检索结果-南通市图书馆

Supramolecular Assembly Models of siRNA Delivery Systems

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Chemistry 2015年第1期33卷 79-89页

作者： Jing Sun Jiancheng Wang zhenjun yang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Small interfering RNA(siRNA)technology,which could be able to silence specific targeted mRNAs rapidly and efficiently,has been regarded as a novel and potent gene therapeutic approach for diseases,such as cancers,in-fections,inflammations and neurological ***,some conspicuous intrinsic defects of siRNA including the poor cellular uptake,low biological stability,unfavorable pharmacokinetics and bio-distribution properties,have hindered further applications in ***,it is prerequisite to design safe and effective siRNA delivery systems for the successful development of siRNA-based various diseases *** review aims to analyze and summarize these supramolecular assembly models in the process of siRNA delivery,namely recent nanotech-nological strategies for carrying siRNA by using diverse non-viral vehicles such as cationic liposomes,stable nucleic acid lipid particles(SNALPs),cationic polymers,cationic dendrimers,inorganic nanoparticles and ***,it is concluded with future perspectives of siRNA therapeutics in the field of non-viral carriers.

关键词： siRNA delivery supramolecular assembly non-viral vectors nanocarriers

FINITE ELEMENT MODELLING OF COMPLEX 3D STATIC AND DYNAMIC CRACK PROPAGATION BY EMBEDDING COHESIVE ELEMENTS IN ABAQUS

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Mechanica Solida Sinica 2010年第3期23卷 271-282页

作者： Xiangting Su zhenjun yang Guohua Liu College of Civil Engineering and Architecture Zhejiang University Hangzhou 310027 China Department of Engineering the University of Liverpool L69 3GQ UK

This study proposes an algorithm of embedding cohesive elements in Abaqus and develops the computer code to model 3D complex cragk propagation in quasi-brittle materials in a relatively easy and efficient manner. The cohesive elements with softening traction-separation relations and damage initiation and evolution laws are embedded between solid elements in regions of interest in the initial mesh to model potential cracks. The initial mesh can consist of tetrahedrons, wedges, bricks or a mixture of these elements. Neither remeshing nor objective crack propagation criteria are needed. Four examples of concrete specimens, including a wedgesplitting test, a notched beam under torsion, a pull-out test of an anchored cylinder and a notched beam under impact, were modelled and analysed. The simulated crack propagation processes and load-displacement curves agreed well with test results or other numerical simulations for all the examples using initial meshes with reasonable densities. Making use of Abaqus＇s rich pre/post- processing functionalities and powerful standard/explicit solvers, the developed method offers a practical tool for engineering analysts to model complex 3D fracture problems.

关键词： finite element method cohesive elements three-dimensional crack propagation discrete crack model concrete structures Abaqus

Synthesis and Antitumor Activity Evaluation of γ-Monofluorinated and γγy-Difluorinated Goniothalamin Analogues

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Chemistry 2013年第6期31卷 805-812页

作者： Yi yang zhenjun yang Chunru Cheng Fengling Qing School of Chemistry and Pharmaceutical Engineering Sichuan University of Science & Engineering Zigong Sichuan 643000 China Key Laboratory of Organofluorine Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University 38 Xueyuan Road Beijing 100083 China

A series of novel γ,γ-difluorinated Goniothalamin analogues 4a--4i and 6a--6i were synthesized. The key steps included the construction of C-5 stereocenter adjacent to gem-difluoromethylene group by way of lipase AK catalyzed kinetic resolution, the introduction of aryl group via Stille coupling, and lactonization by 1,5-oxidative cycli- zation. These γ,γ-difluorinated Goniothalamin analogues 4a-4i and their enanfiomers 6a--6i, together with several corresponding 7-monofluorinated Goniothalamin analogues were biologically evaluated against four different cancer cell lines. Compound 7h showed a nearly equivalent potency as the parent （R）-Goniothalamin in the micromolar range. The different fluorine effects between fluoromethylene and gem-difluoromethylene on antitumor activity were discussed through the analysis of bioassay data.

