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High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

Nano-Micro Letters 2025年第2期17卷 187-203页

作者： Si Chen Fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin Yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China shanghai frontiers Science center of nanocatalytic medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： nanocatalytic medicine Single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang Department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National center for Neurological Disorders ShanghaiChina shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration ShanghaiChina State Key Laboratory of Medical Neurobiology and MOE frontiers center for Brain Science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

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nanocatalytic bacteria disintegration reverses immunosuppression of colorectal cancer

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National Science Review 2022年第11期9卷 208-222页

作者： Han Jiang Yuedong Guo Zhiguo Yu Ping Hu Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructures Shanghai Institute of Ceramics Chinese Academy of SciencesResearch Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease Chinese Academy of Medical Sciences center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences shanghai Tenth People's Hospital Shanghai Frontiers Science Center of Nanocatalytic Medicine School of Medicine Tongji University

Tumor-associated bacteria(TAB) play a critically important role in regulating the microenvironment of a tumor, which consequently greatly deteriorates the therapeutic effects by chemo-and radiotherapy deactivation and, more considerably, leads to substantial immunosuppression. On the contrary, herein we propose a nanocatalytic tumor-immunotherapeutic modality based on the bacteria disintegration by bacteria-specific oxidative damage under magnetic hyperthermia for highly effective immune response activation-promoted tumor regression. A monodispersed and superparamagnetic nanocatalytic medicine modified by arginyl-glycyl-aspartic acid(RGD) and(3-carboxypropyl)triphenylphosphonium bromide(TPP), named as MNP-RGD-TPP herein, has been synthesized, which features selective accumulation at the TAB by the electrostatic affinity, enabling effective TAB disintegration by the nanocatalytic Fenton reaction producing abundant cytotoxic hydroxyl radicals in situ under alternating magnetic field-induced hyperthermia. More importantly, the lipopolysaccharide has been metabolically secreted from the destructed TAB as pathogen-associated molecular patterns(PAMPs) to M1-polarize tumor-associated macrophages(TAMs) and promote the maturation of dendritic cells(DCs) for innate immuno-response activation of TAMs, followed by cytotoxic T lymphocytes awakening under the PAMPs presentation by the mature DCs against tumor cells. The integrated innate and adaptive immunity activations based on this TAB-promoted nanocatalytic immunomedicine, instead of magnetic heating-induced hyperthermia or the released Fe2+/Fe3+Fenton agent, has been found to achieve excellent therapeutic efficacy in an orthotopic colorectal cancer model, demonstrating the great potential of such an integrated immunity strategy in clinical tumor immunotherapy.

关键词： tumor-associated bacteria nanocatalytic bacteria disintegration immunosuppressive reversal colorectal cancer immunotherapy

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Neural stem cell-derived extracellular vesicles mitigate Alzheimer’s disease-like phenotypes in a preclinical mouse model

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3232-3235页

作者： Ge Gao Congcong Li Yizhao Ma Zhanping Liang Yun Li Xiangyu Li Shengyang Fu Yi Wang Xiaohuan Xia Jialin C.Zheng center for Translational Neurodegeneration and Regenerative Therapy Tongji Hospital affiliated to Tongji University School of MedicineShanghai 200065China Translational Research center Shanghai Yangzhi Rehabilitation Hospital affiliated to Tongji University School of MedicineShanghai 201613China shanghai frontiers Science center of nanocatalytic medicine Tongji UniversityShanghai 200331China

Dear Editor,Alzheimer’s disease(AD)is the most common neurodegenerative disorder and the No.1 cause of dementia in elderly with no effective treatments.1 The application of stem cell-derived extracellular vesicles(EVs)has emerged as a promising therapeutic strategy for AD.2 EVs are small bilipid layer-enclosed vesicles that display blood-brain barrier(BBB)penetrating ability and similar potency to their parental cells.

