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COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors

World Journal of Clinical Cases 2024年第11期12卷 1929-1935页

作者： Zhuo-Fan Ye Yi-Han Hong Jian-Lin Yang Meng-Qing Tan Ju-Min Xie Zu-Cai Xu Department of Neurology The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Hubei Key Laboratory of Renal Disease Occurrence and Intervention Medical SchoolHubei Polytechnic UniversityHuangshi 435003Hubei ProvinceChina Psychological Children's Ward Mental Health Center of HuangshiHuangshi 435111Hubei ProvinceChina The collaborative innovation center of tissue damage repair and regeneration medicine Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

BACKGROUND Recently,a growing number of adolescents have been afflicted with mental disorders,with annual morbidity rates on the rise.This trend has been exacerbated by the global coronavirus disease 2019(COVID-19)pandemic,leading to a surge in suicide and self-harm rates among this demographic.AIM To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder(BD),along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents.METHODS A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians.Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders,international classification of diseases-11,and the National institute of mental health research domain criteria.Statistical analyses were performed using SPSS 26.0 software,with significance set at P<0.05.RESULTS A cohort of 171 adolescents diagnosed with BD between January 1,2018,and December 31,2022,was included in the analysis.The gender distribution was 2.8:1(female to male),with ages ranging from 11 to 18 years old.Major factors contributing to adolescent BDs included familial influences,academic stress,genetic predisposition and exposure to school-related violence.Notably,a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic.Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress,thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents.CONCLUSION The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD.This study underscores the urgent need for societal,familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention,diagnosis and treatment of ad

关键词： Adolescents Bipolar disorder COVID-19 Suicide Self-harm

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Mettl3依赖的m^(6)A甲基化调控CD8^(+)T细胞效应分化和记忆形成

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Science Bulletin 2024年第1期69卷 82-96页

作者：郭文慧王昭张雅娇李亚书杜倩张田田胡瑾姚英鹏张家睿徐迎弟崔晓孙振游孟昊余国涛张好建杜旭光徐靖宇于舒洋 State Key Laboratory of Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China Frontier Science center for Immunology and Metabolism Medical Research InstituteSchool of MedicineWuhan UniversityWuhan 430071China the collaborative innovation center of tissue damage repair and regeneration medicine of zunyi medical university Zunyi 563000China

Efficient immune responses rely on the proper differentiation of CD8^(+)T cells into effector and memory cells.Here,we show a critical requirement of N^6-Methyladenosine(m^(6)A)methyltransferase Mettl3 during CD8^(+)T cell responses upon acute viral infection.Conditional deletion of Mettl3 in CD8^(+)T cells impairs effector expansion and terminal differentiation in an m^(6)A-dependent manner,subsequently affecting memory formation and the secondary response of CD8^(+)T cells.Our combined RNA-seq and m^(6)AmiCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators.Remarkably,Mettl3 binds to the Tbx21 transcript and stabilizes it,promoting effector differentiation of CD8^(+)T cells.Moreover,ectopic expression of T-bet partially restores the defects in CD8^(+)T cell differentiation in the absence of Mettl3.Thus,our study highlights the role of Mettl3 in regulating multiple target genes in an m^(6)A-dependent manner and underscores the importance of m^(6)A modification during CD8^(+)T cell response.

关键词： CD8^(+)T cell T cell response Mettl3 m^(6)A Effector Memory

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The emerging role of exosomes in the development of testicular

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Asian Journal of Andrology 2023年第5期25卷 547-555页

作者： Chun-Yang Li Song-Po Liu Xiao-Fang Dai Dong-Feng Lan Tao Song Xian-Yao Wang Qing-Hong Kong Jun Tan Ji-Dong Zhang Department of Immunology Zunyi Medical UniversityZunyi 563000China Special Key Laboratory of Gene Detection and Therapy of Guizhou Province Zunyi Medical UniversityZunyi 563000China collaborative innovation center of tissue damage repair and regeneration medicine Zunyi Medical UniversityZunyi 563000China Guizhou Provincial College-Based Key Lab for Tumor Prevention and Treatment with Distinctive medicines Zunyi Medical UniversityZunyi 563000China Department of Histology and Embryology Zunyi Medical UniversityZunyi 563000China

The mechanisms of testicular development in mammals are complex.Testis is an organ that produces sperm and secretes androgens.It is rich in exosomes and cytokines that mediate signal transduction between tubule germ cells and distal cells,promoting testicular development and spermatogenesis.Exosomes are nanoscale extracellular vesicles that transmit information between cells.By transmitting information,exosomes play an important role in male infertility diseases such as azoospermia,varicocele,and testicular torsion.However,due to the wide range of sources of exosomes,extraction methods are numerous and complex.Therefore,there are many difficulties in studying the mechanisms of exosomal effects on normal development and male infertility.Therefore,in this review,first,we introduce the formation of exosomes and methods for culturing testis and sperm.Then,we introduce the effects of exosomes on different stages of testicular development.Finally,we summarize the prospects and shortcomings of exosomes when used in clinical applications.We lay the theoretical foundation for the mechanism of the influence of exosomes on normal development and male infertility.

