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Glycolytic dysregulation in Alzheimer's disease:unveiling new avenues for understanding pathogenesis and improving therapy

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Neural Regeneration Research 2025年第8期20卷 2264-2278页

作者： You Wu Lijie yang Wanrong Jiang Xinyuan Zhang Zhaohui yao Department of Geriatrics Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative *** current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's *** studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's *** in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's *** changes impact neuronal health and function,thus offering promising targets for therapeutic *** purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and *** focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.

关键词： Alzheimer’s disease glial cells glycolysis neuronal metabolism pathogenesis therapeutic targets

Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 176-198页

作者： Zhong-Xia yang Li-ting Zhang Xiao-Jun Liu Xue-Bin Peng Xiao-Rong Mao The First School of Clinical Medicine Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Infectious Diseases The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Radiotherapy Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal *** has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor *** regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy ***-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different *** hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in *** upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow *** studies were conducted with gene knockout models and pathway *** function of IL-17A in immune evasion was explored through coculture of T cells and HCC *** effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in *** IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by ***-17A enhanced the survival of HCC cells in the coculture ***-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic *** D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression *** combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse *** IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against

关键词： Interleukin-17A Programmed death ligand-1 Interleukin-17A receptor Small mothers against decapentaplegic 2 Hepatocellular carcinoma Immunotherapy

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

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Neural Regeneration Research 2025年第7期20卷 2116-2128页

作者： Yuxue Mu Ning Zhang Dongyu Wei Guoqing yang Lilingxuan yao Xinyue Xu yang Li Junhui Xue Zuoming Zhang Tao Chen Aerospace Clinical Medical Center School of Aerospace MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Aviation Medicine Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Emergency Medicine Wuhan No.1 HospitalWuhanHubei ProvinceChina Third Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Fourth Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain ***,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under *** 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic *** investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail *** results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly *** addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated *** findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

关键词： glial fibrous acidic protein gliosis Müller cells nerve growth factor neural differentiation neurodegeneration proteomic retinal degeneration retinal outer nuclear layer simulated weightlessness

大学生健全人格培育中融入传统文化理念的思考

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边疆经济与文化 2022年第7期 97-99页

作者：葛翠茹杨廷尧广东茂名幼儿师范专科学校马克思主义学院广东茂名525022 广东茂名幼儿师范专科学校财经学院广东茂名525022

在大学生健全人格培育实践机制中融入传统文化理念,具体包括在高校各门专业课程设置实践中融入传统文化理念,在选修课程设置实践中融入传统文化理念,在大学生社团活动实践中融入传统文化理念,在高校学术报告和专题讲座中融入传统文化理... 详细信息

在大学生健全人格培育实践机制中融入传统文化理念,具体包括在高校各门专业课程设置实践中融入传统文化理念,在选修课程设置实践中融入传统文化理念,在大学生社团活动实践中融入传统文化理念,在高校学术报告和专题讲座中融入传统文化理念,在多种新信息技术应用实践中融入传统文化理念等。总之,在大学生健全人格培育中融入传统文化理念具有十分重要的现实意义。

关键词：传统文化理念大学生健全人格培育融入

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-ting Sun Li-ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development

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World Journal of Gastroenterology 2025年第2期31卷 42-51页

作者： Wen-Chong Zhen Jing Sun Xue-ting Bai Qian Zhang Zi-Han Li Yi-Xin Zhang Rong-Xuan Xu Wei Wu Zhi-Han yao Chun-Wen Pu Xiao-Feng Li School of Public Health Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Graduate School Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Dalian Public Health Clinical Center Dalian Municipal Research Institute for Public HealthDalian 116001Liaoning ProvinceChina Department of Epidemiology and Health Statistics Dalian Medical UniversityDalian 116044Liaoning ProvinceChina

BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality *** detection of HCC is crucial,yet *** To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio(APR)in hepatitis B progression to *** Data from 4843 patients with hepatitis B(January 2015 to January 2024)were *** incidence rates in males and females were compared using the log-rank *** were evaluated using Kaplan–Meier *** Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over ***,Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC *** The incidence of HCC was higher in *** ensure the model’s normality assumption,this study applied a logarithmic transformation to APR,yielding *** levels were higher in females(t=5.26,P<0.01).A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males(95%CI:1.653-2.431)and a 2.273-fold higher risk in females(95%CI:1.620-3.190).CONCLUSION Males are more prone to HCC,while females have higher APR *** no baseline APR link,rising APR indicates a higher HCC risk.

关键词： Alkaline phosphatase to prealbumin ratio Chronic hepatitis B patients Hepatocellular carcinoma Retrospective cohort study Linear Mixed-Effect Mode Joint Modelling of Longitudinal and Survival data

Nomogram for overall survival in ampullary adenocarcinoma using the surveillance,epidemiology,and end results database and external validation

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World Journal of Clinical Oncology 2025年第2期16卷 36-51页

作者： Jia yang Zi-Yi Wang Jing Chen yao Zhang Lei Chen Department of Gastroenterology The First Affiliated Hospital of Army Medical UniversityChongqing 400038China Department of Epidemiology College of Preventive MedicineArmy Medical UniversityChongqing 400038China

BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal ***,only a few cases have been reported,resulting in limited information on *** To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary *** Data were sourced from the surveillance,epidemiology,and end results stat *** patients in the database were randomized in a 7:3 ratio into training and validation *** Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the *** nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical *** For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the *** area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific *** internal and external validation cohorts indicated good consistency of the *** The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.

关键词： Ampullary adenocarcinoma Dynamic nomogram Gastrointestinal tract Surveillance Epidemiology End results database Survival rate

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution