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Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

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Neural Regeneration Research 2024年第9期19卷 2057-2067页

作者： Bismark Gatica-Garcia Michael J.Bannon Irma Alicia Martínez-Dávila Luis O.Soto-Rojas David Reyes-Corona Lourdes Escobedo Minerva Maldonado-Berny ME Gutierrez-Castillo Armando J.Espadas-Alvarez Manuel A.Fernandez-Parrilla Juan U.Mascotte-Cruz CP Rodríguez-Oviedo Irais E.Valenzuela-Arzeta claudia luna-herrera Francisco E.Lopez-Salas Jaime Santoyo-Salazar Daniel Martinez-Fong Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Laboratorio de Patogénesis Molecular Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Red de Medicina para la Educación y Desarrollo y la Investigación Científica de Iztacala(Red MEDICI) Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Nanoparticle Therapy Institute AguascalientesMéxico Departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Escuela Nacional de Medicina y Homeopatía Instituto Politécnico NacionalCiudad de MéxicoMéxico Departamento de Fisiología Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCiudad de MéxicoMéxico Departamento de Biología Molecular y Biotecnología Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico Departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa de Nanociencias y Nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate t

关键词： A1 astrocytes A2 astrocytes gene therapy microglia motor deficits nanoparticles neurodegeneration neuroinflammation senescence α-synuclein aggregates

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Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration

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Neural Regeneration Research 2022年第4期17卷 854-866页

作者： Manuel A.Fernandez-Parrilla David Reyes-Corona Yazmin M.Flores-Martinez Rasajna Nadella Michael J.Bannon Lourdes Escobedo Minerva Maldonado-Berny Jaime Santoyo-Salazar Luis O.Soto-Rojas claudia luna-herrera Jose Ayala-Davila Juan A.Gonzalez-Barrios Gonzalo Flores Maria E.Gutierrez-Castillo Armando JEspadas-Alvarez Irma A.Martínez-Dávila Porfirio Nava Daniel Martinez-Fong Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa Institucional de Biomedicina Molecular Escuela Nacional de Medicina y HomeopatíaInstituto Politécnico NacionalCiudad de MéxicoMéxico Department of Biosciences IIIT-SrikakulamRajiv Gandhi University of Knowledge Technologies(RGUKT)Andhra PradeshIndia Department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de MéxicoTlalnepantla de BazEdo.de MéxicoMéxico Departamento de Fisiología Escuela Nacional de Ciencias BiológicasCiudad de MéxicoMéxico Laboratorio de Medicina Genómica Hospital Regional“1°de Octubre”ISSSTECiudad de MéxicoMéxico Laboratorio de Neuropsiquiatría Instituto de FisiologíaBenemérita Universidad Autónoma de PueblaPueblaPueblaMéxico Departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Programa de Nanociencias y nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system,a hallmark in Parkinson's disease.The human cerebral dopamine neurotrophic factor(h CDNF)has recently emerged as a strong candidate for Parkinson's disease therapy.This study shows that h CDNF expression in dopamine neurons using the neurotensinpolyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological,biochemical,and behavioral alterations.Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the h CDNF gene,ranging in size from 20 to 150 nm,enabled the expression of a secretable h CDNF in vitro.Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable h CDNF in dopamine neurons,whose levels remained constant throughout the study in the substantia nigra compacta and striatum.Compared with the lesioned group,tyrosine hydroxylase-positive(TH^(+))nigral cell population and TH+fiber density rose in the substantia nigra compacta and striatum after h CDNF transfection.An increase inβIII-tubulin and growth-associated protein 43 phospho-S41(GAP43 p)followed TH^(+)cell recovery,as well as dopamine and its catabolite levels.Partial reversal(80%)of drugactivated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved.Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects.These findings support the potential of nanoparticle-mediated h CDNF gene delivery to develop a disease-modifying treatment against Parkinson's disease.The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use(authorization No.162-15)on June 9,2019.

关键词： axonal growth brain-derived neurotrophic factor gene delivery nanoparticles neuritogenesis neuronal cytoskeleton neuroregeneration neurorestoration neurotrophic therapy Parkinson's disease reinnervation substantia nigra

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“If Somebody Needed Help, I Went Over”: Social Capital and Therapeutic Communities of Older Adult Farmers in British Columbia Floods

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International Journal of Disaster Risk Science 2024年第2期15卷 290-301页

作者： Kyle Breen Siyu Ru luna Vandeweghe Jenna Chiu Lindsay Heyland Haorui Wu School of Social Work Dalhousie University

Older adults in disaster contexts are often thought of as a passive, vulnerable population that lacks agency and capacities to cope in the aftermath. However, it can be argued that older adults may have underrecognized strengths that can be utilized pre-, peri-, and post-disaster. One of these strengths is older adults' unique social capital that stems from long-standing connections with other members of their respective communities. Using data from in-depth, semistructured interviews with farmers in British Columbia 3–11 months after the 2021 floods, this research explored the experiences of older adult farmers' recovery. The farmers discussed how they leveraged their social capital to aid in their recovery efforts from the flood event. By using their bonding social capital, older adult farmers transformed their existing, deep-rooted connections into post-disaster assistance. This, in turn, generated the idea of the therapeutic community, helping community members cope in the aftermath. This research indicated the need to further examine how older adults in disaster settings can be viewed as assets with community knowledge and skills as opposed to solely as a vulnerable population.

