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The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China Life Sciences 2024年

作者： Weixiao yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen xingjie Liang Yu Han Dandan Liu Jinchao Zhang State Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationCollege of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei Province Hebei University CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology

Cancer stem cells(CSCs) play an important role in metastasis development, tumor recurrence, and treatment resistance, and are essential for the eradication of cancer. Currently, therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape, which leads to enhanced aggressive behaviors compared with CSCs that have never been treated. However, the underlying mechanisms regulating the therapeutic escape remain unknown. To this end, we established a model to isolate the therapeutic escaped CSCs(TSCSCs) from breast CSCs and performed the transcription profile to reveal the mechanism. Mechanistically, we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway, resulting in TSCSCs exhibiting enhanced motility and metastasis. Notably,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo, which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and N-cadherin.The obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

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Approximation of Smooth Stable Invariant Manifolds for Stochastic Partial Differential Equations

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Journal of Partial Differential Equations 2019年第2期32卷 112-128页

作者： GUO Zhongkai yan xingjie yanG Xin-Guang School of Mathematics and Statistics South-Central University for NationalitiesWuhan 430074China Department of Mathematics China University of Mining and TechnologyXuzhou 221008China Department of Mathematics and Information Science Henan Normal UniversityXinxiang 453007China.

Invariant manifolds are complicate random sets useful for describing and understanding the qualitative behavior of nonlinear dynamical systems.The purpose of the present paper is try to approximate smooth stable invariant manifolds for a type of stochastic partial differential equations with multiplicative white noise near the fixed point.Two examples are given to illustrate our results.

关键词： Stochastic partial differential equation smooth stable invariant manifold geometric shape analytical approximation

硝酸异山梨酯对奶牛体外模拟瘤胃发酵甲烷产量、瘤胃发酵参数和营养物质降解率的影响

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动物营养学报 2024年第5期36卷 3061-3069页

作者：付帅旗杜兴杰姚朝辉王世伟张岩虎业浩高腾云河南农业大学动物科技学院河南省家畜营养调控与生态养殖国际联合实验室郑州450002

本试验旨在研究不同水平硝酸异山梨酯(ISDN)对奶牛体外模拟瘤胃发酵甲烷产量、瘤胃发酵参数和营养物质降解率的影响。采用单因素完全随机试验设计,设置2个平行批次,分为5组,每组5个重复。各组底物中ISDN添加水平分别为0(A组,作为对照组)... 详细信息

本试验旨在研究不同水平硝酸异山梨酯(ISDN)对奶牛体外模拟瘤胃发酵甲烷产量、瘤胃发酵参数和营养物质降解率的影响。采用单因素完全随机试验设计,设置2个平行批次,分为5组,每组5个重复。各组底物中ISDN添加水平分别为0(A组,作为对照组)、0.1%(B组)、0.2%(C组)、0.4%(D组)、0.6%(E组)。试验所用底物为全混合日粮(TMR),瘤胃液供体为5头体况相近的成年健康荷斯坦公牛。发酵24和48 h时,测量发酵甲烷产量、瘤胃发酵参数和营养物质降解率。结果表明:1)发酵24和48 h时,D组、E组的产气量、甲烷产量和甲烷比例均显著低于A组(P0.05),但D组和E组的瘤胃乙酸比例、乙酸/丙酸显著低于A组(P0.05)。综上所述,添加0.4%的ISDN可以有效降低体外模拟瘤胃发酵过程中甲烷产量,且对于营养物质降解率影响较小。

关键词：体外模拟瘤胃发酵甲烷硝酸异山梨酯瘤胃发酵参数奶牛

Camptothecin-based nanodrug delivery systems

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Cancer Biology & Medicine 2017年第4期14卷 363-370页

作者： yan Wen Yingze Wang Xiaoli Liu Wei Zhang Xinhe Xiong Zhongxiao Han xingjie Liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology Beijing 100190 China University of Chinese Academy of Sciences Beijing 100049 China College of Biological Science and Engineering Hebei University of Science and Technology Shijiazhuang 050018 China Department of Materials Science and Engineering Herbert Wertheim College of Engineering University of Florida Gainesville FL 32611 USA School of Biological Sciences and Medical Engineering Southeast University Nanjing 220096 China

The drug camptothecin has a wide range of antitumor effects in cancers including gastric cancer,rectal and colon cancer,liver cancer,and lung cancer.Camptothecin-based drugs inhibit topoisomerase 1(Topo 1),leading to destruction of DNA,and are currently being used as important chemotherapeutic agents in clinical antitumor treatment.However,the main obstacle associated with cancer therapy is represented by systemic toxicity of conventional anticancer drugs and their low accumulation at the tumor site.In addition,low bioavailability,poor water solubility,and other shortcomings hinder their anticancer activity.Different from traditional pharmaceutical preparations,nanotechnology-dependent nanopharmaceutical preparations have become one of the main strategies for different countries worldwide to overcome drug development problems.In this review,we summarized the current hotspots and discussed a variety of camptothecin-based nanodrugs for cancer therapy.We hope that through this review,more efficient drug delivery systems could be designed with potential applications in clinical cancer therapy.

