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Neural Regeneration research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and Stem Cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic Clinical program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

Brain age estimation:premise,promise,and problems

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Neural Regeneration research 2025年第8期20卷 2313-2314页

作者： Jarrad Perron Ji Hyun Ko Graduate program in Biomedical Engineering Price Faculty of EngineeringUniversity of ManitobaWinnipegMBCanada PrairieNeuro research Centre Kleysen Institute for Advanced MedicineHealth Sciences CentreWinnipegMBCanada Department of Human Anatomy and Cell Science Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada

Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North *** old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.

关键词： estimation providing birth

Functions of nuclear factor Y in nervous system development,function and health

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Neural Regeneration research 2025年第10期20卷 2887-2894页

作者： Pedro Moreira Roger Pocock Development and Stem Cells program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and *** the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently ***,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains *** this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

关键词： axon guidance CCAAT boxes neuronal degeneration neuronal differentiation neuronal regeneration nuclear factor Y complex transcription factor transcriptional regulation

Proapoptotic RECS1: a requisite gateway to lysosomal dysfunction and death

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Neural Regeneration research 2022年第12期17卷 2695-2696页

作者： Philippe Pihán Mateus Milani Claudio Hetz Biomedical Neuroscience Institute Faculty of MedicineUniversity of ChileSantiagoChile Center for Geroscience Brain Health and Metabolism(GERO)SantiagoChile program of Cellular and Molecular Biology Institute of Biomedical SciencesUniversity of ChileSantiagoChile Buck Institute for research on aging NovatoCAUSA

For a long time since their discovery by Christian de Duve in the 1950s,lysosomes have been referred to almost exclusively as passive garbage bags;the endpoint in the degradation of intra-and extracellular *** catabolic function of lysosomes is accomplished by an array of more than 60 acid hydrolases,which together break down a wide variety of biological macromolecules,including proteins,lipids,carbohydrates,and nucleic acids,for reutilization in the metabolic processes of the *** their optimal function,these enzymes require an acidic intraluminal pH of~4.5,which is maintained by the joint action of a proton pump,the vacuolar H+-ATPase,and several ion channels embedded in the lysosomal limiting membrane.

关键词： maintained limiting function

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Co-production of hydrogen, oxygen, and electricity via an integrated solar-driven system with decoupled water electrolyzer and Na-Zn ion battery

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Journal of Energy Chemistry 2025年第1期100卷 621-627页

作者： Fei Lv Longjie Liu Jiazhe Wu Pengfei Wang Lixia Pan Dengwei Jing Yubin Chen International research Center for Renewable Energy State Key Laboratory of Multiphase Flow in Power Engineering Xi'an Jiaotong University

Combining water electrolysis and rechargeable battery technologies into a single system holds great promise for the co-production of hydrogen （H2） and ***,the design and development of such systems is still in its ***,an integrated hydrogen-oxygen （O2）-electricity co-production system featuring a bipolar membrane-assisted decoupled electrolyzer and a Na-Zn ion battery was established with sodium nickelhexacyanoferrate （NaNiHCF） and Zn2+/Zn as dual redox *** decoupled electrolyzer enables to produce H2and O2in different time and space with almost 100%Faradaic efficiency at 100 mA ***,the charged NaNiHCF and Zn electrodes after the electrolysis processes formed a Na-Zn ion battery,which can generate electricity with an average cell voltage of 1.75 V at 10 m A *** connecting Si photovoltaics with the modular electrochemical device,a well-matched solar driven system was built to convert the intermittent solar energy into hydrogen and electric energy with a solar to hydrogen-electricity efficiency of 16.7%,demonstrating the flexible storage and conversion of renewables.

关键词： Hydrogen Electricity Decoupled water electrolyzer Na-Zn ion battery Solar energy

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice

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Protein & Cell 2014年第1期5卷 80-89页

作者： Yulin Chen Runan Yang Peng Guo Zhenyu Ju Institute of aging research School of Medicine Hangzhou Normal University Hangzhou 311121 China

Ataxia telangiectasia mutated （ATM） kinase plays an essential role in the maintenance of genomic stability. ATM-deficient （ATM-/-） mice exhibit hematopoietic stem cell （HSC） dysfunction and a high incidence of lym- phoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM-/- HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM-/- mice. Instead, ATM and Gadd45a double knockout （ATM-/- Gadd45a-/-） HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM-/- HSCs in HSC transplantation experiments. Fur- ther experiments revealed that the aggravated defect of ATM-/- Gadd45a-/- HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signal- ing pathway. Additionally, ATM-/- Gadd45a-/- mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM-/- mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which sub- sequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM-/- HSCs.

关键词： Gadd45a ATM hematopoietic stem cellsDNA damage

HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway

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World Journal of Gastroenterology 2010年第39期16卷 4932-4937页

作者： Hye-Lin Ha Dae-Yeul Yu Disease Model research Laboratory Aging Research CenterKorea Research Institute of Bioscience and Biotechnology Department of Functional Genomics University of Science and Technology

AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx ***:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was *** ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by *** of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing ***:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in *** ROS were detected by *** suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased *** oxidized PTEN activated the mitogenic pathway through over-activated ***,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced *** produced ROS also stimulated HBx ***:HBx induced ROS promoted Akt pathways via oxidized inactive *** and ROS maintained a positive regulatory loop,which aggravated carcinogenesis.

关键词： Hepatitis B virus X protein Hepatocellular carcinoma Akt Reactive oxygen species Phosphatase and tensin homolog