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Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression

Chinese Medical Journal 2011年第1期124卷 26-31页

作者： tian xin-rui tian xin-li BO Jian-ping LI Shao-gang LIU Zhuo-la NIU Bo Department of Respiratory Diseases Second Hospital of Shanxi Medical University Taiyuan Shanxi 030001 China Capital Institute of Pediatrics Beijing 100020 China

Background The signal transducer and activator of transcription 6 （STAT6） expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 （Th2） cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation. Methods In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide （ASODN） overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA （pANTI-STAT6）, then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma. Results In vitro, we showed suppression of STAT6 expression and interleukin （IL）-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin （OVA）-sensitized mice, local intranasal administration of fluorescein isothiocyanate （FITC）-Iabeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production. Conclusion These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

关键词： signal transducer and activator of transcription 6 antisense asthma lymphocyte Th2 cytokine

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DMF-scMT-seq linking methylome and transcriptome within single cells with digital microfluidics

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Science China Chemistry 2024年第6期67卷 2070-2078页

作者： xing Xu Xi Zeng xin Lin Shiyan Lin Shanshan Liang tian tian rui Su Jia Song Chaoyong Yang Collaborative Innovation Center of Chemistry for Energy Materials The MOE Key Laboratory of Spectrochemical Analysis and InstrumentationState Key Laboratory of Physical Chemistry of Solid SurfacesDepartment of Chemical BiologyCollege of Chemistry and Chemical EngineeringThe First Affiliated Hospital of Xiamen UniversityXiamen UniversityXiamen361005China Institute of Molecular Medicine Renji HospitalShanghai Jiao Tong University School of MedicineShanghai200127China Chemistry and Materials Science College Shanghai Normal UniversityShanghai200234China Chemistry and Biomedicine Innovation Center(ChemBIC) School of Chemistry and Chemical EngineeringNanjing UniversityNanjing210023China

Single-cell joint analysis of methylome and transcriptome reveals how the methylation regulates the transcriptional activity.However,traditional bench-top protocols for single-cell DNA methylation and RNA transcription co-detection are laborintensive,cost-ineffective and contaminant-prone.Herein,we establish the DMF-sc MT-seq,a highly-efficient and cost-effective method to simultaneously analyze single-cell DNA methylation and transcriptional activity based on digital microfluidics.DMFsc MT-seq automates the workflow of single-cell isolation,cellular hypotonic lysis,nucleic acid separation and methylome/transcriptome library construction in a contactless and addressable way.The system ensures high accuracy(R>0.85),high gene detection ability(14,697 genes per cell at 4 million sequencing depth),and high CpG coverage(677,198 CpG sites per cell at 1million sequencing depth).By using DMF-sc MT-seq,the relationship of DNA methylation and RNA transcription under different genomic contexts is resolved.We further apply DMF-sc MT-seq to study the dynamics of transcription regulation with methylation-inhibiting anti-tumor Decitabine,and identify the methylated promoter/gene body driven genes in response to Decitabine treatment.DMF-sc MT-seq facilitates the construction of the correlation of DNA methylation and transcriptional activity at the single-cell level in a flexible,sensitive and accurate way,which is anticipated to be a powerful tool in studying single-cell biological systems.

关键词： single-cell analysis digital microfluidics methylome sequencing transcriptome sequencing

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Interface property of dissimilar Ti-6Al-4V/AA1050 composite laminate made by non-equal channel lateral co-extrusion and heat treatment

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Defence Technology（防务技术） 2024年第3期33卷 197-208页

作者： Juan Liao Mengmeng tian xin Xue School of Mechanical Engineering and Automation Fuzhou UniversityFuzhou 350116China

The purpose of this paper is to examine the effect of processing parameters and subsequent heat treatments on the microstructures and bonding strengths of Ti-6Al-4V/AA1050 laminations formed via a non-equal channel lateral co-extrusion process.The microstructural evolution and growth mechanism in the diffusion layer were discussed further to optimize the bonding quality by appropriately adjusting process parameters.Scanning electron microscopes(SEM),energy dispersive spectrometer(EDS),and X-ray diffraction(XRD)were used to characterize interfacial diffusion layers.The shear test was used to determine the mechanical properties of the interfacial diffusion layer.The experimental results indicate that it is possible to co-extrusion Ti-6Al-4V/AA1050 compound profiles using non-equal channel lateral co-extrusion.Different heat treatment processes affect the thickness of the diffusion layer.When the temperature and time of heat treatment increase,the thickness of the reaction layers increases dramatically.Additionally,the shear strength of the Ti-6Al-4V/AA1050 composite interface is proportional to the diffusion layer thickness.It is observed that a medium interface thickness results in superior mechanical performance when compared to neither a greater nor a lesser interface thickness.Microstructural characterization of all heat treatments reveals that the only intermetallic compound observed in the diffusion layers is TiAl_(3).Due to the inter-diffusion of Ti and Al atoms,the TiAl_(3) layer grows primarily at AA1050/TiAl_(3) interfaces.