关键词： Goniothalamin Stille coupling fluorine antitumor activity

Development of a Three-Dimensional Multiscale Octree SBFEM for Viscoelastic Problems of Heterogeneous Materials

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Computer Modeling in Engineering & Sciences 2024年第8期140卷 1831-1861页

作者： Xu Xu Xiaoteng Wang Haitian yang zhenjun yang Yiqian He State Key Laboratory of Structural Analysis Optimization and CAE Software for Industrial EquipmentDepartment of Engineering MechanicsDalian University of TechnologyDalian116024China Hubei Key Laboratory of Geotechnical and Structural Safety School of Civil EngineeringWuhan UniversityWuhan430072China Mechanik–Materialtheorie Ruhr-Universität BochumBochum44801Germany

The multiscale method provides an effective approach for the numerical analysis of heterogeneous viscoelastic materials by reducing the degree of freedoms(DOFs).A basic framework of the Multiscale Scaled Boundary Finite Element Method(MsSBFEM)was presented in our previous works,but those works only addressed two-dimensional *** order to solve more realistic problems,a three-dimensional MsSBFEM is further developed in this *** the proposed method,the octree SBFEM is used to deal with the three-dimensional calculation for numerical base functions to bridge small and large scales,the three-dimensional image-based analysis can be conveniently conducted in small-scale and coarse nodes can be flexibly adjusted to improve the computational ***,the Temporally Piecewise Adaptive Algorithm(TPAA)is used to maintain the computational accuracy of multiscale analysis by adaptive calculation in time *** results of numerical examples show that the proposed method can significantly reduce the DOFs for three-dimensional viscoelastic analysis with good *** instance,the DOFs can be reduced by 9021 times compared with Direct Numerical Simulation(DNS)with an average error of 1.87%in the third example,and it is very effective in dealing with three-dimensional complex microstructures directly based on images without any geometric modelling process.

关键词： Three-dimensionalmultiscale viscoelastic analysis numerical base functions octree SBFEM image-based analysis temporally piecewise adaptive algorithm

Discussion on the interrelationship among Cu-Ni sulfide deposits,mafic volcanic rocks and intrusive rocks in the Sipu region,northern Guangxi,China

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal Of Geochemistry 2012年第3期31卷 282-296页

作者： yang zhenjun ZHANG Wenshan LIU Jishun YIN Lijun Beijing Institute of Geology and Mineral Resources Beijing 100012China China Nonferrous Metals Mineral Resources Geological Survey Center Donia Resources Co.Ltd.Beijing 100012China School of Geoscience and Environmental Engineering Central South UniversityChangsha 410083China

The Sipu region of North Guangxi is located in the southwest of the "Jiangnan Ancient Land",where there are developed the oldest stratum in southern China,the Proterozoic Sipu Group,and there are also largely ex-posed mafic intrusive rocks,mafic volcanic rocks and copper-nickel sulfide *** mafic intrusive rocks and volcanic rocks are rich in MgO(6.52%-26.39%),but poor in K2O(0.05%-1.00%) and TiO2(0.33%-0.89%).They are also rich in trace elements such as Rb and Ba while poor in Ta,Nb and the *** of them have medium con-tents of rare-earth elements,30.26×10-6-126.71×10-6,in which LREEs are slightly rich with ΣLREE/ΣHREE of 1.35-2.46,δEu 0.79-1.33,displaying weak or no δEu anomaly,with the same geochemical *** right-inclined distribution patterns and the features show that magma would be formed at the comagmatic un-diagenetic *** studies show that mafic intrusive rocks and volcanic rocks are the products of the same source region evolving in different stages and *** copper-nickel sulfide deposits are characterized by liquation,crys-tallization and fractionation of mafic rocks,and have some interrelations with mafic intrusive rocks and volcanic rocks with respect to magmatic genesis.

