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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu Jie Chen ping He Yan cheng Kunrui Zhu Dan Zheng jing jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

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An engineered DNA aptamer-based PROTAC for precise therapy of p53-R175H hotspot mutant-driven cancer

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Science Bulletin 2024年第13期69卷 2122-2135页

作者： Lingping Kong Fanlu Meng ping Zhou Ruixin Ge Xiaoshan Geng Zhihao Yang Guo Li Linlin Zhang jing Wang jinfeng Ma cheng Dong Jun Zhou Sijin Wu Diansheng Zhong Songbo Xie Department of Medical Oncology Tianjin Medical University General HospitalTianjin 300052China Center for Cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinan 250014China The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease(Ministry of Education)School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Haihe Laboratory of Cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai UniversityTianjin 300071China Wisdom Lake Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215028China Department of Ophthalmology Tianjin Medical University General HospitalLaboratory of Molecular OphthalmologyTianjin Key Laboratory of Ocular TraumaTianjin Medical UniversityTianjin 300052China

Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various cancer *** extensive efforts,the absence of a druggable active site for small molecules has rendered these mutants therapeutically *** we develop a selective and effective proteolysis-targeting chimera(PROTAC)for p53-R175H,a common hotspot mutant with dominant-negative and oncogenic *** a novel iterative molecular docking-guided post-SELEX(systematic evolution of ligands by exponential enrichment)approach,we rationally engineer a high-performance DNA aptamer with improved affinity and specificity for *** this resulting aptamer as a binder for PROTACs,we successfully developed a selective p53-R175H degrader,named ***53m induces the ubiquitin–protea some-dependent degradation of p53-R175H while sparing wildtype ***,dp53m demonstrates significant antitumor efficacy in p53-R175H-driven cancer cells both in vitro and in vivo,without ***,dp53m significantly and synergistically improves the sensitivity of these cells to cisplatin,a commonly used chemotherapy *** findings provide evidence of the potential therapeutic value of dp53m in p53-R175H-driven cancers.

关键词： P53 Aptamer PROTAC Cancer Drug resistance

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Preparation and properties of ZrO_(2)-strengthened porous mullite insulation materials using Y_(2)O_(3) additive

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Journal of Iron and Steel Research International 2024年第6期31卷 1514-1521页

作者： Wang-zhi Yu Yi-hong Shi ping Liu Yong-wan Wu cheng-hao Song Xian-gong Deng Xiang Ding Song-lin Ran Yi Zhang Hai-jun Zhang Hai-liang Deng Advanced Ceramics Research Center School of Materials Science and EngineeringAnhui University of TechnologyMa'anshan 243002AnhuiChina The State Key Laboratory of Refractories and Metallurgy Wuhan University of Science and TechnologyWuhan 430081HubeiChina

ZrO_(2)-strengthened porous mullite insulation materials were prepared by foaming technology utilizing ZrSiO_(4) and Al_(2)O_(3) as primary materials and Y_(2)O_(3) as an *** effects of Y_(2)O_(3) contents on the phase composition,microstructure,mechanical properties,and heat conductivity of the porous mullite insulation materials were investigated.A suitable Y_(2)O_(3) content could promote phase transition of monoclinic ZrO_(2)(m-ZrO_(2))to tetragonal ZrO_(2)(t-ZrO_(2)),reduce pore size,and improve the strengths of as-prepared *** cold crushing strength and bending strength of as-prepared specimens with a 119µm spherical pore size using 6 wt.%Y_(2)O_(3) were 35.2 and 13.0 MPa,respectively,with a heat conductivity being only 0.248 W/(m K).

关键词： Porous mullite insulation material Zirconium oxide Y_(2)O_(3) Mechanical property Heat conductivity

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Analyzing the surface passivity effect of germanium oxynitride:a comprehensive approach through first principles simulation and interface state density

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Nuclear Science and Techniques 2024年第5期35卷 74-84页

作者： Sheng-Jie Du Xiu-Xia Li Yang Tian Yuan-Yuan Liu Ke Jia Zhong-Zheng Tang Jian-ping cheng Zhi Deng Yu-Lan Li Zheng-Cao Li Sha-Sha Lv College of Nuclear Science and Technology Joint Laboratory of jinping Ultra‑Low Radiation Background Measurement of Ministry of Ecology and Environment Key Laboratory of Beam Technology of Ministry of Education Beijing Normal UniversityBeijing Normal UniversityBeijing 100875China Joint Research Center Nuctech Company LimitedBeijing 100084China Department of Engineering Physics Key Laboratory of Particle&Radiation Imaging of Ministry of EducationTsinghua UniversityBeijing 100084China Key Laboratory of Advanced Materials(MOE) School of Materials Science and EngineeringTsinghua UniversityBeijing 100084China