关键词： Shear strength Co-extrusion Heat treatment Microstructure Intermetallic compounds

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1α,25-dihydroxyvitamin D 3 inhibits transforming growth factorβ1-induced epithelial-mesenchymal transition viaβ-catenin pathway

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Chinese Medical Journal 2020年第11期133卷 1298-1303页

作者： xin-Rong Xiong xin-Li tian Ru-Jie Huo Yan-Ting Dong Dai Liu Jing-Cui Bai Yun-Feng Qi xin-rui tian Shanxi medical university TaiyuanShanxi 030001China Cardiopulmonary Center The Seventh Medical Center of People's Liberation Army General HospitalBeijing 100730China Department of Respiratory and Critical Care Medicine The Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China Department of Respiratory Medicine Jinhua Hospital of Traditional Chinese MedicineJinhuaZhejiang 321017China

Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway plays an important role,notably with regard to TGF-β1.Recent studies have shown that 1α,25-dihydroxyvitamin D 3(1α,25(OH)2D 3)inhibits TGF-β1-induced EMT,although the underlying mechanism have not yet been fully elucidated.Methods::Alveolar epithelial cells were exposed to 1α,25(OH)2D 3,ICG-001,or a combination of both,followed by stimulation with TGF-β1.The protein expression of E-cadherin,α-smooth muscle actin,fibronectin,andβ-catenin was analyzed by western blotting and immunofluorescence analysis.The mRNA transcript of Snail was analyzed using RT-qPCR,and matrix metalloproteinase 9(MMP-9)activity was analyzed by gelatin zymogram.The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results::Both 1α,25(OH)2D 3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells.In addition,the Top/Fop Flash reporters showed that 1α,25(OH)2D 3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes,including MMP-9 and Snail,in synergy with ICG-001.Conclusion::1α,25(OH)2D 3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.

关键词： 1α,25-Dihydroxyvitamin D3 Vitamin D β-Catenin Epithelial-mesenchymal transition Airway remodeling Asthma

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Epileptic brain network mechanisms and neuroimaging techniques for the brain network

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Neural Regeneration Research 2024年第12期19卷 2637-2648页

作者： Yi Guo Zhonghua Lin Zhen Fan xin tian Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Sichuan Provincial Center for Mental Health Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Geriatrics Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurology Chongqing Key Laboratory of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal discharges.Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice.An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic networks.In this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

关键词： electrophysiological techniques epilepsy functional brain network functional magnetic resonance imaging functional near-infrared spectroscopy machine leaning molecular imaging neuroimaging techniques structural brain network virtual epileptic models

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Model-driven path planning for robotic plasma cutting of branch pipe with single Y-groove based on pipe-rotating scheme

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Advances in Manufacturing 2024年第1期12卷 94-107页

作者： Yan Liu Qiu Tang xin-Cheng tian School of Control Science and Engineering Shandong UniversityJinan250061People’s Republic of China Engineering Research Center of Intelligent Unmanned System Ministry of EducationJinan250061People’s Republic of China School of Mechanical and Electronic Engineering Shandong Jianzhu UniversityJinan250101People’s Republic of China

The automatic cutting of intersecting pipes is a challenging task in manufacturing.For improved automation and accuracy,this paper proposes a model-driven path planning approach for the robotic plasma cutting of a branch pipe with a single Y-groove.Firstly,it summarizes the intersection forms and introduces a dual-pipe intersection model.Based on this model,the moving three-plane structure(a description unit of the geometric characteristics of the intersecting curve)is constructed,and a geometric model of the branch pipe with a single Y-groove is defined.Secondly,a novel mathematical model for plasma radius and taper compensation is established.Then,the compensation model and groove model are integrated by establishing movable frames.Thirdly,to prevent collisions between the plasma torch and workpiece,the torch height is planned and a branch pipe-rotating scheme is proposed.Through the established models and moving frames,the planned path description of cutting robot is provided in this novel scheme.The accuracy of the proposed method is verified by simulations and robotic cutting experiments.

