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Sex differences in aging and injured brain

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Neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： Jordan N.Williamson Yuan Yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA Northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of Surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of Pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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

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

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang department of Neurology Henry Ford HospitalDetroitMIUSA department of Physics Oakland UniversityRochesterMIUSA department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

Overnight pulse oximetry for screening of obstructive sleep apnea in at-risk adult patients in the primary care setting:prospective case series

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family medicine and Community Health 2017年第3期5卷 215-222页

作者： Lap-Kin Chiang Cheuk-Wai Kam Lorna V.Ng family medicine and General outpatient department Kwong Wah HospitalHong Kong

Objective:To estimate prevalence of OSA among at risk adult patients in primary care *** test the correlation and agreement between overnight pulse oximetry and polysomnography(PSG).To test the OSA screening performance of overnight pulse *** and Setting:Prospective case series involving adult Chinese patients with risk fac-tors for OSA at a primary care clinic of Hong ***:The prevalence and severity of OSA were established based on overnight pulse oximetry derived oxygen desaturation index(ODI).Screening performance of overnight pulse oxi-metry was compared directly with gold standard diagnostic test ***:Three hundred and five male and 229 female patients were ***(48.3%)was the top presenting *** hundred and twenty five patients(60.9%)were screened positive to have *** hundred and nine patients had performed PSG,the ODI_4 and apnoea-hypopnea index(AHI)had Pearson correlation coefficient 0.71(P<0.001).Bland and Alt-man plot showed good *** designation criteria of ODI_4≥5 events/hr,the sensitivity and specificity for OSA diagnosis are 94.4%and 78.9%***:The prevalence of OSA is 60.9% among adult primary care population who are at risk for *** pulse oximetry shows good performance as a screening tool for the screening of OSA.

关键词： Obstructive sleep apnea overnight pulse oximetry primary care

Characteristics of patients with erectile dysfunction in a family physicianled erectile dysfunction clinic:Retrospective case series

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family medicine and Community Health 2017年第1期5卷 85-91页

作者： Lap Kin Chiang Cheuk-Wai Kam Kin-Chung Michael Yau Lorna Ng family medicine and General outpatient department Kwong Wah HospitalMongkokHong KongChina

Objectives:*** examine the characteristics of patients with erectile dysfunction in a family physician led erectile dysfunction clinic;*** review association of chronic disease spectrum and erectile dysfunction;*** review initial treatment pattern and ***:Retrospective case series ***:All consecutive patients seen in a regional hospital family physician led erectile dysfunction clinic from April 2014 to March *** outcome measures:*** severity of erectile dysfunction,based on International Index of Erectile Function(IIEF-5).*** associated chronic comorbidities of *** patterns and patient ***:One hundred and eighty three patients presented with erectile dysfunction(ED)with mean age 58.7(range 23 to 82)years old were seen during the study *** hundred and twenty seven patients(69.4%)had comorbidity of chronic diseases,including 50.8%had hypertension,38.8%had diabetes mellitus and 33.9%had *** mean body mass index was 25.2 kg/m2,the mean blood pressure was 137.3/79.5 mm Hg(1 mm Hg=0.133 kPa).According to IIEF-5 score,50.3%,30.6%and 18.6%had severe,moderate and mild erectile dysfunction *** average duration of ED before seeking medical help was 3.9 *** 5(PDE5)inhibitors were prescribed to 119 patients(65%),and 57.1%of them achieved good *** nine patients(15.8%)were referred to other specialty for further management,including 27.6%had contraindication for PDE5 ***:High proportion of erectile dysfunction patients had comorbitiy of chronic dis-eases.57.1%of those patients receiving PDE5 inhibitors showed good response.

关键词： Erectile dysfunction chronic diseases family physician

Clinical observation of white eye distribution in patients with hyperlipidemia: an artificial intelligence digital visual examination technique

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Journal of Traditional Chinese medicine 2025年

作者： SONG Tianli LI Haixia LIU Li'an department of Cardiology， the Guang'anmen Hospital， China Academy of Chinese Medical Sciences National College， Beijing University of Chinese medicine

Objective: To explore the clinical observation of white eye distribution characteristics of hyperlipidemic patients based on artificial intelligence digital eye diagnosis technology. Methods: One hundred and fifty subjects were examined in the outpatient and inpatient departments of Guang'anmen Hospital of the China Academy of Traditional Chinese medicine from 01 February 2022 to 01 February 2023， including 80 cases in the hyperlipidemic patient (HLP) group and 70 cases in the normal lipid level patient (NC) group. The two groups were collected and extracted by the artificial intelligence visual diagnostic instrument and analyzed by the MyEyeD-10 white eye shadowless imaging health intelligence analysis system. Finally， SPSS 26.0 (Version X; IBM Corp.， Armonk， NY， USA) was used for statistical processing. Results: Significant differences were noted in the scores of "spot" and "foggy" features between the two groups. Between groups， the "spot" feature score of the white eye morphology in the HLP group (11.07 ± 3.22) was higher than that in the NC group (7.50 ± 4.11) (P < 0.01). Moreover， the "foggy" feature score of the eye morphology in the HLP group (8.37 ± 2.25) was higher than that in the NC group (P < 0.01)， higher than that of the NC group (5.72 ± 1.21) (P < 0.05). There were significant differences in the "A" (stomach)， "B"， "O" (spleen)， and "M" (liver) eye-contact region scores between the two groups， and the "B"， "O" (spleen) and "M" (liver) eye-contact region scores were significantly different. The scores of the white eye channel region in the HLP group were significantly higher than those in the control group， with the "A"， "B"， and "O" regions (P < 0.01)， "M" region (P < 0.01)， "A"， "B"， "O"， and "M" region (P < 0.01). "M" zone (P < 0.05). The scores of "dull red" and "yellow" features were significantly different， and the scores of "dull red" and "yellow" colors of the white eye choroid in the HLP group were significantly higher than those in the HLP g

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