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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： xudong li Wei li Yanli Zhang linping Xu Yongping Song Department of Hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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Pore Formation Mechanism in W-C Hard Coatings Using Directed Energy Deposition on Tungsten Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 89-101页

作者： Xinrui Zhang Weijie Fu Chen Wang Zhenglong Lei Haoran Sun xudong li State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin150001China

Porosity is a common phenomenon and can significantly hinder the quality of the ***,the pore formation mechanism and the characteristics of the single tracks of the W-C coating using directed energy deposition(DED)are systematically *** forming quality of the tracks,the distribution of the pores,and the elemental distribution near the pores are analyzed by the observations of the cross-sections of the *** temperature field of the melt pool is discussed comprehensively to reveal the pore formation *** results confirm that Ni and Co evaporated during the DED process due to the high temperature of the melt *** were continuously produced adjacent to the fusion line when the melt pool was about to solidify since the temperature at the solidification front was higher than the boiling point of *** vaporization area at the fusion line was proposed,where Ni could also evaporate at the time the melt pool started to *** relationship between the solidification rate,the size of the vaporization area and the DED parameters(laser power and scanning speed)was established to discuss the causes of severe pores above the fusion *** work contains a practical guide to reduce or eliminate the porosity in the coating preparation process on the surface of the tungsten alloy.

关键词： Directed energy deposition(DED)process Tungsten alloy W-C coating Pores Binder phase

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Chimeric antigen receptor-immune cells against solid tumors:Structures,mechanisms,recent advances,and future developments

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Chinese Medical Journal 2024年第11期137卷 1285-1302页

作者： xudong li Wei li linping Xu Yongping Song Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China

The advent of chimeric antigen receptor(CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological ***,their success in treating solid tumors has been ***-natural killer(NK)cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex(MHC),which means they are more likely to become an"off-the-shelf"***,they can kill cancer cells via CAR-dependent/independent pathways and have limited *** are the most malleable immune cells in the *** cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments(TMEs).Importantly,CAR-macrophages(CAR-Ms)have recently yielded exciting preclinical results in several solid ***,CAR-T,CAR-NK,and CAR-M all have their own advantages and *** this review,we systematically discuss the current status,progress,and the major hurdles of CAR-T cells,CAR-NK cells,and CAR-M as they relate to five aspects:CAR structure,therapeutic mechanisms,the latest research progress,current challenges and solutions,and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.

关键词： Immunotherapy Chimeric antigen receptor-T cells Chimeric antigen receptor-NK cells Chimeric antigen receptor-macrophage Solid tumors

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Enhanced Redox Electrocatalysis in High‑Entropy Perovskite Fluorides by Tailoring d–p Hybridization

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Nano-Micro Letters 2024年第3期16卷 333-350页

作者： xudong li Zhuomin Qiang Guokang Han Shuyun Guan Yang Zhao Shuaifeng Lou Yongming Zhu Department of Applied Chemistry Harbin Institute of Technology at WeihaiWeihai 264209People’s Republic of China MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage School of Chemistry and Chemical EngineeringHarbin Institute of TechnologyHarbin 150001People’s Republic of China

High-entropy catalysts featuring exceptional properties are,in no doubt,playing an increasingly significant role in aprotic lithium-oxygen *** extensive effort devoted to tracing the origin of their unparalleled performance,the relationships between multiple active sites and reaction intermediates are still ***,enlightened by theoretical screening,we tailor a high-entropy perovskite fluoride(KCoMnNiMgZnF_(3)-HEC)with various active sites to overcome the limitations of conventional catalysts in redox *** entropy effect modulates the d-band center and d orbital occupancy of active centers,which optimizes the d–p hybridization between catalytic sites and key intermediates,enabling a moderate adsorption of liO_(2)and thus reinforcing the reaction *** a result,the li–O2 battery with KCoMnNiMgZnF_(3)-HEC catalyst delivers a minimal discharge/charge polarization and long-term cycle stability,preceding majority of traditional catalysts *** encouraging results provide inspiring insights into the electron manipulation and d orbital structure optimization for advanced electrocatalyst.

关键词： lithium-oxygen batteries KCoMnNiMgZnF_(3)-HEC perovskite fluoride Entropy effect Catalytic kinetics d-p orbital hybridization

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Discovering Cathodic Biocompatibility for Aqueous Zn–MnO_(2) Battery:An Integrating Biomass Carbon Strategy

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Nano-Micro Letters 2024年第6期16卷 111-126页

作者： Wei Lv Zilei Shen xudong li Jingwen Meng Weijie Yang Fang Ding Xing Ju Feng Ye Yiming li Xuefeng Lyu Miaomiao Wang Yonglan Tian Chao Xu Institute of Energy Power Innovation North China Electric Power UniversityBeijing 102206People’s Republic of China Department of Power Engineering School of EnergyPower and Mechanical EngineeringNorth China Electric Power UniversityBaoding 071003People’s Republic of China Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101People’s Republic of China Collaborative Innovation Center of Integrated Exploitation of Bayan Obo Multi‑Metal Resources Inner Mongolia University of Science and TechnologyBaotou 014010People’s Republic of China

