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Systematic screening reveals synergistic interactions that overcome MAPK inhibitor resistance in cancer cells

Cancer Biology & Medicine 2022年第2期19卷 229-252页

作者： Yu Yu Minzhen Tao libin xu Lei Cao Baoyu Le Na An Jilin Dong Yajie xu Baoxing Yang Wei Li Bing Liu Qiong Wu Yinying Lu Zhen Xie Xiaohua Lian Department of Cell Biology Basic Medical CollegeArmy Medical University(Third Military Medical University)Chongqing 400038China MOE Key Laboratory of Bioinformatics and Bioinformatics Division Center for Synthetic and System BiologyDepartment of AutomationBeijing National Research Center for Information Science and TechnologyTsinghua UniversityBeijing 100084China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Thoracic Surgery Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Beijing Syngentech Co. LtdBeijing 102206China School of Life Sciences Tsinghua UniversityBeijing 100084China The Comprehensive Liver Cancer Center The 5th Medical Center of PLA General HospitalBeijing 100039China

Objective:Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor(MAPKi)resistance,which is one of the most common forms of resistance that has emerged in many types of ***,we aimed to systematically identify the genetic interactions underlying MAPKi resistance,and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi ***:We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi,and validated 3 genetic combinations through competitive growth,cell viability,and spheroid formation *** next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic *** also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation,Western blot,qRTPCR,and immunofluorescence ***:We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance(ITGB3+IGF1R,ITGB3+JNK,and HDGF+LGR5).We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi ***,we discovered a novel protein complex,HDGF-LGR5,that adaptively responded to MAPKi to enhance cancer cell stemness,which was up-or downregulated by the inhibitors of ITGB3+JNK or ITGB3+***:Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer ***3-+IGF1R-targeting drugs(cilengitide+linsitinib)could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex,which enhanced cancer stemness during MAPKi stress.

关键词： Pair-wise sgRNA library genetic interactions MAPKi resistance combinatorial therapy cancer stemness

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Microstructure and Mechanical Properties of High-Cr Cast Iron Bars Reinforced Hadfield Steel Matrix Composites

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Journal of Wuhan University of Technology(Materials Science) 2010年第3期25卷 464-468页

作者：牛立斌 Institute of Wear-Resistance Materials School of Mechanical and Electrical EngineeringXi'an University of Architecture and Technology

To obtain the compatible material of high hardness and high toughness,Hadfield steel matrix composites,reinforced by high-Cr cast iron bars made of flux-cored welding wires,which were inserted into the Hadfield steel melt,were *** mechanical properties of three materials,i e,composites for as-cast and quenching-water condition,as well as Hadfield steel,were *** results show that the alloy powder inside flux-cored welding wires can be melted by the heat capacity of Hadfield steel melt and solidify into high-Cr cast iron *** impact toughness of the composite for quenching-water condition is higher than that of the composite for as-cast condition and is lower than that of the Hadfield steel,but it can still meet the requirements of hardness and toughness in industrial *** of load variation,composite for quenching-water condition shows better wear resistance than those of the composite for as-cast condition and Hadfield *** modified fracture toughness and wear resistance of composites are attributed to not only the combining actions of Hadfield steel matrix and high-Cr cast iron bars,but also the effect of heat treatment.

关键词： composites flux-cored welding wires impact toughness hadfield steel

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“Go/NoGo”任务范式下乒乓球运动员对发球知觉判断的ERP研究

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天津体育学院学报 2019年第3期34卷 250-255页

作者：徐立彬阜阳师范学院体育学院安徽阜阳236037

目的:探讨优秀运动员在"Go/NoGo"任务中的脑电活动特征。方法:采用经典的"Go/NoGo"任务范式,请15名乒乓球运动员(专家组)和与之相匹配的15名乒乓球专项大学生(新手组),依据3D模拟的包含乒乓球和发球时击球部位的信息结构图片,识别能够... 详细信息

