In the clinical treatment of cancer,chemotherapy often induces tumor cell senescence due to its genotoxicity.The secretion of senescence associated secretory phenotype(SASP)and the emergence of stem cell populations a...In the clinical treatment of cancer,chemotherapy often induces tumor cell senescence due to its genotoxicity.The secretion of senescence associated secretory phenotype(SASP)and the emergence of stem cell populations are important factors driving acquired resistance to chemotherapy.Direct removal of senescent tumor cells or indirect inhibition of SASP and stemness-related phenotypes are effective strategies to overcome chemoresistance.Cisplatin(CDDP),a broad-spectrum first-line chemotherapeutic agent,has been observed to induce tumor cell senescence in clinical settings,yet the properties of these senescent cells remain largely unexplored.Herein,we simulated the induction of tumor senescence using the sublethal doses of CDDP and confirmed the pivotal role of senescence in promoting chemoresistance,as well as the interdependent relationship between SASP and senescence-associated stemness.Notably,we discovered that glutaminase-1(GLS1)is highly expressed in cisplatin-induced senescent tumor cells and is intimately linked to their survival.Furthermore,we identified a natural cyclopeptide,RA-V,derived from Rubia yunnanensis,which partially eliminated senescent tumor cells,inhibited SASP secretion and stemness-related phenotypes.Mechanistically,RA-V disrupted senescent cell survival by inhibiting GLS1 protein expression through the modulation of c-Myc/GLS1 axis.Our findings reveal for the first time that GLS1 might serve as a vulnerable target in cisplatin-induced senescent tumor cells and discover the potential of RA-V as a senolytics agent,offering a promising approach to circumvent cisplatin chemoresistance.展开更多
A longstanding challenge in materials science has been the computational modeling of interfaces between materials with different lattice parameters.Traditional approaches using plane-wave basis sets require either int...A longstanding challenge in materials science has been the computational modeling of interfaces between materials with different lattice parameters.Traditional approaches using plane-wave basis sets require either introducing artificial strain through unified lattice parameters or constructing prohibitively large supercells to accommodate the mismatch.These limitations have often deterred researchers from investigating large,mismatched interfaces,creating a gap in the understanding of these important systems.This work introduces an innovative algorithm that adaptively tunes the plane-wave basis sets to match the periodic structure of each material across the interface.By eliminating the need for extensive supercells or compromised lattice parameters,this new method reduces computational costs while retaining reliable results.The ability to efficiently calculate the eigen-energies of such mismatched systems,a crucial step for full density functional theory(DFT)calculations,is demonstrated with two dimensional versions of InAs/Si and SiC/Si interface potentials.展开更多
将专利组合设计的思想与发明问题解决理论(theory of inlentive prob,TRIZ)创新方法相集成,提出基于企业核心技术的专利组合设计模型。在此模型的基础上,将TRIZ方法与专利组合类型进行分类匹配,建立基于TRIZ理论的专利组合设计流程,用...将专利组合设计的思想与发明问题解决理论(theory of inlentive prob,TRIZ)创新方法相集成,提出基于企业核心技术的专利组合设计模型。在此模型的基础上,将TRIZ方法与专利组合类型进行分类匹配,建立基于TRIZ理论的专利组合设计流程,用不同的TRIZ方法构建相应的专利组合。以TRIZ理论为依据,将创新方法学、专利法律学、管理学等学科交叉进行协同创新设计研究,符合国家知识产权战略及企业的专利战略,能够培育企业的核心竞争力。展开更多
基金supported by the grants from the National Natural Science Foundation of China(No.32070356,82474065).
文摘In the clinical treatment of cancer,chemotherapy often induces tumor cell senescence due to its genotoxicity.The secretion of senescence associated secretory phenotype(SASP)and the emergence of stem cell populations are important factors driving acquired resistance to chemotherapy.Direct removal of senescent tumor cells or indirect inhibition of SASP and stemness-related phenotypes are effective strategies to overcome chemoresistance.Cisplatin(CDDP),a broad-spectrum first-line chemotherapeutic agent,has been observed to induce tumor cell senescence in clinical settings,yet the properties of these senescent cells remain largely unexplored.Herein,we simulated the induction of tumor senescence using the sublethal doses of CDDP and confirmed the pivotal role of senescence in promoting chemoresistance,as well as the interdependent relationship between SASP and senescence-associated stemness.Notably,we discovered that glutaminase-1(GLS1)is highly expressed in cisplatin-induced senescent tumor cells and is intimately linked to their survival.Furthermore,we identified a natural cyclopeptide,RA-V,derived from Rubia yunnanensis,which partially eliminated senescent tumor cells,inhibited SASP secretion and stemness-related phenotypes.Mechanistically,RA-V disrupted senescent cell survival by inhibiting GLS1 protein expression through the modulation of c-Myc/GLS1 axis.Our findings reveal for the first time that GLS1 might serve as a vulnerable target in cisplatin-induced senescent tumor cells and discover the potential of RA-V as a senolytics agent,offering a promising approach to circumvent cisplatin chemoresistance.
基金support of The Boeing Company,as part of the Boeing-Technion Sustainable Aviation Fuel Innovation CenterWe sincerely thank Boeing for their valuable support and collaboration.This project was also conducted within the framework of the Guy Sella Memorial Project at Technion,established by SolarEdge Technologies LTD.Partial funding from The Israeli Sustainable Aviation Fuel Knowledge Center–iSAF,supported by The Israeli Ministry of Innovation,Science,and Technology,is gratefully acknowledgedThis article is based upon work from COST IG18234(NanoCatML),supported by COST(European Cooperation in Science and Technology)http://www.cost.eu.
文摘A longstanding challenge in materials science has been the computational modeling of interfaces between materials with different lattice parameters.Traditional approaches using plane-wave basis sets require either introducing artificial strain through unified lattice parameters or constructing prohibitively large supercells to accommodate the mismatch.These limitations have often deterred researchers from investigating large,mismatched interfaces,creating a gap in the understanding of these important systems.This work introduces an innovative algorithm that adaptively tunes the plane-wave basis sets to match the periodic structure of each material across the interface.By eliminating the need for extensive supercells or compromised lattice parameters,this new method reduces computational costs while retaining reliable results.The ability to efficiently calculate the eigen-energies of such mismatched systems,a crucial step for full density functional theory(DFT)calculations,is demonstrated with two dimensional versions of InAs/Si and SiC/Si interface potentials.
文摘将专利组合设计的思想与发明问题解决理论(theory of inlentive prob,TRIZ)创新方法相集成,提出基于企业核心技术的专利组合设计模型。在此模型的基础上,将TRIZ方法与专利组合类型进行分类匹配,建立基于TRIZ理论的专利组合设计流程,用不同的TRIZ方法构建相应的专利组合。以TRIZ理论为依据,将创新方法学、专利法律学、管理学等学科交叉进行协同创新设计研究,符合国家知识产权战略及企业的专利战略,能够培育企业的核心竞争力。