关键词： British Columbia Flood disaster Older adults Qualitative research Social capital Therapeutic community

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Design of Ca-type todorokite catalysts with highly active for the selective reduction of NO_(x) by NH_(3) at low temperatures

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Journal of Environmental Sciences 2024年第4期138卷 697-708页

作者： Chuang Chang Zidi Yan Chunlei Zhang Yanshuang Zhang Miao Jiang luna Ruan Min Xiao Yunbo Yu Hong He School of Rare Earths University of Science and Technology of ChinaHefei 230026China Ganjiang Innovation Academy Chinese Academy of SciencesGanzhou 341000China State Key Joint Laboratory of Environment Simulation and Pollution Control Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Ca-type todorokite catalysts were designed and prepared by a simple redox method and applied to the selective reduction of NO_(x) by NH_(3)(NH_(3)-SCR)for the first time.Compared with the Na-type manjiroite prepared by the same method,the todorokite catalysts with different Mn/Ca ratios showed greatly improved catalytic activity for NO_(x) reduction.Among them,Mn8Ca4 catalyst exhibited the best NH_(3)-SCR performance,achieving 90%NO_(x) conversion within temperature range of 70-275℃ and having a high sulphur resistance.Compared to the Na-type manjiroite sample,Ca-type todorokite catalysts possessed an increased size of tunnel,resulting in a larger specific surface area.As increased the amounts of Ca doping,the Na content in Ca-type todorokite catalysts significantly decreased,providing larger amounts of Bronsted acid sites for NH_(3) adsorption to produce NH_(4)^(+).The NH_(4)^(+)species were highly active for reaction with NO+O_(2),playing a determining role in NH_(3)-SCR process at low temperatures.Meanwhile,larger amounts of surface adsorbed oxygen contained over the Ca-doping samples than that over Na-type manjiroite,promoting the oxidation of NO and fast SCR processes.Over the Ca-type todorokite catalysts,furthermore,nitrates produced during the flow of NO+O_(2),were more active for reaction with NH_(3) than that over Na-type manjiroite,benefiting the occurrence of NH_(3)-SCR process.This study provides novel insights into the design of NH_(3)-SCR catalysts with high performance.

关键词： NO_(x) NH_(3)-SCR Mn-based oxides Ca-type todorokite Bronsted acid sites

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Sex differences in Alzheimer's disease:an urgent research venue to follow

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Neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： Raquel Jiménez-herrera Ana Contreras Juan D.Navarro-López Lydia Jiménez-Díaz Neurophysiology&Behavior Lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the year 2050.Among the various forms of dementia.Alzheimer's disease(AD)stands out as the predominant and most prevalent.

关键词： Alzheimer predominant estimates

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Contrast-enhanced guided endoscopic ultrasound procedures

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World Journal of Gastroenterology 2024年第17期30卷 2311-2320页

作者： Marcel Ioan Gheorghiu Andrada Seicean Cristina Pojoga claudia Hagiu Radu Seicean Zeno Sparchez Department of Gastroenterology “Prof.Dr.Octavian Fodor”Regional Institute of Gastroenterology and Hepatology"Iuliu Hatieganu"University of Medicine and PharmacyCluj-Napoca 400162ClujRomania Department of Clinical Psychology and Psychotherapy International Institute for Advanced Study of Psychotherapy and Applied Mental HealthBabeș-Bolyai UniversityCluj-Napoca 400375ClujRomania The First Surgical Clinic "Iuliu Hatieganu"University of Medicine and PharmacyCluj Napoca 400006ClujRomania

Contrast-enhanced endoscopic ultrasound(CH-EUS)can overcome the limi-tations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours.Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions,further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS.This review details the knowledge based on the available data on contrast-guided procedures.The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions,which occur in select cases.Additionally,the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage,and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented.Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours,in which case CH-EUS can be used to reveal the incomplete tumour destruction.

