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A dynamic stiffness-based framework for harmonic input estimation and response reconstruction considering damage

Frontiers of Structural and Civil Engineering 2022年第4期16卷 448-460页

作者： yixian li limin SUN Wang ZHU Wei ZHANG Department of Bridge Engineering College of Civil EngineeringTongji UniversityShanghai 200092China State Key Laboratory of Disaster Reduction in Civil Engineering Department of Bridge EngineeringCollege of Civil EngineeringTongji UniversityShanghai 200092China Shanghai Qizhi Institute Shanghai 200092China Sichuan Highway Planning SurveyDesignand Research Institute Ltd.Chengdu 610000China Fujian Key Laboratory of Green Building Technology Fujian Academy of Building ResearchFuzhou 350028China

In structural health monitoring(SHM),the measurement is point-wise but structures are ***,input estimation has become a hot research subject with which the full-field structural response can be calculated with a finite element model(FEM).This paper proposes a framework based on the dynamic stiffness theory,to estimate harmonic input,reconstruct responses,and to localize damages from seriously deficient *** begin,Fourier transform converts the dynamic equilibrium equation to an equivalent static one in the frequency domain,which is underdetermined since the dimension of measurement vector is far less than the FEM-node *** principal component analysis has been adopted to“compress”the under-determined equation,and formed an over-determined equation to estimate the unknown ***,inverse Fourier transform converts the estimated input in the frequency domain to the time *** this to the FEM can reconstruct the target *** a structure is damaged,the estimated nodal force can localize the *** improve the damage-detection accuracy,a multi-measurement-based indicator has been *** simulations have validated that the proposed framework can capably estimate input and reconstruct multi-types of full-field responses,and the damage indicator can localize minor damages even with the existence of noise.

关键词： dynamic stiffness principal component analysis response reconstruction damage localization underdetermined equation

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Temperature is a cryptic factor shaping the geographical pattern of genetic variation in Ceratophyllum demersum across a subtropical freshwater lake

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Plant Diversity 2024年第5期46卷 630-639页

作者： yixian li Xuyao Zhao Manli Xia Xinzeng Wei Hongwei Hou The State Key Laboratory of Freshwater Ecology and Biotechnology The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of SciencesInstitute of HydrobiologyChinese Academy of SciencesWuhan 430072HubeiChina University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Aquatic Botany and Watershed Ecology Wuhan Botanical GardenChinese Academy of SciencesWuhan 430074HubeiChina

Macrophyte habitats exhibit remarkable heterogeneity,encompassing the spatial variation of abiotic and biotic components such as changes in water conditions and weather as well as anthropogenic *** factors are thought to be important drivers shaping the genetic and epigenetic variation of aquatic ***,the links among genetic diversity,epigenetic variation,and environmental variables remain largely unclear,especially for clonal aquatic ***,we performed population genetic and epigenetic analyses in conjunction with habitat discrimination to elucidate the environmental factors driving intraspecies genetic and epigenetic variation in hornwort(Ceratophyllum demersum)in a subtropical *** factors were highly correlated with the genetic and epigenetic variation of ***,with temperature being a key driver of the genetic *** temperature was detected to be correlated with greater genetic and epigenetic *** and epigenetic variation were positively driven by water temperature,but were negatively affected by ambient air *** findings indicate that the genetic and epigenetic variation of this clonal aquatic herb is not related to the geographic feature but is instead driven by environmental conditions,and demonstrate the effects of temperature on local genetic and epigenetic variation in aquatic systems.

关键词： Genetic diversity Epigenetic variation Temperature Macrophyte Restoration

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Crosstalk between the B7/CD28 and EGFR pathways:Mechanisms and therapeutic opportunities

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Genes & Diseases 2022年第5期9卷 1181-1193页

作者： Xiaoxin Ren yixian li Christopher Nishimura Xingxing Zang Department of Microbiology and Immunology Albert Einstein College of MedicineNew YorkNY 10461USA Division of Pediatric Hematology/Oncology/Transplant and Cellular Therapy Children's Hospital at MontefioreBronxNY 10467USA Department of Medicine Albert Einstein College of MedicineNew YorkNY 10461USA Department of Urology Albert Einstein College of MedicineNew YorkNY 10461USA

Somatic activating mutations in the epidermal growth factor receptor(EGFR)are one of the most common oncogenic drivers in cancers such as non-small-cell lung cancer(NSCLC),metastatic colorectal cancer,glioblastoma,head and neck cancer,pancreatic cancer,and breast ***-targeted agents against EGFR signaling pathways have shown robust clinical efficacy,but patients inevitably experience acquired *** immune checkpoint inhibitors(ICIs)targeting PD-1/PD-L1 have exhibited durable anti-tumor responses in a subset of patients across multiple cancer types,their efficacy is limited in cancers harboring activating gene alterations of *** studies have demonstrated that upregulation of new B7/CD28 family members such as B7-H3,B7x and HHLA2,is associated with EGFR signaling and may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment(TME).In this review,we discuss the regulatory effect of EGFR signaling on the PD-1/PD-L1 pathway and new B7/CD28 family member *** these interactions may inform combination therapeutic strategies and potentially overcome the current challenge of resistance to EGFR-targeted *** also summarize clinical data of anti-PD-1/PD-L1 therapies in EGFR-mutated cancers,as well as ongoing clinical trials of combination of EGFR-targeted therapies and anti-PD-1/PD-L1 immunotherapies.

