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The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes

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Animal Models and Experimental medicine 2025年第1期8卷 126-141页

作者： Avia Paz Kareem Midlej Osayd Zohud Iqbal MLone Fuad A.Iraqi department of clinical Microbiology and immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and *** studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including *** is imperative to further understand the relation-ship between obesity,T2D,and cognitive ***:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)*** CC mice are a genetically diverse panel derived from eight inbred ***:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/***037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on *** tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on *** weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to *** tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic ***:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and *** genetic components may offer new tools for early prediction and prevention.

关键词： collaborative cross mouse diabetes host genetic background memory impairments obesity

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STIL enhances the development of lung adenocarcinoma by regulating the glycolysis pathway

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Oncology Research 2025年第1期33卷 123-132页

作者： LEI WANG XIANJIN XIE department of respiratory medicine Jen Ching Memorial HospitalSuzhou215300China department of respiratory medicine Shandong Provincial Third HospitalJinan250010China

Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and *** set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose ***:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse *** enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of *** E2F1 reversed the promotion effect of the STIL overexpression on cell viability and ***,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD ***:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic *** comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.

关键词： SCL/TAL1 interrupting locus(STIL) Lung adenocarcinoma E2 promoter binding factor 1 Glycolysis

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Long noncoding RNA LINC01106 promotes lung adenocarcinoma progression via upregulation of autophagy

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Oncology Research 2025年第1期33卷 171-184页

作者： GENGYUN SUN YIPING ZHENG JIANFENG CAI JIE GAO LIE DONG XIANGBIN ZHANG YINGHUI HUANG department of respiratory and Critical Care medicine The First Affiliated Hospital of Anhui Medical UniversityHefei230022China department of respiratory and Critical Care medicine Nanping First Hospital Affiliated to Fujian Medical UniversityNanping353006China

Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain ***:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was *** cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor *** downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)***,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD ***:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell *** silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of ***,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its *** assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 ***:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.

关键词： LINC01106 TAF15 TEAD4 ATG5 Lung adenocarcinoma(LUAD) Non-small cell lung cancer(NSCLC)

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Incidence of hematological toxicity with use of immunotherapy and chemotherapy in advanced non-small cell lung cancer

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中华医学杂志(英文版) 2025年第2期138卷 2024 Sep 19页

作者： Fu Wenhai Jiang Yu Ye Wenjun Zhong Ran Xiong Shan Li Jianfu Li Caichen He Jianxing Liang Wenhua department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong China State Key Laboratory of respiratory Disease Guangzhou Guangdong China National clinical Research Center for respiratory Disease Guangzhou Guangdong China Guangzhou Institute of respiratory Health Guangzhou Guangdong China

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Impact of Spinal Manipulative Therapy on Brain Function and Pain Alleviation in Lumbar Disc Herniation:A Resting-State fMRI Study

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Chinese Journal of Integrative medicine 2025年第2期31卷 108-117页

作者： ZHOU Xing-chen WU Shuang WANG Kai-zheng CHEN Long-hao WEI Zi-cheng LI Tao HUA Zi-han XIA Qiong LYU Zhi-zhen LYU Li-jiang department of Spine The Third Affiliated Hospital of Zhejiang Chinese Medicine UniversityHangzhou(310053)China department of Spine The Third School of Clinical MedicineZhejiang Chinese Medicine UniversityHangzhou(310053)China Research Institute of Tuina(Spinal Disease) Zhejiang Chinese Medicine UniversityHangzhou(310053)China

