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Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2132-2142页

作者： Xinglong Han Lina Qu Miao Yu Lingqun Ye Liujia Shi Guangfu Ye Jingsi Yang Yaning Wang Hao Fan Yong Wang Yingjun Tan Chunyan Wang Qi Li Wei Lei Jianghai Chen Zhaoxia Liu zhenya shen Yinghui Li Shijun Hu Department of Cardiovascular Surgery of the First Affiliated Hospital&Institute for Cardiovascular Science State Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouChina State Key Laboratory of Space Medicine China Astronaut Research and Training CenterBeijingChina Department of Hand Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further investigated.Since China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the CSS.In this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling.Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine metabolism.The microgravity condition blocked the thiamine intake in hPSC-CMs.The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle.It decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs.More importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity.This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research.These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

关键词： programming battery modified

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Green intelligent fertilizers——A novel approach for aligning sustainable agriculture with green development

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Frontiers of Agricultural Science and Engineering 2024年第1期11卷 186-196页

作者： Maoying WANG Lingyun CHENG Chengdong HUANG Yang LYU Lin ZHANG zhenya LU Changzhou WEI Wenqi MA Zed RENGEL Jianbo shen Fusuo ZHANG State Key Laboratory of Nutrient Use and Management College of Resources and Environmental SciencesNational Academy of Agriculture Green DevelopmentKey Laboratory of Plant–Soil Interactions(Ministry of Education)China Agricultural UniversityBeijing 100193China College of Agronomy Shihezi UniversityShihezi 832000China College of Resources and Environmental Science Hebei Agricultural UniversityBaoding 071000China Soil Science and Plant Nutrition UWA School of Agriculture and EnvironmentThe University of Western AustraliaPerthWA 6009Australia Institute for Adriatic Crops and Karst Reclamation Split 21000Croatia

This review addresses the growing disparity between the current state of fertilizer production in China and the evolving demands of green agriculture in the 21st century. It explores major advances in fertilizers, proposes the concept of green intelligent fertilizers and develops new strategies aligned with the principles of green development in fertilizer industry and agriculture.Green intelligent fertilizers may be designed to maximize the synergistic effects among plants, soils, microorganisms, nutrient sources and the environment. This concept emphasizes the integration of industry and agriculture toward green development for entire industry chain, using an interdisciplinary approach to drive the green transformation of fertilizer industry, and promote green and sustainable development of agriculture. By bridging the gap between the current state of fertilizer industry and a growing need for environmentally responsible agricultural practices, this review highlights a path toward harmonizing fertilizer production with the imperatives of green agriculture.

关键词： Root-nutrient feedback green development intelligent fertilizers new fertilizer plant-soil-fertilizer interaction rhizosphere engineering

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Injectable decellularized extracellular matrix hydrogel loaded with exosomes encapsulating curcumin for prevention of cardiac fibrosis after myocardial infarction

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Journal of Materials Science & Technology 2023年第36期167卷 50-58页

作者： Yuanyuan Wang Jingjing Wang Chunxia Liu Jingjing Li Kunyan Lu Qian Yu Yanxia Zhang zhenya shen Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215007China State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China

Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to prevent or alleviate cardiac fibrosis.Curcumin,a natural molecule with antifibrotic activity,is encapsulated in the exosomes that are isolated from bone marrow-derived mesenchymal stem cells to enhance its water solubility and bioavailability.These composite exosomes are efficiently internalised by fibroblasts and effectively inhibit their transition to myofibroblasts in vitro.Decellularized porcine cardiac extracellular matrix(dECM)hydrogel is used as the carrier for delivering these composite exosomes to the infarcted myocardium,not only improving the retention of exosomes but also providing mechani-cal support and structural protection.Injection of this hydrogel into the infarcted heart of a mouse MI model leads to a decrease in collagen deposition,alleviation of fibrosis,a reduction in infarct size,and an improvement in cardiac function.The reported composite hydrogel comprising natural materials and biomolecules exhibits good biocompatibility and bioactivity.Altogether,this study demonstrates that the dECM hydrogel is a suitable platform for the local delivery of antifibrotic biomolecule-encapsulating exo-somes to prevent myocardial fibrosis after MI and have great potential for the treatment of MI in clinical settings.

