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Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang Juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation Base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina department of rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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Passive activity enhances residual control ability in patients with complete spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng Rao Guiyun Song Wei Song Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina department of rehabilitation Evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina department of rehabilitation Engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically *** findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu Emily Choi Michael QJiang Ling Wei department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning Shi Lv Qian Wang Yuzhen Xu department of rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S Y Yau Kwok-Fai So Li Zhang Haining Ou department of rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina department of rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury:state of the art and future perspectives

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Neural Regeneration Research 2025年第11期20卷 3151-3171页

作者： Fatima Aldali Chunchu Deng Mingbo Nie Hong Chen department of rehabilitation Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal *** nerve injury results in movements or sensation impairments,and represents a serious public health *** severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain *** emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and *** stem cells,as large living cells responsive to the environment,secrete various factors and *** latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem *** have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based *** ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical *** review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying ***,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and ***,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.

关键词： clinical trials exosome extracellular vesicles mesenchymal stem cells nerve regeneration peripheral nerve injury pre-clinical experiments

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent rehabilitation Ministry of EducationShanghaiChina department of rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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An Enhanced Lung Cancer Detection Approach Using Dual-Model Deep Learning Technique

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 835-867页

作者： Sumaia Mohamed Elhassan Saad Mohamed Darwish Saleh Mesbah Elkaffas department of Information Technology Institute of Graduate Studies and ResearchAlexandria UniversityAlexandria21526Egypt College of Computing and Information Technology Arab Academy for ScienceTechnology and Maritime TransportAlexandriaP.O.Box 1029Egypt

Lung cancer continues to be a leading cause of cancer-related deaths worldwide,emphasizing the critical need for improved diagnostic *** detection of lung tumors significantly increases the chances of successful treatment and ***,current diagnostic methods often fail to detect tumors at an early stage or to accurately pinpoint their location within the lung ***-model deep learning technologies for lung cancer detection,while beneficial,cannot capture the full range of features present in medical imaging data,leading to incomplete or inaccurate ***,it may not be robust enough to handle the wide variability in medical images due to different imaging conditions,patient anatomy,and tumor *** overcome these disadvantages,dual-model or multi-model approaches can be *** research focuses on enhancing the detection of lung cancer by utilizing a combination of two learning models:a Convolutional Neural Network(CNN)for categorization and the You Only Look Once(YOLOv8)architecture for real-time identification and pinpointing of *** automatically learn to extract hierarchical features from raw image data,capturing patterns such as edges,textures,and complex structures that are crucial for identifying lung ***8 incorporates multiscale feature extraction,enabling the detection of tumors of varying sizes and scales within a single *** is particularly beneficial for identifying small or irregularly shaped tumors that may be challenging to ***,through the utilization of cutting-edge data augmentation methods,such as Deep Convolutional Generative Adversarial Networks(DCGAN),the suggested approach can handle the issue of limited data and boost the models’ability to learn from diverse and comprehensive *** combined method not only improved accuracy and localization but also ensured efficient real-time processing,which is crucial for practical clinical applicati

关键词： Lung cancer detection dual-model deep learning technique data augmentation CNN YOLOv8

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Impact of Pollutant Concentration and Particle Deposition on the Radiative Flow of Casson-Micropolar Fluid between Parallel Plates

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 665-690页

作者： Ghaliah Alhamzi Badr Saad T.Alkahtani Ravi Shanker Dubey Vinutha Kalleshachar Neelima Nizampatnam department of Mathematics and Statistics College of ScienceImam Mohammad Ibn Saud Islamic University(IMSIU)Riyadh11564Saudi Arabia department of Mathematics College of ScienceKing Saud UniversityRiyadh11989Saudi Arabia department of Mathematics Amity School of Applied SciencesAmity University RajasthanJaipur302002RajasthanIndia department of studies in Mathematics Davangere UniversityDavangere577002India department of Electronics and Communication Engineering Amrita School of EngineeringAmrita Vishwa VidyapeethamBengaluru560035India

Assessing the behaviour and concentration of waste pollutants deposited between two parallel plates is essential for effective environmental *** the effectiveness of treatment methods in reducing pollution scales is made easier by analysing waste discharge *** waste discharge concentration analysis is useful for assessing how effectively wastewater treatment techniques reduce pollution *** study aims to explore the Casson micropolar fluid flow through two parallel plates with the influence of pollutant concentration and thermophoretic particle *** explore the mass and heat transport features,thermophoretic particle deposition and thermal radiation are *** governing equations are transformed into ordinary differential equations with the help of suitable similarity *** Runge-Kutta-Fehlberg’s fourthfifth order technique and shooting procedure are used to solve the reduced set of equations and boundary *** integration of a neural network model based on the Levenberg-Marquardt algorithm serves to improve the accuracy of predictions and optimize the analysis of *** outcomes are displayed to analyze the characteristics of the relevant dimensionless parameters in the current *** reveal that concentration upsurges as the micropolar parameter *** concentration reduces with an upsurge in the thermophoretic *** upsurge in the external pollutant source variation and the local pollutant external source parameters enhances mass *** surface drag force declines for improved values of porosity and micropolar parameters.

关键词： Micropolar fluid thermal radiation porous medium thermophoretic particle deposition waste discharge concentration

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