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A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity

Angewandte Chemie 2024年第31期136卷

作者： Tao Feng Zixin Tang Jun Shu Xianbo Wu Hui Jiang Zhuoli Chen Dr. Yu Chen Prof. Liangnian Ji Prof. Dr. Hui Chao MOE Key Laboratory of Bioinorganic and Synthetic Chemistry State Key Laboratory of Anti-Infective Drug Discovery and Development Guangdong Basic Research Center of Excellence for Functional Molecular Engineering School of Chemistry Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital Sun Yat-Sen University Guangzhou 510006 P. R. China MOE Key Laboratory of Theoretical Organic Chemistry and Functional Molecule School of Chemistry and Chemical Engineering Hunan University of Science and Technology Xiangtan 400201 P. R. China

An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor-immune responses. Research has shown that non-apoptotic cell death, such as pyroptosis and ferroptosis, can enhance the immune response. Despite this, there has been limited investigation and reporting on the mechanisms of oncosis and its correlation with immune response. Herein, we designed and synthesized a Ru(II) complex that targeted the nucleus and mitochondria to induce cell oncosis. Briefly, the Ru(II) complex disrupts the nucleus and mitochondria DNA, which active polyADP-ribose polymerase 1, accompanied by ATP consumption and porimin activation. Concurrently, mitochondrial damage and endoplasmic reticulum stress result in the release of Ca 2+ ions and increased expression of Calpain 1. Subsequently, specific pore proteins porimin and Calpain 1 promote cristae destruction or vacuolation, ultimately leading to cell membrane rupture. The analysis of RNA sequencing demonstrates that the Ru(II) complex can initiate the oncosis-associated pathway and activate both innate and adaptive immunity. In vivo experiments have confirmed that oncosis promotes dendritic cell maturation and awakens adaptive cytotoxic T lymphocytes but also activates the innate immune by inducing the polarization of macrophages towards an M1 phenotype.

关键词： Medicinal Inorganic Chemistry Ruthenium DNA Damage Oncosis Innate and Adaptive Immunity

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Corrigendum to “Performance Investigation of Tunnel Lining with Cavities around Surrounding Rocks”

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Advances in Civil Engineering 2021年第1期2021卷

作者： Jiajia Li Yong Fang Cheng Liu Yongxing Zhang Weihua Lu Hunan Provincial Key Laboratory of Hydropower Development Key Technology Changsha 410014 China Key Laboratory of Transportation Tunnel Engineering (Southwest Jiaotong University) Ministry of Education Chengdu 610031 Chinameb.gov.tr Nanjing Forestry University Nanjing 210037 ***

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Direct Measurement of the Astrophysical F19(p,αγ)O16 Reaction in the Deepest Operational Underground laboratory

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Physical Review Letters 2021年第15期127卷 152702-152702页

作者： L. Y. Zhang J. Su J. J. He M. Wiescher R. J. deBoer D. Kahl Y. J. Chen X. Y. Li J. G. Wang L. Zhang F. Q. Cao H. Zhang Z. C. Zhang T. Y. Jiao Y. D. Sheng L. H. Wang L. Y. Song X. Z. Jiang Z. M. Li E. T. Li S. Wang G. Lian Z. H. Li X. D. Tang H. W. Zhao L. T. Sun Q. Wu J. Q. Li B. Q. Cui L. H. Chen R. G. Ma B. Guo S. W. Xu J. Y. Li N. C. Qi W. L. Sun X. Y. Guo P. Zhang Y. H. Chen Y. Zhou J. F. Zhou J. R. He C. S. Shang M. C. Li X. H. Zhou Y. H. Zhang F. S. Zhang Z. G. Hu H. S. Xu J. P. Chen W. P. Liu Key Laboratory of Beam Technology and Material Modification of Ministry of Education College of Nuclear Science and Technology Beijing Normal University Beijing 100875 China Department of Physics and The Joint Institute for Nuclear Astrophysics University of Notre Dame Notre Dame Indiana 46556 USA Extreme Light Infrastructure—Nuclear Physics Horia Hulubei National Institute for Research and Development in Physics and Nuclear Engineering (IFIN-HH) Bucharest-Măgurele 077125 Romania Institute of Modern Physics Chinese Academy of Sciences Lanzhou 730000 China China Institute of Atomic Energy Beijing 102413 China College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen 518060 China Shandong Provincial Key Laboratory of Optical Astronomy and Solar-Terrestrial Environment Institute of Space Sciences Shandong University Weihai 264209 China Yalong River Hydropower Development Company Chengdu 610051 China

Fluorine is one of the most interesting elements in nuclear astrophysics, where the F19(p,α)O16 reaction is of crucial importance for Galactic F19 abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential F19(p,αγ)O16 reaction channel. The γ-ray yields were measured over Ec.m.=72.4–344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear F19(p,αγ)O16 reaction rate has been determined directly at the relevant astrophysical energies.

