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BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation

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World Journal of gastrointestinal Oncology 2025年第1期17卷 214-225页

作者： Qin Wang Qing-Rong Li Lei Xu Zi-Chun Yuan Xiao Liu Mao-Ju Tang Man Luo Xiao-wu Zhong Qiang Ma Xiao-Lan guo Department of Clinical Laboratory Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of Laboratory Medicine&Translational Medicine Research Center North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

BACKgROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic *** are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of ***,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for ***150 and KYSE410 cells were cultured and exposed to various concentrations of *** viability was assessed at 48 hours and 72 hours to determine the IC50 *** effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,*** blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,*** values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 ***1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular ***,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 ***1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein *** a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein *** and eosin staining of various organs,including the heart,liver,s

关键词： Esophageal squamous cell carcinoma BIBR1532 Human telomerase reverse transcriptase DNA damage response Telomere-binding proteins

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Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping wu Fuming Liang Huayi Wang Junjie Yang ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng gong Yangping Zhuang Jiali wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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The cgAS-STINg-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

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Neural Regeneration Research 2025年第8期20卷 2361-2372页

作者： Shengyang Zhou Ting Li Wei Zhang Jian wu Hui Hong Wei Quan Xinyu Qiao Chun Cui Chenmeng Qiao Weijiang Zhao Yanqin Shen Laboratory of Neurodegenerative and Neuroinjury Diseases Wuxi Medicine SchoolJiangnan UniversityWuxiJiangsu ProvinceChina

Interferon regulatory factor 7 plays a crucial role in the innate immune ***,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains *** we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial *** the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 *** addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARg1 and *** together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

关键词： cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease neuroinflammation Parkinson’s disease RU521 STINg type I interferon

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LOW CYCLE FATIgUE AND DEFORMATION BEHAVIOR IN AN 8090 Al-Li ALLOY

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Acta Metallurgica Sinica(English Letters) 1998年第1期11卷 1-11页

作者： S.H.Ai Y.Q.wu Z.g.Wang Y.Zhang Chinese Acad of Sciences Shenyang China

Low cycle fatigue (LCF)tests under different total strain amplitudes have been conducted in order to ascertain the effect of precipitate sizes on LCF behavior of 8090 Al-Li alloy. A constant strain rate of 3×10-3s-1 and symmetrical triangular waveform were employed for all tests. It is found that the cyclic stress response of the alloy varied with the precipitate sizes and strain amplitudes. The materials in all conditions cyclically handen at first and the higher the strain amplitude, the greater the amount of hardening. The low cyclic flow stress is the highest in the peakaged condition. TEM and SEM observations demonstrated that cyclic stress-strain behavior and fracture mode of Al-Li alloy are closely related to an increase in the dislocation density and interaction between the precipitates and dislocations, sizes of δ particles and pricipitate free zone (PFZ) at grain boundaries.

关键词： Al-Li alloy low cycle fatigue aged condition

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CALCULATION OF TRANSFORMATION VOLUME FRACTION TO HQ590 HOT ROLLED STRIP STEEL DURINg CONTINUOUS COOLINg

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Acta Metallurgica Sinica(English Letters) 2004年第5期17卷 754-760页

作者： X.g.Zhou X.M.Zhao Y.B.Xu D.wu TheStateKeyLab.ofRollingTechnologyandAutomation NortheasternUniversityShenyang110004China

On the basis of phase transformation kinetics, the transformation of γ→α,P,B have been investigated through considering the effect of deformation. The calculation methods of volume fraction have also been given. Co... 详细信息

关键词： transformation kinetics volume fraction nucleation rate

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EFFECT OF THE DEFECT STATES DENSITY ON OPTICAL BAND gAP OF CdIn_(2)O_(4)THIN FILM

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Acta Metallurgica Sinica(English Letters) 2005年第3期18卷 403-410页

作者： H.S.San Z.g.wu B.Li B.X.Feng KeyLaboratoryforMagnetismandMagneticMaterialofMinistryofEducation LanzhouUniversityLanzhou730000China ShanghaiInstituteofTechnicalPhysics TheChineseAcademyofSciencesShanghai200083China

Transparent conducting oxides CdIn2O4 thin films were prepared by radio-frequenc y reactive sputtering from a Cd-In alloy target in Ar+O2 atmosphere. By transmis sion spectrum and Hall measurement for different samples prepared at different s ubstrate temperatures, it could be found that the carrier concentration would in crease with the decrease of substrate temperature, but absorption edge showed an abrupt variation from a blue shift to a red shift. Theoretically, the paper for mulated the effect of high-density point defects on band structures; it embodied the formation of band tailing, Burstein-Moss shift and band-gap narrowing. The density of holes will influence the magnitude of optical band gap and transmitta nce of light. Since extrapolation method does not fit degenerate semiconductor m aterials, a more accurate method of obtaining optical band gap is curve fitting. In addition, ionized impurities scattering is the main damping mechanism of the free electrons in CdIn2O4 films, the density of ionized impurities induced by a ltering substrate temperature will affect the carriers mobility.