关键词： Myocardial fibrosis Myocardial infarction Decellularized extracellular matrix Exosomes Curcumin

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An injectable alginate/fibrin hydrogel encapsulated with cardiomyocytes and VEGF for myocardial infarction treatment

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Journal of Materials Science & Technology 2023年第12期143卷 198-206页

作者： Chunxia Liu Yong Wu Hong Yang Kunyan Lu Haixin Zhang Yuanyuan Wang Jingjing Wang Linan Ruan zhenya shen Qian Yu Yanxia Zhang Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215000China State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function Soochow UniversitySuzhou 215123China

Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.

关键词： Injectable hydrogel Alginate Fibrin Cardiomyocytes VEGF Myocardial infarction

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Inflammasomes as therapeutic targets in human diseases

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2334-2347页

作者： Yangxin Li Hui Huang Bin Liu Yu Zhang Xiangbin Pan Xi-Yong Yu zhenya shen Yao-Hua Song Institute for Cardiovascular Science and Department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow UniversityCollaborative Innovation Center of HematologySoochow UniversitySuzhouJiangsuP.R.China Cardiovascular Department The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China Department of Cardiology The Second Hospital of Jilin UniversityChangchunJilinP.R.China Department of Cardiac Surgery Fuwai HospitalBeijingP.R.China Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhouGuangdongP.R.China Cyrus Tang Hematology Center Collaborative Innovation Center of HematologySoochow UniversityNational Clinical Research Center for Hematologic Diseasesthe First Affiliated Hospital of Soochow UniversityState Key Laboratory of Radiation Medicine and ProtectionSoochow UniversitySuzhouChina

Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.

关键词： diseases inflammation endogenous

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Biomaterials based cardiac patches for the treatment of myocardial infarction

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Journal of Materials Science & Technology 2021年第35期94卷 77-89页

作者： Tianqi Chang Chunxia Liu Kunyan Lu Yong Wu Mingzhu Xu Qian Yu zhenya shen Tingbo Jiang Yanxia Zhang Department of Cardiovascular Surgery of the First Affiliated Hospital&Institute for Cardiovascular Science Soochow University.Suzhou 215006China Department of Cardiology The First Affiliated Hospital of Soochow UniversitySuzhou 215006China State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China

Myocardial infarction(MI)is one of the common cardiovascular diseases that occurs with a blockage in one or more of the coronary arteries to lead to the damage of the myocardium,resulting in a lifethreatening condition.To repair the damaged myocardium in MI,researchers are looking forwards to new ways to postpone the progression of myocardial injury.Cardiac patches,the scaffolds layered on the heart surface,can provide mechanical support for the infarction site and improve cardiac function by delivering various bioactive factors or cells,showing considerable curative effect in the treatment of MI.Biomaterials with certain biocompatibility and mechanical properties have received widespread attention for the application in cardiac patches.In this review,we focus on the recent progress on these biomaterialsbased cardiac patches,which could be categorized into two types according to the sources of materials including(ⅰ)natural materials and(ⅱ)synthetic materials.The major advantages and current challenges of each type are discussed and a brief perspective on the future research directions is presented.

关键词： Biomaterials Cardiac patches Myocardial infarction

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Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction

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Bioactive Materials 2021年第2期6卷 520-528页

作者： Yong Wu Tianqi Chang Weiqian Chen Xiaoyu Wang Jingjing Li Yueqiu Chen You Yu zhenya shen Qian Yu Yanxia Zhang Institute for Cardiovascular Science&Department of Cardiovascular Surgery of the First Affiliated Hospital Medical CollegeSoochow UniversitySuzhou215000PR China State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou215123PR China

Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery,necrosis of myocardial cells,inflammation,and myocardial fibrosis.Aiming at the treatment of different stages of MI,in this work,an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor(VEGF)and silk fibroin(SF)microspheres containing bone morphogenetic protein 9(BMP9)for releasing VEGF and BMP9 to realize their respective functions.The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days,facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage,respectively.Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size.Taken together,these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function,showing a promising potential for cardiac clinical application.

