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Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su Institute of translational medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China national Center for translational medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China Department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

Additively Manufactured High-Entropy Alloys:Exceptional Mechanical Properties and Advanced Fabrication

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 3-16页

作者： Changxi Liu Yingchen Wang Yintao Zhang Liqiang Wang State Key Laboratory of Metal Matrix Composites School of Material Science and EngineeringShanghai Jiao Tong UniversityShanghai200240China national Center for translational medicine Shanghai Jiao Tong UniversityShanghai200240China

High-entropy alloys(HEA)represent a novel material class,with significant potential for research on performance and preparation in additive manufacturing(AM).Currently,FCC HEA dominates the research on AM-fabricated HEA,with a shift in focus from preparation to microstructure design and mechanical properties *** on BCC HEA is currently primarily focused on preparation and process ***,it is important to note that the biomedical potential of AM-fabricated BCC HEA should not be *** review provides a concise summary of the properties and preparation techniques of exceptional HEAs in recent *** specifically emphasizes the novel microstructure achieved through AM techniques,which significantly enhance the mechanical properties of ***,the review outlines the various preparation methods employed to mitigate defect introduction during AM ***,it offers insights into the future research directions and potential applications of additively manufactured HEA.

关键词： High-entropy alloy Additive manufacture Microstructure Mechanical property

Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation

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Food Science and Human Wellness 2024年第3期13卷 1201-1211页

作者： Dingwu Qu Zhennan Gu Saisai Feng Leilei Yu Fengwei Tian Hao Zhang Wei Chen Qixiao Zhai State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China national Engineering Research Center for Functional Food Jiangnan UniversityWuxi 214122China Wuxi translational medicine Research Center and Jiangsu translational medicine Research Institute Wuxi Branch Wuxi 214122China

Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome *** commensals have shown different functions in IBD prevention and *** gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut ***-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture *** showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal *** probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not ***,*** JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated ***,*** FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial ***,we provided insight into the clinical application of probiotics in IBD treatment.

关键词： Gut commensals Dextran sulfate sodium(DSS)colitis Intestinal barrier Immunoregulation

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

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Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： Xiang Ren Tan Mary C.Stephenson Sharifah Badriyah Alhadad Kelvin W.Z.Loh Tuck Wah Soong Jason K.W.Lee Ivan C.C.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore Human Potential translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Centre for translational Magnetic Resonance Research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and Performance Centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore Campus for Research Excellence and Technological Enterprise(CREATE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive *** heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and ***:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,*** a separate trial,blended ice was ingested before and during exercise as a cooling *** were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging ***:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive *** function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital ***,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural ***:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity Cognition Heat stress Hyperthermia Motor function

Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

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Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe Chen Kai Wang Jie Ju Xue Yu Wanpeng Yu Cuiyun Liu Yin Wang Institute for translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China College of medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and *** development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac *** the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial *** implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial ***,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further *** is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart ***,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart *** addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte ***,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

Rapid and chemoselective imidation of sulfides in aqueous buffer enabled by a novel guanidine-derived N-O reagent

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Science China Chemistry 2024年第6期67卷 1929-1934页

作者： Hanzheng Li Long Xu Jiajia Dong Key Laboratory of Organofluorine Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032China Institute of translational medicine National Facility for Translational Medicine(Shanghai)Shanghai Jiao Tong UniversityShanghai200240China School of Chemistry and Chemical Engineering Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai200240China Shanghai Artificial Intelligence Laboratory Shanghai200232China

Herein we report the facile synthesis of a series of novel N-O reagents and identify N′-di-Boc-N′′-[(mesitylsulfonyl)oxy]-guanidine as an efficient imidating *** reagent is synthetically scalable and bench-stable,yet it shows unprecedented reactivity and chemoselectivity towards S(II)in buffer/hexafluoroisopropanol(HFIP)system,to generate a new class of Nguanyl *** transformation of N-guanyl sulfilimines to N-guanyl sulfoximines provides us a chance to investigate these rarely reached compounds,which are shown to be versatile precursors to a variety of N-heterocyclic and *** work provides an addition to the tool box of both sulfur imidation and guanidine synthesis,especially for the need of rapid and selective modifications of sulfur(II)center under biocompatible conditions.

关键词： sulfur imidation N-O reagent

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Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

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Frontiers of medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang Zhiyun Zhao Weiqing Wang Yufang Bi Meng Dai Yuhong Chen Jieli Lu Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai national Clinical Research Center for Endocrine and Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains *** study included 5323 community-dwelling subjects aged⩾40 years from ***-life famine exposure was identified based on the participants’birth *** obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or *** to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in *** interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture

Trojan horses in tumor: engineered pyroelectric and photodynamic nanocomposites for NIR-induced cell apoptosis and tumor growth inhibition

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Science China Chemistry 2024年第9期67卷 3050-3062页

作者： Yanxi Yang Xinru Kong Xueli Ren Yandai Lin Zhe Liu Academy of Medical Engineering and translational medicine Tianjin University Tianjin Key Laboratory of Brain Science and Neural Engineering Tianjin University

It is desirable but always challenging to develop a cutting-edge tumor treatment strategy with high therapeutic efficacy, lesiontargeted precision and mild accessibility. Compared to traditional treatment modalities, photodynamic therapy has been widely studied since the generation of reactive oxygen species（ROS） at cancerous lesions unprecedentedly offers a convenient approach for localized tumor eliminations. Nevertheless, the consumption of oxygen for ROS production in a hypoxic tumor microenvironment has dramatically limited its feasibility and efficacy. Herein, the engineered nanocomposites of BTO@PDA-ICGHA with photodynamic and pyroelectric performances have been fabricated and applied to the photodynamic-pyroelectric dynamic treatments. The continuing ROS production derived from intracellular oxygen（O2） and water（H2O） by laser irradiation contributed to the superb tumor cell apoptosis and significant tumor growth inhibition. Thus, this study has validated a new concept by depositing the engineered nanocomposites at the tumor just like Trojan horses, facilitating ROS release as killers and exerting the NIR-induced cell apoptosis and tumor growth inhibition with high therapeutic efficiency and expectable translational perspectives.

关键词： nanocomposites pyroelectric effect photodynamic therapy cell apoptosis tumor growth inhibition

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EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1187-1203页

作者： Yongyun Li Tianyu Zhu Jie Yang Qianqian Zhang Shiqiong Xu Shengfang Ge Renbing Jia Jianming Zhang Xianqun Fan Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology Shanghai 200001China national Research Center for translational medicine(Shanghai) State Key Laboratory of Medical GenomicsShanghai Institute of HematologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of translational medicine Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 200240China

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma(UM).Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular *** search of genetic vulnerability for UM,we found that inhibition of euchromatic histone lysine methyltransferase 2(EHMT2)expression or activity significantly reduced the proliferation and migration capacity of cancer ***,elevated expression of EHMT2 had been validated in UM ***,Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T *** immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of *** transcription was suppressed by EHMT2 in a methyltransferasedependent pattern in GNAQ/11-mutant UM cells,leading to elevated RhoA *** constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic *** blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth,suggesting the driver role of these two key *** summary,our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

关键词： Uveal melanoma EHMT2 RhoA pathway ARHGAP29 G protein GNAQ GNA11