目的:探讨优秀运动员在"Go/NoGo"任务中的脑电活动特征。方法:采用经典的"Go/NoGo"任务范式,请15名乒乓球运动员(专家组)和与之相匹配的15名乒乓球专项大学生(新手组),依据3D模拟的包含乒乓球和发球时击球部位的信息结构图片,识别能够发出侧下旋球的图片(Go)并按键做出反应,识别不能够发出侧下旋球的图片(NoGo)不按键(抑制),Go刺激和NoGo刺激的概率相等。试验过程中,采用64导事件相关电位系统(ERPs)记录与分析脑电活动数据,E-Prime2.0软件采集行为反应数据。试验后,采用SPSS19.0统计软件包对行为数据和ERPs成分的潜伏期、波幅等数据进行重复测量方差分析和事后比较。结果:(1)乒乓球运动员识别Go刺激的反应时显著短于专项大学生(P<0.05),反应正确率显著高于专项大学生(P=0.001);(2)乒乓球运动员在2种刺激条件下(Go和NoGo)的N2成分潜伏期不存在显著性差异,但在额区-中央区NoGo条件下的N2成分波幅显著大于Go条件(P<0.05);(3)乒乓球运动员在2种刺激条件下(Go和NoGo)的P3成分潜伏期不存在显著性差异,但在中央-顶区NoGo条件下的P3成分波幅显著大于Go条件(P<0.01)。结论:(1)乒乓球运动员识别发球旋转方式的速度快、准确性高;(2)乒乓球运动员在Go和NoGo条件下,额-中央区、中央-顶区比乒乓球专项大学生均有更大程度的激活,在N2、P3成分上出现了明显的"NoGo效应",即更大的NoGo-N2和NoGo-P3波幅,而乒乓球专项大学生则没有,说明乒乓球运动员抑制功能较强。

关键词：乒乓球运动员 Go/NoGo ERP

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Mechanical response of continuously reinforced concrete pavement on foam concrete interlayer for two-way curved arch bridge

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Journal of Southeast University(English Edition) 2018年第3期34卷 349-355页

作者： Chen Xiaobing xu libin Liu Han He Chusheng School of Transportation Southeast UniversityNanjing 210096China

In order to research the mechanical response of continuously reinforced concrete pavement on foam concrete interlayer for a two-way curved arch bridge, the elliptical vehicle load is translated into the rectangular load based on the equivalence method. Then, a three-dimensional finite element model of the whole bridge is established. The reliability of the model is verified. Additionally, the mechanical response of continuously reinforced concrete pavement under vehicle loading is analyzed. Finally, the most unfavorable loading conditions of tensile stress, shear stress and vertical displacement are determined. The results show that the most unfavorable loading condition of tensile stress, which is at the bottom of continuously reinforced concrete pavement on the two-way curved arch bridge, is changed compared with that on homogeneous foundation. The most unfavorable loading condition of shear stress at the top is also changed. However, the most unfavorable loading condition of vertical displacement remains unchanged. The tensile stress at the bottom of about 1/4 span of the longitudinal joint, the shear stress at the top of intersection of transverse and longitudinal joint, together with the vertical displacement at the central part of longitudinal joint, are taken as design indices during the structural design of continuously reinforced concrete pavement on the two-way curved arch bridge. The results are helpful for the design of continuously reinforced concrete pavement on unequal- thickness base for the two-way curved arch bridge.

关键词： two-way curved arch bridge bridge deckpavement unequal-thickness base continuously reinforcedconcrete pavement unfavorable loading condition finiteelement method (FEM)

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乒乓球运动员在不同提示条件下知觉发球旋转方式的脑电活动特征

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天津体育学院学报 2020年第5期35卷 554-559页

作者：徐立彬阜阳师范大学体育学院安徽阜阳236037

目的:探讨乒乓球运动员在不同提示条件下知觉发球旋转方式的脑电活动特征。方法:采用“提示范式”,15名乒乓球二级运动员(专家组)和与之相匹配的15名专项大学生(新手组),依据3D模拟的包含发球时乒乓球触拍部位和拍型的信息结构图片,在... 详细信息