关键词： Combination therapies EGFR Immune checkpoint blockade New B7/CD28 members PD-1/PD-L1 pathway

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On-resin peptide modification of methionine residue by employing 2-bromoacetate derivatives

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Chinese Chemical Letters 2023年第4期34卷 198-202页

作者： Qi-Long Hu Jia-Tian liu Guangjin Fan Jian li yixian li Albert S.C.Chan Xiao-Feng Xiong Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China

On-resin peptide modification renders an easy-to-operate method that combines solid-phase peptide synthesis efficiency and avoids tedious purification procedures. Herein, we report the transition-metal-free and redox-neutral approach for solid-phase Met diversification with substrate diversity, which could be applied to synthesize cyclic peptides of different sizes.

关键词： Methionine 2-Bromoacetate derivatives On-resin modification Peptide Cyclization

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Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1380-1399页

作者： yixian li Peng Yang Ran Meng Shuting Xu lingling Zhou Kang Qian Pengzhen Wang Yunlong Cheng Dongyu Sheng Minjun Xu Tianying Wang Jing Wu Jinxu Cao Qizhi Zhang Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal *** the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological ***,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD ***,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside *** by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected *** nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ ***,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic *** research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

关键词： Autophagy-lysosome pathway Alzheimer’s disease Proteostasis Neuroinflammation Multi-target therapy Rapamycin Gypenoside XVII Cascade dual-targeting

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Modulating autophagic flux via ROS-responsive targeted micelles to restore neuronal proteostasis in Alzheimer’s disease

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Bioactive Materials 2022年第5期7卷 300-316页

作者： Shuting Xu Peng Yang Kang Qian yixian li Qian Guo Pengzhen Wang Ran Meng Jing Wu Jinxu Cao Yunlong Cheng Minjun Xu Qizhi Zhang Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai201203China

Compromised autophagy and defective lysosomal clearance significantly contribute to impaired neuronal proteostasis,which represents a hallmark of Alzheimer’s disease(AD)and other age-related neurodegenerative *** evidence has implicated that modulating autophagic flux,instead of inducing autophagosome formation alone,would be more reliable to rescue neuronal ***,selectively enhancing drug concentrations in the leision areas,instead of the whole brain,will maximize therapeutic efficacy while reduing non-selective autophagy ***,we design a ROS-responsive targeted micelle system(TT-NM/Rapa)to enhance the delivery efficiency of rapamycin to neurons in AD lesions guided by the fusion peptide TPL,and facilitate its intracellular release via ROS-mediated disassembly of micelles,thereby maximizing autophagic flux modulating efficacy of rapamycin in ***,it promotes the efficient clearance of intracellular neurotoxic proteins,β-amyloid and hyperphosphorylated tau proteins,and ameliorates memory defects and neuronal damage in 3×Tg-AD transgenic *** studies demonstrate a promising strategy to restore autophagic flux and improve neuronal proteostasis by rationally-engineered nano-systems for delaying the progression of AD.

关键词： Autophagic flux ROS-Responsive micelle system Brain-neuron targeting Rapamycin Alzheimer’s disease

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Rational fusion design inspired by cell-penetrating peptide:SS31/S-14 G Humanin hybrid peptide with amplified multimodal efficacy and bio-permeability for the treatment of Alzheimer’s disease

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Asian Journal of Pharmaceutical Sciences 2024年第4期19卷 128-143页

作者： Kang Qian Peng Yang yixian li RanMeng Yunlong Cheng lingling Zhou Jing Wu Shuting Xu Xiaoyan Bao Qian Guo Pengzhen Wang Minjun Xu Dongyu Sheng Qizhi Zhang Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhou 325035China

Alzheimer’s disease is a neurodegenerative disease induced by multiple interconnected *** drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet ***,clinical translation of peptide drugs is greatly hampered by their low permeability into ***,a hybrid peptide HNSS is generated by merging two therapeutic peptides(SS31 and S-14 G Humanin(HNG)),using a different approach from the classical shuttle-therapeutic peptide conjugate *** demonstrated increased bio-permeability,with a 2-fold improvement in brain distribution over HNG,thanks to its structure mimicking the design of signal peptide-derived cell-penetrating *** efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting,ROS scavenging and p-STAT3 ***,HNSS with increased Aβaffinity greatly inhibited Aβoligomerization/fibrillation,and interrupted Aβinteraction with neuron/microglia by reducing neuronal mitochondrial Aβdeposition and promoting microglial phagocytosis of Aβ.In3×Tg-AD transgenic mice,HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive *** work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification,providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.

