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Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats

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Neuroscience Bulletin 2024年第5期40卷 577-593页

作者： Jing-Jing Yang Ying-Xin Liu Yan-fang Wang Bi-Ying Ge Ying Wang Qing-Shan Wang Sheng Li Jian-jie Zhang Ling-Ling Jin Jau-Shyong Hong Sheng-Ming Yin jie Zhao College of Basic Medical Sciences Dalian Medical UniversityDalian116044China department of Neurology The First Affiliated Hospital of Dalian Medical UniversityDalian116011China National and Local Joint Engineering Research Center for Drug Research and Development of Neurodegenerative Diseases Dalian116044China School of Public Health Dalian Medical UniversityDalian116044China Neurobiology Laboratory National Institute of Environmental Health SciencesNational Institutes of HealthResearch Triangle ParkDurhamNC27709USA

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative *** results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure *** addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal *** found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE ***,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

关键词： Temporal lobe epilepsy Dextromethorphan NADPH oxidase Ultra-low dose

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Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2404-2418页

作者： jie Song Xiang-Xiu Yan fang-Liang Zhang Yong-Yi Lei Zi-Yin Ke fang Li Kai Zhang Yu-Qi He Wei Li Chao Li Yuan-Ming Pan department of Gastroenterology Dongying People’s HospitalDongying Hospital of Shandong Provincial Hospital GroupDongying 257000Shandong ProvinceChina Gastrointestinal Surgery department Suining Central HospitalSuining 629000Sichuan ProvinceChina Obstetrical department Suining Central HospitalSuining 629000Sichuan ProvinceChina School of Medicine Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107Guangdong ProvinceChina department of Pathology Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049China General department Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China department of Gastroenterology Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China department of Thoracic Surgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina department of Gastroenterology Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049China Cancer Research Center Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China

BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative *** To investigate the prognosis of GMA and develop predictive *** From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with *** random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s *** This model had an AUC of 0.743.[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.723.-0.7254)in the validation cohort,and 0.73.8(95%CI:0.73.8-0.73.8)in the test *** packaged it into Windows software for doctors’use and uploaded *** gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA *** surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.

关键词： Deep learning Gastrointestinal mucous adenocarcinoma Overall survival Surgery Clinical tool

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Is Peer Victimization Associated with Higher Online Trolling among Adolescents?The Mediation of Hostile Attribution Bias and the Moderation of Trait Mindfulness

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International Journal of Mental Health Promotion 2024年第8期26卷 623-632页

作者： Yuedong Qiu Qi Sun jie Zhou Ni Jiang Wenyu Zeng Biyun Wu fang Li School of Psychology Sichuan Normal UniversityChengdu610066China Center of Adolescent Growth Services Sichuan Dazhu Middle SchoolDazhou635100China Center of Mental Health Education Guangzhou University of Chinese MedicineGuangzhou510470China Sichuan Key Laboratory of Psychology and Behavior of Discipline Inspection and Supervision Sichuan Normal UniversityChengdu610066China

Background:In recent years,online trolling has garnered significant attention due to its detrimental effects on mental health and social *** current study examined the influence of peer victimization on adolescent online trolling behavior,proposing that hostile attribution bias mediated this relationship and that trait mindfulness moderated both the direct and indirect ***:A total of 83. Chinese adolescents completed the measurements of peer victimization,hostile attribution bias,trait mindfulness,and online *** mediation analysis was performed to examine the relationships between these ***:After controlling for gender and residential address,the study found a significant positive correlation between peer victimization and online trolling,with hostile attribution bias serving as a *** addition,trait mindfulness moderated the direct relationship between peer victimization and online ***,the effect of peer victimization on online trolling was attenuated when adolescents had high levels of trait *** results of the study emphasized the joint role of peer and personal factors in adolescents’online trolling behavior and provide certain strategies for intervening in adolescents’online trolling ***:The results of the study suggest that strategies focusing on peer support and mindfulness training can have a positive impact on reducing online trolling behavior,promoting adolescents’mental health,and their long-term development.

