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Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3063-3076页

作者： Wenjing Zai Min Yang Kuan Jiang Juan Guan Huijing wang Kongying Hu Chao Huang Jieliang Chen Wei Fu Changyou zhan Zhenghong yuan Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Research Unit of Cure of Chronic Hepatitis B Virus Infection(CAMS)Shanghai Frontiers Science Center of Pathogenic Microbes and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghaiP.R.China Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghaiP.R.China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghaiP.R.China Eye Institute and Department of Ophthamology Eye and ENT HospitalFudan UniversityShanghaiP.R.China Pharmacy Department of Huashan Hospital Fudan UniversityShanghaiP.R.China Institute of Pediatric Translational Medicine Shanghai Institute for Pediatric Congenital Heart DiseaseShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Institute of Infectious Disease and Biosecurity ShanghaiP.R.China

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA(siRNA)against hepatitis B virus(HBV)with an efficient delivery system for treating chronic hepatitis B(CHB),and explore combined RNA interference(RNAi)and immune modulatory modalities for better viral *** synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and *** lipid nanoparticle(LNP)formulation was optimized by adopting HO-PEG_(2000)-DMG lipid and modifying the molar ratio of traditional polyethylene glycol(PEG)lipid in LNP *** efficacy and safety of this formulation in delivering siHBV(tLNP/siHBV)along with the mouse IL-2(mIL-2)mRNA(tLNP/siHBVIL2)were evaluated in the rAAVHBV1.3 mouse model.A siRNA combination(terms“siHBV”)with a genotypic coverage of 98.55%was selected,chemically modified,and encapsulated within an optimized LNP(tLNP)of high efficacy and security to fabricate a therapeutic formulation for *** results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA(up to 3log_(10)reduction;vs PBS)in dose-and time-dependent manners at single-dose or multi-dose frequencies,with satisfactory safety *** studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus,via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4^(+)and CD8^(+)T cell responses by expressed mIL-2 *** adopting tLNP as nucleic acid nanocarriers,the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV,thus offering a promising translational therapeutic strategy for treating CHB.

关键词： formulation enable offering

Functional microfluidics:theory,microfabrication,and applications

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International Journal of Extreme Manufacturing 2024年第3期6卷 140-173页

作者： Mingzhu Xie Ziheng zhan Yinfeng Li Junkai Zhao Ce zhang Zhaolong wang Zuankai wang Interdisciplinary Research Center of Low-carbon Technology and Equipment College of Mechanical and Vehicle EngineeringHunan UniversityChangsha 410082People’s Republic of China Energy Research Institute of Shandong Academy of Sciences Qilu University of Technology(Shandong Academy of Sciences)Jinan 250014People’s Republic of China Qian Xuesen Laboratory of Space Technology China Academy of Space Technology(CAST)Beijing 100094People’s Republic of China Department of Mechanical Engineering Hong Kong Polytechnic UniversityHong Kong Special Administrative Region of China 999077People’s Republic of China

Microfluidic devices are composed of microchannels with a diameter ranging from ten to a few hundred ***,quite a small(10-9–10-18l)amount of liquid can be manipulated by such a precise *** the past three decades,significant progress in materials science,microfabrication,and various applications has boosted the development of promising functional microfluidic *** this review,the recent progress on novel microfluidic devices with various functions and applications is ***,the theory and numerical methods for studying the performance of microfluidic devices are briefly ***,materials and fabrication methods of functional microfluidic devices are ***,the recent significant advances in applications of microfluidic devices are highlighted,including heat sinks,clean water production,chemical reactions,sensors,biomedicine,capillaric circuits,wearable electronic devices,and ***,perspectives on the challenges and future developments of functional microfluidic devices are *** review aims to inspire researchers from various fields engineering,materials,chemistry,mathematics,physics,and more—to collaborate and drive forward the development and applications of functional microfluidic devices,specifically for achieving carbon neutrality.

关键词： capillary theory functional devices functional microfluidics

Coherence entropy during propagation through complex media

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Advanced Photonics 2024年第4期6卷 25-35页

作者： Xingyuan Lu Zhuoyi wang Qiwen zhan Yangjian Cai Chengliang Zhao Soochow University School of Physical Science and TechnologyJiangsu Key Laboratory of Frontier Material Physics and DevicesSuzhouChina University of Shanghai for Science and Technology School of Optical-Electrical and Computer EngineeringShanghaiChina Shandong Normal University School of Physics and ElectronicsShandong Provincial Engineering and Technical Center of Light ManipulationsShandong Provincial Key Laboratory of Optics and Photonic DeviceJinanChina East China Normal University Joint Research Center of Light Manipulation Science and Photonic Integrated Chip of East China Normal University and Shandong Normal UniversityShanghaiChina

The deformation,flicker,and drift of a light field owing to complex media such as a turbulent atmosphere have limited its practical ***,research on invariants in randomly fluctuated light fields has garnered considerable attention in recent *** is a statistical property of light,while its full and quantitative characterization is ***,we successfully realize the orthogonal modal decomposition of partially coherent beams and introduce the application of coherence entropy as a global coherence characteristic of such randomly fluctuated light *** is demonstrated that coherence entropy remains consistent during propagation in a unitary system by unraveling complex *** representative examples,we study the robustness of coherence entropy for partially coherent beams as they propagate through deformed optical systems and turbulent *** entropy is anticipated to serve as a key metric for evaluating the propagation of partially coherent beams in complex *** study paves the way for a broader application scope of a customized low-coherence light field through nonideal optical systems and complex media.