关键词： Alzheimer clinical extracellular

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Clinical applications of stem cell-derived exosomes

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Signal Transduction and Targeted Therapy 2024年第2期9卷 621-651页

作者： Fei Tan Xuran Li Zhao Wang Jiaojiao Li Khawar Shahzad Jialin Zheng Department of ORL-HNS Shanghai Fourth People’s Hospitaland School of MedicineTongji UniversityShanghaiChina Plasma medicine and Surgical Implants center Tongji UniversityShanghaiChina The Royal College of Surgeons in Ireland DublinIreland The Royal College of Surgeons of England LondonUK center for Translational Neurodegeneration and Regenerative Therapy Tongji Hospital affiliated to Tongji University School of MedicineShanghaiChina shanghai frontiers Science center of nanocatalytic medicine Tongji UniversityShanghaiChina

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery,it nevertheless comes with inescapable drawbacks that might limit its clinical *** to stem cells,stem cell-derived exosomes possess numerous advantages,such as non-immunogenicity,non-infusion toxicity,easy access,effortless preservation,and freedom from tumorigenic potential and ethical *** can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or *** a thorough search and meticulous dissection of relevant literature from the last five years,we present this comprehensive,up-to-date,specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived *** derived from stem cells(e.g.,embryonic,induced pluripotent,hematopoietic,mesenchymal,neural,and endothelial stem cells)are capable of treating numerous diseases encountered in orthopedic surgery,neurosurgery,plastic surgery,general surgery,cardiothoracic surgery,urology,head and neck surgery,ophthalmology,and obstetrics and *** diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses,and cell-specific molecular signaling *** this review,we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical *** recommend that future research combines wisdoms from surgeons,nanomedicine practitioners,and stem cell researchers in this relevant and intriguing research area.

关键词： viable stem capable

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Toosendanin:upgrade of an old agent in cancer treatment

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Chinese Journal of Natural medicines 2024年第10期22卷 887-899页

作者： LI Shuwei XIONG Qingyi SHEN Yiwen LIN Jiayi ZHANG Lijun WU Ye JIN Jinmei LUAN Xin shanghai frontiers Science center for Chinese medicine Chemical Biology Institute of Interdisciplinary Integrative Medicine Research and Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China

Toosendanin(TSN),a tetracyclic triterpenoid derived from Melia toosendan and ***,demonstrates broad application prospects in cancer *** previously employed as a pesticide,recent studies have revealed its potential therapeutic value in treating various types of *** exerts an anticancer effect via mechanisms including proliferation inhibition,apoptosis induction,migration suppression,and angiogenesis ***,TSN's toxicity,particularly its hepatotoxicity,significantly limits its therapeutic *** review explored the dual nature of TSN,evaluating both its anticancer potential and toxicological risks,emphasizing the importance of balancing these aspects in therapeutic ***,we investigated the incorporation of TSN into novel therapeutic strategies,such as Proteolysis-targeting chimeras(PROTAC)technology and nanotechnology-based drug delivery systems(DDS),which enhance treatment efficacy while mitigating toxicity in normal tissues.

关键词： Toosendanin Cancer therapy Hepatotoxicity PROTAC Nano-delivery systems

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Sustainable utilization of precious Chinese medicines:challenges and the road ahead

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Chinese Journal of Natural medicines 2022年第11期20卷 801-804页

作者： GONG Jiahao LI Haiying XU Jianguang CHEN Hongzhuan GE Guangbo shanghai frontiers Science center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China

Traditional Chinese medicine(TCM)is considered as a unique treasure of Chinese civilization for its profound theoretical system and extensive experience in clinical practice for more than two thousand *** one of the most commonly used folk medicines,Chinese medicines have made indelible contributions to well-being maintenance and disease treatment,as well as the progress of human civilization[1].

关键词： medicines civilization ahead

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A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells

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Signal Transduction and Targeted Therapy 2024年第10期9卷 4564-4578页

作者： Zheyi Lin Bowen Lin Chengwen Hang Renhong Lu Hui Xiong Junyang Liu Siyu Wang Zheng Gong Mingshuai Zhang Desheng Li Guojian Fang Jie Ding Xuling Su Huixin Guo Dan Shi Duanyang Xie Yi Liu Dandan Liang Jian Yang Yi-Han Chen State Key Laboratory of Cardiovascular Diseases Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200120China shanghai Arrhythmia Research center Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200120China Department of Cardiology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200120China shanghai frontiers center of nanocatalytic medicine Shanghai200092China Department of Pathology and Pathophysiology School of MedicineTongji UniversityShanghai200092China Clinical center for Heart Disease Research Tongji UniversityShanghai200092China Department of Cell Biology School of MedicineTongji UniversityShanghai200092China Department of Cardiology The Second Hospital of Shanxi Medical UniversityTaiyuan030001China Research Units of Origin and Regulation of Heart Rhythm Chinese Academy of Medical SciencesShanghai200092China