关键词： sputtering CdIn2O4 thin film electrical property optical property

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RESEARCH AND SIMULATION OF THE INFLUENCE OF THREE-AXIAL COMPACTION ON POWDER METALLURgIC PRODUCT PROPERTIES

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Acta Metallurgica Sinica(English Letters) 2008年第2期21卷 116-124页

作者： D. g. Wang Y.C. wu M.H. Jiao T.Xie J.W. Yu K g. Fin School of Material and Engineering Hefei University of Technology Hefei 230009 China Institute of Tribology Hefei University of Technology Hefei 230009 China

The warm powder compaction process is simulated by the finite element analysis software, MSCJMARC. The thermal mechanically coupled analysis method is applied on the basis of the updated Lagrangian Method, to simulate the warm powder compaction process. The warm powder compaction process is simulated, and the influence of friction condition and pressing styles are researched on the density of powder green and the mechanics behavior at certain temperature. The results indicate that for cylindrical compacts, with the improvement of the friction condition, the uniformity of distribution of green relative density is largely improved, the pressing force and stress decrease, and the nonconforming pressing processes influence the distribution of green density to some degree. The status of stress distribution of the process that punches firstly press and die finally press is different from the other three processes, and presents the figure of ＇flume ＇.

关键词： Density FEM Property Three-axial compaction

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MAT1 correlates with molecular subtypes and predicts poor survival in breast cancer

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Chinese Journal of Cancer Research 2018年第3期30卷 351-363页

作者： Hanxiao Xu Xianguang Bai Shengnan Yu Qian Liu Richard g Pestell Kongming wu Department of Oncology Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Medical School of Pingdingshan University Pingdingshan 467000 China Pennsylvania Center for Cancer and Regenerative Medicine Wynnewood PA 19096 USA

Objective：Menage a trois 1（MAT1）is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA *** dysregulation is responsible for diseases including *** further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer ***：We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer ***,we performed Kyoto Encyclopedia of genes and genomes pathway analysis,correlation analysis and prognosis analysis on public ***：MAT1 was involved in multiple pathways including normal physiology signaling and disease-related ***,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein *** analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and ***,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog ***,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free ***：MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.

关键词： Menage a trois 1(MAT1) breast cancer molecular subtypes prognosis proliferation

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Coupling virio-and bacterioplankton populations with environmental variable changes in the Bohai Sea

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Acta Oceanologica Sinica 2020年第6期39卷 72-83页

作者： Caixia Wang Lin wu Yibo Wang James S.Paterson James g.Mitchell Xiaoke Hu Key Laboratory of Coastal Biology and Bioresource Utilization Yantai Institute of Coastal Zone ResearchChinese Academy of SciencesYantai 264003China Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China University of Chinese Academy of Sciences Beijing 100049China Ocean School Yantai UniversityYantai 264003China College of Science and Engineering Flinders UniversityAdelaideSA 5001Australia

Uncovering the role of environmental factors and finding critical factors which harbor significant fractions in governing microbial communities remain key questions in coastal marine *** detect the interactions between environmental factors and distributions of virio-and bacterioplankton in trophic coastal areas,we used flow cytometry to investigate the abundance of virio-and bacterioplankton covering 31 stations in the Bohai Sea of *** results suggested that the average abundance of total virus(TV)in winter(~2.29×108 particles/mL)was slightly lower than in summer(~3.83×108 particles/mL).The mean total bacterial abundance(TB)was much lower in winter(~2.54×107 particles/mL)than in summer(~5.43×107 particles/mL).Correlation analysis via redundancy analysis(RDA)and network analysis among virioplankton,bacterioplankton and environmental factors revealed that the abundances of viral and bacterial subpopulations depend on environmental *** winter,only temperature significantly influenced the abundances of virio-and *** summer,in addition to temperature,both salinity and nutrient(SiO2)had a remarkable impact on the distribution of virioand *** results showed a clear seasonal and trophic pattern throughout the whole water system,which revealed that temperature and eutrophication may play crucial roles in microbial distribution pattern.

关键词： virioplankton bacterioplankton flow cytometry network Bohai Sea

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