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Mitochondrial sensitive probe with aggregation-induced emission characteristics for early brain diagnosis of Parkinson’s disease

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Aggregate 2024年第1期5卷 216-227页

作者： Liwen Huang Yutong Zhou Di Jiao Jing Ren Yilin Qi Heping Wang Yang Shi Dan Ding Xue Xue State Key laboratory of Medicinal Chemical Biology College of PharmacyNankai UniversityTianjinP.R.China State Key laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of Educationand College of Life SciencesNankai UniversityTianjinP.R.China

The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our *** a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of ***,the method for detecting mitochondrial abnormalities-associated early PD has not been fully *** herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative *** probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design *** research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative *** intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high *** together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.

关键词： aggregation-induced emission early diagnosis Parkinson’s disease

Structure,ligands,and roles of GPR126/ADGRG6 in the development and diseases

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Genes & diseases 2024年第1期11卷 294-305页

作者： Qi Li Anran Huo Mengqi Li Jiali Wang Qiao Yin Lumiao Chen Xin Chu Yuan Qin Yuwan Qi Yang Li Hengxiang Cui Qifei Cong Institute of Neuroscience and Jiangsu Key laboratory of Neuropsychiatric diseases Soochow UniversitySuzhouJiangsu215123China Department of Neurology and Clinical Research Center of Neurological disease The Second Affliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Department of Nephrology The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Department of Emergency Center The Second Affiliated Hospital of Nantong UniversityNantongJiangsu226001China Department of Neurology Huzhou Central HospitalThe Affiliated Huzhou HospitalZhejiang University School of MedicineHuzhouZhejiang 313000China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Key laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China

Adhesion G protein-coupled receptors(aGPCRs)are the second largest diverse group within the GPCR superfamily,which play critical roles in many physiological and patho-logical processes through cell-cell and cell-extracellular matrix *** adhesion GPCR Adgrg6,also known as GPR126,is one of the better-characterized ***126 was previously found to have critical developmental roles in Schwann cell maturation and its mediated myelination in the peripheral nervous system in both zebrafish and *** studies have extended our understanding of GPR126-mediated roles during develop-ment and in human *** this review,we highlighted these recent advances in GPR126 in expression profile,molecular structure,ligand-receptor interactions,and associated physiological and pathological functions in development and diseases.

关键词： Adhesion G protein-coupled receptor Function GPR126/Adgrg6 Ligand Structure

Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research Peking University100871 BeijingChina Key laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina Key laboratory of Animal Models and Human disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on Drug Dependence and Beijing Key laboratory of Drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

Pain perception enhancement in consecutive secondeye phacoemulsification cataract surgeries under topical anesthesia

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1510-1518页

作者： Jia-Wei Luo Yan-Hua Chen Jian-Feng Yu Yi-Xun Chen Min Ji Huai-Jin Guan Eye Institute Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001Jiangsu ProvinceChina Nantong Center for disease Control and Prevention Nantong 226001Jiangsu ProvinceChina

Cataract is the main cause of visual impairment and blindness worldwide while the only effective cure for cataract is still *** phacoemulsification under topical anesthesia has been the routine procedure for cataract ***,patients often grumbled that they felt more painful during the second-eye surgery compared to the first-eye *** intraoperative pain experience has negative influence on satisfaction and willingness for second-eye cataract surgery of patients with bilateral *** ocular pain is a complicated process induced by the nociceptors activation in the peripheral nervous ***,neuropsychological,and pharmacological factors work together in the enhancement of intraoperative *** published literatures have focused on the pain enhancement during the secondeye phacoemulsification *** this review,we searched PubMed database for articles associated with pain perception differences between consecutive cataract surgeries published up to Feb.1,*** summarized the recent research progress in mechanisms and interventions for pain perception enhancement in consecutive secondeye phacoemulsification cataract *** review aimed to provide novel insights into strategies for improving patients’intraoperative experience in second-eye cataract surgeries.

