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Chinese Chemical Letters 2024年第7期35卷 319-324页

作者： Zengchao Guo Weiwei Liu Tengfei Liu Jinpeng Wang Hui Jiang Xiaohui Liu Yossi Weizmann Xuemei Wang State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Department of Chemistry Ben-Gurion University of the NegevBeer-Sheva 8410501Israel

With the increasing emergence of bacterial infections,especially multidrug-resistant(MDR)bacteria,poses an urgent *** study demonstrated a novel multifunctional nanotheranostics platform developed by the strategic integration of both in-situ bio-assembly imaging and target bacteria *** the introduction of copper ions into bacteria,the Cu^(2+)could spontaneously bio-selfassembled into a multifunctional copper nanoclusters(NCs)which efficiently enhanced epigallocatechin gallate(EGCG)uptake into *** visualizing the bacteria,the developed theranostic nanoplatform exhibited highly efficient disinfection activities with negligible side effects as reflected by higher cell viability and insignificant hemolytic ***,the exosomal formulation of EGCG integrated with Cu^(2+)showed an increased intracellular antibacterial activity,which could eliminate most of the methicillin-resistant Staphylococcus aureus(MRSA)phagocytosed by macrophages,guide macrophages toward M2-like phenotype polarization and alleviate inflammation,without exhibiting obvious cytotoxicity on host *** regimen could be viewed as an effective strategy for the sterilization of intractable bacterial infections.

关键词： In situ self-assembled Exosome Antibacterial agents Bioimaging Intracellular infection

Generative pretrained transformer 4:an innovative approach to facilitate value-based healthcare

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Intelligent Medicine 2024年第1期4卷 10-15页

作者： Han Lyu Zhixiang Wang Jia Li Jing Sun Xinghao Wang Pengling Ren Linkun Cai Zhenchang Wang Max Wintermark Department of Radiology Capital Medical University Affiliated Beijing Friendship HospitalBeijing 100050China Department of medical Imaging Capital Medical University Affiliated Beijing Friendship HospitalBeijing 100050China School of Biological Science and medical Engineering Beihang UniversityBeijing 100191China Department of Neuroradiology University of Texas MD Anderson CenterHoustonTX 77030USA

Objective Appropriate medical imaging is important for value-based *** aim to evaluate the performance of generative pretrained transformer 4(GPT-4),an innovative natural language processing model,providing appropriate medical imaging automatically in different clinical *** Institutional Review Boards(IRB)approval was not required due to the use of nonidentifiable ***,we used 112 questions from the American College of Radiology(ACR)Radiology-TEACHES Program as prompts,which is an open-sourced question and answer program to guide appropriate medical *** included 69 free-text case vignettes and 43 simplified *** the performance evaluation of GPT-4 and GPT-3.5,we considered the recommendations of ACR guidelines as the gold standard,and then three radiologists analyzed the consistency of the responses from the GPT models with those of the *** set a five-score criterion for the evaluation of the consistency.A paired t-test was applied to assess the statistical significance of the *** For the performance of the GPT models in free-text case vignettes,the accuracy of GPT-4 was 92.9%,whereas the accuracy of GPT-3.5 was just 78.3%.GPT-4 can provide more appropriate suggestions to reduce the overutilization of medical imaging than GPT-3.5(t=3.429,P=0.001).For the performance of the GPT models in simplified scenarios,the accuracy of GPT-4 and GPT-3.5 was 66.5%and 60.0%,*** differences were not statistically significant(t=1.858,P=0.070).GPT-4 was characterized by longer reaction times(27.1 s in average)and extensive responses(137.1 words on average)than *** As an advanced tool for improving value-based healthcare in clinics,GPT-4 may guide appropriate medical imaging accurately and efficiently。

关键词： Generative pretrained transformer 4 model Natural language processing medical imaging Appropriateness

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

Ischemia-reperfusion injury:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted therapy 2024年第2期9卷 558-596页

作者： Meng Zhang Qian Liu Hui Meng Hongxia Duan Xin Liu Jian Wu Fei Gao Shijun Wang Rubin Tan Jinxiang Yuan The Collaborative Innovation Center Jining Medical UniversityJiningShandong 272067China Clinical medical College Jining Medical UniversityJiningShandong 272067China Second Clinical medical College Jining Medical UniversityJiningShandong 272067China Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital and Institutes of Biomedical SciencesFudan UniversityShanghaiChina Institute of Zoology Chinese Academy of SciencesBeijingChina Department of Physiology Basic medical schoolXuzhou Medical UniversityXuzhou 221004China