目的:探讨乒乓球运动员在不同提示条件下知觉发球旋转方式的脑电活动特征。方法:采用“提示范式”,15名乒乓球二级运动员(专家组)和与之相匹配的15名专项大学生(新手组),依据3D模拟的包含发球时乒乓球触拍部位和拍型的信息结构图片,在不同提示条件下知觉发球旋转方式。试验过程中,采用64导事件相关电位系统(ERPs)记录与分析脑电活动数据,E-Prime2.0软件采集行为反应数据。试验后,利用SPSS19.0软件统计分析反应时、反应正确率等行为数据,以及N1、P3等事件诱发脑电成分的潜伏期、波幅数据。结果:(1)专家在有效提示条件下的反应时显著短于无效提示条件(P<0.01),反应正确率显著高于无效提示和中性提示条件(P<0.001);(2)专家在有效提示条件下的N1成分波幅显著小于无效提示条件(P<0.05);(3)专家在有效提示条件下的P3成分波幅显著小于无效提示条件(P<0.01)。结论:(1)乒乓球运动员识别发球旋转方式的速度快、准确性高,行为反应上的启动效应显著;(2)乒乓球运动员对发球模式中的特征感知迅速,相关脑区的激活程度更高,额-中央区N1成分波幅启动效应显著;(3)乒乓球运动员采取了更为有效的加工策略,促进记忆编码,额-中央区、顶-枕区P3成分波幅启动效应显著。而乒乓球专项大学生无论在行为反应,还是脑电活动特征方面均未出现显著的启动效应。这说明,乒乓球运动员长时记忆系统中可能存在若干由球触拍部位和拍型2个特征构成的简化的信息结构模式,使其能够快速有效的识别发球旋转方式。

关键词：乒乓球运动员启动效应脑电活动

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Influence of longitudinal slope on the mechanical response of steel deck pavement

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Journal of Southeast University(English Edition) 2018年第1期34卷 71-77页

作者： Chen Xiaobing　 xu libin Luo Ruilin Liu Han School of Transportation Southeast UniversityNanjing 210096China

In order to study the influence of longitudinal slope on the mechanical response of steel deck pavement,a method of slope-modulus transformation was proposed for the mechanical analysis of the steel deck pavement based on the time-temperature equivalence *** the mechanical action on a slope,a finite element model of the deck pavement was established to determine the critical load position of tensileand shear stress of the steel deck ***,the influence of longitudinal slope on the mechanical response of the deck pavement under the conditions of uniform speed and emergency braking was *** results indicate that the maximum transverse tensile stress at the pavement surface and the maximum transverse shear stress at the pavement bottom are always greater than their longitudinal counterparts under uniform *** emergency braking,however,the critical slope gradient of t e maximum transverse and longitudinal tensile stress at t e pavement surface is 6%.The maximum longitudinal shear stess at t e pavement bottom is always greater ta n t e maximum tansverse shear *** stidy is helpful in t e strctural design of large longitudinal slope steel deck pavements.

关键词： longitudinal slope steel deck pavement stress critical load position time-temperature equivalence finite element method

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Learning of Iterative Learning Control for Batch Processes

Learning of Iterative Learning Control for Batch Processes

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第32届中国过程控制会议(CPCC2021)

作者： Zhixing Cao libin xu Jingyi Lu Furong Gao Feng Qian MOE Key Laboratory of Smart Manufacturing in Energy Chemical Process East China University of Science and Technology Department of Electrical Engineering Paderborn University Department of Chemical and Biological Engineering Hong Kong University of Science and Technology

Flexible manufacturing as an essential component of smart manufacturing implements the customized production mode,thereby requesting fast controller adaptation for producing different goods but still with high *** problem becomes even acute for batch *** we present a solution called learning of iterative learning control(ILC) based neural *** is able to recommend control parameters for ILC controllers accordingly,so as to yield fast tracking error convergence and smaller steady-state error for disparate set-point profiles,which is deemed an abstraction of different production *** method substantially outperforms a benchmark ILC on a variety of systems and cases,thereby showing its potential of deployment on the industrial internet of things.

