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Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He Bo Peng Qi Wang Jie Tian ping Liu Jie Feng Yiwei Liao Longyi Chen ping jia jian Tang Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide

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Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 354-363页

作者： Li Zheng Bin Li Ling Lei Li-jia Wang Zhi-ping Zeng jian-Dong Yang Department of Gastroenterology The First Hospital of NanchangNanchang 330008Jiangxi ProvinceChina Department of General Surgery The First Hospital of NanchangNanchang 330008Jiangxi ProvinceChina

BACKGROUND Colorectal cancer is a common malignant tumor in China,and its incidence in the elderly is increasing annually.Inflammatory bowel disease is a group of chronic non-specific intestinal inflammatory diseases,including ulcerative colitis and Crohn’s disease.We included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December 2022.Surgical indicators,oncological indicators,and survival rates were compared between the groups.The results of 104 patients who met the above criteria were extracted from the database(laparoscopic colectomy group=63,open colectomy group=41),and there were no statistically significant differences in the baseline data or follow-up time between the two groups.RESULTS Intraoperative blood loss,time to first ambulation,and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy group.The differences in overall mortality,tumor-related mortality,and recurrence rates between the two groups were not statistically significant,and survival analysis showed that the differences in the cumulative overall survival,tumor-related survival,and cumulative recurrence-free rates between the two groups were not statistically significant.CONCLUSION In elderly patients with colorectal cancer,laparoscopic colectomy has better short-term outcomes than open colectomy,and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

关键词： Colorectal cancer Laparoscopic surgery Open surgery Prognosis Laparoscopic colectomy Open colectomy

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Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

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Biomedical and Environmental Sciences 2024年第2期37卷 187-195页

作者： LIU jia jia SU Qiu Dong YI Yao SHEN Li ping BI Sheng Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

关键词： Anti-OX40 antibody Hepatitis B core virus-like particles Tumor Combination therapy

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Grain refinement of 5A06 aluminum alloy welds caused by tungsten inert gas welding arc characteristics under Ar-He alternating gas supply conditions:a coupled method of water-cooled copper plate test/numerical simulation

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Journal of Iron and Steel Research(International) 2024年第3期31卷 767-777页

作者： Hong-bin Dai jian Miao jia-xin Lin School of Materials Science and Engineering Harbin University of Science and TechnologyHarbin 150040HeilongjiangChina

The welding arc,as a carrier for the conversion of electrical energy to thermal energy,has a direct impact on the quality of welding by its properties and states.In the tungsten inert gas(TIG)welding process under the condition of Ar-He alternating gas supply,the arc is alternately converted between Ar arc and He arc with an alternating gas supply cycle,which has obvious arc change characteristics.The FLUENT software was used to numerically simulate the characteristics of the TIG arc under the condition of alternating gas supply,and the arc temperature field,arc pressure,electric potential and current density distribution under the condition of alternating gas supply were obtained.Combined with the real-time data of arc pressure measured by the water-cooled copper plate with holes,it is proved that the TIG arc has obvious dynamic characteristics under the condition of Ar-He alternating gas supply.This unique dynamic TIG arc acts on the 5A06 aluminum alloy weld,causing the molten pool to stir,resulting in uniform microstructure and grain refinement at the weld,and thereby improving the mechanical properties of the welded joint.

关键词： Alternating gas supply Grain refinement Numerical simulation Tungsten argon arc morphology Microstructure Mechanical property

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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative Medicine 2024年第2期22卷 188-198页

作者： Meng Li Yang Zhou Hui Zhu Lie-ming Xu jian ping Institute of Liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of Traditional Chinese Medicine Shanghai 201203China Key Laboratory of Liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in chol

关键词： Liver cirrhosis biliary Long non-coding RNA H19 Danhongqing formula Cholangiocyte Hepatic stellate cells STAT3 transcription factor

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The evolution and functional divergence of 10 Apolipoprotein D-like genes in Nilaparvata lugens

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Insect Science 2024年第1期31卷 91-105页

作者： jia-Bao Lu Peng-Peng Ren Qiao Li Fang He Zhong-Tian Xu Sai-Nan Wang jian-ping Chen Jun-Min Li Chuan-Xi Zhang Citrus Research Institute Southwest University/Chinese Academy of Agricultural SciencesNational Engineering Research Center for CitrusChongqingChina Technology Center of Wuhan Customs District HubeiChina Institute of Insect Science Zhejiang UniversityHangzhouChina

Apolipoprotein D(ApoD),a member of the lipocalin superfamily of proteins,is involved in lipid transport and stress resistance.Whereas only a single copy of the ApoD gene is found in humans and some other vertebrates,there are typically several ApoD-like genes in insects.To date,there have been relatively few studies that have examined the evolution and functional differentiation of ApoD-like genes in insects,particularly hemi-metabolous insects.In this study,we identified 10 ApoD-like genes(NlApoD1−10)with distinct spatiotemporal expression patterns in Nilaparvata lugens(BPH),which is an important pest of rice.NlApoD1−10 were found to be distributed on 3 chromosomes in a tandem array of NlApoD1/2,NlApoD3−5,and NlApoD7/8,and show sequence and gene structural divergence in the coding regions,indicating that multiple gene duplication events occurred during evolution.Phylogenetic analysis revealed that NlApoD1−10 can be clustered into 5 clades,with NlApoD3−5 and NlApoD7/8 potentially evolving exclusively in the Delphacidae family.Functional screening using an RNA interference approach revealed that only NlApoD2 was essential for BPH development and survival,whereas NlApoD4/5 are highly expressed in testes,and might play roles in reproduction.Moreover,stress response analysis revealed that NlApoD3−5/9,NlApoD3−5,and NlApoD9 were up-regulated after treatment with lipopolysaccharide,H2O2,and ultraviolet-C,respectively,indicating their potential roles in stress resistance.

