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Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population

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Journal of Environmental Sciences 2025年第1期147卷 332-341页

作者： Haiyan Jiang Simei Zhang Yaoyao Lin Lin Meng Jiayi Li Wenqing Wang Kaixuan Yang Mingjuan Jin Jianbing Wang Mengling Tang Kun Chen department of Public Health Fourth Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China department of Public Health Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China department of Public Health National Clinical Research Center for Child Health of Children’s HospitalZhejiang University School of MedicineHangzhou 310058China

Growing evidences showed that heavy metals exposure may be associated with metabolic ***,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully *** we aimed to prospectively investigate the role of serum uric acid(SUA)on the association between blood As exposure and incident MetS.A sample of 1045 older participants in a community in China was *** determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly *** events were defined according to the criteria of the International Diabetes Federation(IDF).Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident *** investigate the role of SUA in the association between As andMetS,amediation analysiswas *** the fully adjusted log-binominal model,per interquartile range increment of As,the risk of MetS increased *** with the lowest quartile of As,the adjusted relative risk(RR)of MetS in the highest quartile was 1.42(95%confidence interval,CI:1.03,2.00).Additionally,blood As was positively associated with SUA,while SUA had significant association with MetS *** mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA,with the proportion of 15.7%.Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults *** analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

关键词： Arsenic(As)exposure Metabolic syndrome(MetS) Serum uric acid(SUA) Cohort study Mediation effect Older adults

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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

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Neural Regeneration Research 2025年第1期20卷 184-185页

作者： Teruyuki Ishikura Tatsusada Okuno department of Molecular Neuroscience Graduate School of MedicineOsaka UniversityOsakaJapan department of Neurology Osaka University Graduate School of MedicineOsaka UniversityOsakaJapan

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

关键词： pain acute pathology

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Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： Hideki Kanamaru Hidenori Suzuki department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and *** the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm *** may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient *** complications such as brain volume loss and chronic hydrocephalus can further impact *** the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective *** cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable *** review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

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Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

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Neural Regeneration Research 2025年第1期20卷 188-190页

作者： Shiho Ito Takeshi Kawauchi department of Adaptive and Maladaptive Responses in Health and Disease Graduate School of MedicineKyoto UniversityKyotoJapan department of Physiology Keio University School of MedicineTokyoJapan

Cell adhesion plays pivotal roles in the morphogenesis of multicellular *** cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

关键词： cerebral skeletal cooperation

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Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin Lim department of Biochemistry&Molecular Biology Ajou University School of MedicineSuwonSouth Korea department of Biomedical Sciences Graduate School of Ajou UniversitySuwonSouth Korea department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi department of Brain Science Ajou University School of MedicineSuwonSouth Korea department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea department of Neurology Ajou University School of MedicineSuwonSouth Korea department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Associations of multiple metals exposure with immunoglobulin levels in pregnant women:Hangzhou Birth Cohort Study

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Journal of Environmental Sciences 2025年第5期151卷 560-572页

作者： Jiena Zhou Lanfei Jin Yexinyi Zhou Kunhong Zhong Kegui Huang Qi Zhang Jun Tang Xue Zhang Lihe Peng Shuai Li Na Lv Dongdong Yu Qinheng Zhu Jing Guo Qiong Luo Guangdi Chen department of Public Health and Key Laboratory of Reproductive Genetics(Ministry of Education)Women’s HospitalZhejiang University School of MedicineHangzhou 310058China department of Clinical Laboratory Shaw HospitalZhejiang University School of MedicineHangzhou 310018China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 310051China Jiashan County Center for Disease Control and Prevention JiashanZhejiang 314199China department of Clinical Laboratory Women’s HospitalZhejiang University School of MedicineHangzhou 310020China department of Obstetrics Women’s HospitalZhejiang University School of MedicineHangzhou 310020China

Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)*** on the Hangzhou Birth Cohort Study,1059 participants were included,and eleven metals in whole blood samples and serum IgA,IgG,IgE and IgM levels were *** regression,quantile-based g-computation(QGC),and Bayesian kernel machine regression(BKMR)models were used to evaluate the *** with the first tertile of metal levels,arsenic(As)was negatively associated with IgE(β=-0.25,95%confidence interval(CI)=-0.48 to-0.02).Moreover,significant associations of manganese(Mn)with IgA,IgG and IgM were demonstrated(β=0.10,95%CI=0.04 to 0.18;β=0.07,95%CI=0.03 to 0.12;β=0.10,95%CI=0.03 to 0.18,respectively).Cadmium(Cd)were associated with higher levels of *** models showed the positive association of the metalmixtures with IgA and IgG,with Mn playing amajor *** and Cd had positive contributions to IgM,while As had negative contributions to *** the BKMR models,the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th ***,exposure to metals was associated with maternal Igs,and mainly showed that Mn was associated with increased levels of IgA,IgG and IgM,and As was associated with low IgE levels.

关键词： Metals Immunoglobulin Pregnant woman Quantile-based g-computation (QGC) Bayesian kernel machine regression (BKMR)

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Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration Research 2025年第1期20卷 195-196页

作者： Hyun Sung department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Medical Research Institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

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Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

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World Journal of Gastroenterology 2025年第6期31卷 44-61页

作者： Han-Ning Xuan Yuan Hyun Sung Kim Gye Ryeol Park Jae Eun Ryu Ji Eun Kim In Young Kang Hye Young Kim Seung Min Lee Ju Hee Oh Eileen L Yoon Dae Won Jun department of Internal medicine Hanyang University School of MedicineSeoul 04763South Korea department of Pathology Hanyang University School of MedicineSeoul 04763South Korea department of Translational medicine Graduate School of Biomedical Science and EngineeringHanyang UniversitySeoul 04763South Korea department of Obstetrics and Gynecology Institute of Women’s Medical Life ScienceYonsei Cancer CenterSeverance HospitalYonsei University College of MedicineSeoul 04763South Korea department of Internal medicine Sanggye Paik HospitalInje University College of MedicineSeoul 01757South Korea

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver *** study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease *** focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related *** To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver *** Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various *** human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate ***,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver *** While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and ***,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid *** MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease *** MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

关键词： RAW 264.7 cell Cell death Necroptosis Mixed lineage kinase domain-like protein Non-alcoholic fatty liver disease Mixed lineage kinase domain-like protein adenosine triphosphate binding inhibitor Alcoholic liver disease

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