关键词： ocular pain cataract surgery topical anesthesia intraoperative experience second-eye phacoemulsification

Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease

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Chinese Journal of Traumatology 2024年第3期27卷 125-133页

作者： Yan Zhao Yuan-Guo Zhou Jiang-Fan Chen Department of Army Occupational disease State Key Laboratory of TraumaBurns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical University.Chongqing400042China The Molecular Neuropharmacology laboratory and the Eye-Brain Research Center The State Key Laboratory of OphthalmologyOptometry and Vision ScienceWenzhou Medical UniversityWenzhou325035Zhejiang ProvinceChina Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou325035Zhejiang ProvinceChina

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A *** adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)*** approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving *** this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive *** further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of ***,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease ***,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

关键词： Receptor,Adenosine A2A Adenosine A2 receptor antagonists Parkinson's disease Brain injuries,traumatic

Research advances in the function and anti-aging effects of nicotinamide mononucleotide

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第9期25卷 723-735页

作者： Min WANG Yuan CAO Yun LI Lu WANG Yuyan LIU Zihui DENG Lianrong ZHU Hongjun KANG Chinese PLA Medical School Beijing100853China Department of Critical Care Medicine the First Medical CentreChinese PLA General HospitalBeijing100853China Department of Emergency The Second Hospital of Hebei Medical UniversityShijiazhuang050004China Department of Biochemistry Chinese PLA Medical SchoolBeijing100853China Department of Clinical Nutrition the First Medical CentreChinese PLA General HospitalBeijing100853China Nephrology Institute of the Chinese People’s Liberation Army State Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchDepartment of Nephrologythe First Medical CenterChinese PLA General HospitalBeijing100853China

aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary *** these concerns is an imperative task,with the aims of postponing the aging process and finding effective treatments for age-related degenerative *** investigations have highlighted the significant roles of nicotinamide adenine dinucleotide(NAD+)in the realm of *** has been empirically evidenced that supplementation with nicotinamide mononucleotide(NMN)can elevate NAD+levels in the body,thereby ameliorating certain age-related degenerative *** principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism,inhibition of cell apoptosis,modulation of immune function,and preservation of genomic stability,which collectively contribute to the deferral of the aging *** paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN,elucidates the inherent limitations of current research,and proposes novel avenues for anti-aging investigations.

关键词： Nicotinamide mononucleotide(NMN) Anti-aging Energy metabolism Apoptosis DNA repair

Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network

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Genes & diseases 2024年第3期11卷 248-263页

作者： Shuo Li Tiande Zou Jun Chen Jiaming Li Jinming You Jiangxi Province Key laboratory of Animal Nutrition Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Fibroblast growth factor 21(FGF21)was originally identified as an important meta-bolic regulator which plays a crucial physiological role in regulating a variety of metabolic pa-rameters through the metabolic *** a novel multifunctional endocrine growth factor,the role of FGF21 in the metabolic network warrants extensive *** insight was obtained from the observation that the FGF21-dependent mechanism that regulates lipid metabolism,glycogen transformation,and biological effectiveness occurs through the coordi-nated participation of the liver,adipose tissue,central nervous system,and sympathetic *** review focuses on the role of FGF21-uncoupling protein 1(UCP1)signaling in lipid metabolism and how FGF21 alleviates non-alcoholic fatty liver disease(NAFLD).Additionally,this review reveals the mechanism by which FGF21 governs glucolipid *** research on the role of FGF21 in the metabolic network has mostly focused on the crucial pathway of glucolipid ***21 has been shown to have multiple regulatory roles in the metabolic *** an adequate understanding of the concrete regulatory path-ways of FGF21 in the metabolic network has not been attained,this review sheds new light on the metabolic mechanisms of FGF21,explores how FGF21 engages different tissues and organs,and lays a theoretical foundation for future in-depth research on FGF21-targeted treatment of metabolic diseases.

