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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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Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

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Food Science and Human Wellness 2024年第1期13卷 154-165页

作者： Dechang Xu Jielun Hu Yadong Zhong yanli zhang Wenting Liu Shaoping Nie Mingyong Xie State Key Laboratory of Food Science and Technology China-Canada Joint Laboratory of Food Science and Technology(Nanchang)Key Laboratory of Bioactive Polysaccharides of Jiangxi ProvinceNanchang UniversityNanchang 330047China

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide *** this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were *** showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T *** addition,it attenuated intestinal mucosal damage and improved intestinal cellular *** administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small ***,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as *** also increased the production of fecal short-chain fatty *** indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

关键词： Fermented foods Immunosuppressed mice Immune response Gut microbiota Short-chain fatty acids

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Theoretical analysis of frequency modulation-to-amplitude modulation on the final optics and target of the SG Ⅱ-Up laser facility

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High Power Laser Science and Engineering 2024年第1期12卷 84-98页

作者： Yujia zhang Wei Fan Jiangfeng Wang Xiaochao Wang Xinghua Lu Dajie Huang Shouying Xu yanli zhang Mingying Sun Zhaoyang Jiao Shenlei Zhou Xiuqing Jiang Key Laboratory of High Power Laser and Physics Shanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghaiChina Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijingChina

Frequency modulation(FM)-to-amplitude modulation(AM) conversion is an important factor that affects the time±power curve of inertial confinement fusion(ICF) high-power laser facilities. This conversion can impact uniform compression and increase the risk of damage to optics. However, the dispersive grating used in the smoothing by spectral dispersion technology will introduce a temporal delay and can spatially smooth the target. The combined effect of the dispersive grating and the focusing lens is equivalent to a Gaussian low-pass filter, which is equivalent to 8 GHz bandwidth and can reduce the intensity modulation on the target to below 5% with 0.3 nm @ 3 GHz + 20 GHz spectrum phase modulation. The results play an important role in the testing and evaluating of the FM-to-AM on the final optics and the target, which is beneficial for comprehensively evaluating the load capacity of the facility and isentropic compression experiment for ICF.

关键词： dispersion grating frequency modulation-to-amplitude modulation conversion high-power laser facility inertial confinement fusion phase modulation

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Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

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Neural Regeneration Research 2025年第2期20卷 533-547页

作者： yanli zhang Tian Li Jie Miao Zhina zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei zhang Haiting Li Qiang Su Junhong Guo Department of Neurology First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Neurology Sixth Hospital of Shanxi Medical University(General Hospital of Tisco)TaiyuanShanxi ProvinceChina Department of Physiology Key Laboratory of Cellular PhysiologyMinistry of EducationShanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Hernia and Abdominal Wall Surgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Laboratory Medicine of Fenyang College Shanxi Medical UniversityFenyangShanxi ProvinceChina

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial ***,the functional role of GGT5 in the development of Alzheimer’s disease remains *** study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying *** observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse ***,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive ***,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 *** effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa *** findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 *** findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1

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基于MODIS积雪覆盖度数据的青藏高原两套被动微波雪深产品降尺度对比研究

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冰川冻土 2024年第1期46卷 65-76页

作者：徐帆张彦丽李克恭西北师范大学地理与环境科学学院甘肃兰州730070 甘肃省绿洲资源环境与可持续发展重点实验室甘肃兰州730070 甘肃省测绘工程院甘肃兰州730050

积雪深度(雪深)是流域水量平衡、融雪径流模拟等模型的重要输入参数,被动微波雪深遥感产品被广泛用于雪深监测。然而,由于山区积雪时空异质性强,这些空间分辨率较粗的雪深产品受到极大限制。本研究基于MODIS积雪覆盖度数据,根据经验融... 详细信息