关键词： H & He burning H & He induced nuclear reactions Nuclear astrophysics Resonance reactions

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Direct measurement of the astrophysical F19(p,αγ)O16 reaction in a deep-underground laboratory

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Physical Review C 2022年第5期106卷 055803-055803页

作者： L. Y. Zhang J. Su J. J. He R. J. deBoer D. Kahl M. Wiescher D. Odell Y. J. Chen X. Y. Li J. G. Wang L. Zhang F. Q. Cao H. Zhang Z. C. Zhang T. Y. Jiao Y. D. Sheng L. H. Wang L. Y. Song X. Z. Jiang Z. M. Li E. T. Li S. Wang G. Lian Z. H. Li B. Guo X. D. Tang L. T. Sun Q. Wu J. Q. Li B. Q. Cui L. H. Chen R. G. Ma N. C. Qi W. L. Sun X. Y. Guo P. Zhang Y. H. Chen Y. Zhou J. F. Zhou J. R. He C. S. Shang M. C. Li J. P. Cheng W. P. Liu Key Laboratory of Beam Technology of Ministry of Education College of Nuclear Science and Technology Beijing Normal University Beijing 100875 China Institute of Radiation Technology Beijing Academy of Science and Technology Beijing 100875 China The Joint Institute for Nuclear Astrophysics Department of Physics University of Notre Dame Notre Dame Indiana 46556 USA Extreme Light Infrastructure - Nuclear Physics Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH) Bucharest-Măgurele 077125 Romania Institute of Nuclear and Particle Physics and Department of Physics and Astronomy Ohio University Athens Ohio 45701 USA Institute of Modern Physics Chinese Academy of Sciences Lanzhou 730000 China China Institute of Atomic Energy Beijing 102413 China College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen 518060 China Shandong Provincial Key Laboratory of Optical Astronomy and Solar-Terrestrial Environment Institute of Space Sciences Shandong University Weihai 264209 China Yalong River Hydropower Development Company Chengdu 610051 China

Fluorine is one of the most interesting elements in nuclear astrophysics. The F19(p,α)O16 reaction is of astrophysical importance in addressing fluorine abundances in the universe and CNO material loss in the first generation stars. As a day-1 campaign in the Jinping Underground Nuclear Astrophysics experiment facility (JUNA), we report the full direct measurement results of the F19(p,αγ)O16 reaction, which is one of the important channels in the F19(p,α)O16 reaction. The γ-ray yields were measured over a center-of-mass energy range of Ec.m. = 72.4–344 keV, covering the astrophysical Gamow window. The measurement has reached down to an unprecedentedly low energy of 72.4 keV. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing underground laboratory (CJPL), one of the deepest underground laboratories in the world (2400 m). The astrophysical S factors in the energy region of 72.4–188.8 keV have been derived experimentally for the first time. The present low-energy astrophysical S factors deviate significantly from previous theoretical predictions, and the associated uncertainties are remarkably reduced. The thermonuclear F19(p,αγ)O16 rate has been determined down to a low temperature of ≈0.05 GK, for astrophysical modeling, based on a firmer experimental basis. Furthermore, the present work shows that the contribution owing to the (p,α0) channel dominates the total (p,α) rate over the entire low temperature region below 0.12 GK, clarifying the role these two channels contributing to the total rate.

关键词： H & He burning Hydrostatic stellar nucleosynthesis Nuclear astrophysics Nuclear reactions 20 ≤ A ≤ 38 6 ≤ A ≤ 19 Monte Carlo methods Nuclear data analysis & compilation Particle sources & targets Radiation detectors

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Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis

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International Journal of Oral Science 2025年第02期 147-154页

