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Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

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Nano Research 2024年第7期17卷 6386-6399页

作者： Jun Zhu Shoujie Zhao Yejing Zhu Shouzheng Ma Tenghui Han Fenghua Xu Huichen Li Bo Wang Zhixiong Guo Da Chen Yongquan Qu zhimin tian Junlong Zhao Lei Liu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers National Clinical Research Center for Digestive DiseasesXijing HospitalFourth Military Medical UniversityXi’an 710032China Department of General Surgery The Southern Theater Air Force HospitalGuangzhou 510602China Department of General Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Thoracic Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Neurology Airborne Army HospitalWuhan 430012China Key Laboratory of Modern Teaching Technology(Ministry of Education) Shaanxi Normal UniversityXi’an 710062China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China Department of Pediatrics Tangdu HospitalFourth Military Medical UniversityXi’an 710000China

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate ***,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to *** this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of ***,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal *** prominent ferroptosis biomarkers,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ***,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@*** orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@*** conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

关键词： anti-tumor ferroptosis Fe-Material of Institut Lavoisier(Fe-MIL) sorafenib adenosine monophosphate(AMP)-activated protein kinase(AMPK)

Insights on catalytic mechanism of CeO2 as multiple nanozymes

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Nano Research 2022年第12期15卷 10328-10342页

作者： Yuanyuan Ma zhimin tian Wenfang Zhai Yongquan Qu Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an710072China

CeO2 with the reversible Ce3+/Ce4+redox pair exhibits multiple enzyme-like catalytic performance,which has been recognized as a promising nanozyme with potentials for disease diagnosis and *** surface physicochemical properties of various CeO2 catalysts with controllable sizes,morphologies,and surface states enable a rich surface chemistry for their interactions with various molecules and species,thus delivering a wide variety of catalytic behaviors under different *** the significant progress made in developing CeO2-based nanozymes and their explorations for practical applications,their catalytic activity and specificity are still uncompetitive to their counterparts of natural enzymes under physiological *** the attempt to provide the insights on the rational design of highly performed CeO2 nanozymes,this review focuses on the recent explorations on the catalytic mechanisms of CeO2 with multiple enzyme-like *** the detailed discussion and proposed perspectives,we hope this review can raise more interest and stimulate more efforts on this multi-disciplinary field.

关键词： heterogeneous catalysis ceria nanozyme oxygen vacancy

小檗碱和XAV939联合应用可抑制骨肉瘤细胞MG-63的迁移与凋亡

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中国肿瘤生物治疗杂志 2024年第5期31卷 469-476页

作者：吴昊越康兵田志敏张浩强李旭升宁夏医科大学第一临床医学院宁夏银川750004 联勤保障部队第九四〇医院关节外科甘肃兰州730050

目的:探讨小檗碱(BBR)联合XAV939对骨肉瘤MG-63细胞迁移与凋亡的影响及其可能的机制。方法:培养MG-63细胞,分别加入20~120μmol/L的BBR和5~60μmol/L的XAV939,通过CCK-8法测定BBR和XAV939的细胞毒性,采用Chou-Talalay分析法计算两药的... 详细信息

目的:探讨小檗碱(BBR)联合XAV939对骨肉瘤MG-63细胞迁移与凋亡的影响及其可能的机制。方法:培养MG-63细胞,分别加入20~120μmol/L的BBR和5~60μmol/L的XAV939,通过CCK-8法测定BBR和XAV939的细胞毒性,采用Chou-Talalay分析法计算两药的联合指数,确定后续实验的干预剂量;将MG-63细胞随机分为空白对照(NC)组、BBR组、XAV939组和BBR+XAV939联合组,采用划痕愈合实验、Transwell小室法检测BBR与XAV939单独或联合处理对MG-63细胞迁移能力的影响,Hoechst 33258染色、JC-1染色及AnnexinⅤ-FITC/PI双染流式细胞术检测对细胞线粒体膜电位和凋亡的影响,免疫荧光法检测BAX蛋白的表达,WB法检测对细胞中MMP-2表达的影响,qPCR法检测对MMP-2基因表达的影响。结果:BBR和XAV939以剂量依赖方式抑制MG-63细胞的增殖,选定30μmol/L BBR、7.5μmol/L XAV939用于后续实验。与NC组相比,BBR(30μmol/L)、XAV939(7.5μmol/L)及BBR+XAV939联合处理细胞24 h后,MG-63细胞迁移能力显著降低、凋亡细胞显著增加(均P<0.05),线粒体膜电位下降(P<0.01),MMP-2的基因表达和MMP-2、BAX蛋白水平均降低(均P<0.05),并且,联合组的效应明显强于单药处理且(P<0.05或P<0.01)。结论:BBR和XAV939单独或联合应用可以抑制骨肉瘤MG-63细胞的迁移、促进凋亡,其机制可能与迁移相关蛋白MMP-2的表达降低,凋亡相关蛋白BAX的水平增加有关。