关键词： Camptothecins nanomedicine cancer therapy drug delivery system

Deformation response of roof in solid backfilling coal mining based on viscoelastic properties of waste gangue

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International Journal of Mining Science and Technology 2021年第2期31卷 279-289页

作者： Peng Huang Jixiong Zhang xingjie yan Anthony John Spencer Spearing Meng Li Shiwei Liu School of Mines China University of Mining and TechnologyXuzhou 221116China State Key Laboratory of Coal Resources and Safe Mining China University of Mining and TechnologyXuzhou 221116China School of Mathematics China University of Mining and TechnologyXuzhou 221116China National Engineering Laboratory For Surface Transportation Weather Impacts Prevention Broadvision Engineering ConsultantsKunming 650041China

Solid backfill mining(SBM)is a form of green mining,the core of which is to control and minimize the deformation and movement of strata above longwall coal mines.Establishing a mechanical model that can reliably describe roof deformation by considering the viscoelastic properties of waste gangue is important as it assists in improving mine designs and reducing the environmental impact on the surface.In this paper,the time-dependent deformation characteristics of gangue under different stress levels were obtained by using lateral confinement compression,that reliably represents the compaction of goaf.The viscoelastic foundation model for gangue mechanical response is different from the traditionally used elastic foundation model,as it considers the time factor and viscoelasticity.A mechanical model using a thin plate on a fractional viscoelastic foundation was established,and the roof deflection,bending moment,time-dependent,viscous and other characteristics of SBM were included and analyzed.Compared with the existing elastic foundation model,the proposed fractional order viscoelastic foundation model has higher accuracy with laboratory data.The plate deflection increases by 50.9%and the bending moment increases by 37.9%after 100 days,which the elastic model would not have been able to predict.

关键词： SBM Fractional order Thin plate Time factor Viscoelastic foundation Roof deflection and bending moment

Formation and crystallization behavior of Fe-based amorphous precursors with pre-existingα-Fe nanoparticles-Structure and magnetic properties of high-Cu-content Fe-Si-B-Cu-Nb nanocrystalline alloys

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Journal of Materials Science & Technology 2021年第6期65卷 171-181页

作者： yanhui Li xingjie Jia Wei Zhang yan Zhang Guoqiang Xie Zhiyong Qiu Junhua Luan Zengbao Jiao Key Laboratory of Materials Modification by Laser Ionand Electron Beams(Ministry of Education)School of Materials Science and EngineeringDalian University of TechnologyDalian 116024China Institute for Materials Research Tohoku UniversitySendai 980-8577Japan School of Materials Science and Engineering Harbin Institute of Technology(Shenzhen)Shenzhen 518055China Center for Advanced Structural Materials Department of Materials Science and EngineeringCity University of Hong KongHong KongChina Department of Mechanical Engineering The Hong Kong Polytechnic UniversityHong KongChina

Structure,crystallization behavior,and magnetic properties of as-quenched and annealed Fe_(81.3)Si_(4)O_(13)Cu_(1.7)(Cu1.7)alloy ribbons and effects of Nb alloying have been studied.Three-dimensional atom probe and transmission electron microscopy analyses reveal that high-number-density Cu-clusters and Pre-existing Nano-sized a-Fe Particles(PN-a-Fe)are coexistence in the melt-spun Cu1.7 amorphous matrix,and the PN-α-Fe form by manners of one-direction adjoining and enveloping the Cu-clusters.Two-step crystallization behavior associated with growth of the PN-a-Fe and subsequent nucleation and growth of newly-formedα-Fe is found in the primary crystallization stage of the Cu1.7 alloy.The number densities of the Cu-clusters and PN-a-Fe in melt-spun Fe8_(1.3-x)Si_(4)B_(13)Cu_(1.7)Nb_(x)alloys are gradually reduced with enriching of Nb,and a fully amorphous structure forms at 4 at.%Nb,although smaller Cu-clusters still exist.After annealing,2 at.%Nb coarsens the average size(D_(α-F)e)of theα-Fe grains from 14.0 nm of the Nb-free alloy to 21.6 nm,and 4 at.%Nb refines the D_(α-Fe)to 8.9 nm.The mechanisms of theα-Fe nucleation and growth during quenching and annealing for the alloys with large quantities of PN-α-Fe as well as after Nb alloying have been discussed,and an annealing-induced oc-Fe growth mechanism in term of the barrier co-contributed by competitive growth among the PN-a-Fe and diffusion-suppression effect of Nb atoms has been proposed.A coercivity(HC)αDα-Fe^(3)correlation has been found for the nanocrystalline alloys,and the permeability is inverse with the H_(C).