作者： Lu Zhang Chen Lin Zhuo Chen Lin Yue Qing Yu Benxiang Hou Junqi Ling Jingping Liang Xi Wei Wenxia Chen Lihong Qiu Jiyao Li Yumei Niu Zhengmei Lin Lei Cheng Wenxi He Xiaoyan Wang Dingming Huang Zhengwei Huang Weidong Niu Qi Zhang Chen Zhang Deqin Yang Jinhua Yu Jin Zhao Yihuai Pan Jingzhi Ma Shuli Deng Xiaoli Xie Xiuping Meng Jian Yang Xuedong Zhou Zhi Chen Department of Cariology and Endodontics Wuhan University & State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Department of Endodontics Stomatological Hospital of Xiamen Medical College Stomatology Hospital School of Stomatology Zhejiang University School of Medicine Department of Cariology and Endodontology Peking University School and Hospital of Stomatology National Center of Stomatology National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Oral Diseases Department of Operative Dentistry & EndodonticsSchool of Stomatology The Fourth Military Medical University Center for Microscope Enhanced Dentistry Beijing Stomatological Hospital Capital Medical University Department of Operative Dentistry and Endodontics Hospital of Stomatology Guanghua School of Stomatology Guangdong Provincial Key Laboratory of Stomatology Sun Yat-Sen University Department of Endodontics Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Clinical Research Center for Oral Diseases National Center for Stomatology Shanghai Key Laboratory of Stomatology Shanghai Jiao Tong University College & Hospital of Stomatology Guangxi Medical University Department of Endodontics School of Stomatology China Medical University State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatolo

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered *** is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient’s general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.

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Expert consensus on the diagnosis and treatment of non-small cell lung cancer with MET alteration

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Cancer Biology & Medicine 2025年第3期22卷 237-265页

作者： Huijing Feng Yang Xia Wenxian Wang Chunwei Xu Qian Wang Zhengbo Song Ziming Li Jinpu Yu Wenzhao Zhong Zhijie Wang Yongchang Zhang Jingjing Liu Shirong Zhang Xiuyu Cai Anwen Liu Wen Li Ping Zhan Hongbing Liu Tangfeng Lyu Liyun Miao Lingfeng Min Gen Lin Long Huang Jingping Yuan Zhansheng Jiang Xingxiang Pu Chuangzhou Rao DongqingLyu Zongyang Yu Xiaoyan Li Chuanhao Tang Chengzhi Zhou Qi Mei Hui Guo Qian Chu Rui Meng Xuewen Liu Jingxun Wu Jin Zhou Zhengfei Zhu Weiwei Pan Fei Pang Meizhen Hu Kai Wang Fan Wu Bingwei Xu Ling Xu Liping Wang Youcai Zhu Jisheng Li Yanru Xie Xinqing Lin Jing Cai Lin Wang Yingying Du Wang Yao Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Jing Kang Jiatao Zhang Chao Zhang Wenbin Gao Jianhui Huang Yinbin Zhang Pingli Sun Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Yue Hao Zheng Wang Bing Wan Donglai Lyu Xiaodong Jiao Lin Shi Gang Lan Shengjie Yang Yanhong Shang Yina Wang Bihui Li Gang Jin Kang Zheng Jun Ma Wenfeng Li Zhang Zhang Zhongwu Li Yuan Li Zhefeng Liu Xuelei Ma Nong Yang Lin Wu Qiming Wang Guansong Wang Zhuan Hong Jiandong Wang Meiyu Fang Yong Fang Xixu Zhu Yi Shen Ke Wang Xiubao Ren Yiping Zhang Shenglin Ma Junping Zhang Yong Song Wenfeng Fang Yuanzhi Lu Department of Thoracic Oncology Shanxi Academy of Medical SciencesShanxi Bethune HospitalTaiyuan 030032China Key Laboratory of Respiratory Disease of Zhejiang Province Department of Respiratory and Critical Care MedicineSecond Affiliated Hospital of Zhejiang University School of MedicineCancer CenterZhejiang UniversityHangzhou 310009China Department of Chemotherapy Chinese Academy of Sciences University Cancer Hospital(Zhejiang Cancer Hospital)Hangzhou 310022China Institute of Cancer and Basic Medicine(ICBM) Chinese Academy of SciencesHangzhou 310022China Department of Respiratory Medicine Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China Department of Respiratory Medicine Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjing 210029China Department of Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Cancer Molecular Diagnostics Core Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Guangdong Lung Cancer Institute Guangdong Provincial Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSchool of MedicineGuangzhou 510080China State Key Laboratory of Molecular Oncology Department of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Thoracic Cancer Jilin Cancer HospitalChangchun 130012China Translational Medicine Research Center Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang ProvinceAffiliated Hangzhou First People’s HospitalCancer CenterZhejiang Unive

Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC *** alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein *** identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical *** East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET *** consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment *** offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.