Objective:To elucidate how spinal manipulative therapy(SMT)exerts its analgesic effects through regulating brain function in lumbar disc herniation(LDH)patients by utilizing resting-state functional magnetic resonance imaging(rs-f MRI).Methods:From September 2021 to September 2023,we enrolled LDH patients(LDH group,n=31)and age-and sex-matched healthy controls(HCs,n=28).LDH group underwent rs-f MRI at 2 distinct time points(TPs):prior to the initiation of SMT(TP1)and subsequent to the completion of the SMT sessions(TP2).SMT was administered once every other day for 30 min per session,totally 14 treatment sessions over a span of 4 *** did not receive SMT treatment and underwent only one f MRI ***,participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale(VAS)and the Japanese Orthopedic Association(JOA)score,whereas HCs did not undergo clinical scale *** effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations(ALFF)and regional homogeneity(Re Ho).Correlation analyses were conducted between specific brain regions and clinical ***:Following SMT treatment,pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the *** comparison to TP1,TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L(voxelwise P30;FDR correction).Additionally,the most substantial enhancement in Re Ho values was observed for the Cuneus_R,while the most prominent reduction was noted for the Olfactory_R(voxelwise P30;FDR correction).Moreover,a comparative analysis revealed that,in contrast to HCs,LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L(voxelwise P30;FDR correction).Fur

关键词： functional magnetic resonance imaging lumbar disc herniation spinal manipulative therapy pain

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

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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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Bufalin Suppresses Esophageal Squamous Cell Carcinoma Progression through Protein Arginine Methyltransferase-6/AKT/Mammalian Target of Rapamycin Pathway Inhibition

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World Journal of Traditional Chinese medicine 2025年第01期 148-156页

作者： Yao-Ke Jia Qian-Qian Ju Hui Shi Xin-Xin Si department of clinical medicine Nanjing Medical University department of clinical medicine Medical College of Nantong University department of Thoracic Surgery School of Medicine Shanghai Chest Hospital Shanghai Jiao Tong University department of Medical Biology School of Pharmacy Jiangsu Ocean University

Objective: Esophageal squamous cell carcinoma(ESCC), a commonly encountered malignant tumor in the gastrointestinal tract, poses a significant health burden. Bufalin, a pharmacologically active molecule, has been shown to exhibit antitumor activity against various types of cancers. This study investigates the molecular mechanism underpinning the effects of bufalin on ESCCs. Materials and Methods: The impact of bufalin on the proliferation and migration of ESCC cells was evaluated through the utilization of the Cell Counting Kit-8(CCK-8), scratch assay, and transwell assay. In addition, ribonucleic acid(RNA) sequencing was performed to identify genes that were abnormally expressed in response to bufalin treatment. Western blotting was utilized to ascertain the expression levels of protein arginine methyltransferase-6(PRMT6), phosphorylated AKT(p-AKT), and phosphorylated mammalian target of rapamycin(p-m TOR). Cell transfection was then performed to observe the rescue effect of PRMT6 on bufalin. Results: Bufalin displayed a significant time-dependent inhibition of the proliferation, migration, and invasion of ECA109 cells. An RNA sequencing(RNA-seq) analysis revealed that PRMT6 expression was downregulated in the cells treated with bufalin. PRMT6 promoted the proliferation, migration, and invasive potential of ECA109 cells. The overexpression of PRMT6 boosted p-AKT and p-m TOR levels in ECA109 cells and reversed bufalin inhibition. Conclusions: These findings indicate that bufalin exerts its inhibitory effects on ESCCs through the PRMT6/AKT/m TOR signaling pathway. These findings lay the groundwork for bufalin as a promising therapeutic candidate for the treatment of ESCC.

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Bidirectional regulation of the cyclic guanosine monophosphateadenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 246-261页

作者： Ai-Yu Nie Zhong-Hui Xiao Jia-Li Deng Na Li Li-Yuan Hao Sheng-Hao Li Xiao-Yu Hu College of clinical medicine Chengdu University of Traditional Chinese MedicineChengdu 610075Sichuan ProvinceChina department of Infection Affiliated Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are *** cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune *** a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in ***,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor *** To investigate the dual-regulation mechanism of cGAS-STING in *** This review was conducted according to the PRISMA *** study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science *** rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC *** All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 *** removing duplicates,remaining 964 records were ***,55 articles met the inclusion criteria and were included in this *** Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its *** cGAS-STING pathway activation will result in a suppressive tumor microenvironment.

关键词： Hepatocellular carcinoma Cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene Interferon genes The metastasis of a tumor immunology

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