Ischemia-reperfusion(I/R)injury paradoxically occurs during reperfusion following ischemia,exacerbating the initial tissue *** limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic *** Wnt signaling pathway exhibits extensive crosstalk with various other pathways,forming a network system of signaling pathways involved in I/R *** review article elucidates the underlying mechanisms involved in Wnt signaling,as well as the complex interplay between Wnt and other pathways,including Notch,phosphatidylinositol 3-kinase/protein kinase B,transforming growth factor-β,nuclear factor kappa,bone morphogenetic protein,N-methyl-D-aspartic acid receptor-Ca2+-Activin A,Hippo-Yes-associated protein,toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β,and hepatocyte growth factor/mesenchymal-epithelial transition *** particular,we delve into their respective contributions to key pathological processes,including apoptosis,the inflammatory response,oxidative stress,extracellular matrix remodeling,angiogenesis,cell hypertrophy,fibrosis,ferroptosis,neurogenesis,and blood-brain barrier damage during I/R *** comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery,while activation of the non-canonical Wnt pathways exacerbates ***,we explore novel therapeutic approaches based on these mechanistic findings,incorporating evidence from animal experiments,current standards,and clinical *** objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction,to facilitate the development of innovative therapeutic agents for I/R injury.

关键词： therapeutic reperfusion damage

The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： Yu Fu Jia Li Wenyun Cai Yulan Huang Xinlong Liu Zhongyi Ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in *** accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional ***,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying ***,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed *** hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy Outer membrane vesicles

Biological scaffold as potential platforms for stem cells:Current development and applications in wound healing

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World Journal of Stem Cells 2024年第4期16卷 334-352页

作者： Jie-Yu Xiang Lin Kang Zi-Ming Li Song-Lu Tseng Li-Quan Wang Tian-Hao Li Zhu-Jun Li Jiu-Zuo Huang Nan-Ze Yu Xiao Long Department of Plastic and Reconstructive Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Biomedical Engineering Facility Institute of Clinical MedicinePeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100021China

Wound repair is a complex challenge for both clinical practitioners and *** approaches for wound repair have several *** cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin ***,the use of stem cells in skin regeneration presents several ***,stem cells and biomaterials have been identified as crucial components of the wound-healing *** therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable *** scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the *** scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound *** article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine ***,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

关键词： Stem-cell-based therapy Biological scaffolds Wound healing Extracellular matrix mimicry Cellular activities enhancement Scaffold characteristics

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Human brain organoid:trends,evolution,and remaining challenges

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Neural Regeneration Research 2024年第11期19卷 2387-2399页

作者： Minghui Li Yuhan Yuan Zongkun Hou Shilei Hao Liang Jin Bochu Wang Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqingChina Southwest Hospital/Southwest Eye Hospital Third Military Medical University(Army Medical University)ChongqingChina School of Biology and Engineering/School of Basic medical Sciences Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and *** various studies and reviews have described developments and advancements in brain organoids,few studies have comprehensively summarized and analyzed the global trends in this area of *** identify and further facilitate the development of cerebral organoids,we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 ***,annual publications,countries/regions,organizations,journals,authors,co-citations,and keywords relating to brain organoids were *** hotspots in this field were also systematically ***,current applications for brain organoids in neuroscience,including human neural development,neural disorders,infectious diseases,regenerative medicine,drug discovery,and toxicity assessment studies,are comprehensively *** that end,several considerations regarding the current challenges in brain organoid research and future strategies to advance neuroscience will be presented to further promote their application in neurological research.

关键词： bibliometric analysis brain organoids cerebral organoids global trends neuroscience

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

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Signal Transduction and Targeted therapy 2024年第1期9卷 105-149页

作者： Yumin Wang Jing Hu Shuang Wu Joshua S.Fleishman Yulin Li Yinshi Xu Wailong Zou Jinhua Wang Yukuan Feng Jichao Chen Hongquan Wang Department of Respiratory and Critical Care Medicine Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Department of Pathogen Biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300060PR China Department of Neurology Zhongnan Hospital of Wuhan UniversityWuhan 430000PR China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA Department of Outpatient Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050PR China Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060PR China

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug *** epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and *** studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney *** this review,we first summarize the core molecular mechanisms of ***,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely *** roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in *** the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other *** addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

关键词： diseases epigenetic overcome