关键词： Mesenchymal-epithelial transition factor MET exon 14 skipping mutation MET amplification non-small cell lung cancer precision medicine targeted therapy tyrosine kinase

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Source of propagules of the fouling green macroalgae in the Subei Shoal,China

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Acta Oceanologica Sinica 2018年第4期37卷 102-108页

作者： SONG Wei JIANG Meijie WANG Zongling WANG Hongping ZHANG Xuelei FU Mingzhu Key Laboratory of Science and Engineering for Marine Ecology and Environment The First Institute of OceanographyState Oceanic Administration Laboratory of Marine Ecology and Environmental Science Qingdao National Laboratory for Marine Science and Technology Hunan Provincial Key Laboratory of Phytohormones and Growth Development Hunan Agricultural University

Since 2007,large-scale green tides dominated by Ulva prolifera consecutively bloomed in the Yellow Sea and caused great economic *** fouling *** on the Pyropia yezoensis aquaculture rafts in the Subei Shoal was regarded as the major source of the floating ***,it was still unclear about the seed source of fouling green macroalgae attached on the *** this study,the field surveys and the indoor experiments were conducted to reveal the source of propagules of the fouling green macroalgae on the rafts and to study the anti-fouling material for *** aquaculture rafts which could possibly be a feasible strategy to control the green tides in the Yellow *** results showed that（1） micro-propagules of several green macroalgal species,including ***,***,***,***,and Blidingia *** in the waters and sediments in the Subei Shoal and their proportion remarkably changed over time;（2） the bamboo poles with peeling treatment could significantly reduce the amount of *** micro-propagules *** study confirmed that the micro-propagules distributed in the Subei Shoal area were the precursors of the green tides,and provided a feasible method to control the Yellow Sea large-scale green tides at the beginning.

关键词： green tides source of propagules Ulva prolifera anti-fouling

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Reduced dietary nitrogen with a high Lys:CP ratio restricted dietary N excretion without negatively affecting weaned piglets

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Animal Nutrition 2019年第2期5卷 115-123页

作者： Hongnan Liu Li Wu Hui Han Yuying Li Lijian Wang Jie Yin Wenjun Fan Miaomiao Bai Jiming Yao Xingguo Huang Tiejun Li Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-Ecological Processes in Subtropical RegionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha410125China Hunan Co-Innovation Center of Animal Production Safety Changsha410128China University of Chinese Academy of Sciences Beijing100039China Department of Animal Science Hunan Agriculture UniversityChangsha410128China Guangdong Wangda Group Academician Workstation for Clean Feed Technology Research and Development in Swine Guangdong Wangda Group Co.Ltd.Guangzhou510663China

We hypothesized that balancing the content of exogenous amino acids, especially lysine, to reduce protein content in swine diets could reduce nitrogen(N) pollution associated with animal husbandry. Two experiments(45 d each experiment) were performed on weaned piglets(Duroc x Landrace x Yorkshire,28 d of age) to test this and to determine the optimal lysine to crude protein(Lys:CP) ratio in diet. In Exp. 1,12 piglets(6 replicates [n = 6]) were fed diets containing different levels of CP(17% and 20%) but the same level of Lys, Increased CP content resulted in significant increases(P < 0.05) of average daily gain(ADG), average daily feed intake(ADFI), and body weight(BW);but did not affect the feed to gain ratio. In Exp. 2,24 piglets(8 replicates [n = 8]) were fed 1 of 3 diets as follows: 1) 20% CP with a regular Lys:CP ratio(6.23%, control);2) 17% CP with a reduced Lys:CP ratio(6.14%, LL);or 3) 17% CP with a standard Lys:CP ratio(7.32%, SL). The ADG, final BW, serum concentrations of growth hormone and insulin-like growth factor-1, villus height in the jejunum, and villus height to crypt depth ratio were the lowest in piglets fed LL diet, whereas blood urea N concentration was the lowest and the value of lipase activity was the highest in the piglets fed SL diet. The SL diet did not affect growth performance,intestinal morphology, or serum hormone concentrations, indicating that reduced dietary N with a high Lys:CP ratio can efficiently reduce dietary N excretion without negatively affecting weaned piglets.