关键词： Online trolling peer victimization hostile attribution bias trait mindfulness adolescent

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Triangle-free Graphs with Three Positive Eigenvalues

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Algebra Colloquium 2024年第3期31卷 525-540页

作者： fang Duan School of Mathematical Sciences Xinjiang Normal UniversityUrumqi 830017China

A graph G is called triangle-free if G does not contain any triangle as its induced *** G_(n)be the set of triangle-free graphs of order n each of which has three positive *** this paper,we find 20 specific graphs in G_(n),each of which has nullity no more than 2,and we show that in terms of three graph transformations all the other graphs of G_(n)can be constructed from these 20 specific ***,we completely characterize the triangle-free graphs with exactly three positive eigenvalues.

关键词： positive(negative)inertia index nullity triangle-free graph

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RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 307-318页

作者： Lu Xu Zhi-Hao Xie Jun Li Shi Tao fang-Li Ren Yin-Yin Wang Zhi-jie Chang Xin-Bao Hao department of Hematology The First Affiliated Hospital of Hainan Medical UniversityHaikou570102China State Key Laboratory of Membrane Biology School of MedicineTsinghua UniversityBeijing 100084China Heya Beijing Med-Biotech Inc. Beijing 100084China department of Hematology Roswell Park Comprehensive Cancer CenterNY 14263USA

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic ***:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival *** vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and ***:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor *** vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling ***:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular *** RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

关键词： RPRD1B RNAPⅡ Diffuse large B-cell lymphoma NF-κB Apoptosis

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Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang fang jie Zhoua Qiyong Gong Kui Luo department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-23.)*** cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

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Superior compound coatings prepared by low-temperature vanadium-nitrocarburizing duplex treatment

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Rare Metals 2024年第4期43卷 1828-1835页

作者： Gen Jin fang-fang Xu Xun-Xun Hu Yue Xu School of Chemistry Beihang UniversityBeijing100191China Guobiao(Beijing)Testing and Certification Co. LtdBeijing100088China School of Materials Science and Engineering Beihang UniversityBeijing100191China

Superior compound coatings were prepared on CK45 steel surface by vanadium-nitrocarburizing duplex treatment in low-temperature salt *** this study,the microhardness,the phase constitution and the compositional distribution in the coatings prepared under different conditions were systematically *** results indicated that the reactions among activated vanadium,carbon and nitrogen atoms occurred on the steel surface,leading to the formation of compound coatings composed of outermost and compound *** mechanism for the formation of compound layer as well as the growth kinetics of the layer was also *** the duplex treatment,the wear and corrosion resistances of steel surface were significantly *** was found that the growth kinetics of compound layer obeyed the parabolic law,with the activation energy of 122.82 kJ·moL^(-1).

关键词： Vanadium-nitrocarburizing duplex treatment Compound coatings Microstructure Formation mechanism Growth kinetics

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Gut microbial metabolite targets HDAC3.FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

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Bone Research 2024年第2期12卷 421-437页

作者： Hongzhen Chen Xuekun Fu Xiaohao Wu Junyi Zhao fang Qiu Zhenghong Wang Zhuqian Wang Xinxin Chen Duoli Xie jie Huang Junyu Fan Xu Yang Yi Song jie Li Dongyi He Guozhi Xiao Aiping Lu Chao Liang department of Systems Biology School of Life SciencesSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Institute of Integrated Bioinfomedicine and Translational Science(IBTS) School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Division of Immunology and Rheumatology Stanford UniversityStanfordCA 94305USA VA Palo Alto Health Care System Palo AltoCA 94304USA Institute of Plant and Food Science Department of BiologySouthern University of Science and TechnologyShenzhen 518055China department of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghaiChina department of Computational Biology St.Jude Children’s Research HospitalMemphisTNUSA department of Laboratory Medicine Peking University Shenzhen HospitalShenzhenChina Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou 510006China Shanghai university of Traditional Chinese Medicine Shanghai 200032China State Key Laboratory of Proteomics National Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850 BeijingChina

Rheumatoid arthritis(RA)is an autoimmune *** studies hold an opinion that gut microbiota is environmentally acquired and associated with RA ***,accumulating evidence demonstrates that genetics also shape the gut *** is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to ***,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched *** than DBA/1J mice and RA *** of *** prevents CIA in DBA/1J *** identify that *** mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of ***-like synoviocytes(FLSs)in RA are activated to undergo tumor-like *** disrupts HDAC3.FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of *** treat CIA mice with propionate and show that propionate attenuates ***,a combination of propionate with anti-TNF etanercept synergistically relieves *** results suggest that *** or propionate could be an alternative or complementary approach to the current therapies.