关键词： Fe-based nanocrystalline alloy Cu-cluster Pre-existingα-Fe nanoparticle Crystallization behavior Soft magnetic property

丁酸前药BBA纳米晶的构建及其对结肠癌细胞的抑制作用

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西南医科大学学报 2024年第2期47卷 123-129页

作者：林燕兰华琪吕诺男熊梦佳王诚梽吴越孙小端杜兴杰刘中兵钟志容西南医科大学药学院泸州646000 西南医科大学附属医院药学部泸州646000 西南医科大学附属中医医院药学部泸州646000

目的本研究将丁酸与5-氨基水杨酸(5-aminosalicylic acid,5-ASA)通过化学反应合成2-丁酰氧基-5-丁酰胺基苯甲酸(2-butyloxide-5-butylaminobenzoic acid,BBA),作为治疗结肠癌的前体药物,利用纳米技术制备BBA纳米晶缓控释制剂,并探讨BBA纳米晶对结肠癌细胞的抑制作用。方法采用溶剂反溶剂沉淀法制备BBA纳米晶,通过核磁共振扫描、红外光谱仪和透射电镜等进行物理化学表征;使用高效液相色谱法检测含量;并通过MTT实验检测不同浓度的BBA、BBA纳米晶、空白纳米晶、5-氟尿嘧啶、5-氨基水杨酸和丁酸钠与结肠癌细胞SW620共同孵育24、48、72 h后细胞的存活率,以探索BBA纳米晶对结肠癌细胞SW620的抑制效果。结果本实验成功制备了BBA纳米晶。MTT结果显示,作用时间为24 h时,各个浓度条件下BBA纳米晶与BBA对结肠癌细胞SW620的抑制率较低,两组间差异无统计学意义(P>0.05);作用时间分别为48 h和72 h,药物浓度为30μm和40μm时,BBA纳米晶对结肠癌细胞SW620的体外抑制效果低于阳性对照5-氟尿嘧啶组,但明显优于其余各同浓度给药组;BBA纳米晶与BBA,两组间比较对结肠癌细胞SW620的抑制率差异有统计学意义(P<0.05),从而表明BBA纳米晶具有缓释性,并对结肠癌细胞SW620有较好的抑制作用。结论本研究成功制备了丁酸前药BBA纳米晶,并证明了该新型药物制剂对结肠癌细胞具有抑制作用,这一结果将为结肠癌的临床治疗提供新的思路和方法。

关键词：结肠癌丁酸 5-氨基水杨酸纳米晶

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基于轨迹灵敏度的励磁系统参数可辨识性分析

电力系统自动化 2019年第1期43卷 209-214,227页

作者：刘兴杰闫亮华北电力大学电气与电子工程学院河北省保定市071003

针对在有限测点下励磁系统部分参数关联形成隐函数导致辨识结果不稳定的情况,提出一种关联参数的辨识方法。首先,利用奇异值分解选取子列集的方法将励磁系统参数划分为关联参数集和非关联参数集。其次,为降低对关联参数赋经验值消除关... 详细信息

针对在有限测点下励磁系统部分参数关联形成隐函数导致辨识结果不稳定的情况,提出一种关联参数的辨识方法。首先,利用奇异值分解选取子列集的方法将励磁系统参数划分为关联参数集和非关联参数集。其次,为降低对关联参数赋经验值消除关联性时,经验值与实际真值存在偏差对系统参数辨识结果精度的影响,选择灵敏度较小的参数作为关联参数代表赋值。为避免选取参数代表时重新引入关联参数,需进一步明确每个参数间的关联关系。为此,构造轨迹灵敏度矩阵求出判别系数,根据判别系数将相关联的系统参数划分至几个独立的隐函数参数集。仿真结果表明,该方法不仅能够有效判别励磁系统参数的可辨识性,而且可以尽可能地降低由于赋值偏差而对降阶后系统参数的辨识精度影响。

关键词：励磁系统可辨识性轨迹灵敏度隐函数参数集参数辨识

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装车站称重系统故障自动检测技术研究

煤矿机械 2022年第9期43卷 45-47页

作者：牛艳赵星杰中煤科工集团智能储装技术有限公司北京100013

针对煤矿装车站称重系统设计了一种基于PLC控制的故障自动检测方案,对系统结构设计和逻辑算法与分析进行了阐述。装车站称重系统出现故障时,可自动对故障进行诊断分析,提高了检修工作效率,减少了装车站的检修停产时间,降低了人工成本,... 详细信息

针对煤矿装车站称重系统设计了一种基于PLC控制的故障自动检测方案,对系统结构设计和逻辑算法与分析进行了阐述。装车站称重系统出现故障时,可自动对故障进行诊断分析,提高了检修工作效率,减少了装车站的检修停产时间,降低了人工成本,对煤矿智能化发展的推进具有重要意义。

关键词： PLC 称重传感器装车站故障检测自动化