA Dartmouth Cancer Center Darmouth CollegeHanoverNH 03755USA

Chemoresistance is a primary cause of treatment failure in pancreatic *** cell surface markers specifically expressed in chemoresistant cancer cells(CCCs)could facilitate targeted therapies to overcome *** performed an antibody-based screen and found that TRA-1-60 and TRA-1-81,two‘stemness’cell surface markers,are highly enriched in ***-more,TRA-1-60^(+)/TRA-1-81^(+)cells are chemoresistant compared to TRA-1-60^(-)/TRA-1-81^(-)*** profiling identified UGT1A10,shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and *** a high-content chemical screen,we identified Cymarin,which downregulates UGT1A10,eliminates TRA-1-60/TRA-1-81 expression,and increases chemosensitivity both in vitro and in ***,TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival,which highlights their potentiality for targeted ***,we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance,as well as a leading drug candidate to target this pathway.

关键词： pancreatic cancer TRA-1-60/TRA-1-81 chemoresistance UGT1A10 Cymarin

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