关键词： HDAC3 cytes interferon

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Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3507-3520页

作者： Wen Liu Hong-Yu Wu Jia-Xi Lin Shu-Ting Qu Yi-jie Gu Jin-Zhou Zhu Chun-fang Xu department of Gastroenterology Changzhou Hospital of Traditional Chinese MedicineChangzhou 213000Jiangsu ProvinceChina department of Gastroenterology The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina department of Gastroenterology Suzhou Ninth Hospital Affiliated to Soochow UniversitySuzhou 215200Jiangsu ProvinceChina

BACKGROUND Lymph node ratio(LNR)was demonstrated to play a crucial role in the prognosis of many ***,research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm(NEN)patients was *** To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic *** A total of 286 patients from the Surveillance,Epidemiology,and End Results database were divided into the training set and validation set at a ratio of 8:2.92 patients from the First Affiliated Hospital of Soochow university in china were designated as a test *** regression analysis was used to explore the relationship between LNR and disease-specific survival(DSS)of gastric NEN *** survival forest(RSF)algorithm and Cox proportional hazards(CoxPH)analysis were applied to develop models to predict DSS respectively,and compared with the 8th edition American Joint Committee on Cancer(AJCC)tumornode-metastasis(TNM)*** Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of *** RSF model exhibited the best performance in predicting DSS,with the C-index in the test set being 0.769[95%confidence interval(CI):0.691-0.846]outperforming the CoxPH model(0.744,95%CI:0.665-0.822)and the 8th edition AJCC TNM staging(0.723.95%CI:0.613.0.83.).The calibration curves and decision curve analysis(DCA)demonstrated the RSF model had good calibration and clinical ***,the RSF model could perform risk stratification and individual prognosis prediction *** A higher LNR indicated a lower DSS in postoperative gastric NEN *** RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set,showing potential in clinical practice.

关键词： Gastric neuroendocrine neoplasm Lymph node ratio Disease-specific survival Random survival forest Predictive model

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Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators

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World Journal of Stem Cells 2024年第6期16卷 670-689页

作者： Ying Gao Mei-fang Liu Yang Li Xi Liu Yu-jie Cao Qian-Fa Long Jun Yu Jian-Ying Li department of Respiratory and Critical Care Medicine Shaanxi Provincial Rehabilitation HospitalXi’an 710000Shaanxi ProvinceChina department of Respiratory and Critical Care Medicine Second Affiliated Hospital of Ningxia Medical University(The First People’s Hospital of Yinchuan)Yinchuan 750001Ningxia Hui Autonomous RegionChina School of Clinical Medicine Xi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina department of Respiratory and Critical Care Medicine Xi’an Central HospitalXi’an 710000Shaanxi ProvinceChina department of Neurosurgery Xi’an Central HospitalXi’an 710000Shaanxi ProvinceChina department of Emergency Xi’an Central HospitalXi’an 710000Shaanxi ProvinceChina

BACKGROUND Pulmonary fibrosis(PF)is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation,causing structural damage and lung *** cell therapy and mesenchymal stem cells-extracellular vesicles(MSC-EVs)offer new hope for PF *** To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis,oxidative stress,and immune inflammation in A549 cells and bleomycin(BLM)-induced mouse *** The effect of MSC-EVs on A549 cells was assessed by fibrosis markers[collagen I andα-smooth muscle actin(α-SMA),oxidative stress regulators[nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1),and inflammatory regu-lators[nuclear factor-kappaB(NF-κB)p65,interleukin(IL)-1β,and IL-2].Similarly,they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV ***-EVs ion PF mice were detected by pathological staining and western ***-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in *** Transforming growth factor(TGF)-β1 enhanced fibrosis in A549 cells,significantly increasing collagen I andα-SMA ***,treatment with MSC-EVs demonstrated a remarkable alleviation of these ***,the expression of oxidative stress regulators,such as Nrf2 and HO-1,along with inflammatory regulators,including NF-κB p65 and IL-1β,were mitigated by MSC-EV ***,in a parallel manner,MSC-EVs exhibited a downregulatory impact on collagen deposition,oxidative stress injuries,and inflammatory-related cytokines in the lungs of mice with ***,the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory *** findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes,oxidative stres

关键词： Mesenchymal stem cells Extracellular vesicles Pulmonary fibrosis Oxidative stress response Epithelial-mesenchymal transition

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