关键词： complex media propagation invariant modal decomposition orbital angular momentum statistical optics coherence

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滨海软土非线性流变模型及其工程应用研究

岩土力学 2009年第9期30卷 2679-2685页

作者：王元战王婷婷王军天津大学建筑工程学院天津市港口与海洋工程重点实验室天津300072

基于室内一维固结蠕变试验,研究了天津滨海淤泥质软黏土的蠕变变形规律,建立了反映滨海软黏土的非线性流变本构模型,确定了模型中的各个参数。通过此本构模型推导出天津软黏土的沉降计算公式,利用该公式对天津滨海地区北塘水库大坝软土... 详细信息

基于室内一维固结蠕变试验,研究了天津滨海淤泥质软黏土的蠕变变形规律,建立了反映滨海软黏土的非线性流变本构模型,确定了模型中的各个参数。通过此本构模型推导出天津软黏土的沉降计算公式,利用该公式对天津滨海地区北塘水库大坝软土堤基进行了沉降计算和分析,计算值与实测值比较吻合,证明了流变模型的合理性,同时也说明在软土地基沉降计算中,考虑非线性流变性状的影响是必要的。并对天津滨海新区软土长期蠕变沉降作出预测。

关键词：滨海软土流变模型黏弹塑性蠕变沉降

Effect of Al_(2)O_(3)/SiO_(2) mass ratio and CaO content on viscosity and structure of slag for pyrometallurgical processing of spent automotive catalysts

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Journal of Iron and Steel Research International 2024年第3期31卷 608-621页

作者： Zhe wang Qi-long Wei Cheng-bin Shi zhan-cheng Guo State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

The effect of Al_(2)O_(3)/SiO_(2) mass ratio and CaO content on the viscosity and structure of the CaO-Al_(2)O_(3)-SiO_(2)-6MgO-1.5ZrO_(2)-1.5CeO_(2) slag was *** results show that with the increase in Al_(2)O_(3)/SiO_(2) mass ratio,the viscous flow units within the slag gradually change from Si-O-Si to Al-O-Al and ***,the substitution of Al_(2)O_(3) for SiO_(2) leads to the transformation of Si-O bonds towards weaker Al-O bonds,which weaken the bond strength of the aluminosilicate networks,thus leading to a decrease in the viscosity of *** increase in CaO content effectively promotes the depolymerization of the aluminosilicate networks,resulting in a significant decrease in the viscosity of the *** slag with Al_(2)O_(3)/SiO_(2) of 0.7-1.5 and CaO of 30 wt.%shows promise as the reference slag system for the Fe-collection smelting of spent automotive catalysts due to its good comprehensive performance.

关键词： Aluminosilicate slag Al_(2)O_(3)/SiO_(2)mass ratio CaO content Viscosity Slag structure

A Study on the Impact of Chemical Structure on the Evolution of Aggregate Structure in Fiber-shaped High Density Polyethylene Vitrimer

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Chinese Journal of Polymer Science 2024年第10期42卷 1557-1565,I0013页

作者： Bing wang yuan-Chu Gao Hai wang Hui Niu State Key Laboratory of Fine Chemicals School of Chemical EngineeringDalian University of TechnologyDalian116024China

Vitrimers have emerged as a prominent research area in the field of polymer *** of the studies have focused on synthesizing polymers with versatile dynamic crosslinking structures,while the impact of chemical structure on aggregate structure of vitrimers,particularly during polymer processing,remains insufficiently *** present study employed commercial maleic anhydride-grafted-high density polyethylene(M-g-HDPE)as the matrix and hexanediol as the crosslinker to facilely obtain fiber-shaped HDPE vitrimers through a reaction extrusion and post-drawing *** chemical structure characterization,morphology observation,thermal and mechanical properties investigation,as well as aggregate structure analysis,this work revealed the influence of dynamic bonds on the formation of aggregate structures during fiber-shaped vitrimers processing.A small amount of dynamic bonds in HDPE restricts the motion of PE chain during melt-extruding and post-drawing,resulting in a lower orientation of the PE ***,lamellar growth and fibril formation during post-drawing at high temperature are enhanced to some extent due to the competition between dynamic bond and chain *** uneven morphology of fibershaped HDPE vitrimers can be attributed to the stronger elastic effect brought by dynamic bonding,which plays a more dominant role in determining the mechanical properties of fiber-shaped vitrimers compared to aggregate *** Vitrimers have emerged as a prominent research area in the field of polymer *** of the studies have focused on synthesizing polymers with versatile dynamic crosslinking structures,while the impact of chemical structure on aggregate structure of vitrimers,particularly during polymer processing,remains insufficiently *** present study employed commercial maleic anhydride-grafted-high density polyethylene(M-g-HDPE)as the matrix and hexanediol as the crosslinker to facilely obtain fiber-shap