Developing high-performance aqueous Zn-ion batteries from sustainable biomass becomes increasingly vital for large-scale energy storage in the foreseeable ***,γ-MnO_(2) uniformly loaded on N-doped carbon derived from grapefruit peel is successfully fabricated in this work,and particularly the composite cathode with carbon carrier quality percentage of 20 wt%delivers the specific capacity of 391.2 mAh g^(−1)at 0.1 A g^(−1),outstanding cyclic stability of 92.17%after 3000 cycles at 5 A g^(−1),and remarkable energy density of 553.12 Wh kg^(−1) together with superior coulombic efficiency of~100%.Additionally,the cathodic biosafety is further explored specifically through in vitro cell toxicity experiments,which verifies its tremendous potential in the application of clinical ***,Zinc ion energy storage mechanism of the cathode is mainly discussed from the aspects of Jahn–Teller effect and Mn domains distribution combined with theoretical analysis and experimental ***,a novel perspective of the conversion from biomass waste to biocompatible Mn-based cathode is successfully developed.

关键词： Aqueous Zn-ion batteries Biocompatibility Jahn-Teller effect Mn domains γ-MnO_(2)

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Spatial Dynamics of Chickenpox Outbreaks in Rapidly Developing Regions:Implications for Global Public Health

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Biomedical and Environmental Sciences 2024年第7期37卷 687-697页

作者： li Wang Miaomiao Wang Chengdong Xu Peihan Wang Meiying You Zihan li Xinmei Chen Xinyu liu xudong li Yuanyuan Wang Yuehua Hu Dapeng Yin College of Geography and Environmental Science Henan UniversityKaifeng 475001HenanChina State Key Laboratory of Resources and Environmental Information System Institute of Geographic Science and Natural Resource ResearchChinese Academy of SciencesBeijing 100101BeijingChina Key Laboratory of Geospatial Technology for the Middle and Lower Yellow River Regions(Henan University) Ministry of EducationKaifeng 475001HenanChina Office of Epidemiology Chinese Center for Disease Control and PreventionBeijing 102206BeijingChina University of Chinese Academy of Sciences(UCAS) Beijing 100101BeijingChina Weifang Municipal Center for Disease Control and Prevention Weifang 261061ShandongChina Hainan Center for Disease Control and Prevention Haikou 570203HainanChina

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to ***,certain factors influencing local chickenpox outbreaks have not been ***,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern *** We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing *** analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran’s I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q *** There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living ***,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,*** This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease *** implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

关键词： Chickenpox Spatial dynamics Socioeconomic factors

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新质生产力的劳动正义审视

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理论探索 2024年第2期 87-93页

作者：李桂花李旭东吉林大学长春130012

“新质生产力”是马克思经典生产力概念的时代发展,将其置于劳动正义视域下阐释能够挖掘出完整的理论结构和丰富内涵。视域本身的内容是对客体的阐释前提,劳动正义在同自然、工具、主体与资本的四重关系下审视表现为生态正义规约之下的... 详细信息

“新质生产力”是马克思经典生产力概念的时代发展,将其置于劳动正义视域下阐释能够挖掘出完整的理论结构和丰富内涵。视域本身的内容是对客体的阐释前提,劳动正义在同自然、工具、主体与资本的四重关系下审视表现为生态正义规约之下的需要正义、技术正义、分配正义与“资本正义”。新质生产力之“新”在劳动正义视域下表现为如下四个方面:新质生产力之“新”在于生态之新,保护“自然生产力”以需要正义进行生态规约;在于科技之新,它是“死的生产力”对“活的生产力”禁锢的纾解;在于主体之新,“主体的生产力”在不同的经济形态中呈现劳动正义的两阶样态;在于运筹之新,“集体力”在扬弃了“资本正义”后获得新的运筹方式。在劳动正义的视角下,要求新质生产力要遵循生态正义、恪守科技伦理,它不仅召唤新质分配标准,并且必须在新发展阶段上继续发挥资本的积极作用,同时也要驾驭资本,防止其无序扩张。

关键词：新质生产力劳动正义技术正义资本的生产力

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何谓与何为:体育共同富裕的四重逻辑

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上海体育大学学报 2024年第7期48卷 86-96页

作者：李桂花李旭东吉林大学马克思主义学院吉林长春130012

体育共同富裕是中国式现代化两个内在要求在新发展阶段上套嵌生成的实践型概念,从多维度理顺和建构其内在逻辑是把握其生成规律、引导其发展趋向的基础。从概念逻辑看,对体育共同富裕概念进行合取式阐释和析取式阐释较为单薄,关系式阐... 详细信息