关键词：铜镍硫化物矿床基性火山岩基性侵入岩中国南方西北部地球化学特征同源岩浆江南古陆

In vitro selection of G-rich RNA aptamers that target HIV-1 integrase

在线全文

学校读者我要写书评

暂无评论

Science China Chemistry 2008年第5期51卷 401-413页

作者： LIU YingChun ZHANG Yan YE GuoZhu yang zhenjun ZHANG LiangRen ZHANG LiHe State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100083China

Aptamers that interact with various HIV-1 proteins,such as reverse transcriptase,Rev,Tat protein,and nuclear capsule protein,have been prepared through SELEX (systematic evolution of ligands by ex-ponential enrichment) technique. However,there are few reports about the DNA or RNA aptamers that target HIV-1 integrase. In this investigation,we selected alternative RNA aptamers specific for the HIV-1 integrase by using a different binding buffer containing 10 mmol·L-1 MgCl2 and 100 mmol·L-1 KCl. Aptamer IN1,IN2,IN3 had similar and the highest Kd values from 145 to 239 nmol·L-1. Structural studies showed that they formed similar stem-loop structure. Deletion of any stem structure resulted in diminished affinity. In addition,structure probing study with antisense DNA indicated that the stem-loop structure in the random region was critical for integrase binding. Although aptamer IN1 failed to form G-quartet structure,it might directly interact with the DDE motif of integrase,which is the virus DNA-binding site,because G-quadruplex T40214 competitively inhibited the interaction between IN1 and integrase. Together,this study generated a novel RNA aptamer IN1,which could be useful in basic research and anti-HIV drug screening.

关键词： RNA aptamer HIV-1 integrase G-quadruplex

Loss of silencing activity caused by 5′-terminal modification with D-/L-isonucleotide(isoNA) or locked nucleic acid(LNA) could not be restored by 5′-terminal phosphorylation

在线全文

学校读者我要写书评

暂无评论

Science China Chemistry 2014年第2期57卷 329-334页

作者： HUANG Ye CHEN Zhuo WANG Zhuo LI YaTing CHEN Yue yang zhenjun ZHANG LiHe The State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University

In this study,a series of 5′-phosphorylated siRNAs with D-/L-isonucleotide(isoNA)or locked nucleic acid(LNA)incorporated at the 5′-terminus were *** was found that after incorporating either isoNA or LNA at the 5′-terminus of the antisense strand or sense strand,the silencing activity of modified strands has been inhibited,which cannot be recovered by phosphorylation at the 5′-terminus;however,the silencing activity of unmodified strand to its own target was *** work indicates that the isoNA and LNA modification at 5′-terminus can interfere with the strand selection during the RISC assembling process,and the disturbance of the 5′-phosporylation should not be the only viable mechanism.

关键词： isonucleotide locked nucleic acid (LNA) 5'-terminal phosphorylation

Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker

在线全文

学校读者我要写书评

暂无评论

Science China Chemistry 2013年第11期56卷 1542-1549页

作者： WANG XiaoFeng HUANG Ye LIU yang CHEN Yue JIN HongWei ZHENG Yi DU Quan yang zhenjun ZHANG LiHe The State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd.

In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise *** conjugation of peptides at either 3’-terminus of siCdc2 bring no change to the classical A-form of RNA duplex,but slightly compromise the thermodynamic *** conjugation at the 3’-terminus of sense strand could improve the serum stability obviously,however,the opposite peptide conjugation at the 3’-terminus of antisense strand shows no such *** to the results of artificial silencing activity assay system,peptide conjugation at 3’-terminus of antisense strand slightly weakens the silencing activity of *** sense strand peptide conjugation exhibits similar silencing activity as native siCdc2,meanwhile,it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA.

关键词： siRNA peptide conjugate solid synthesis

Synthesis and Anti-HIV Activity of a Series of 6-Modified 2＇,3＇-Dideoxyguanosine and 2＇,3＇-Didehydro-2＇,3＇- dideoxyguanosine Analogs

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Chemistry 2013年第9期31卷 1207-1218页

作者： Lujia Xie Xiantao yang Delin Pan Yingli Cao Mou Cao Guichun Lin Zhu Guan Ying Guo Lihe Zhang zhenjun yang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Beijing 100191 China Institute ofMateria Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China

In search of potential 2＇,3＇-dideoxyguanosine （ddG） and 2＇,3＇-didehydro-2＇,3＇-dideoxyguanosine （D4G） prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile ＂one-pot＂ method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase （RT） incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.

关键词： 2',3'-dideoxyguanosine (ddG) 2',3'-didehydro-2',3'-dideoxyguanosine (D4G) prodrug anti-HIV activity