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Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor

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Cancer Communications 2020年第7期40卷 285-300页

作者： Yuqi Yang Ning Ji chao-yun cai Jing-Quan Wang Zi-Ning Lei Qiu-Xu Teng Zhuo-Xun Wu Qingbin Cui Yihang Pan Zhe-Sheng Chen Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNew York 11439USA State Key Laboratory of Experimental Hematology Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Hematology and Blood Diseases HospitalTianjin 300020P.R.China School of Public Health Guangzhou Medical UniversityGuangzhouGuangdong 511436P.R.China Tomas Lindahl Nobel Laureate Laboratory the Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107P.R.China

Background:Overexpression of ATP-binding cassette(ABC)transporter is a major contributor to multidrug resistance(MDR),in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic *** this work,we evaluated the sensitizing effect of sitravatinib,a broad-spectrum tyrosine kinase inhibitor(TKI),on ATP-binding cassette subfamily B member 1(ABCB1)-and ATP-binding cassette subfamily C member 10(ABCC10)-mediated ***:MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non-toxic ***-labeled paclitaxel transportation,Western blotting,immunofluorescence analysis,and ATPase assay were carried out to elucidate the mechanism of sitravatinib-induced *** in vitro findings were translated into preclinical evaluation with the establishment of xenograft ***:Sitravatinib considerably reversed MDR mediated by ABCB1 and partially antagonized ABCC10-mediated *** in silico docking simulation analysis indicated that sitravatinib strongly and stably bound to the transmembrane domain of ABCB1 human-mouse chimeric ***,sitravatinib inhibited hydrolysis of ATP and synchronously decreased the efflux function of ***,sitravatinib could considerably enhance the intracellular concentration of anticancer ***,no significant alterations of both expression level and localization of ABCB1 were *** importantly,sitravatinib could remarkably restore the antitumor activity of vincristine in ABCB1-mediated xenograft model without observable toxic ***:The findings in this study suggest that the combination of sitrvatinib and substrate antineoplastic drugs of ABCB1 could attenuate the MDR mediated by the overexpression of ABCB1.

关键词： Sitravatinib

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Discovery of novel urea-indole derivatives as reversal agents against ABCG2-mediated drug resistance

Discovery of novel urea-indole derivatives as reversal agent...

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第十一届全国化学生物学学术会议

作者： Gao-Jie Ye chao-yun cai Yu-qi Yang Zhe-Sheng Chen Zhuo-Xun Wu Bo Wang School of Chemistry Sun Yat-Sen University Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John's University The Seventh Affiliated Hospital Sun Yat-Sen University

Multidrug resistance is characterized by the resistance of cancer cells to structurally unrelated anticancer drugs. Herein,we synthesized series of indole derivatives and identified urea-indole derivatives as reversal agents that reversed ABCG2-mediated multidrug *** compounds significantly increased the accumulation of mitoxantrone(MX) in ABCG2-overexpressing NCI-H460/MX20 *** studies revealed that reversal efficacies were not due to an alteration in the localization or expression level of ABCG2 in ABCG2-overexpressing cell lines,but stimulated the ATP hydrolysis of ABCG2 transporter.

关键词： Indole derivatives ABCG2 Multidrug resistance

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企业“大”与“强”的辩证法

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河南机电高等专科学校学报 2003年第3期11卷 92-93页

作者：钞彩云白辉河南石油工程技术研究院咨询中心河南石油勘探局规划计划处河南南阳473132

企业的发展不仅受资源投入量的限制 ,同时也受时间、管理、技术等诸多因素的影响。一个企业的规模“大”但不一定“强” ,要实现由“大”到“强” ,就应该在加大投入的同时 ,不断地进行技术创新、制度创新、管理创新 ,减少影响“规模不... 详细信息

企业的发展不仅受资源投入量的限制 ,同时也受时间、管理、技术等诸多因素的影响。一个企业的规模“大”但不一定“强” ,要实现由“大”到“强” ,就应该在加大投入的同时 ,不断地进行技术创新、制度创新、管理创新 ,减少影响“规模不经济”的因素 ,在把企业做“大”的同时 ,把企业做“强”。

关键词：企业规模经济 “大” “强” 辩证法技术创新制度创新管理创新

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加强风险预测减少决策失误

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焦作大学学报 2003年第3期17卷 40-41页

作者：白辉钞彩云河南油田河南南阳473132

分析了目前建设项目可行性研究存在的问题 ,并有针对性地提出项目可行性研究风险预测应注意的几个主要方面 ,为项目决策者减少决策失误提供了有益的参考。

关键词：建设项目可行性研究风险预测投资决策筹资风险布局安全风险决策失误

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Correlation between the rock mass properties and maximum horizontal stress:A case study of overcoring stress measurements

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 39-48页

作者： Peng Li Meifeng cai Shengjun Miao Yuan Li Yu Wang Key Laboratory of Ministry of Education for Efficient Mining and Safety of Metal Mines University of Science and Technology BeijingBeijing 100083China State Key Laboratory of Coal Resources and Safe Mining China University of Mining and TechnologyXuzhou 221116China

Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress *** investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution *** results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with *** is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and ***,there is no obvious relationship between the rock quality designation(RQD)and *** maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same *** addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.