关键词： exosomes miRNA Sertoli cells sperm testis

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Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

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Cellular & Molecular Immunology 2023年第8期20卷 924-940页

作者： Yongsheng Teng Rui Xie Jingyu Xu Pan Wang Wanyan Chen Zhiguo Shan Zongbao Yan Fangyuan Mao Ping Cheng Liusheng Peng Jinyu Zhang Wenqing Tian Shiming Yang Yongliang Zhao Weisan Chen Quanming Zou Yuan Zhuang Department of Microbiology and Biochemical Pharmacy College of Pharmacy and Laboratory MedicineThird Military Medical UniversityChongqingChina The 940th Hospital of Joint Logistics Support Force of PLA LanzhouChina the collaborative innovation center of tissue damage repair and regeneration medicine of zunyi medical university ZunyiGuizhouChina Department of General Surgery and center of Minimal Invasive Gastrointestinal Surgery Southwest HospitalThird Military Medical UniversityChongqingChina Department of Gastroenterology Chongqing University Cancer HospitalChongqingChina Department of Gastroenterology XinQiao HospitalThird Military Medical UniversityChongqingChina La Trobe Institute of Molecular Science La Trobe UniversityBundooraVICAustralia Department of Gastroenterology Affiliated Hospital of Southwest Medical UniversityLuzhouSichuanChina National Engineering Research center of Immunological Products Third Military Medical UniversityChongqingChina

The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.

关键词： Helicobacter pylori TINAGL1 Colonization Gastritis

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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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TGF-β1-supplemented decellularized annulus fibrosus matrix hydrogels promote annulus fibrosus repair

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Bioactive Materials 2023年第1期19卷 581-593页

作者： Qiang Wei Dachuan Liu Genglei Chu Qifan Yu Zhao Liu Jiaying Li Qingchen Meng Weishan Wang Fengxuan Han Bin Li Department of Orthopaedic Surgery Orthopaedic InstituteThe First Affiliated HospitalSuzhou Medical CollegeSoochow UniversitySuzhouJiangsuChina Department of Orthopaedic Surgery The First Affiliated HospitalShihezi University School of MedicineShiheziXinjiangChina collaborative innovation center of Hematology Soochow UniversitySuzhouJiangsuChina

Annulus fibrosus(AF)repair remains a challenge because of its limited self-healing ability.Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair.Although the unique and beneficial characteristics of decellularized extracellular matrix(ECM)in tissue repair have been demonstrated,the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration.In the present study,we combined polyethylene glycol diacrylate(PEGDA)and decellularized annulus fibrosus matrix(DAFM)to develop an injectable,photocurable hydrogel for AF repair.We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure.Transforming growth factor-β1(TGF-β1)was further incorporated into PEGDA/DAFM hydrogels,and it could be continuously released from the hydrogel.The in vitro experiments showed that TGF-β1 facilitated the migration of AF cells.Furthermore,PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion,proliferation,and increased ECM production of AF cells.In vivo repair performance of the hydrogels was assessed using a rat AF defect model.The results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect,prevented nucleus pulposus atrophy,retained disc height,and partially restored the biomechanical properties of disc.In addition,the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF tissue.In summary,findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.

关键词： Decellularized matrix Annulus fibrosus Hydrogel TGF-β1 tissue repair

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Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis

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Research 2023年第4期2023卷 163-180页

作者： Jinhong Cai Lian-feng Liu Zainen Qin Shuhan Liu Yonglin Wang Zhengrong Chen Yi Yao Li Zheng Jinmin Zhao Ming Gao collaborative innovation Centre of Regenerative medicine and medical Bioresource Development and Application Co-constructed by the Province and Ministry The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Guangxi Engineering center in Biomedical Materials for tissue and Organ regeneration Guangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of Ultrasound Guangxi Medical University Cancer HospitalNanning530021China Department of Orthopedics The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Life Sciences Institute Guangxi Medical UniversityNanning530021China.

Osteoarthritis(OA)is always characterized as excessive reactive oxygen species(ROS)inside articular cavity.Mimicking natural metalloenzymes with metal ions as the active centers,stable metal organic framework(MOF)formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases.Herein,a series of novel copper-morin-based MOF(CuMHs)with different molar ratios of Cu^(2+)and MH were employed to serve as ROS scavengers for OA therapy.As a result,CuMHs exhibited enhanced dispersion in aqueous solution,improved biocompatibility,and efficient ROS-scavenging ability compared to MH.On the basis of H_(2)O_(2)-stimulated chondrocytes,intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu_(6)MH(Cu^(2+)and MH molar ratio of 6:1).Meanwhile,Cu_(6)MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6,MMP13,and MMP3,and up-regulating cartilage specific gene expression as well.Importantly,Cu_(6)MH could repair mitochondrial function by increasing mitochondrial membrane potential,reducing the accumulation of calcium ions,as well as promoting ATP content production.In OA joint model,intra-articular(IA)injected Cu_(6)MH suppressed the progression of OA.It endowed that Cu_(6)MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