积雪深度(雪深)是流域水量平衡、融雪径流模拟等模型的重要输入参数,被动微波雪深遥感产品被广泛用于雪深监测。然而,由于山区积雪时空异质性强,这些空间分辨率较粗的雪深产品受到极大限制。本研究基于MODIS积雪覆盖度数据,根据经验融合规则以及积雪衰退曲线对“中国雪深长时间序列数据集”的两套雪深产品(由SMMR、SSMI和SSMI/S反演的称为Che_SSMI/S产品;由AMSR-2反演称为Che_AMSR2产品)进行空间降尺度,最终获得青藏高原500 m降尺度雪深数据(Che_SSMI/S_NSD和Che_AMSR2_NSD)。利用6景Landsat-8影像对两套降尺度雪深数据进行对比分析,结果发现两套降尺度数据与Landsat-8影像积雪空间分布吻合度均较高。与29个气象站点雪深数据相比,Che_AMSR2_NSD与实测雪深更为接近,相关系数(R)达到0.72,均方根误差(RMSE)为3.21 cm;而Che_SSMI/S_NSD精度较低(R=0.67,RMSE=4.44 cm),可能是由于采用不同传感器亮温数据的两套原始雪深产品精度不同所致。除此之外,实验表明被动微波雪深产品降尺度精度还受积雪深度、积雪期等因素的影响。当积雪深度小于10 cm且在积雪稳定期时,两套雪深产品降尺度精度均最高;当积雪深度大于30 cm且在积雪消融期时,两套雪深产品降尺度精度均最低。通过对比两套降尺度雪深产品,有助于全面地了解青藏高原雪深时空分布变化及其应用提供数据支持。

关键词：积雪深度被动微波遥感积雪覆盖度降尺度算法

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加拿大第三支柱养老金竞争性互补的主要特征分析

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辽宁大学学报（哲学社会科学版） 2024年第2期52卷 35-47页

作者：张彦丽山东工商学院公共管理学院山东烟台264005

注册退休储蓄计划(RRSP)和免税储蓄账户(TFSA)作为加拿大第三支柱个人养老金制度,在供款与提款、税收模式等方面存在着明显区别。免税储蓄账户(TFSA)比注册退休储蓄计划(RRSP)的参与条件限制少,提款免税并且不影响个人获取政府收入审查... 详细信息

注册退休储蓄计划(RRSP)和免税储蓄账户(TFSA)作为加拿大第三支柱个人养老金制度,在供款与提款、税收模式等方面存在着明显区别。免税储蓄账户(TFSA)比注册退休储蓄计划(RRSP)的参与条件限制少,提款免税并且不影响个人获取政府收入审查福利的资格,其税收模式使个人拥有更多的终身套利机会。注册退休储蓄计划(RRSP)的缴费参与方式更加多样化,并且具有更加灵活的转账机制。加拿大第三支柱养老金不但具有养老保障属性,还具有金融属性。注册退休储蓄计划(RRSP)和免税储蓄账户(TFSA)既相互竞争又相互补充,近年来持续大幅增长,缓解了第一支柱公共养老金的支出压力,减轻了政府财政负担,成为保证老年人获得优质退休生活的必要条件;作为多支柱养老保险体系的重要组成部分,有利于实现养老保险体系的财务可持续性和资金充足性。

关键词：加拿大第三支柱养老金注册退休储蓄计划免税储蓄账户

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司马迁评鲁仲连“指意虽不合大义”辨析

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渭南师范学院学报 2024年第6期39卷 43-50页

作者：张艳丽山东理工大学《管子学刊》编辑部山东淄博255000

鲁仲连是战国末期齐国人,擅长辩论而急人困危,功成之后不受赏赐而飘然世外。司马迁《史记·鲁仲连列传》主要讲述鲁仲连的两件史事,一是力劝新垣衍不复言帝秦,二是一射箭书解聊城之围。司马迁在文末赞语中,认为鲁仲连“指意虽不合大义”... 详细信息

