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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei college of Pharmacy and First clinical Medical college Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Heterochronic gastric adenosquamous carcinoma combined with colonic adenoma:A case report

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 418-423页

作者： Gui-Jiang Liu Xiao-Yi Long Fei Zhang Tao Ren Xun Xia Department of Neurosurgery Clinical Medical College and the First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina Department of Pathology Clinical Medical College and the First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina Department of Oncology The First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina

BACKGROUND Metachronous gastric cancer usually refers to a tumor that occurs in the stomach more than half a year after esophageal cancer surgery,and metastasis of primary esophageal cancer should be *** are few reports of metachronous gastric adenosquamous carcinoma with signet ring cell carcinoma combined with early tubular adenoma of the colon after esophageal cancer surgery,which has a high degree of *** is also the reason for the poor treatment *** SUMMARY A 54-year-old male patient was admitted to the hospital with“dysphagia obstruction”.Seven years ago,the patient was diagnosed with well-differentiated squamous cell carcinoma in the middle esophagus(T4N1M0 stage)and left gastric lymph node *** the final resection of the esophageal cancer,no residual cancer tissue was found in the esophageal and gastric *** patient’s medical history 7 years ago(preoperative gastroscopy and other examinations)revealed no gastric *** with the patient’s history,the diagnosis of recurrent esophageal cancer was made on this *** final pathological results were surprising:Metachronous gastric adenosquamous carcinoma with signet ring cell carcinoma combined with early tubular adenoma of the *** the high malignancy of the tumor,the complexity of the second operation,and many complications,the patient received *** He had a history of esophageal cancer *** should be performed simultaneously to avoid missed diagnosis and misdiagnosis.

关键词： Heterochronic tumor Gastric adenosquamous carcinoma Colonic adenoma Esophageal cancer Signet ring cell carcinoma Case report

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Health risks of rare earth elements exposure:Impact on mitochondrial DNA copy number and micronucleus frequency

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Journal of Environmental Sciences 2025年第5期151卷 150-160页

作者： Shiyi Hong Yali Zhang Qiaojian Zhang Zekang Su Guiping Hu Li Wang Shanfa Yu Xiaojun Zhu Guang Jia Department of Occupational and Environmental Health Sciences School of Public HealthPeking UniversityBeijing 100083China School of Engineering Medicine and Beijing Advanced Innovation Center for Big Data-Based Precision Medicine Beihang UniversityBeijing 100083China Department of Toxicology School of Public HealthBaotou Medical CollegeBaotouInner Mongolia 014040China Henan Institute for Occupational Medicine Zhengzhou 450052China National Center for Occupational Safety and Health Beijing 102308China Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety School of Public HealthPeking UniversityBeijing 100083China

Toxic effects in terms of mitochondria and hereditary substances have been characterized in vitro for individual rare earth elements,while,the joint effects of mixed elements exposure in the population remain *** on the Occupational Chromate Exposure Dynamic Cohort of China,this study investigated the relationship between 15 blood rare earth elements(cerium,dysprosium,erbium,europium,gadolinium,holmium,lanthanum,lutetium,neodymium,praseodymium,samarium,terbium,thulium,yttrium,and ytterbium)and mitochondrial DNA copy number(MtDNACN)as well as peripheral blood lymphocyte micronucleus frequency(MNF).The elastic net was used to select elements highly correlated with effect indicators,whose dose-response relationships were further illustrated by restricted cubic *** kernel regressionwas employed to explore the combined effects of elements and the contributions of single *** results showed that most rare earth elementswere positively correlatedwith effect indicators,with yttrium showing the strongest association(β(95%CI):0.139(0.1089–0.189)for MtDNACN,0.937(0.345–1.684)for MNF).In the mixed exposure model,with the exposure level fixed at the 50th percentile as the reference,the effect estimates on MtDNACN and MNF increased by 0.228 and 0.598 units,respectively,at the 75th *** single effect analysis implied that yttrium,lanthanum and terbium contributed the most to the elevation of MtDNACN,while yttrium posed the highest risk for genetic damage,accordingly,we provided recommendations to prioritize these elements of *** addition,we observed a chief mediating effect of MtDNACN on the elevation of MNF caused by lanthanum,whereas further mechanistic exploration is required to confirm this finding.