Cardiac biological pacing(BP)is one of the future directions for bradyarrhythmias ***,cardiac pacemaker cells(PCs)used for cardiac BP are mainly derived from pluripotent stem cells(PSCs).However,the production of high-quality cardiac PCs from PSCs remains a ***,we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of ***,two PC markers,Shox2 and Hcn4,were selected to establish Shox2:EGFP;Hcn4:mCherry mouse PSC reporter ***,by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation,we designed the FSK method that increased the yield of SHOX2^(+);HCN4^(+)cells with typical PC characteristics,which was 12 and 42 folds higher than that of the embryoid body(EB)and the monolayer M10 methods *** addition,the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing(scRNA-seq),which resembled in vivo PCs development,and ZFP503 was verified as a key regulator of cardiac PCs *** PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology,help with the understanding of PCs(patho)physiology,and benefit drug discovery for PC-related diseases as well.

关键词： cardiac generating stepwise

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Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome

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World Journal of Gastroenterology 2022年第38期28卷 5547-5556页

作者： Si-Yue Chen Tong-Yao Wang Chao Zhao Hui-Jing Wang Laboratory of Neuropsychopharmacology College of Fundamental MedicineShanghai University of Medicine&Health ScienceShanghai 201318China Key Laboratory of Medical Molecular Virology School of Basic Medical SciencesShanghai Medical College&National Clinical Research Center for Aging and MedicineHuashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200032China shanghai frontiers Science center of Pathogenic Microbes and Infection Shanghai Frontiers Science CenterShanghai 200032China

The incidence of frailty gradually increases with *** condition places a heavy burden on modern society,of which the aging population is *** is one of the most complicated clinical syndromes;thus,it is difficult to uncover its underlying *** stress(OS)is involved in frailty in multiple *** association between the gut microbiota(GM)and frailty was recently ***,we propose that OS is involved in the association between the GM and the occurrence of frailty *** imbalance between oxidation and antioxidants can eventually lead to frailty,and the GM probably participates in this process through the production of reactive oxygen *** the other hand,OS can disturb the *** dysbiosis consequently induces or exacerbates tissue damage,leading to the occurrence of frailty ***,we discuss the possibility of improving frailty by intervening in the vicious cycle between the imbalance of OS and dysbiosis.

关键词： Oxidative stress Gut microbiota Frail syndrome Traditional Chinese medicine

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Histone modification landscape and the key significance of H3K27me3 in myocardial ischaemia/reperfusion injury

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Science China(Life Sciences) 2023年第6期66卷 1264-1279页

作者： Le Ni Bowen Lin Yanping Zhang Lingjie Hu Jianghua Lin Fengmei Fu Meiting Shen Can Li Lei Chen Jian Yang Dan Shi Yi-Han Chen Department of Cardiology Shanghai East HospitalTongji University School of MedicineShanghai200120China Key Laboratory of Arrhythmias of the Ministry of Education of China Shanghai East HospitalTongji University School of MedicineShanghai200120China Department of Vascular and Cardiology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Jinzhou Medical University Liaoning121000China shanghai frontiers Science center of nanocatalytic medicine Shanghai200092China Department of Pathology and Pathophysiology Tongji University School of MedicineShanghai200092China Research Units of Origin and Regulation of Heart Rhythm Chinese Academy of Medical SciencesShanghai200092China

Histone modifications play crucial roles in the pathogenesis of myocardial ischaemia/reperfusion(I/R)***,a genome-wide map of histone modifications and the underlying epigenetic signatures in myocardial I/R injury have not been ***,we integrated transcriptome and epigenome of histone modifications to characterize epigenetic signatures after I/R ***-specific histone mark alterations were mainly found in H3K27me3-,H3K27ac-,and H3K4me1-marked regions 24 and 48 h after I/*** differentially modified by H3K27ac,H3K4me1 and H3K27me3 were involved in immune response,heart conduction or contraction,cytoskeleton,and angiogenesis.H3K27me3 and its methyltransferase polycomb repressor complex 2(PRC2)were upregulated in myocardial tissues after I/*** selective inhibition of EZH2(the catalytic core of PRC2),the mice manifest improved cardiac function,enhanced angiogenesis,and reduced *** investigations confirmed that EZH2 inhibition regulated H3K27me3 modification of multiple pro-angiogenic genes and ultimately enhanced angiogenic properties in vivo and in *** study delineates a landscape of histone modifications in myocardial I/R injury,and identifies H3K27me3 as a key epigenetic modifier in I/R *** inhibition of H3K27me3 and its methyltransferase might be a potential strategy for myocardial I/R injury intervention.

关键词： histone modification myocardial ischemia/reperfusion EZH2 H3K27me3 angiogenesis

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