关键词： Hybrid peptide S-14 G Humanin SS31 Permeability Aβ Alzheimer’s disease

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Kuru-Tegerek金铜矿南矿体露天开采的生产设计研究

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中国矿业 2024年第S2期33卷 314-317页

作者：李羿贤中国黄金集团公司凯奇-恰拉特封闭式股份公司甘肃会宁730700

针对原Micromine块体模型在Surpac软件中不通用的情况,在保留了原数据不变的前提下进行了Surpac软件格式的转换分析,达到数据完整一致的目的;合理分析矿体赋存条件等因素,确定最优露天境界;并建立具有指导生产的露天境界块体模型,精确... 详细信息

针对原Micromine块体模型在Surpac软件中不通用的情况,在保留了原数据不变的前提下进行了Surpac软件格式的转换分析,达到数据完整一致的目的;合理分析矿体赋存条件等因素,确定最优露天境界;并建立具有指导生产的露天境界块体模型,精确管理矿山资源并提高资源开采利用率;在Surpac软件中进行露天爆破设计,优化采矿工艺流程。在实际生产作业中,应用于Surpac软件的设计,减少了生产中的无效作业,经济效益显著提高,并在全局掌控资源、提高资源利用率方面取得显著成果。

关键词： Surpac 块体模型转换露天采矿工艺露天爆破境界模型

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TC4合金在不同环境介质中的磨损行为及磨损机制研究

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稀有金属 2015年第9期39卷 793-798页

作者：李新星李奕贤王树奇宿迁学院金属材料教研室江苏宿迁223800 江苏大学材料科学与工程学院江苏镇江212013

采用MPX-2000型销盘式摩擦磨损试验机,研究了TC4合金在空气、纯水和模拟海水环境下与GCr15轴承钢对磨时的磨损行为和磨损机制,评价不同环境介质对TC4合金耐磨性的影响。结果表明:TC4合金在模拟海水中的磨损率始终最高,明显高于其在纯水... 详细信息

采用MPX-2000型销盘式摩擦磨损试验机,研究了TC4合金在空气、纯水和模拟海水环境下与GCr15轴承钢对磨时的磨损行为和磨损机制,评价不同环境介质对TC4合金耐磨性的影响。结果表明:TC4合金在模拟海水中的磨损率始终最高,明显高于其在纯水和空气中的磨损率,且在模拟海水中磨损时TC4合金腐蚀速度大大加快,可见腐蚀和磨损之间存在明显的相互促进作用。TC4合金在模拟海水中形成的润滑膜可以明显降低摩擦系数,因而不同工况下模拟海水中的摩擦系数始终较低,纯水中的摩擦系数略高于海水,而空气中的摩擦系数在0.50及0.75 m·s-1,1.02 MPa时明显高于纯水和海水,在0.75 m·s-1,2.55 MPa时反而略低于纯水和模拟海水。TC4合金在空气中的磨损机制为氧化磨损并伴有一定程度的磨粒磨损和粘着磨损;在纯水中的磨损机制为磨粒磨损;而在模拟海水中则为疲劳磨损和磨粒磨损混合作用机制。

关键词： TC4合金环境介质磨损行为磨损机制

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商品价值与人的发展——从马克思哲学变革的“主体—客体”范式谈起

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改革与战略 2015年第6期31卷 16-21页

作者：黎一献广西师范大学马克思主义学院广西桂林541006

人的自由全面发展是马克思关切的终极价值目标。马克思哲学的变革是对主客二分的批判和简单同一的超越,主体和客体是对立同一的辩证发展过程。马克思对商品价值的分析蕴含了对人的发展维度的关注,对资本主义私有制条件下商品价值秘密的... 详细信息

人的自由全面发展是马克思关切的终极价值目标。马克思哲学的变革是对主客二分的批判和简单同一的超越,主体和客体是对立同一的辩证发展过程。马克思对商品价值的分析蕴含了对人的发展维度的关注,对资本主义私有制条件下商品价值秘密的揭示,发掘了以物为依赖的人的主体独立性。马克思的商品价值归根到底关注的是人的发展问题,是人自身的发展以及人与人之间的整个人类社会的发展,人的个性自由全面发展是马克思商品价值中人的发展依归。

关键词：商品价值主体客体人的发展

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