High-purity germanium(HPGe)detectors,which are used for direct dark matter detection,have the advantages of a low threshold and excellent energy *** surface passivation of HPGe has become crucial for achieving an extremely low energy *** this study,first-principles simulations,passivation film preparation,and metal oxide semiconductor(MOS)capacitor characterization were combined to study surface *** calculations of the energy band structure of the -H,-OH,and -NH_(2) passivation groups on the surface of Ge were performed,and the interface state density and potential with five different passivation groups with N/O atomic ratios were accurately analyzed to obtain a stable surface *** on the theoretical calculation results,the surface passivation layers of the Ge_(2)ON_(2) film were prepared via magnetron sputtering in accordance with the optimum atomic ratio *** microstructure,C-V,and I-V electrical properties of the layers,and the passivation effect of the Al/Ge_(2)ON_(2)/Ge MOS were characterized to test the interface state *** mean interface state density obtained by the Terman method was 8.4×10^(11) cm^(-2) eV^(-1).The processing of germanium oxynitrogen passivation films is expected to be used in direct dark matter detection of the HPGe detector surface passivation technology to reduce the detector leakage currents.

关键词： Surface passivation High purity germanium detector Germanium nitrogen oxide Interface state density

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Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults:30 years’overview and forecasted trends

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4177-4193页

作者： De-Sheng Chen Ze-ping Chen Dong-Zi Zhu Lv-Xin Guan Qi Zhu Yi-Chao Lou Ze-ping He Hao-Nan Chen Hong-cheng Sun Department of General Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of General Surgery Shanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Shenzhen Institute of Translational Medicine The First Affiliated Hospital of Shenzhen UniversityShenzhen 518035Guangdong ProvinceChina Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016Zhejiang ProvinceChina

BACKGROUND Hepatobiliary and pancreatic(HBP)cancers impose a considerable burden on young populations(aged 15 to 49 years),resulting in a substantial number of new cases and fatalities each *** young populations,the HBP cancers shows extensive variance worldwide and the updated data in China is *** To investigate the current status,trends,projections,and underlying risk factors of HBP cancers among young populations in *** The Global Burden of Disease Study 2019 provided data on the annual incidence,mortality,disability-adjusted life years(DALYs),age-standardized incidence rate(ASIR),mortality rate(ASMR),and DALYs rate(ASDR)of HBP cancers in young Chinese adults between 1990 and *** trends were assessed using estimated annual percentage change and hierarchical ***-specific mortality and DALYs caused by various risks were analyzed across China and other regions,with future trends until 2035 projected using the Bayesian age-period-cohort *** From 1990 to 2019,incident cases,deaths,DALYs,ASIR,ASMR,and ASDR for liver cancer(LC)in young Chinese individuals decreased,classified into'significant decrease'***,cases of gallbladder and biliary tract cancer and pancreatic cancer rose,categorized as either'significant increase'or'minor increase'*** contribution of risk factors to mortality and DALYs for HBP tumors increased to varying *** lifestyle behaviors,such as tobacco control,weight management,alcohol moderation,and drug avoidance,could lower HBP cancers ***,except for LC in females,which is likely to initially decline slightly and then rise,the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young *** HBP cancers burden among young adults in China is expected to increase until 2035,necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these

关键词： Hepatobiliary and pancreatic cancers Burden landscape Young adults Projection China

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Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia:A Prospective,Randomized,Open,Parallel Controlled and Multicenter Clinical Study

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Current Medical Science 2024年第3期44卷 603-610页