关键词： Osteoarthritis prevention inflammation

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Hierarchical ultrastructure:An overview of what is known about tendons and future perspective for tendon engineering

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Bioactive Materials 2022年第2期7卷 124-139页

作者： Shichen Zhang Wei Ju Xiaoyi Chen Yanyan Zhao Lingchong Feng Zi Yin Xiao Chen Dr.Li Dak Sum&Yip Yio Chin center for Stem Cell and Regenerative medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital School of MedicineZhejiang UniversityHangzhou310052China Key Laboratory of tissue Engineering and Regenerative medicine of Zhejiang Province School of MedicineZhejiang UniversityHangzhou310058China Guangxi Key Laboratory of Regenerative medicine Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and TreatmentGuangxi Medical UniversityGuangxi530021China State Key Laboratory of Clean Energy Utilization Zhejiang UniversityHangzhou310058ZhejiangChina Dr.Li Dak Sum&Yip Yio Chin center for Stem Cell and Regenerative medicine and Regenerative medicine and Department of Orthopedic Surgery of Sir Run Run Shaw Hospital School of MedicineZhejiang UniversityHangzhou310058China Department of Sports medicine School of MedicineZhejiang UniversityHangzhou310058China China Orthopedic Regenerative medicine Group(CORMed) Hangzhou310058China

Abnormal tendons are rarely ever repaired to the natural structure and morphology of normal tendons.To better guide the repair and regeneration of injured tendons through a tissue engineering method,it is necessary to have insights into the internal morphology,organization,and composition of natural tendons.This review summarized recent researches on the structure and function of the extracellular matrix(ECM)components of tendons and highlight the application of multiple detection methodologies concerning the structure of ECMs.In addition,we look forward to the future of multi-dimensional biomaterial design methods and the potential of structural repair for tendon ECM components.In addition,focus is placed on the macro to micro detection methods for tendons,and current techniques for evaluating the extracellular matrix of tendons at the micro level are introduced in detail.Finally,emphasis is given to future extracellular matrix detection methods,as well as to how future efforts could concentrate on fabricating the biomimetic tendons.

关键词： Tendon Collagen fibrillogenesis Extracellular matrix FIB-SEM Biomimetic

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Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels

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Bioactive Materials 2022年第8期7卷 97-109页

作者： Junxiang Hao Baoshuai Bai Zheng Ci Jincheng Tang Guanhuai Hu Chengxiang Dai Mengyuan Yu Meng Li Wei Zhang Yixin Zhang Wenjie Ren Yujie Hua Guangdong Zhou Research Institute of Plastic Surgery Weifang Medical UniversityWeifangShandongChina Department of Plastic and Reconstructive Surgery Shanghai 9th People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Tissue EngineeringShanghaiChina National tissue Engineering center of China ShanghaiChina Institute of Regenerative medicine and Orthopedics Institutes of Health Central PlainXinxiang Medical UniversityXinxiangHenanChina Cellular Biomedicine Group Inc.ShanghaiChina

Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.

关键词： Microgels Large-sized bone defect repair Bone regeneration units Photo-crosslinking Decalcified bone matrix

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Conductive PS inverse opals for regulating proliferation and differentiation of neural stem cells

再生工程(英文)

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再生工程(英文) 2023年第2期4卷 214-221页

作者： Yangnan Hu Han Zhang Hao Wei Menghui Liao Xiaoyan Chen Jiayue Xing Lian Duan Cuntu Cheng Weicheng Lu Xuechun Yang Peina Wu Huan Wang Jingdun Xie Renjie Chai State Key Laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing210096China Co-innovation center of Neuroregeneration Nantong UniversityNantong 226001China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Department of Otolaryngology Head and Neck Surgery Affiliated Drum Tower Hospital of Nanjing university medical School Jiangsu Provincial Key medical Discipline Nanjing 210008China Department of Anesthesiology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in Southern ChinaCollaborative Innovation for Cancer MedicineGuangdong 510060China Department of Otolaryngology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou510080China School of medicine South China University of TechnologyGuangzhou510006China The Eighth Affiliated Hospital of Sun Yat-Sen university Shenzhen518033China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina Institute for Stem Cell and regeneration Chinese Academy of ScienceBeijingChina Beijing Key Laboratory of Neural regeneration and repair Capital Medical UniversityBeijing100069China

The development of neural tissue engineering has brought new hope to the treatment of spinal cord injury(SCI).Up to date,various scaffolds have been developed to induce the oriented growth and arrangement of nerves to facilitate the repair after injury.In this work,a conductive and anisotropic inverse opal substrate was presented by modifying polystyrene(PS)inverse opal films with carbon nanotubes and then stretching them to varying degrees.The film had good biocompatibility,and neural stem cells(NSCs)grown on the film displayed good orientation along the stretching direction.In addition,benefiting from the conductivity and anisotropy of the film,NSCs differentiated into neurons significantly.These results suggest that the conductive and anisotropic PS inverse opal substrates possess value in nerve tissue engineering regeneration.

关键词： Nerve regeneration Inverse opal Neural stem cells Oriented growth tissue engineering

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