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Electroacupuncture activates AMPKa1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics

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Journal of Integrative medicine 2024年第5期22卷 588-599页

作者： Wei-wei Jia Hua-wei Lin Min-guang Yang Ya-ling Dai Yan-yi Ding Wen-shan Xu Si-nuo Wang Ya-jun Cao Sheng-xiang Liang Zhi-fu Wang Cong Chen Wei-lin Liu College of rehabilitation medicine Fujian University of Traditional Chinese Medicine The institute of rehabilitation Industry Fujian University of Traditional Chinese Medicine National-Local Joint Engineering research Center of rehabilitation medicine Technology Fujian University of Traditional Chinese Medicine Traditional Chinese medicine rehabilitation research Center of State Administration of Traditional Chinese medicine Fujian University of Traditional Chinese Medicine

Objective: Studies have shown that electroacupuncture(EA) can alleviate cognitive impairments from Alzheimer's disease(AD) by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial ***: The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKa1-subunit conditional knockout(AMPKa1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition,chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 ***: Both APP/PS1 mice and AMPKa1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferatoractivated receptor-γ coactivator-1a(PGC-1a) pathway increased pathological amyloid-β(Aβ) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1a pathway, specifically by reducing pathological Aβ deposition, normalizing energy metabolism, protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by ***: The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1a pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关键词： Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment Electroacupuncture Hippocampus Mitochondrial dynamics

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Exercise-with-melatonin therapy improves sleep disorder and motor dysfunction in a rat model of ischemic stroke

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Neural Regeneration research 2024年第6期19卷 1336-1343页

作者： Haitao Zhao Tong Zhang Haojie Zhang Yunlei Wang Lingna Cheng School of rehabilitation medicine Capital Medical UniversityBeijingChina Department of Neurological rehabilitation Beijing Bo’ai HospitalChina Rehabilitation Research CenterBeijingChina School of rehabilitation medicine University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina Laboratory of Brain Injury Repair and rehabilitation China Rehabilitation Science InstituteBeijingChina

Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly *** this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 *** treated the rats with exercise and melatonin therapy for 7 consecutive *** showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats,increased delta power values,and regularized delta power ***,exercise-with-melatonin therapy improved coordination,endurance,and grip strength,as well as learning and memory *** the same time,it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy *** findings suggest that exercise-withmelatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.

关键词： exercise glutamate receptor 2 hippocampus ischemic stroke learning melatonin memory sleep disorder synaptic plasticity

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Aza-BODIPY dye with unexpected bromination and high singlet oxygen quantum yield for photoacoustic imaging-guided synergetic photodynamic/photothermal therapy

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Chinese Chemical Letters 2024年第6期35卷 445-450页

作者： Leichen Wang Anqing Mei Na Li Xiaohong Ruan Xu Sun Yu Cai Jinjun Shao Xiaochen Dong Key Laboratory of Flexible Electronics(KLOFE)&institute of Advanced Materials(IAM) Nanjing Tech University(NanjingTech)Nanjing 211800China School of Chemistry&Materials Science Jiangsu Normal UniversityXuzhou 221116China Center for rehabilitation medicine Rehabilitation&Sports Medicine Research Institute of Zhejiang ProvinceDepartment of Rehabilitation MedicineZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014China

Introducing heavy halogen atoms into organic small molecules is a practical strategy for efficient singlet oxygen(^(1)O_(2))***,bromine or iodine atoms are introduced on the aza-borondipyrromethene(aza-BODIPY)core,rather than on the periphery aryl rings for efficient~1O_(2) ***,an aza-BODIPY dye NBDPBr with unexpected bromination on the periphery aryl rings was synthesized for photoacoustic(PA)imaging-guided synergistic photothermal therapy(PTT)and photodynamic therapy(PDT)in tumor *** to unexcepted bromination at the periphery aryl rings,NBDPBr demonstrated an outstanding singlet oxygen quantum yield(Φ_(Δ))of 66% which was superior to similar brominated photosensitizers previously *** encapsulation with amphiphilic polymer F-127,hydrophilic NBDPBr nanoparticles(NPs)were fabricated and exhibited an excellent photothermal conversion efficiency(η)of 43.0% under 660 nm *** vivo PA imaging results demonstrated that NBDPBr NPs could specifically accumulate at tumor sites and realized the maximum tumor retention at 7 h *** the in vitro and in vivo results indicated the significant potence of NBDPBr with unexpected bis-bromination for PA imaging-guided synergetic PDT/PTT.

关键词： Unexpected bromination Aza-BODIPY Photodynamic therapy Photothermal therapy Synergetic therapy

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Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li Department of rehabilitation medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

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Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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Neural Regeneration research 2024年第7期19卷 1584-1592页

作者： Jong Mi Park Masoud Rahmati Sang Chul Lee Jae Il Shin Yong Wook Kim Department and research institute of rehabilitation medicine Yonsei University College of MedicineSeoulSouth Korea Department of Physical Education and Sport Sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran Department of Pediatrics Yonsei University College of MedicineSeoulSouth Korea

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease *** cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s *** stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of *** performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal *** searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,*** study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control *** use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the *** with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational *** the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a

关键词： animal animal experimentation mesenchymal stem cells models Parkinson’s disease stem cell transplantation

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Delphi study for developing a checklist of adverse events associated with acupotomy

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Journal of Integrative medicine 2024年第5期22卷 579-587页