关键词： Myocardial infarction Injectable hydrogel Silk fibroin microspheres Angiogenesis Myocardial fibrosis

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Stem cell-derived exosomes repair ischemic muscle injury by inhibiting the tumor suppressor Rbl-mediated NLRP3 inflammasome pathway

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1110-1112页

作者： Yanli Wang Wenping Xie Bin Liu Hui Huang Wei Luo Yu Zhang Xiangbin Pan Xi-Yong Yu zhenya shen Yangxin Li Institute for Cardiovascular Science and Department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow UniversityCollaborative Innovation Center of HematologySoochow UniversitySuzhouJiangsuPR China Deportment of Cardiology The Second Hospital of Jilin UniversityChangchunJilinPR China Cardiovascular Department The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongPR China Department of Cardiac Surgery Fuwai HospitalBeijingPR China Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhouGuangdongPR China

Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing inflammatory cytokines including IL-1β and IL-18.1 However,the molecular mechanisms underlying activation of the NLRP3 inflammasome remain largely unknown.

关键词： NLRP3 inflam inhibiting

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圆结构光系统深孔圆度测量方法研究

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红外与激光工程 2024年第4期53卷 194-200页

作者：陈振亚马卓强李翔沈兴全杨尚进苗鸿宾卢传杰中北大学机械工程学院山西太原030051 中国船舶集团有限公司第七一三研究所河南郑州450015 恶劣环境下智能装备技术山西省重点实验室山西太原030051 山东普利森集团有限公司山东德州253000

圆结构光系统测量深孔(通孔)圆度时存在激光器、相机和深孔难以保持平行或同轴的问题,导致无法测量准确的圆截面,从而产生系统误差。搭建了基于圆结构光的测量系统,分析了系统误差的产生机理并提出了一种基于圆结构光系统测量圆度的方法... 详细信息

圆结构光系统测量深孔(通孔)圆度时存在激光器、相机和深孔难以保持平行或同轴的问题,导致无法测量准确的圆截面,从而产生系统误差。搭建了基于圆结构光的测量系统,分析了系统误差的产生机理并提出了一种基于圆结构光系统测量圆度的方法,可对系统误差进行一定补偿:首先,获取待测深孔的内表面高分辨率三维点云,拟合点云轴线,通过刚体变换将三维点云变换到深孔轴线与相机光轴平行的位置;然后,选定一个测量截面,搜索该截面上的点和与该截面范围较近的点作为圆度评定点;最后,采用网格搜索算法完成圆度评定。测量实验的结果表明,该方法对于圆度误差的补偿效果良好,其中测量不确定度为4.78μm。

关键词：圆结构光圆度测量刚体变换误差补偿

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Timing of transplantation of autologous bone marrow derived mesenchymal stem cells for treating myocardial infarction

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Science China(Life Sciences) 2014年第2期57卷 195-200页

作者： CHEN YiHuan TENG XiaoMei CHEN WeiQian YANG JunJie YANG ZiYing YU Yunsheng shen zhenya Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science of Soochow University

It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction.The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion.However,the adverse inflammatory environment,with its high oxidative stress,might be deleterious if cells are administered too early after reperfusion.Here we highlight several aspects of the timing of intracoronary stem cell therapy.Our results showed that transplantation of bone marrow mesenchymal stem cells at 2 4 weeks after myocardial infarction is more favorable for reduction of the scar area,inhibition of left ventricular remodeling,and recovery of heart function.Coronary injection of autologous bone marrow mesenchymal stem cells at 2 4 weeks after acute myocardial infarction is safe and does not increase the incidence of complications.

关键词：骨髓间充质干细胞急性心肌梗死移植治疗自体干细胞治疗衍生定时冠状动脉

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