关键词： Apolipoprotein D BPH evolution functional divergence gene duplication NIApoD

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Efficacy of transjugular intrahepatic portosystemic shunts in treating cirrhotic esophageal-gastric variceal bleeding

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 471-480页

作者： Xiao-Gang Hu jian-Ji Dai Jun Lu Gang Li jia-Min Wang Yi Deng Rui Feng Kai-ping Lu Department of Interventional Radiology The Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000Zhejiang ProvinceChina Department of Interventional Medicine Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310000Zhejiang ProvinceChina Department of Vascular Surgery Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Esophageal-gastric variceal bleeding(EGVB)represents a severe complication among patients with cirrhosis and often culminates in fatal outcomes.Interven-tional therapy,a rapidly developing treatment modality over the past few years,has found widespread application in clinical practice due to its minimally inva-sive characteristics.However,whether transjugular intrahepatic portosystemic shunt(TIPS)treatment has an impact on patient prognosis remains controversial.METHODS A retrospective study was conducted on ninety-two patients presenting with cirrhotic EGVB who were admitted to our hospital between September 2020 and September 2022.Based on the different modes of treatment,the patients were assigned to the study group(TIPS received,n=50)or the control group(per-cutaneous transhepatic varices embolization received,n=42).Comparative ana-lyses were performed between the two groups preoperatively and one month postoperatively for the following parameters:Varicosity status;hemodynamic parameters[portal vein flow velocity(PVV)and portal vein diameter(PVD);platelet count(PLT);red blood cell count;white blood cell count(WBC);and hepatic function[albumin(ALB),total bilirubin(TBIL),and aspartate transaminase(AST)].The Generic Quality of Life Inventory-74 was utilized to assess quality of life in the two groups,and the 1-year postoperative rebleeding and survival rates were compared.RESULTS Following surgical intervention,there was an improvement in the incidence of varicosity compared to the preoperative status in both cohorts.Notably,the study group exhibited more pronounced enhancements than did the control group(P<0.05).PVV increased,and PVD decreased compared to the preoperative values,with the study cohort achieving better outcomes(P<0.05).PLT and WBC counts were elevated postoperatively in the two groups,with the study cohort displaying higher PLT and WBC counts(P<0.05).No differences were detected between the two groups in terms of serum ALB,TBIL,or AST levels either preoperatively or postoperatively(P<0

关键词： Liver cirrhosis Esophagogastric variceal bleeding Transjugular intrahepatic portosystemic shunt Prognosis

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Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

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Neural Regeneration Research 2024年第5期19卷 1112-1118页

作者： Meng Wang Shi-Qi Yao Yao Huang jia-jian Liang Yanxuan Xu Shaowan Chen Yuhang Wang Tsz Kin Ng Wai Kit Chu Qi Cui Ling-ping Cen Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong ShantouGuangdong ProvinceChina Shantou University Medical College ShantouGuangdong ProvinceChina Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijingChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible blindness.We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury.To investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal injection.We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages.Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors.Furthermore,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure elevation.Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

关键词： casein kinase-2 glaucoma intraocular pressure elevation macrophages retinal ganglion cells

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Protein translation:biological processes and therapeutic strategies for human diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1048-1064页

作者： Xuechao jia Xinyu He Chuntian Huang jian Li Zigang Dong Kangdong Liu Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450000China China-US(Henan)Hormel Cancer Institute ZhengzhouHenan 450000China Department of Pathology and Pathophysiology Henan University of Chinese MedicineZhengzhouHenan 450000China Tianjian Laboratory of Advanced Biomedical Sciences ZhengzhouHenan 450052China Research Center for Basic Medicine Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052 HenanChina Provincial Cooperative Innovation Center for Cancer Chemoprevention Zhengzhou UniversityZhengzhouHenan 450000China State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenan 450000China The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention ZhengzhouHenan 450000China

Protein translation is a tightly regulated cellular process that is essential for gene expression and protein synthesis.The deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human diseases.In this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease progression.We explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome function.Deregulated translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease pathogenesis.The development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation errors.Importantly,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular diseases.Moreover,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is discussed.In conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic target.Advancements in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human diseases.Additionally,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.

关键词： translation offering precise

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Spherical Confinement Generates Entropic Force to Accelerate Polymer Chain Detachment

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Chinese Journal of Polymer Science 2024年第3期42卷 407-416,I0010页

作者： Yu-Shan Zheng jian-ping Zhou Yan Xu Kai Li Mechanical Engineering Xinjiang UniversityUrumqi 830002China

To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape of a Brownian particle from the potential well of the spring. However, as the free dangling length of the polymer chain increases, the conformational entropy of the chain is affected by geometric confinement. It means that the wall exerts a repulsive force on the chain, resulting in accelerated link detachment from a macroscopic perspective. In this work, we investigate the effect of entropy on the detachment rate in the case where the substrate is spherical. We demonstrate that spherical confinement accelerates chain detachment both inside and outside the sphere. An analytical expression for the mean detachment time of breakable links is given, which includes an additional pre-factor that is related to the partition function. Additionally, we analyze the expressions for entropic forces inside the sphere, outside the sphere, and on a flat wall, comparing their magnitudes to explain the difference in mean detachment time.

关键词： Polymer detachment Breakable link Entropic force Mean first passage time

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