鲁仲连是战国末期齐国人,擅长辩论而急人困危,功成之后不受赏赐而飘然世外。司马迁《史记·鲁仲连列传》主要讲述鲁仲连的两件史事,一是力劝新垣衍不复言帝秦,二是一射箭书解聊城之围。司马迁在文末赞语中,认为鲁仲连“指意虽不合大义”,却颂扬他的高风亮节。围绕这一评价,后世文人或肯定鲁仲连宗周、不屑名利、排难解患等“义”的秉性;或围绕司马迁的看法,指出鲁仲连“指意虽不合大义”主要体现在宣扬的“势数”思想不符合“圣贤大义”、说服的时候使用了“恫吓”的方式、诱使燕将投降齐国不符合“忠君”大道等方面。学者对鲁仲连的多元评价,显示出鲁仲连独特的历史地位,值得深入研究。

关键词：鲁仲连 “义” 《史记》司马迁

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Space advanced technology demonstration satellite

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Science China(Technological Sciences) 2024年第1期67卷 240-258页

作者： zhang XiaoFeng CHEN Wen ZHU XiaoCheng MENG Na HE JunWang BI XingZi zhang YongHe SHI Qi LI Fei LIU Rui FENG ZhengGong LIU Liu LI JinSong WU HaiChen XU DongXiao LI TaiJie HUANG JiangJiang LIU Shuo LI TianTong YU XianSheng GAO Yang ZHOU Heng BAN HanYu zhang yanli zhang YueTing YANG YingQuan HE Tao DUAN XuLiang CHEN Xin WANG YaMin SUN AnTai zhang KuoXiang SUN Ying WANG YaoBin FAN ChengCheng XIONG ShaoLin LI XinQiao WEN XiangYang LING ZhiXing SUN XiaoJin zhang Chen BAI XianYong WANG ZhanShan DENG YuanYong TIAN Hui YANG JianFeng XUE HongBo SANG Peng LIU JinGuo ZHENG HuiLong ZHU Xiang HE JianWu LI Hui XU LuXiang XU ShuYan CHEN WenWu LIU ZhenDong WANG ZhaoLi MAO XiangLong GAO Rong LI ZongXuan DING GuoPeng WANG XinYu DOU RunJiang WENG LuBin LUO Hao WANG YaPing LIANG XianFeng FANG ZiRuo Innovation Academy for Microsatellites Chinese Academy of SciencesShanghai 201203China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China National Astronomical Observatory of China Beijing 100101China Shanghai Institute of Technical Physics Chinese Academy of SciencesShanghai 200083China Institute of Precision Optical Engineering School of Physics Science and EngineeringTongji UniversityShanghai 200092China School of Earth and Space Sciences Peking UniversityBeijing 100871China Xi’an Institute of Optics and Precision Mechanics Chinese Academy of SciencesXi’an 710119China National Space Science Center Chinese Academy of SciencesBeijing 100190China Shenyang Institute of Automation Chinese Academy of SciencesShenyang 110016China Institute of Engineering Thermophysics Chinese Academy of SciencesBeijing 100190China Institute of Mechanics Chinese Academy of SciencesBeijing 100190China Shanghai Institute of Organic Chemistry Chinese Academy of SciencesShanghai 200032China Hangzhou Institute for Advanced Study University of Chinese Academy of SciencesHangzhou 310024China Nanyang Technological University Singapore 569830Singapore Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China Technical Institute of Physics and Chemistry Chinese Academy of SciencesBeijing 100049China Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchun 130033China Institute of Semiconductors Chinese Academy of SciencesBeijing 100083China Institute of Automation Chinese Academy of SciencesBeijing 100190China School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310058China

The Space Advanced Technology demonstration satellite(SATech-01),a mission for low-cost space science and new technology experiments,organized by Chinese Academy of Sciences(CAS),was successfully launched into a Sun-synchronous orbit at an altitude of~500 km on July 27,2022,from the Jiuquan Satellite Launch *** as an experimental platform for space science exploration and the demonstration of advanced common technologies in orbit,SATech-01 is equipped with 16 experimental payloads,including the solar upper transition region imager(SUTRI),the lobster eye imager for astronomy(LEIA),the high energy burst searcher(HEBS),and a High Precision Magnetic Field Measurement System based on a CPT Magnetometer(CPT).It also incorporates an imager with freeform optics,an integrated thermal imaging sensor,and a multi-functional integrated imager,*** paper provides an overview of SATech-01,including a technical description of the satellite and its scientific payloads,along with their on-orbit performance.