关键词： Endosonography Contrast-enhanced endoscopic ultrasound Tissue acquisition Fine needle aspiration Fine needle biopsy Drainage Pancreatic fluid collections Biopsy Pancreas

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The prolactin receptor(PRLR)gene is linked to and associated with the comorbidity of depression and type 2 diabetes in Italian families

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Genes & Diseases 2024年第3期11卷 15-17页

作者： Mutaz Amin Rongling Wu Teodor T.Postolache claudia Gragnoli INSERM US14-OrphanetParis 75014France University of Paris Paris 75013France Department of Biochemistryand Molecular Biology Faculty of MedicineAl-Neelain UniversityKhartoum 11121Sudan Department of Public Health Sciences Penn State College of MedicineHersheyPA 17033USA Department of Statistics Penn State College of MedicineHersheyPA 17033USA Mood and Anxiety Program Department of PsychiatryUniversity of Maryland School of MedicineBaltimoreMD 21201USA Rocky Mountain Mental Illness Research Education and Clinical Center(MIRECC) Veterans Integrated Service Network(VISN)19Military and Veteran Microbiome:Consortium for Research and Education(MVM-CoRE)DenverCO80246USA Mental illness Research Education and Clinical Center(MIRECC) Veterans Integrated Service Network(VISN)5VA Capitol Health Care NetworkBaltimoreMD 21090USA Division of Endocrinology Department of MedicineCreighton University School of MedicineOmahaNE 68124USA Molecular Biology Laboratory Bios Biotech Multi-Diagnostic Health CenterRome 00197Italy

Major depressive disorder(MDD)and type 2 diabetes(T2D)are two common complex multifactorial disorders that share several genetic and environmental risk factors such as hypercortisolism and related genes'riskvariants within the stress response and the neuroendocrine hypothalamicpituitary axis.Under stress,the pituitary gland releases prolactin(PRL),whose effects are pleiotropic and include mood control and insulin secretion from the beta cells.1 Variations in the prolactin receptor(PRLR)gene are associated in rodent models with stress level,depressionlike behavior,2 and hepatic insulin sensitivity3 and in humans with maternal glucose homeostasis and gestational diabetes.

关键词： diabetes prolactin pituitary

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Quick and easy assessment of sarcopenia in cirrhosis: Can ultrasound be the solution?

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World Journal of Gastroenterology 2024年第17期30卷 2287-2293页

作者： Francesca Campani Tancredi Vincenzo Li Cavoli Umberto Arena Fabio Marra Erica Nicola Lynch claudia Campani Department of Health Science University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Internal Medicine and Liver Unit University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence 50134Italy Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”University of FlorenceFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy

Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.

关键词： Sarcopenia Ultrasound Cirrhosis Hepatocellular carcinoma Computed tomography

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超高酸原油中石油酸分子组成表征与腐蚀性预测

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石油学报（石油加工） 2024年第3期40卷 833-840页

作者：牛鲁娜中石化安全工程研究院有限公司化学品安全国家重点实验室山东青岛266000

采用傅里叶变换离子回旋共振质谱法对国内某超高酸原油及其馏分油中的石油酸分子组成进行表征,研究Q345R、1Cr5Mo、304L和316L 4种典型炼油装置用材在不同酸值(Total acid number,TAN)油品中的静态腐蚀行为,并构建高温酸腐蚀预测模型。... 详细信息

采用傅里叶变换离子回旋共振质谱法对国内某超高酸原油及其馏分油中的石油酸分子组成进行表征,研究Q345R、1Cr5Mo、304L和316L 4种典型炼油装置用材在不同酸值(Total acid number,TAN)油品中的静态腐蚀行为,并构建高温酸腐蚀预测模型。结果表明,TAN为10.403 mg KOH/g、含2个氧原子的O2类石油羧酸是石油酸的主要成分,其中二环、三环环烷酸和单环芳香羧酸含量相对较高。168 h静态挂片腐蚀实验结果表明,4种材质腐蚀速率均随温度升高而增加,高于280℃后增加趋势逐渐变缓。不同材质微观腐蚀形貌存在显著差异:Q345R整体呈现均匀腐蚀形态;1Cr5Mo表面形成密集蚀坑;304L表面分布少量浅表性腐蚀区;316L仍可见金属光泽。根据腐蚀速率结果,考虑脂肪酸、环烷酸和芳香酸与金属的结合作用,将石油酸分子组成作为腐蚀预测模型的修正项,采用Levenberg-Marquardt(LM)算法拟合模型参数,模型相关系数R 2大于0.950,均方根误差RMSE小于0.089,可实现超高酸原油腐蚀性的早期预测,为指导超高酸原油加工装置合理选材、制定检维修计划提供支持。

关键词：腐蚀环烷酸傅里叶变换离子回旋共振质谱超高酸原油预测

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A systematic review of salivary biomarkers in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2613-2625页

作者： Maria Ilenia De Bartolo Daniele Belvisi Romina Mancinelli Matteo Costanzo claudia Caturano Giorgio Leodori Alfredo Berardelli Giovanni Fabbrini Giorgio Vivacqua IRCCS Neuromed PozzilliItaly Department of Human Neurosciences Sapienza University of RomeRomeItaly Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly Department of Experimental Morphology and Microscopy-Integrated Research Center(PRAAB)-Campus Biomedico University of Rome RomeItaly

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,a

关键词： alpha-synuclein amyloid-beta autophagy DJ-1 neurodegeneration neuroinflammation Parkinson's disease salivary biomarkers tau

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