作者： Hyungsun Jun Haebeom Lee Sang-Hoon Yoon Chan-Young Kwon Damin Jeon Jun-Hwan Lee Jungtae Leem Department of Diagnostics College of Korean Medicine Wonkwang University 7Days Inc. Chung-Yeon Korean medicine Clinic Department of Oriental Neuropsychiatry Dong-Eui University College of Korean Medicine Chonnam National University Hwasun Hospital KM Science research Division Korea Institute of Oriental Medicine Department of Korean Convergence Medical Science KIOM School University of Science & Technology (UST) Department of Physical medicine and rehabilitation Spaulding Rehabilitation Hospital Harvard Medical School research Center of Traditional Korean medicine College of Korean Medicine Wonkwang University

Background: Acupotomy, a more invasive procedure than acupuncture, involves the use of a thicker needle with an integrated knife at the tip, necessitating safety research. We aimed to define relevant adverse events(AEs) and create a standardized form of the ACUPOtomy-related AEs CHECKlist(ACUPOCHECK).Methods: Before conducting the Delphi process, a systematic review and pilot prospective study were conducted to gather information on previously reported AEs. Using these data, pilot versions of the ACUPOCHECK and Delphi questionnaires were developed. The Delphi questionnaire involved selecting types of AE for inclusion, establishing separate criteria for acupotomy-related AEs, and achieving a consensus on AE assessment. Thirteen Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi round. Consensus was considered to have been reached if the critical value for the content validity ratio met or exceeded ***: The final ACUPOCHECK was developed using four rounds of the Delphi method and one face-toface consensus meeting. It included 12 local AEs(pain, hemorrhage, bruise, hematoma, edema, pruritus,rash, infection, nerve damage, dysesthesia, movement impairment, and pneumothorax) and 14 systemic AEs(disease aggravation, needle fatigue, sleepiness, procedural nausea, procedural vomiting, procedural headache, procedural dizziness, sweating, procedural shock, syncope, dyspnea, procedural pain, sleep disorder, and postprocedural infection). Separate criteria were established for pain, hemorrhage and bruising: pain was defined as pain that occurrs during daily activities and persists for longer than 72 h,hemorrhage as bleeding that continues for ≥ 3 min despite pressure application, and bruising as having a bruise with a diameter of ≥ 3 cm. Open-ended descriptions were allowed for AEs not covered by the checklist, and severity and causality were assessed using the Common Terminology Criteria for Adverse Events and modif

关键词： Acupotomy Delphi technique Patient safety Safety management Adverse event

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Immune consequences of exercise in hypoxia:A narrative review

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Journal of Sport and Health Science 2024年第3期13卷 297-310,I0002页

作者： Johannes Burtscher Qadar Pasha Neha Chanana Gregoire P.Millet Martin Burtscher Barbara Strasser institute of Sport Sciences University of LausanneLausanne 1015Switzerland institute of Hypoxia research New Delhi 110067India Department of Biochemistry Jamia HamdardNew Delhi 110062India Department of Sport Science University of InnsbruckInnsbruck 6020Austria Faculty of medicine Sigmund Freud Private UniversityVienna 1020Austria Ludwig Boltzmann institute for rehabilitation research Vienna 1100Austria

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual ***,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to *** combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly ***,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune *** review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional ***,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune *** review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system *** acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

关键词： Altitude Exercise Hypoxia Immune response Training

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Single transmembrane GPCR modulating proteins:neither single nor simple

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Protein & Cell 2024年第6期15卷 395-402页

作者： Meng Wang Jianjun Lyu Chao Zhang Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Hubei Topgene research institute of Hubei Topgene Biotechnology Co. LtdEast Lake High-Tech Development ZoneWuhan 430205China Fundamental research Center Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji UniversityShanghai 200092China

The discovery of G-protein coupled receptor(GPCR)accessory proteins has fundamentally redefined the pharmacological concept of GPCR signaling,demonstrating a more complex molecular basis for receptor specificity on the plasma membrane and impressionable downstream intracellular *** accessory proteins not only contribute to the proper folding and trafficking of receptors but also exhibit selectable receptor preferences.

关键词： specificity GPCR neither

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The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases

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Protein & Cell 2024年第9期15卷 633-641页

作者： Zhuoqun Liu Yuchen Xiao Jianjun Lyu Duohui Jing Liu Liu Yanbin Fu Wenxin Niu Lingjing Jin Chao Zhang Fundamental research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghai 201619China Hubei Topgene research institute of Hubei Topgene Biotechnology Co. Ltd.East Lake High-Tech Development ZoneWuhan 430205China Shanghai institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Yuhui Pharmaceutical Technology(Group)Co. Ltd.and Shanghai Ruishen Technology Development Co.Ltd.Shanghai 201203China Shanghai Cancer institute Department of Biliary-Pancreatic SurgeryRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China

As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic malignancies and multiple solid *** evidence has expanded the medical application of CAR-T therapy for the treatment of many other human diseases beyond *** this article,we discuss the principle of CAR-T and enumerate the current application and limitation in ***,we provide a comprehensive perspective of current advance and future directions of CAR-T in treating multiple non-tumoral diseases.

关键词： diseases expanded treatment

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PD-L1-driven efficient enrichment and elimination of circulating cancer cells by magnetic MoSe_(2) nanosheet

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Nano research 2024年第5期17卷 4350-4358页

作者： Hongjie Huang Binhua Zou Shanlin Zhu Xingchen Zhang Jiale Huang Jinlin Wang Xiaoling Li Tianfeng Chen The Sixth Affiliated Hospital Jinan UniversityDongguan 523566China Department of Chemistry Institute of Food Safety and NutritionJinan UniversityGuangzhou 510632China Department of rehabilitation medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Pulmonary and Critical Care medicine Guangzhou Institute of Respiratory HealthNational Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineState Key Laboratory of Respiratory DiseasesThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer *** presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer ***,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing *** summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.

关键词： circulating tumor cells selenide photothermal therapy(PTT) natural killer(NK)cell immunotherapy

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