关键词： Protein Lysine Feeding Digestion Nutrition Genetic mapping

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Expert consensus on the diagnosis and treatment of solid tumors with BRAF mutations

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The Innovation 2024年第6期5卷 100-116页

作者： Wenxian Wang Bin Lian Chunwei Xu Qian Wang Ziming Li Nan Zheng Aijun Liu Jinpu Yu Wenzhao Zhong Zhijie Wang Yongchang Zhang Jingjing Liu Shirong Zhang Xiuyu Cai Anwen Liu Wen Li Lili Mao Ping Zhan Hongbing Liu Tangfeng Lv Liyun Miao Lingfeng Min Yu Chen Jingping Yuan Feng Wang Zhansheng Jiang Gen Lin Long Huang Xingxiang Pu Rongbo Lin Weifeng Liu Chuangzhou Rao Dongqing Lv Zongyang Yu Xiaoyan Li Chuanhao Tang Chengzhi Zhou Junping Zhang Junli Xue Hui Guo Qian Chu Rui Meng Xuewen Liu Jingxun Wu Rui Zhang Jin Zhou Zhengfei Zhu Yongheng Li Hong Qiu Fan Xia Yuanyuan Lu Xiaofeng Chen Jian Feng Rui Ge Enyong Dai Yu Han Weiwei Pan Fei Pang Xin Huang Meizhen Hu Qing Hao Kai Wang Fan Wu Binbin Song Bingwei Xu Liping Wang Youcai Zhu Li Lin Yanru Xie Xinqing Lin Jing Cai Ling Xu Jisheng Li Xiaodong Jiao Kainan Li Jia Wei Huijing Feng Lin Wang Yingying Du Wang Yao Xuefei Shi Xiaomin Niu Dongmei Yuan Yanwen Yao Jianhui Huang Yue Feng Yinbin Zhang Pingli Sun Hong Wang Mingxiang Ye Dong Wang Zhaofeng Wang Yue Hao Zhen Wang Bin Wan Donglai Lv Shengjie Yang Jin Kang Jiatao Zhang Chao Zhang Wenfeng Li Jianfei Fu Lizhi Wu Shijie Lan Juanjuan Ou Lin Shi Zhanqiang Zhai Yina Wang Bihui Li Zhang Zhang Ke Wang Xuelei Ma Zhongwu Li Zhefeng Liu Nong Yang Lin Wu Huijuan Wang Gu Jin Guansong Wang Jiandong Wang Hubing Shi Meiyu Fang Yong Fang Yuan Li Xiaojia Wang Jing Chen Yiping Zhang Xixu Zhu Yi Shen Shenglin Ma Biyun Wang Yong Song Zhengbo Song Wenfeng Fang Yuanzhi Lu Lu Si Department of Chemotherapy Chinese Academy of Sciences University Cancer Hospital(Zhejiang Cancer Hospital)HangzhouZhejiang 310022P.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Melanoma and SarcomaPeking University Cancer Hospital&InstituteBeijing 100142P.R.China Institute of Cancer and Basic Medicine(ICBM) Chinese Academy of SciencesHangzhouZhejiang 310022P.R.China Department of Respiratory Medicine Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210002P.R.China Department of Respiratory Medicine Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjingJiangsu 210029P.R.China Department of Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030P.R.China Beijing Key Laboratory of Mental Disorders National Clinical Research Center for Mental Disorders&National Center for Mental DisordersBeijing Anding HospitalCapital Medical UniversityBeijing 200030China Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 200030China Senior Department of Pathology the 7th Medical Center of PLA General HospitalBeijing 100700P.R.China Department of Cancer Molecular Diagnostics Core Tianjin Medical University Cancer Institute and HospitalTianjin 300060P.R.China Guangdong Lung Cancer Institute Guangdong Provincial Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSchool of MedicineGuangzhouGuangdong 510080P.R.China State Key Laboratory of Molecular Oncology Department of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School

The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and *** the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of *** mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among *** is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.

关键词： BRAF diagnosis treatment

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Numerical investigation of bolt anchorage with tension force and shear force

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IOP Conference Series: Earth and Environmental Science 2020年第1期525卷

作者： Yu Chen Yongde Li Hunan Provincial Key Laboratory of Hydropower Development Key Technology Changsha Hunan province 410014 China China Construction Fifth Engineering Division Corp. Ltd Changsha Hunan province 410000 China

The bolt anchorage with tension force and shear force are studied numerically by FLAC3D modelling. A tri-linear material model was utilized for the bolt steels in order to simulate the strain hardening behaviour of the materials. The numerical modelling show that different types of bolts have similar load capacities, while their deformation capacities are different. The numerical results match the laboratory test results. The different deformation capacities of rock bolts are attributed to their different bonding conditions and stretching lengths. The axial load in the rebar bolt reduces exponentially from the loading point close to the joint to the bolt end. The axial load in the D-Bolt has its maximum at the joint and reduces slowly as the distance from the joint increases.

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