关键词： Batch Process Iterative Learning Control Neural Network Flexible Manufacturing

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Influence of rainfall on skid resistance performance and driving safety conditions of asphalt pavements

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Journal of Southeast University(English Edition) 2019年第4期35卷 482-490页

作者： Chen Xiaobing Wang Juntian Liu Han xu libin Zhao Ronglong School of Transportation Southeast UniversityNanjing 210096China

To study the influence of rainfall on pavement skid-resistance performance and driving safety,the water film thickness(WFT)concept considering the longitudinal and transverse slopes of the pavement was utilized based on the total discharge formulation and turbulence theory of slope *** experimental data measured using the British pendulum test under varying WFT levels,a model for calculating the skid resistance,namely the British pendulum number(BPN),was formulated and used to quantitatively evaluate the effects of rainfall intensity,transverse,and longitudinal slopes on the computed *** study results reveal that skid resistance is linearly proportional to the pavement transverse slope and inversely proportional to the rainfall intensity and the pavement longitudinal *** particular,rainfall intensity,along with pavement texture depth,exhibited a significant impact on the tire-pavement friction and skid-resistance *** results further indicate that driving safety under wet weather is predominantly governed by skid resistance and *** BPN and sideway force coefficient(SFC60)values for new asphalt pavements under different rainfall intensities are provided along with some modification to the stopping sight distance(SSD)*** driving speed limits are also determined using a safe-driving model to develop the appropriate speed limit *** overall study results provide some insights,methodology approach,and reference data for the evaluation of pavement skid-resistance performance and driving safety conditions under different pavement slopes and rainfall intensities.

关键词： rainfall intensity pavement transverse and longitudinal slopes skid resistance driving safety water film thickness(WFT) British pendulum number(BPN) stopping sight distance(SSD)

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中顺边逆法在深基坑基础中的应用

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施工技术 2017年第5期46卷 43-47页

作者：徐立斌龙信建设集团有限公司江苏海门226100

仁恒海河广场一期公建项目位于天津市海河沿岸,由于该项目地理位置特殊、周边环境复杂且与地铁出入口相连、基坑面积大、深度深,使得该项目地下工程的施工较为复杂,该工程采用"中顺边逆"施工方法,在保障基坑安全的同时加快了施工进度。... 详细信息

仁恒海河广场一期公建项目位于天津市海河沿岸,由于该项目地理位置特殊、周边环境复杂且与地铁出入口相连、基坑面积大、深度深,使得该项目地下工程的施工较为复杂,该工程采用"中顺边逆"施工方法,在保障基坑安全的同时加快了施工进度。对"中顺边逆"的施工工艺流程及主要施工节点的处理方法进行了详细介绍。

关键词：深基坑中顺边逆法钻孔灌注桩施工技术

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Construction and packaging of pseudotype retrovirus containing human N-ras cDNA antisense sequence and its biological effects on human hepatoma cells

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Cell Research 1990年第2期1卷 131-139页

作者： JIA libin, WANG XIANG, xu XITJLAN, MA JIQING, YANG JIN-YING, LIU OHAOTING AND GU JIANRENNational Research Center fcr Orcogenes and Relaied Genes, Shanghai Cancer Institute, China National Research Center for Orcogenes and Related Genes Shanghai Cancer Institute China

N-ras is one of the transforming genes in human hepatic cancer cells. It has been found that N-ras was overexpressed at the mRNA and protein level in hepatoma cells. In order to explore the biological roles of N-ras in human hepatic carcinogenesis and the potential application in control of cancer cell growth, a pseudotype retrovirus containing antisense sequence of human N-ras was constructed and packaged. A recombinant retrovirus vector containing antisense or sense sequences of N-ras cDNA was constructed by pZIP-NeoSV (Ⅹ) 1. The pseudotype virus was packaged and rescued by transfection and infection in PAand ψ2 helper cells, It has been demonstrated that the pseudotype retrovirus containing antisense N-ras sequence did inhibit the growth of human PLC/PRF/5 hepatoma cells aceompanied with inhibition of p21 expression, while the retrovirus containing sense sequence had none. The pseudotype virus had no effect on human diploid fibroblasts.

关键词： N-ras cDNA antisense RNA retroviral vector hepatic cell.

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