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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU su-su yu Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou School of Traditional Chinese Medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Geometric Name Routing for ICN in Dynamic World

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China Communications 2015年第7期12卷 47-59页

作者： suN Yanbin ZHANG yu su Shen ZHANG Hongli fang Binxing School of Computer Science and Technology Harbin Institute of Technology

A new paradigm of scalable routing for ICN is to combine a geometric routing scheme with a Distributed Hash Table. However, for most routing schemes in this paradigm, when a node joins or leaves, large numbers of nodes, even the whole topology, need to be re-embedded, and a great number of contents need to be re-registered. In this paper, we propose D-Griffin, a geometric routing scheme on flat names for dynamic topologies. D-Griffin provides two advantages. First, it avoids re-embedding the topology by using an online greedy embedding scheme and a void handling greedy forwarding scheme. Second, it decreases the number of re-registrations by using a name mapping scheme with a tradeoff between topology independence and load balancing. Theoretical and experimental analyses show that D-Griffin provides guaranteed content lookup, low description complexity, low path stretch, scalable routing update, and acceptable load balancing.

关键词： geometric name routing online greedy embedding name mapping flat name

Seismic stability analysis of slopes with pre-existing slip surfaces

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Journal of Mountain Science 2018年第6期15卷 1331-1341页

作者： su Li-jun suN Chang-ning yu fang-wei ALI Sarfraz Key Laboratory of Mountain Hazards and Earth surface Process of Chinese Academy of Sciences Institute of Mountain Hazards and Environment Chinese Academy of Sciences Chengdu 610041 China CAS Center for Excellence in Tibetan Plateau Earth Sciences Beifing 100101 China University of Chinese Academy of Sciences Beijing 100049 China School ofAdvanced Geomechanieal Engineering （SAGE） and Research Center ofCPEC （RCC） National University of Sciences and Technology （NUST） Pakistan

In analyzing seismic stability of a slope with upper bound limit analysis method, the slip surface is often assumed as a log-spiral or plane slip surface. However, due to the presence of a weak layer and unfavorable geological structural surface or a bedrock interface with overlying soft strata, the preexisting slip surface of the slope may be irregular and composed of a series of planes rather than strictly logspiral or plane shape. A computational model is developed for analyzing the seismic stability of slopes with pre-existing slip surfaces. This model is based on the upper bound limit analysis method and can consider the effect of anchor bolts. The soil or rock is deemed to follow the Mohr-Coulomb yield criterion. The slope is divided into multiple block elements along the slip surface. According to the displacement compatibility and the associated flow rule, a kinematic velocity field of the slope can be obtained computationally. The proposed model allows not only calculation of the rate of external work owing to the combined effect of self-weight and seismic loading, but also that of the energy dissipation rate caused by the slip surface, interfaces of block elements and anchorage effect of the anchors. Considering a direct relationship between the rate of external work and the energy dissipation rate, the expressions of yield acceleration and permanent displacement of anchored slopes can be derived. Finally, the validity of this proposed model is illustrated by analysis on three typical slopes. The results showed that the proposed model is more easily formulated and does not need to solve complex equations or time consuming iterations compared with previous methods based on the conditions of force equilibrium.

关键词： Slope stability Pre-existing slip surface Seismic loading Limit analysis Yield acceleration Permanent displacement

基于MODIS-NDVI数据广西植被覆盖变化特征分析

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湖北农业科学 2015年第2期54卷 321-325页

作者：喻素芳佘光辉罗叶红潘婷李丽娟南京林业大学森林资源与环境学院南京210037 广西大学林学院南宁530004

利用月合成MODIS-NDVI时间序列数据、气象数据、DEM等数据,分析研究了2001-2010年广西省10年间植被覆盖变化的特征。结果表明,广西植被覆盖率较高且总体呈上升趋势,从区域角度分析,桂南地区增加趋势最显著,其次是桂中地区;从海拔梯度角... 详细信息

利用月合成MODIS-NDVI时间序列数据、气象数据、DEM等数据,分析研究了2001-2010年广西省10年间植被覆盖变化的特征。结果表明,广西植被覆盖率较高且总体呈上升趋势,从区域角度分析,桂南地区增加趋势最显著,其次是桂中地区;从海拔梯度角度分析,海拔200 m以下的区域植被覆盖增加趋势最显著,但此区域的植被覆盖率较低,NDVI最高分布在海拔400-800 m的区域。植被覆盖变化受气温、降水及人类活动影响较大,植被覆盖梯度变化除受这些因素影响外,也与植被垂直地理分布特征相关。

关键词： MODIS-NDVI 植被覆盖气温显著

A bi-population immune algorithm for weapon transportation support scheduling problem with pickup and delivery on aircraft carrier deck

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Defence Technology（防务技术） 2023年第4期22卷 119-134页

作者： fang Guo Wei Han Xi-chao su yu-jie Liu Rong-wei Cui Naval Aviation University No.188Ermalu RoadZhifu DistrictYantai264001Shandong ProvinceChina

The weapon transportation support scheduling problem on aircraft carrier deck is the key to restricting the sortie rate and combat capability of carrier-based *** paper studies the problem and presents a novel solution *** the interference of the carrier-based aircraft deck layout on the weapon transportation route and precedence constraint into consideration,a mixed integer formulation is established to minimize the total objective,which is constituted of makespan,load variance and accumulative transfer time of support *** approach is developed for the ***,based on modeling the carrier aircraft parked on deck as convex obstacles,the path library of weapon transportation is constructed through visibility graph and Warshall-Floyd *** then propose a bi-population immune algorithm in which a population-based forward/backward scheduling technique,local search schemes and a chaotic catastrophe operator are ***,the randomkey solution representation and serial scheduling generation scheme are adopted to conveniently obtain a better *** Taguchi method is additionally employed to determine key parameters of the ***,on a set of generated realistic instances,we demonstrate that the proposed algorithm outperforms all compared algorithms designed for similar optimization problems and can significantly improve the efficiency,and that the established model and the bi-population immune algorithm can effectively respond to the weapon support requirements of carrier-based aircraft under different sortie missions.