关键词：小檗碱 XAV939 骨肉瘤 MG-63细胞迁移凋亡

Design and characterization of a novel Cu_(2.3)Al_(1.3)Ni_(1.7)SnCr_(0.3) multi-principal element alloy coating on magnesium alloy by laser cladding

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Journal of Materials Science & Technology 2023年第21期152卷 220-236页

作者： Lipeng Jiang Xiufang Cui Guo Jin zhimin tian Xin Wen Haoliang tian Erbao Liu Institute of Surface/Interface Science and Technology Key Laboratory of Superlight Material and Surface Technology of Ministry of EducationCollege of Materials Science and Chemical EngineeringHarbin Engineering UniversityHarbin 150001China Aviation Key Laboratory of Science and Technology on Advanced Corrosion and Protection for Aviation Material Beijing Beijing Institute of Aeronautical MaterialsBeijing 100095China Institute of Defense Engineering AMSPLABeijing 100850China

The evaporation and dilution of substrate seriously limit the performance of laser cladding coatings on magnesium *** order to overcome the above shortcomings,a multi-step ultrasonic assisted laser remelting technology was proposed to improve the performance of the *** this work,a novel Cu_(2.3)Al_(1.3)Ni_(1.7)SnCr_(0.3) multi-principal element alloy coating(MPEAC)was prepared on the surface of mag-nesium *** techniques such as transmission electron microscopy(TEM),electron back scatter diffraction(EBSD)and scanning electron microscopy(SEM)were employed to characterize the microstructure and phase composition of the *** the phase structure and morphology at the interface between the coating and the substrate were also studied via focus ion beam(FIB)and TEM *** addition,the corrosion and wear resistance ability of the coatings were monitored by potentiodynamic polarization(PDP),and electrochemical impedance spectroscopy(EIS),hardness and friction *** results show that Cu_(2.3)Al_(1.3)Ni_(1.7)SnCr_(0.3) MPEAC with ultrasonic assisted is composed of FCC phase and eutectic phases(Cu_(10)Sn_(3) and Cu_(2)Ni_(3)Sn_(3)).Due to the forced convection generated by ultrasonic waves,some Cu and Ni phases are precipitated around Cu_(2)Ni_(3)Sn_(3) phases,which is beneficial to enhance the corrosion *** of the grain refinement effect caused by ultrasonic,the wear resistance of the coating is also ***,ultrasonic vibration can effectively weaken and eliminate the texture density of the Cu_(2.3)Al_(1.3)Ni_(1.7)SnCr_(0.3) MPEAC fabricated by laser cladding.

关键词： Magnesium alloy Multi-principal element alloy coating Ultrasonic assisted laser cladding Corrosion resistance Wear resistance

Improving internal control quality as a corporate response to the Forbes Rich List

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China Journal of Accounting Research 2023年第3期16卷 25-43页

作者： Bei Luo zhimin tian Department of Finance and Economics BNU-HKBU United International CollegeChina Department of Accounting BNU-HKBU United International CollegeChina

This study takes advantage of the Forbes Rich List as an external shock to examine its effect on internal control quality in China's *** the difference-in-differences(DiD)method for a large sample of 17,910 firm-year observations from 2000 to 2014,we find that firms controlled by entrepreneurs included in the Forbes Rich List tend to have higher internal control quality than firms not controlled by entrepreneurs in the *** listed entrepreneurs improve their firms’internal control quality by means of reducing the information asymmetry between the firms and *** tests show that the event effect is more pronounced when firms have higher misreporting costs and when listed entrepreneurs hold chairman positions than in other *** results remain robust after applying the propensity score matching method,stacked DiD estimation,and an alternative measure of internal control *** findings enrich the literature on the effect of the Rich List and the determinants of internal control quality in emerging markets.