关键词： SATech-01 spacecraft design scientific instruments on-orbit performance

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习近平总书记关于思政课教师队伍建设重要论述的核心要义和理论逻辑

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现代教育科学 2024年第3期 82-88页

作者：张艳丽武汉工程大学湖北武汉430205

思政课教师队伍建设是新时代思政课创新改革取得预期成效的重要保障。习近平总书记关于高校思政课教师队伍建设重要论述系统思考并科学回答了3个核心要义:为什么要重视高校思政课教师队伍建设、建设什么样的高校思政课教师队伍、怎样建... 详细信息

思政课教师队伍建设是新时代思政课创新改革取得预期成效的重要保障。习近平总书记关于高校思政课教师队伍建设重要论述系统思考并科学回答了3个核心要义:为什么要重视高校思政课教师队伍建设、建设什么样的高校思政课教师队伍、怎样建设高校思政课教师队伍。从思政课教师的角色定位、职责使命、职业素养、队伍建设等视角的解读可深刻把握习近平总书记关于高校思政课教师队伍建设思想的理论逻辑。

关键词：高校思政课教师队伍建设核心要义理论逻辑

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类矩形装配式地铁车站纵向等效抗弯刚度研究

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铁道科学与工程学报 2024年第4期21卷 1554-1566页

作者：黄林冲蒋凯梁禹张燕丽丁泽杜风华中山大学·深圳航空航天学院广东深圳518107 中山大学土木工程学院广东珠海519000 中铁十四局集团有限公司山东济南250101

类矩形装配式地铁车站纵向等效抗弯刚度是衡量其力学行为的重要参数,对于构件结构设计、抗弯承载能力验算具有重要作用。为了分析地铁车站纵向抗弯性能及其影响因素,根据等效连续梁的转角计算公式,得出了纵向等效抗弯刚度(EI)eq及纵向... 详细信息

类矩形装配式地铁车站纵向等效抗弯刚度是衡量其力学行为的重要参数,对于构件结构设计、抗弯承载能力验算具有重要作用。为了分析地铁车站纵向抗弯性能及其影响因素,根据等效连续梁的转角计算公式,得出了纵向等效抗弯刚度(EI)eq及纵向等效抗弯刚度有效率η的隐式表达式。通过截面参数分析,探讨了构件长度对中性轴距离c值、等效抗弯刚度有效率η值、截面最大应力的影响;研究了上下圆弧块厚度、曲率半径、圆心角及半短轴长b值对装配式构件截面上的最大应力的影响规律;为了反映装配式车站环缝实际作用范围,引入了环缝影响系数λ,拓展了类矩形装配式衬砌纵向等效连续化模型。研究结果表明:不同构件长度下截面应力分布状态及η值保持不变,且弯矩方向对其影响较小。在弯矩不变的前提下截面最大应力受半短轴长b值影响较大。当顶板块厚度t1处于0.6~2 m范围时,截面最大拉应力随半短轴长b增加而降低6.8%~9.3%;当底板块厚度t3处于0.6~2 m范围时,随着半短轴长b增加,截面最大压应力降低62.5%~63.6%。随着λ由0增加到1,纵向等效抗弯刚度有效率η由1降低到0.05%且变化趋势逐渐降低,与纵向等效连续化模型计算结论一致。本文研究结论对于装配式地铁车站预制构件结构设计及抗弯承载能力验算可提供有效参考。

关键词：类矩形装配式地铁车站纵向等效连续化模型中性轴位置纵向等效抗弯刚度环缝影响范围

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