关键词： Carrier-based aircraft Weapon transportation support scheduling Pickup and delivery Bi-population immune algorithm

Dynamic modeling and parameter identification of a gun saddle ring

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Defence Technology（防务技术） 2020年第2期16卷 325-333页

作者： Tong Lin Lin-fang Qian Qiang Yin Shi-yu Chen Tai-su Liu School of Mechanical Engineering Nanjing University of Science and TechnologyNanjing210094China

In this study,a theoretical nonlinear dynamic model was established for a saddle ring based on a dynamic force analysis of the launching process and the structure according to contact-impact *** ADAMS software was used to build a parameterized dynamic model of the saddle ring.A parameter identification method for the ring was proposed based on the particle swarm optimization algorithm.A loading test was designed and performed several times at different elevation *** response histories of the saddle ring with different loads were then *** parameters of the saddle ring dynamic model were identified from statistics generated at a 500 elevation angle to verify the feasibility and accuracy of the proposed *** actual loading history of the ring at a 70°elevation angle was taken as the model *** response histories of the ring under these working conditions were obtained through a *** simulation results agreed with the actual ***,the effectiveness and applicability of the proposed dynamic model were verified,and it provides an effective method for modeling saddle rings.

关键词： Gun saddle ring Dynamic response Parameter identification Particle swarm optimization

Carbon Isotope Stratigraphy of the Cambrian System in the Eastern Tarim Basin,China

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Acta Geologica Sinica(English Edition) 2022年第4期96卷 1277-1293页

作者： WANG Huajian su Jin WANG Xiaomei YE yuntao WANG yu fang yu ZHANG Shuichang Research Institute of Petroleum Exploration&Development Beijing 100083China

The ultra-deep Cambrian System in the Tarim Basin is an important field for petroleum exploration,while fine division of the Cambrian strata remains *** recent years,carbon isotope stratigraphy of the Cambrian System has been established and widely ***,we report an integrated profile of carbonate and organic carbon isotopic values(δ^(13)C_(carb)andδ^(13)C_(org))from cuttings of the Tadong2 Well in the eastern Tarim *** carbon isotope anomalies of BACE,ROECE and SPICE were recognized on theδ^(13)C_(carb)*** apogees and a nadir on theδ^(13)C_(org)profile and the onset of ROECE on theδ^(13)C_(carb)profile were suggested as boundaries of the present four series of the Cambrian *** boundaries are easily identifiable on the gamma logging profile and is consistent with the previous division scheme,based on biostratigraphic evidence in outcrop *** carbon cycle perturbations and organic carbon burials during the BACE and SPICE events might be related to the reduction and expansion of a huge dissolved organic carbon reservoir in the deep ocean of the ancient Tarim Basin.

关键词： organic carbon black shale dissolved organic carbon BACE SPICE stratigraphic division

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一株棉花根际铁载体产生菌E19的分离鉴定

生物技术 2007年第6期17卷 19-21页

作者：于素芳丁延芹姚良同岳宝强杜秉海山东农业大学生命科学学院山东泰安271018 山东中医药大学山东济南250355

目的:从棉花根际细菌中筛选出铁载体产生能力较强的菌株并对其进行鉴定。方法:用梯度稀释法从棉花根际中分离出细菌,再通过在CAS检测平板上显色圈的大小从中筛选出铁载体产生能力较强的菌株,并对其进行生理生化鉴定和16S rDNA序列分析... 详细信息

目的:从棉花根际细菌中筛选出铁载体产生能力较强的菌株并对其进行鉴定。方法:用梯度稀释法从棉花根际中分离出细菌,再通过在CAS检测平板上显色圈的大小从中筛选出铁载体产生能力较强的菌株,并对其进行生理生化鉴定和16S rDNA序列分析。结果:筛选出一株铁载体产生能力较强的菌株E19,13项生理生化指标除甲基红试验呈阳性外,其它均与恶臭假单胞菌相同。其16S rDNA与恶臭假单胞菌(Pseudomonas putida)的同源性为100%。

关键词：棉花根际铁载体分离鉴定

Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

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Nano Research 2025年第1期18卷 607-617页

作者： Ruo-Lin Jiang Hui-Na Liu yu-Fan Yang Zhi-Cheng Zhang Qi Dai Xiao-Yan Bao Lin-Jie Wu Ya-Xin Qin Xin Tan Xiao-Yan sun Xu-fang Ying Zhi-Qing Ben Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Polytechnic institute Zhejiang UniversityHangzhou 310015China

Traditionally,hyaluronic acid has been widely used for drug delivery,but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative,which makes it difficult to carry hydrophobic drugs and small interfering RNA(siRNA)with the same *** on previous studies,we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP(HSTD)for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic ***,N,N,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting ***,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.

关键词： zwitterionic hyaluronic acid N N N-trimethylcystamine small interfering RNA(siRNA) doxorubicin