关键词： High density polyethylene vitrimer Fiber-shaped Aggregate structures Transesterification reaction

When mRNA meets gene editing

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Nano Research 2024年第8期17卷 7337-7356页

作者： Weijie Li Chen wang yuan Lu Key Laboratory of Industrial Biocatalysis Ministry of EducationDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China Department of Chemical Engineering Tsinghua UniversityBeijing 100084China

The critical challenge of gene therapy lies in delivering gene editing *** with DNA,while RNA is less stable and more accessible to degrade,it comes with the benefit of lower off-target effects since permanent insertion is not *** review focuses on mRNA-based delivery of gene editing agents,highlighting novel mRNA delivery *** provide context,a comparison is made between three main gene editing agents:programmable nucleases,base editors,and prime *** potential of Cas\pi and transposons is also discussed in this ***,a summary of four main barriers to mRNAbased in vivo delivery is ***,this review detailedly introduced different delivery systems,both viral(lentivirus)and non-viral vectors(genome editing via oviductal nucleic acids delivery,lipid nanoparticles,polymer-based nanoparticles,viruslike-particles,extracellular vesicles,and migrasome).Each delivery strategy is assessed by comparing its advantages and disadvantages to offer a comprehensive and objective overview of the delivery ***,we emphasized the vital role of the protein corona as a critical regulator for ***,we concluded the challenges of mRNA-based gene editing strategies(RNA stability,targeting,potential immunogenicity,cytotoxicity,heterogeneity,and rational design).The purpose of this review is to guide further research and provide a comprehensive analysis of mRNA-based in vivo delivery of gene editing agents in this promising field.

关键词： gene editing mRNA delivery viral vectors non-viral vectors CRISPR

桶间距对四桶吸力式基础各单向承载力的影响及最优间距的确定

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岩土力学 2018年第10期39卷 3603-3611页

作者：肖忠王琰王元战刘莺天津大学水利工程仿真与安全国家重点实验室天津300072 天津大学天津市港口与海洋工程重点试验室天津300072

四桶吸力式基础由4个按正方形排列的吸力式桶形基础组成,并通过上部结构连成整体共同承受外部荷载,相比于单桶基础,四桶基础能承受更恶劣的海洋环境荷载,可作为海上风机和海洋平台等结构物的基础,具有广阔的应用前景。为探究饱和软土地... 详细信息

四桶吸力式基础由4个按正方形排列的吸力式桶形基础组成,并通过上部结构连成整体共同承受外部荷载,相比于单桶基础,四桶基础能承受更恶劣的海洋环境荷载,可作为海上风机和海洋平台等结构物的基础,具有广阔的应用前景。为探究饱和软土地基上四桶基础和单桶基础在承载力以及破坏模式方面的关系,优化四桶基础的设计,建立了大量的四桶和单桶基础的三维有限元模型,系统研究了不同基础埋深和土体剪切强度时桶间距对四桶基础各单向承载能力和对应的破坏模式的影响。结果表明,竖向承载力系数受桶间距影响较小,而水平承载力系数受其影响较大,力矩承载力系数受其影响尤为显著;在同一桶间距比时,四桶吸力式基础的各单向承载力系数随基础埋深比的增加逐渐增大,随土体剪切强度不均匀度指标的增大逐渐减小。通过分析四桶基础的各单向承载力、对应的破坏模式和群效应系数,定义了四桶基础的最优桶间距,可为四桶基础桶间距的优化设计提供依据。

关键词：四桶吸力式基础最优桶间距承载特性破坏模式软土地基

Global Spherically Symmetric Solutions for a Coupled Compressible Navier–Stokes/Allen–Cahn System

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Acta Mathematica Sinica,English Series 2024年第8期40卷 2037-2064页

作者： Chang Ming SONG Jian Lin zhanG yuan yuan wang Department of Applied Mathematics School of Mathematics and Information ScienceZhongyuan University of TechnologyZhengzhou 450007P.R.China

In this paper,we consider the global spherically symmetric solutions for the initial boundary value problem of a coupled compressible Navier–Stokes/Allen–Cahn system which describes the motion of two-phase viscous compressible *** prove the existence and uniqueness of global classical solution,weak solution and strong solution under the assumption of spherically symmetry condition for initial dataρ0 without vacuum state.

关键词： Diffuse interface model global solutions Navier-Stokes equations Allen-Cahn equation spherically symmetry