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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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High Fe‑loading Single‑Atom Catalyst Boosts ROS Production by density Effect for Efficient Antibacterial Therapy

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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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Interest of d-dimer level,severity of COVId-19 and cost of management in Gabon

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World Journal of Critical Care Medicine 2025年第1期14卷 91-99页

作者： Berthe A Iroungou Arnaud Nze O Helga M Kandet Y Neil-Michel longo-Pendy Nina d Mezogho-Obame Annicet-Clotaire dikoumba Guignali l Mangouka UnitéMixte de Recherche Centre International de Recherches Médicales de Franceville et le Service de SantéMilitaireLibreville 20404EstuaireGabon AP-HP Health Economics Research UnitHtel Dieu HospitalParis 75004Ilede-FranceFrance laboratory Hôpital D'Instruction des Armées D'AkandaLibreville 20404EstuaireGabo Unitéde Recherche enÉcologie de la Santé Centre Interdisciplinaire de Recherches Médicales de FrancevilleFranceville 769Gabon laboratory Hôpital D'Instruction des Armées Omar Bongo OndimbaLibreville 20404EstuaireGabon department of Medecine Polyvalente Hôpital D'Instruction des Armées Omar Bongo OndimbaLibreville 20404EstuaireGabon

BACKGROUNd Coronavirus disease 2019(COVId-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary *** d-dimer levels are a critical biomarker for assessing this *** Gabon,early implementation of anticoagulation therapy and d-dimer testing has been crucial in managing *** study hypothesizes that elevated ddimer levels are linked to increased COVId-19 *** To determine the impact of d-dimer levels on COVId-19 severity and their role in guiding clinical *** This retrospective study analyzed COVId-19 patients admitted to two hospitals in Gabon between March 2020 and december *** study included patients with confirmed COVId-19 diagnoses and available d-dimer measurements at *** on demographics,clinical outcomes,d-dimer levels,and healthcare costs were ***-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between d-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%*** A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated d-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe *** analysis showed that patients with elevated d-dimer levels had 3.33 times higher odds of severe COVId-19(OR=3.33,95%CI:2.84-3.92,Pd this association remained significant in the multivariable analysis,adjusted for age,sex,and year of *** financial analysis revealed a substantial burden,particularly for uninsured *** d-dimer predicts COVId-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.

关键词： d-dimers COVId-19 Management disease severity Healthcare costs Gabon

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael J.lee Ryota l.Matsuoka department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional Medicine Research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng chen Yu-Chun Xie department of Rehabilitation Medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian Key laboratory of Toxicant and drug Toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAd family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun lingxiao deng Melissa Walker chen chen Heqiao dai Qi Han Ying ding Yongzhi Xia George Smith Rui li Nai-Kui liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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locally Enhanced Flow and Electric Fields Through a Tip Effect for Efficient Flow‑Electrode Capacitive deionization

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Nano-Micro letters 2025年第2期17卷 1-17页

作者： Ziquan Wang Xiangfeng chen Yuan Zhang Jie Ma Zhiqun lin Amor Abdelkader Maria‑Magdalena Titirici libo deng College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060People’s Republic of China Research Center for Environmental Functional Materials College of Environmental Science and EngineeringTongji University1239 Siping RoadShanghai 200092People’s Republic of China department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117585Singapore department of Engineering Faculty of Science and TechnologyBournemouth UniversityTalbot CampusFern BarrowPooleEngland BH125BBUK Institut de Chimie de Nice UniversitéCôte d’AzurUMR CNRS 727228 Av.Valrose06108 NiceFrance department of Chemical Engineering Imperial College LondonSouth Kensington CampusExhibition RdLondon SW72AZUK

low-electrode capacitive deionization(FCdI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of ***,it still suffers from inefficient charge transfer and ion transport kinetics due to weak turbulence and low electric intensity in flow electrodes,both restricted by the current ***,a new tip-array current collector(designated as T-CC)was developed to replace the conventional planar current collectors,which intensifies both the charge transfer and ion transport *** effects of tip arrays on flow and electric fields were studied by both computational simulations and electrochemical impedance spectroscopy,which revealed the reduction of ion transport barrier,charge transport barrier and internal *** the voltage increased from 1.0 to 1.5 and 2.0 V,the T-CC-based FCdI system(T-FCdI)exhibited average salt removal rates(ASRR)of 0.18,0.50,and 0.89μmol cm^(-2) min^(-1),respectively,which are 1.82,2.65,and 2.48 folds higher than that of the conventional serpentine current collectors,and 1.48,1.67,and 1.49 folds higher than that of the planar current ***,with the solid content in flow electrodes increased from 1 to 5 wt%,the ASRR for T-FCdI increased from 0.29 to 0.50μmol cm^(-2) min^(-1),which are 1.70 and 1.67 folds higher than that of the planar current ***,a salt removal efficiency of 99.89%was achieved with T-FCdI and the charge efficiency remained above 95%after 24 h of operation,thus showing its superior long-term stability.

关键词： Flow-electrode Capacitive deionization Current collector Tip effect desalination

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin chen Jinghong Xu Bin Jiang lei li Yawei li Yuliang dai Bing Wang department of Spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCd,TPM2,PNKd,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SdHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated Cd4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

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Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by Neurod1/Ascl1/dlx2

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Neural Regeneration Research 2025年第6期20卷 1801-1815页

作者： Qing He Zhen Wang Yuchen Wang Mengjie Zhu Zhile liang Kanghong Zhang Yuge Xu Gong chen GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––Neurod1, Ascl1, and dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as Neurod1, Ascl1, and dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

关键词： aquaporin-4 Ascl1 astrocyte cortex dlx2 gap junction glia-to-neuron conversion neural regeneration Neurod1 reprogramming

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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： lan Zhang Jingge Wei Xilei liu dai li Xiaoqi Pang Fanglian chen Hailong Cao Ping lei Haihe laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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