关键词： Entrepreneurs Forbes Rich List Internal control Public scrutiny Chinese market

Phytic acid-modified CeO_(2) as Ca^(2+) inhibitor for a security reversal of tumor drug resistance

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Nano Research 2022年第5期15卷 4334-4343页

作者： zhimin tian Junlong Zhao Shoujie Zhao Huicheng Li Zhixiong Guo Zechen Liang Jiayuan Li Yongquan Qu Dongfeng Chen Lei Liu Department Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Cancer Biology Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China Department of General Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China The State Key Laboratory of Cancer Biology Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Department of Gastroenterology Daping HospitalArmy Medical UniversityChongqing 400042China

Ca^(2+)plays critical roles in the development of diseases,whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and *** solve this issue,with the help of Ca overexpressed tumor drug resistance model,the phytic acid(PA)-modified CeO_(2) nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+inhibitor to successfully reverse tumor drug resistance through Ca^(2+)negative regulation *** doxorubicin(Dox)as a model chemotherapeutic drug,the Ca^(2+)nano-inhibitors efficiently deprived intracellular excessive free Ca2+,suppressed P-glycoprotein(P-gp)expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor *** Ca^(2+)negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse ***,nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of *** anticipate that this safe and effective Ca^(2+)negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors,improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca^(2+) associated diseases.

关键词： Ca^(2+)nano-inhibitor nanoceria tumor drug resistance phytic acid nanozyme

Constructing thermoresponsive PNIPAM-based microcarriers for cell culture and enzyme-free cell harvesting

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Chinese Chemical Letters 2024年第7期35卷 412-416页

作者： Yunan Yuan zhimin Luo Jie Chen Chaoliang He Kai Hao Huayu tian CAS Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China College of Chemistry and Chemical Engineering Xiamen UniversityXiamen 361005China Jilin Biomedical Polymers Engineering Laboratory Changchun 130022China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005China

The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical *** using traditional microcarriers for cell culture,trypsinization is often necessary during cell collection,leading to partial cells *** this work,we developed a thermoresponsive glass microcarrier modified with poly(γ-propargyl-L-glutamate)(PPLG)and poly(N-isopropylacrylamide)(PNIPAM).We utilized these microcarriers for three-dimensional cell culture and enzyme-free cell harvesting,and the results indicated that the prepared microcarriers exhibited excellent non-invasive cell culture performance.

关键词： Microcarrier Temperature-responese PNIPAM Polymers Cell culture

Reductive damage induced autophagy inhibition for tumor therapy

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Nano Research 2023年第4期16卷 5226-5236页

作者： Yuqian Wang Yingjian Huang Yu Fu Zhixiong Guo Da Chen Fangxian Cao Qi Ye Qiqi Duan Meng Liu Ning Wang Dan Han Chaoyi Qu zhimin tian Yongquan Qu Yan Zheng Department of Dermatology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Department of Dermatology the Second Affiliated HospitalSchool of MedicineXi’an Jiaotong UniversityXi’an 710004China School of Chemical Engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationXi’an Jiaotong UniversityXi’an 710049China Department of Urology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Xi’an People’s Hospital(Xi’an Fourth Hospital) Shaanxi Eye HospitalAffiliated Guangren HospitalSchool of MedicineXi’an Jiaotong UniversityXi’an 710004China

Numerous therapeutic anti-tumor strategies have been developed in recent ***,their therapeutic efficacy is reduced by the intrinsic protective autophagy of *** plays a key role in tumorigenesis and tumor treatment,in which the overproduction of reactive oxygen species(ROS)is recognized as the direct cause of protective *** a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective *** them,hydroxychloroquine is the most commonly used autophagy inhibitor in clinics,but it is severely limited by its high therapeutic dose,significant toxicity,poor reversal efficacy,and nonspecific ***,we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria(PN-CeO_(2))nanozymes as autophagy *** antineoplastic effects of PN-CeO_(2)were mediated by its high reductive activity for intratumoral ROS degradation,thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell *** investigation highlighted PN-CeO_(2)as a safe and efficient anti-tumor autophagy ***,this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases.

关键词： CeO_(2) reductive damage autophagy inhibitor tumor therapy reactive oxygen species

Bending Resistance of Steel Plate-Reinforced Concrete Beam

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Transactions of tianjin University 2006年第B9期12卷 210-213页

作者： tian zhimin CHEN Jie Beijing Canbao Institute of Architectural Design Beijing 100850 China

The formulas for calculating bending-resistant capacity of a steel plate-reinforced concrete composite beam are derived. To validate the formulas, experiments of the composite beam under three-point bending are carrie... 详细信息

关键词： steel plate-reinforced concrete bending resistance capacity formula experiment