关键词： Adipose FGF21 Insulin homeostasis Lipid metabolism Liver Metabolicnetwork

A Global Decomposition Analysis of the Effect of Population aging on Disability-Adjusted Life Years Associated with Cardiovascular disease—204 Countries and Territories,1990-2021

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China CDC weekly 2024年第39期6卷 1004-1010,I0001-I0006页

作者： Na Sun Xiaocan Jia Xuezhong Shi Feng Jiang Chaojun Yang Yongli Yang Department of Computer and Health Statistics College of Public HealthZhengzhou UniversityZhengzhou CityHenan ProvinceChina Department of disease Prevention and Control Zhengzhou University HospitalZhengzhou CityHenan ProvinceChina

What is already known about this topic?The influence of population aging on the disabilityadjusted life years(DALYs)associated with cardiovascular disease(CVD)is acknowledged,yet the magnitude of this impact remains *** is added by this report?This research quantified the influence of population aging on CVD DALYs from 1990 to 2021 through decomposition *** findings revealed that the proportion of DALYs attributable to aging varied widely,ranging from‒77.0%to 148.9%across 204 *** was significant variation in the attributed DALY proportions among different countries or territories and types of *** heart disease and stroke emerged as the leading contributors to DALYs influenced by *** are the implications for public health practice?Globally,the association of population aging with increased CVD DALYs underscores the critical need for enhancing health systems to cater to the needs of older *** the burden of CVD DALYs linked to demographic aging can be achieved by investing in resources and adjusting fertility policies.

关键词： aging attributed critical

Astrocyte reactivity in related brain regions in a mouse model of MPTP-induced Parkinson's disease

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Neural Regeneration Research 2009年第2期4卷 129-134页

作者： Zhijun Zhang Chunlin Xia Yulin Dong Guangming Lü Juan Liu Lin Ding Hengjian Ni Department of Human Anatomy Institute of Neurobiology Jiangsu Province Key Laboratory of Neural Regeneration Medical School of Nantong University Nantong 226001 Jiangsu Province China Lab of aging and nervous disease & Cytoneurobiology Unit Soochow University Suzhou 215123 Jiangsu Province China

BACKGROUND： Severe injury to dopaminergic neuronal cell bodies and their axon terminals in the substantia nigra pars compacta （SNC） has been observed in both Parkinson＇s disease （PD） patients or in 1-methy-4-phenyl-1,2,3,6-tetrahydropyrindine（MPTP）-induced PD animal models, but only slight injury occurs in the adjacent ventral tegmentat area （VTA）. The mechanisms underlying this selective injury remain poorly understood. OBJECTIVE： To comparatively observe astrocyte reactivity in the SNC, caudate putamen （CPu）, VTA, and frontal association cortex （FrA）. DESIGN, TIME AND SETTING： A cellular and molecular biology, randomized, controlled experiment was performed at the Institute of Neurobiology, Department of Human Anatomy, Medical School of Nantong University, between December 2006 and September 2008. MATERIALS： A total of 80 healthy adult male C57BL/6 mice were included in this study. MPTP was purchased from Sigma, USA. METHODS： Mice were randomly divided into a model group （n = 64） and a sham-operated group （n = 16）. PD was induced in the mice from the model group by intraperitoneal injection of 20 mg/kg MPTP, once every three hours, for a total of 4 times. MAIN OUTCOME MEASURES： Tyrosine hydroxylase （TH）-immunoreactive neurons and glial fibrillary acidic protein （GFAP）-immunoreactive astrocytes were examined by dual immunofluorescence labeling. GFAP-immunoreactive astrocytes in the CPu and FrA were determined by immunofluorescent staining. GFAP mRNA expression in the SNC, CPu, VTA, and FrA was detected using real-time polymerase chain reaction. TH protein levels in the TH-immunoreactive axon terminals of the CPu and FrA were detected by Western blotting. RESULTS： Numbers of TH-immunoreactive neurons in the SNC, and TH protein level in the CPu, markedly decreased （by approximately 68%） 1 day after MPTP injection, and gradually increased at 3 days. Simultaneously, astrocyte reactivity was strengthened, in particular at 7 days. However, after MPTP injection,

关键词： Parkinson's disease 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindine dopaminergic neuron astrocyte mouse