作者： Juan YANG Meng-yuan LIANG Yu LI Hao ZHANG Wei LI jing LV Li-ping DONG jing-song jin cheng YANG Qing-hong ZHANG Li LONG Rong ZOU Yi GAO Dan SONG Chun-qin PAN Ying YAO Xiao-lin ZHAN Xiao-hui WANG Department of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology The First People’s Hospital of GuiyangGuiyang550000China Department of Nephrology The Third Xiangya HospitalCentral South UniversityChangsha410000China Department of Nephrology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710061China Department of Nephrology Wuhan No. 4 HospitalWuhan430033China Department of Nephrology Hubei Provincial Hospital of Traditional Chinese MedicineWuhan430060China Department of Nephrology Central Theater General Hospital of PLAWuhan430064China Department of Nephrology Taihe HospitalShiyan442000China Department of Nephrology Third People’s Hospital of Hubei ProvinceWuhan430033China Department of Nephrology Hubei Province Integrated Traditional Chinese and Western Medicine Hospital of Hubei provinceWuhan430024China Department of Nephrology Xi’an No.3 HospitalAffiliated Hospital of Northwest UniversityXi’an710000China Department of Nephrology Shenzhen Guangming District People’s HospitalShenzhen518000China Department of Nephrology Xiantao First People’s HospitalXiantao433000China Department of Nutrition Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology Huangshi Central HospitalHuangshi435000China Department of Nephrology The Fifth Hospital of WuhanWuhan430050China

Objective This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal *** A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two *** in the control group were treated with polysaccharide-iron complex,and those in the experimental group were administered Jianpi Shengxue *** 8 weeks of continuous treatment,the therapeutic outcomes regarding anemia were compared between the two *** After treatment,the red blood cell(RBC)count,hematocrit(HCT),reticulocyte percentage(RET),ferritin(SF),serum iron(SI),transferrin saturation(TSAT),and serum albumin(ALB)all increased(P<0.01),and the clinical symptom score and total iron binding capacity decreased(P<0.01)in the experimental ***,the improvements in RBC,HCT,RET,SF,SI,TAST,ALB,and clinical symptoms(fatigue,anorexia,dull skin complexion,numbness of hands and feet)in the experimental group were significantly greater than those in the control group(P<0.05).The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group(P<0.01).Conclusion The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia,leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

关键词： Jianpi Shengxue tablet renal anemia randomized open parallel control multicenter clinical study

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Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

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Chinese Journal of Integrative Medicine 2024年第6期30卷 489-498页

作者： CAO Ni-da ZHU Xiao-hong MA Fang-qi XU Yan DONG Jia-huan QIN Meng-meng LIU Tian-shu ZHU Chun-chao GUO Wei-jian DING Hong-hua GUO Yuan-biao LIU Li-kun SONG jin-jie WU Ji-ping cheng Yue-lei ZENG Lin ZHAO Ai-guang Oncology Department I Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai200032China Oncology Department Zhongshan HospitalFudan UniversityShanghai200032China Gastrointestinal Surgery Department Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China Oncology Department Fudan University Shanghai Cancer CenterShanghai200032China Oncology Department Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China Traditional Chinese Medicine Department Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China Oncology Department Shanxi Traditional Chinese Medicine HospitalTaiyuan030012China Oncology Department Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing102445China Oncology Department Yunnan Province Hospital of Traditional Chinese MedicineKunming650021China Oncology Department Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai201203China Shanghai NewCore Biotechnology Co. Ltd.Shanghai200240China

Objective To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC *** This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,*** survival(OS)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for *** A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were *** them,1,607 received systemic chemotherapy,215(10.74%)accepted molecular targeted therapy,44(2.2%)received checkpoint inhibitor therapy,and 769(38.43%)received ***-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09%).While 45.71%(16 cases)of patients with HER2 amplification received trastuzumab in *** application of apatinib increased(33.33%)in *** application of checkpoint inhibitors has increased since *** analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment>6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the OS of *** PSM and IPTW,the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(P<0.001).Conclusions In real-world practice for AGC in China,therapy choices consisted with ***-drug regimen was the main first-line *** CM treatment was an independent

关键词： advancedgastriccancer real-world study treatment pattern survival analysis Chinese medicine

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智慧体育课堂内涵、特征及结构架构研究

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体育研究与教育 2021年第6期36卷 60-65页

作者：叶明金成平湖北医药学院体育课部湖北十堰442000 武汉理工大学体育部湖北武汉430070

运用文献资料和逻辑分析等方法,对智慧体育课堂基本内涵和教与学特征进行分析,并对智慧体育课堂的结构架构进行研究。结果显示:智慧体育课堂本质上是智慧型育人课堂,形式上高度融合现代信息技术的新型体育教学。智慧体育课堂的教学呈现... 详细信息