关键词： overcoring stress measurements elastic modulus Poisson's ratio rock quality designation maximum horizontal stress fuzzy identification

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A Multi-Objective Particle Swarm Optimization Algorithm Based on Decomposition and Multi-Selection Strategy

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Computers, Materials & Continua 2025年第1期82卷 997-1026页

作者： Li Ma cai Dai Xingsi Xue Cheng Peng School of Computer Science Shaanxi Normal UniversityXi’an710119China Fujian Provincial Key Laboratory of Big Data Mining and Applications Fujian University of TechnologyFuzhou350118China Information Construction and Management Center and Institute of Artificial Intelligence and Educational New Productivity Ningxia Normal UniversityGuyuan756099China

The multi-objective particle swarm optimization algorithm(MOPSO)is widely used to solve multi-objective optimization *** the article,amulti-objective particle swarm optimization algorithmbased on decomposition and multi-selection strategy is proposed to improve the search ***,two update strategies based on decomposition are used to update the evolving population and external archive,***,a multiselection strategy is *** first strategy is for the subspace without a non-dominated *** the neighbor particles,the particle with the smallest penalty-based boundary intersection value is selected as the global optimal solution and the particle far away fromthe search particle and the global optimal solution is selected as the personal optimal solution to enhance global *** second strategy is for the subspace with a non-dominated *** the neighbor particles,two particles are randomly selected,one as the global optimal solution and the other as the personal optimal solution,to enhance local *** third strategy is for Pareto optimal front(PF)discontinuity,which is identified by the cumulative number of iterations of the subspace without non-dominated *** the subsequent iteration,a new probability distribution is used to select from the remaining subspaces to ***,an adaptive inertia weight update strategy based on the dominated degree is designed to further improve the search ***,the proposed algorithmis compared with fivemulti-objective particle swarm optimization algorithms and five multi-objective evolutionary algorithms on 22 test *** results show that the proposed algorithm has better performance.

关键词： Multi-objective optimization multi-objective particle swarm optimization decomposition multi-selection strategy

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Bearing Fault Diagnosis Based on the Markov Transition Field and SE-IShufflenetV2 Model

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Structural Durability & Health Monitoring 2025年第1期19卷 125-144页

作者： chaozhi cai Tiexin Xu Jianhua Ren Yingfang Xue School of Mechanical and Equipment Engineering Hebei University of EngineeringHandan056038China

A bearing fault diagnosis method based on the Markov transitionﬁeld(MTF)and SEnet(SE)-IShufﬂenetV2 model is proposed in this paper due to the problems of complex working conditions,low fault diagnosis accuracy,and poor generalization of rolling ***,MTF is used to encode one-dimensional time series vibration sig-nals and convert them into time-dependent and unique two-dimensional feature ***,the generated two-dimensional dataset is fed into the SE-IShufﬂenetV2 model for training to achieve fault feature extraction and classiﬁ*** paper selects the bearing fault datasets from Case Western Reserve University and Paderborn University to experimentally verify the effectiveness and superiority of the proposed *** generalization performance of the proposed method is tested under the variable load condition and different signal-to-noise ratios(SNRs).The experimental results show that the average accuracy of the proposed method under different working conditions is 99.2%without adding *** accuracy under different working conditions from 0 to 1 HP is 100%.When the SNR is 0 dB,the average accuracy of the proposed method can still reach 98.7%under varying working ***,the bearing fault diagnosis method proposed in this paper is characterized by high accuracy,strong anti-noise ability,and ***,the proposed method can also overcome the inﬂuence of variable working conditions on diagnosis accuracy,providing method support for the accurate diagnosis of bearing faults under strong noise and variable working conditions.

关键词： Bearings Markov transitionﬁeld SE-IShufﬂenetV2

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A Cross Attention Transformer-Mixed Feedback Video Recommendation Algorithm Based on DIEN

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Computers, Materials & Continua 2025年第1期82卷 977-996页

作者： Jianwei Zhang Zhishang Zhao Zengyu cai Yuan Feng Liang Zhu Yahui Sun College of Software Engineering Zhengzhou University of Light IndustryZhengzhou450000China Faculty of Information Engineering Xuchang Vocational Technical CollegeXuchang461000China College of Computer Science and Technology Zhengzhou University of Light IndustryZhengzhou450000China College of Electronics and Information Zhengzhou University of Light IndustryZhengzhou450000China

The rapid development of short video platforms poses new challenges for traditional recommendation *** systems typically depend on two types of user behavior feedback to construct user interest profiles:explicit feedback(interactive behavior),which significantly influences users’short-term interests,and implicit feedback(viewing time),which substantially affects their long-term ***,the previous model fails to distinguish between these two feedback methods,leading it to predict only the overall preferences of users based on extensive historical behavior ***,it cannot differentiate between users’long-term and shortterm interests,resulting in low accuracy in describing users’interest states and predicting the evolution of their *** paper introduces a video recommendationmodel calledCAT-MFRec(CrossAttention Transformer-Mixed Feedback Recommendation)designed to differentiate between explicit and implicit user feedback within the DIEN(Deep Interest Evolution Network)*** study emphasizes the separate learning of the two types of behavioral feedback,effectively integrating them through the cross-attention ***,it leverages the long sequence dependence capabilities of Transformer technology to accurately construct user interest profiles and predict the evolution of user *** results indicate that CAT-MF Rec significantly outperforms existing recommendation methods across various performance *** advancement offers new theoretical and practical insights for the development of video recommendations,particularly in addressing complex and dynamic user behavior patterns.

关键词： Video recommendation user interest cross-attention transformer

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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通用电气变量检测与分析装置的研制

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天津轻工业学院学报 2003年第2期18卷 39-42页

作者：王朝玉蔡云飞天津科技大学自动化工程系天津300222

针对目前日益突出的电能质量问题,开发了通用电气变量检测与分析装置,介绍了其硬件及软件构成,并为减小测量误差进行了相应算法的分析与比较,在此基础上进行了仿真测试,取得了良好的成果。

关键词：电能质量通用电气变量检测装置研制测量误差算法硬件软件

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