体育共同富裕是中国式现代化两个内在要求在新发展阶段上套嵌生成的实践型概念,从多维度理顺和建构其内在逻辑是把握其生成规律、引导其发展趋向的基础。从概念逻辑看,对体育共同富裕概念进行合取式阐释和析取式阐释较为单薄,关系式阐释能够辩证地对其进行科学界定;从理论逻辑看,体育共同富裕是历史唯物主义在中国特色社会主义历史空间的特殊展开,批判资本逻辑宰制下的“体育异化”与“两极分化”,以“劳动”为核心范畴在体育与富裕的主客体关系中构建理论框架,并在当代得到理论发展;从实践逻辑看,只有坚持党的领导、完善体育基本公共服务、盘活体育资产并公平分配其价值,方能实现共同富裕,促进体育的“本质复归”;从价值逻辑看,体育共同富裕使体育正义的分配面向更加彰显,是人类文明新形态的生动注脚,也是“两个和解”解放理想的现实开端。

关键词：体育共同富裕体育资产体育正义自由劳动中国式现代化

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边部感应加热过程中的轧件热行为与温度均匀性研究

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机械工程学报 2024年第2期60卷 119-131页

作者：彭文张丽李旭东刘军孙杰张殿华东北大学轧制技术及连轧自动化国家重点实验室沈阳110819 东北大学低碳钢铁前沿技术研究院沈阳110819 首钢集团有限公司技术研究院北京100043 鞍钢集团北京研究院有限公司北京102211

用边部感应加热器提高带材边部温度,改善产品质量是近年来带材生产的新工艺。目前对于边部感应加热过程中带材的温度分布及感应加热后带材的温度均匀性的研究较少。为获得感应加热过程轧件宽向温度的分布规律,利用COMSOL软件建立了C型... 详细信息

用边部感应加热器提高带材边部温度,改善产品质量是近年来带材生产的新工艺。目前对于边部感应加热过程中带材的温度分布及感应加热后带材的温度均匀性的研究较少。为获得感应加热过程轧件宽向温度的分布规律,利用COMSOL软件建立了C型边部感应加热器的电磁-热耦合的有限元模型,系统探讨轧件运动过程中工艺参数变化对电磁场分布、涡流密度及轧件宽向温度分布的影响规律。结果表明,使用边部加热器能够快速补偿边部温降,轧件边部温升与电流频率、电流大小成正比,与轧件厚度和运行速度成反比;为进一步研究感应加热后轧件运行过程中温度变化对温度分布均匀性的影响,用宽向温度标准差对宽向温度分布均匀性进行评价,研究发现边部温度提高有助于减小温度标准差,提升温度分布均匀性,但仍会由于边部过热出现“猫耳状”高温区,在感应加热过程中当边部温度提高约80℃时,精轧入口测温点处的宽向温度分布均匀性最优,温度标准差由13.71℃减小至6.15℃。研究结果能够为运动条件下轧件边部加热工艺的优化提供参考依据。

关键词：热连轧感应加热电磁场温度场温度均匀性

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多层复合材料筒状结构在温度载荷作用下的层间应力建模与试验验证

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复合材料学报 2024年第8期41卷 4398-4407页

作者：李想赵先航钟华谢宇茹佳胜刘鑫李旭东李悦芳中国工程物理研究院电子工程研究所

多层复合材料筒状结构的残余应力可造成内部分层、结构失稳等，有必要结合理论和实验等研究其内部应力形成机制。基于各向异性线弹性本构和平面应力假设，建立了温度载荷作用下多层复合材料筒状结构内部应力的预测模型，并通过有限元仿... 详细信息

多层复合材料筒状结构的残余应力可造成内部分层、结构失稳等，有必要结合理论和实验等研究其内部应力形成机制。基于各向异性线弹性本构和平面应力假设，建立了温度载荷作用下多层复合材料筒状结构内部应力的预测模型，并通过有限元仿真和热膨胀变形测试对模型有效性进行了校核和验证。结果表明：筒状结构环向的热膨胀变形从内层到外层逐渐增大，其中内层附近环向热膨胀系数低于面内热膨胀系数、外层附近环向热膨胀系数则高于面内热膨胀系数。在此基础上，结合模型理论分析揭示了层间应力对多层复合材料筒状结构的热膨胀变形行为的影响机制。在筒状结构形式下，温度加载引起的层间应力由一个涉及热膨胀系数和弹性参数的热力耦合项决定；由于多层复合材料面内与面外热膨胀系数存在差异，该应力耦合项不为0，从而在温度加载下形成了层间应力并影响了环向膨胀变形行为。基于上述认识，提出了调控多层复合材料筒状结构层间应力的有效措施。本文对揭示多层复合材料筒状结构的层间开裂物理机制、优化其热力匹配设计等具有重要意义。

关键词：复合材料筒状结构层间应力解析模型各向异性热应力热膨胀变形

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