运用文献资料和逻辑分析等方法,对智慧体育课堂基本内涵和教与学特征进行分析,并对智慧体育课堂的结构架构进行研究。结果显示:智慧体育课堂本质上是智慧型育人课堂,形式上高度融合现代信息技术的新型体育教学。智慧体育课堂的教学呈现智慧教学的教学新态势,学习呈现智慧学习的学习新范式。智慧体育课堂的结构架构包括智慧体育支持环境、智慧精准体育教学、智慧深度体育学习。智慧体育支持环境主要由"云—台—端"架构来实现,包括智慧云服务、智慧平台、智慧终端等;智慧体育课堂的精准教学包括课前精心设计、课中精致教学、课后精益辅导;智慧体育课堂的深度学习包括课前先学先知、课中深度探知、课后勤练熟知。

关键词：智慧体育课堂体育教育信息化精准体育教学

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OsCPK12 phosphorylates OsCATA and OsCATC to regulate H2O2 homeostasis and improve oxidative stress tolerance in rice

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Plant Communications 2024年第3期5卷 179-196页

作者： Beifang Wang Pao Xue Yingxin Zhang Xiaodeng Zhan Weixun Wu ping Yu Daibo Chen Junlin Fu Yongbo Hong Xihong Shen Lianping Sun Shihua cheng Qunen Liu Liyong Cao State Key Laboratory of Rice Biology and Breeding China National Rice Research InstituteHangzhou 311400China Northern Rice Research Center of Bao Qing Shuangyashan 155600China Zhejiang Key Laboratory of Super Rice Research China National Rice Research InstituteHangzhou 311400China

Calcium-dependent protein kinases(CPKs),the best-characterized calcium sensors in plants,regulate many aspects of plant growth and development as well as plant adaptation to biotic and abiotic ***,how CPKs regulate the antioxidant defense system remains largely *** previously found that impaired function of OsCPK12 leads to oxidative stress in rice,with more H2O2,lower catalase(CAT)activity,and lower ***,we explored the roles of OsCPK12 in oxidative stress tolerance in *** results show that OsCPK12 interacts with and phosphorylates OsCATA and OsCATC at *** of either OsCATA or OsCATC leads to an oxidative stress phenotype accompanied by higher accumulation of *** of the phosphomimetic proteins OsCATAS11D and OsCATCS11D in oscpk12-cr reduced the level of H2O2 ***,OsCATAS11D and OsCATCS11D showed enhanced catalase activity in vivo and in ***12-overexpressing plants exhibited higher CAT activity as well as higher tolerance to oxidative *** demonstrate that OsCPK12 affects CAT enzyme activity by phosphorylating OsCATA and OsCATC at Ser11 to regulate H2O2 homeostasis,thereby mediating oxidative stress tolerance in rice.

关键词： OsCPK12 OsCATs oxidative tolerance Oryza sativa L

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Achieving a remarkable low-temperature tensile ductility in a high-strength tungsten alloy

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Tungsten 2024年第1期6卷 150-161页

作者： Xiang cheng Zhuo-Ming Xie Xue-Feng Xie Long-Fei Zeng Rui Liu Jun-Feng Yang Xue-Bang Wu Xian-ping Wang Chang-Song Liu Qiang-Feng Fang Key Laboratory of Materials Physics Institute of Solid State PhysicsHFIPSChinese Academy of SciencesHefei 230031China University of Science and Technology of China Hefei 230026China Faculty of Materials Metallurgy and Chemistry Jiangxi University of Science and TechnologyGanzhou 341000China

Hot-swaging yields a high ultimate tensile strength of 712 MPa but a limited tensile ductility with the total elongation of3.6%at a testing temperature of 200℃in a representative W-0.5wt.%ZrC *** this work,the evolution of Vickers microhardness with annealing temperatures is investigated in detail,which contributes to a rough index chart to guide the search for an optimized post-annealing *** the post-annealing around 1300℃,an outstanding tensile ductility at200℃,including a uniform elongation of 14%and a total elongation of~25%,has been achieved without the sacrifice of its *** evolution of dislocations and grain structures with the annealing temperatures accessed through backscattered scanning electron microscope and transmission electron microscope analysis reveals that the improved low-temperature tensile ductility has resulted from the reduction of residual dislocations and dislocation tanglement via the static recovery,which provides more room to accommodate dislocations,and hence stronger strain hardening ability and tensile ductility.

关键词： Tungsten Low-temperature ductility Annealing Dislocations

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