关键词： Rare earth elements Mitochondrial DNA copy number Micronucleus frequency Mixed effect

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Rare tumor list provide vast opportunities for novel drug development in China

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Science Bulletin 2025年第2期70卷 132-134页

作者： Rongshou Zheng Shuhang Wang Guo Zhao Wenqiang Wei Ning Li National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China clinical Trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

During the last decade,common cancer understanding and treatment have significantly improved[1,2,3].However,rare tumors are still poorly *** the low incidence of rare tumors,including soft tissue sarcoma,malignant peripheral nerve sheath tumor,malignant pleural mesothelioma,and others,they impose formidable clinical challenges due to inadequate information regarding their diagnosis and treatment,especially in ***,the rare tumor definition was the first issue encountered by researchers in this ***,no unanimous rare tumor definition has been established ***,there are disparities between rare tumor lists in different *** previously defined rare as those with a<50/100,000people prevalence in *** European Union initiated a project known as the Surveillance of Rare Cancer in Europe(RARECARE).

关键词： diagnosis rare Rare

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Amino acid assisted aqueous synthesis of highly stable CsPbBr_(3)nanocrystals for cell imaging

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Nano Research 2025年第1期18卷 675-683页

作者： Xue Li Yanan Guo Guoying Tan Qingyi Liu Nan Song Yu Tang State Key Laboratory of Applied Organic Chemistry Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu ProvinceCollege of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China State Key Laboratory of Baiyunobo Rare Earth Resource Researches and Comprehensive Utilization Baotou Research Institute of Rare EarthsBaotou 014030China

Lead halide perovskite nanocrystals(NCs)exhibit excellent optoelectronic performance and have drawn great interests in the fields of biological imaging and ***,the poor stability of CsPbX_(3)(X=Cl,Br,I)in water is still a challenge to hinder their practical *** this work,a facile strategy has been developed for aqueous synthesis of CsPbX_(3) nanocrystals,in which L-glutamic acid(LGlu)has been used to replace oleic acid in the synthetic *** from the synergic effects of L-Glu and oleylamine(OAm),CsPbBr_(3)nanocrystals(L-Glu/OAm-CsPbBr_(3)NCs)with high water stability have been directly prepared under a mild condition at room temperature in water,facilitated by the process of crystal phase transformation from Cs_(4)PbBr_(6) to CsPbBr_(3).L-Glu/OAm-CsPbBr_(3)NCs exhibit a high quantum yield of 85%and a narrow full width at half maximum of 16 nm,demonstrating their efficient luminescence in ***,L-Glu on the surface have contributed greatly to an acidic environment and passivation of surface defects,improving the water stability and dispersibility of CsPbBr_(3)***,L-Glu/OAm-CsPbBr_(3)NCs exhibit great biocompatibility due to the presence of L-Glu,resulting in their good performance for HeLa cell ***,we propose a facile and effective method to prepare CsPbBr_(3)nanocrystals with excellent water stability by using L-Glu and OAm as cooperated ligands and expand their application in cell imaging.

关键词： aqueous synthesis cell imaging lead halide perovskite nanocrystals L-glutamic acid phase transformation

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Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： Laura Huggon Emma L.Clayton UK Dementia Research Institute at King’s college London LondonUK Department of Basic and clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly *** and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina college of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Mitochondrial dysfunction in the pathogenesis of acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2025年第1期24卷 76-83页

作者： Xia Chen Rui Zhong Bing Hu Department of Gastroenterology and Hepatology West China HospitalSichuan UniversityChengdu 610041China Department of Gastroenterology Clinical Medical College and The First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500China

The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.

关键词： Acute pancreatitis Autophagy Calcium Cell death Inflammation Mitochondria Mitophagy

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Catatonia induced by antipsychotics in an adolescent male patient with systemic lupus erythematosus:A case report

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World Journal of Psychiatry 2025年第2期15卷 257-263页

作者： Wen-Qi Geng Xiao-Xi Yang Jin-Ya Cao Jing Wei Department of Psychological Medicine Chinese Academy of Medical Sciences and Peking Union Medical CollegePeking Union Medical College HospitalBeijing 100730China Department of Rheumatology and clinical Immunology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China National clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID) Ministry of Science&TechnologyBeijing 100730China State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalBeijing 100730China Key Laboratory of Rheumatology and clinical Immunology Ministry of EducationBeijing 100730China

BACKGROUND Systemic lupus erythematosus(SLE)can affect multiple organs or *** involvement of the central nervous system can result in the manifestation of epilepsy,an acute confusional state,and other rare neuropsychiatric presentations,such as *** SUMMARY We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and *** initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia,which was mitigated by discontinuing olanzapine and supplementing with *** this case,whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential *** Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.

关键词： Catatonia Systemic lupus erythematosus Referral consultation Antipsychotics Benzodiazepines Case report

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