关键词： Automatic groove cutting of intersecting pipes Model-driven robot path planning Plasma beam radius and taper compensation

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Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics

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World Journal of Stem Cells 2024年第1期16卷 1-6页

作者： Hang-Qi Hu Xi-Yan xin Yu-tian Zhu rui-Wen Fan Hao-Lin Zhang Yang Ye Dong Li Department of Traditional Chinese Medicine Peking University Third HospitalBeijing 100191China

The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complications that profoundly affect female reproductive function and overall health.Unfortunately,current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes.These approaches typically involve hormone repla-cement therapy combined with psychological support.Recently,mesenchymal stem cell(MSC)therapies for POI have garnered considerable attention in global research.MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms,including controlling differentiation,promoting angiogenesis,regulating ovarian fibrosis,inhibiting apoptosis,enhancing autocrine and paracrine effects,suppressing inflammation,modulating the immune system,and genetic regulation.This editorial offers a succinct summary of the application of MSC therapy in the context of POI,providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

关键词： Mesenchymal stem cell therapy Mechanism Premature ovarian insufficiency Therapeutic Women

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Ru-doped functional porous materials for electrocatalytic water splitting

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Nano Research 2024年第3期17卷 982-1002页

作者： Chongao tian rui Liu Yu Zhang Wenxiu Yang Bo Wang Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials Advanced Technology Research Institute(Jinan)Advanced Research Institute of Multidisciplinary ScienceSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China Beijing Institute of Technology Library Beijing Institute of TechnologyBeijing 100081China

Electrolytic water splitting(EWS)is an attractive and promising technique for the production of hydrogen energy.Nevertheless,the sluggish kinetic rate of hydrogen/oxygen evolution reactions leads to a high overpotential and low energy efficiency.Up to date,Pt/Ir-based nanocatalysts have become the state-of-the-art EWS catalysts,but disadvantages such as high cost and low earth abundance greatly limit their applications in EWS devices.As an attractive candidate for the Pt/Ir catalysts,series of Ru-based nanomaterials have aroused much attention for their low price,Pt-like hydrogen bond strength,and high EWS activity.In particular,Ru-doped functional porous materials have been becoming one of the most representative EWS catalysts,which can not only achieve the dispersion and adjustment for active Ru sites,but also simultaneously solve the problems of mass transfer and catalytic conversion in EWS.In this review,the design and preparation strategies of Ru-doped functional porous materials toward EWS in recent years are summarized,including Ru-doped metal organic frameworks(MOFs),Ru-doped porous organic polymers(POPs),and their derivatives.Meanwhile,detailed structure–activity relationships induced by the tuned geometric/electronic structures of Ru-doped functional porous materials are further depicted in this review.Last but not least,the challenges and perspectives of Ru-doped functional porous materials catalysts are reasonably proposed to provide fresh ideas for the design of Ru-based EWS catalysts.

关键词： Ru-based catalyst functional porous materials electrolytic water splitting oxygen evolution reaction hydrogen evolution reaction

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Dynamic response of buildings under debris flow impact

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Journal of Mountain Science 2024年第5期21卷 1581-1597页

作者： LIU Huan FAN Xiaoyi tian Shujun DENG xin School of Mechanical and Electrical Engineering Southwest Petroleum UniversityChengdu 610500China School of Civil Engineering and Geomatics Southwest Petroleum UniversityChengdu 610500China Housing and Urban-Rural Development Bureau of Mingshan District Ya’an 625100China Engineering Safety Assessment and Protection Research Southwest Petroleum UniversityChengdu 610500China School of Civil Engineering and Architecture Southwest University of Science and TechnologyMianyang 621010China

This study employs the smoothed particle hydrodynamics–finite element method(SPH–FEM) coupling numerical method to investigate the impact of debris flow on reinforced concrete(RC)-frame buildings. The methodology considers the variables of debris flow depth and velocity and introduces the intensity index IDV(IDV = DV) to evaluate three different levels of debris flow impact intensity. The primary focus of this study is to investigate the dynamic response and failure mechanism of RC-frame buildings under debris flow impact, including structural failure patterns, impact force and column displacement. The results show that under a highintensity impact, a gradual collapse process of the RCframe building can be observed, and the damage mode of the frame column reflects shear failure or plastic hinge failure mechanism. First, the longitudinal infill walls are damaged owing to their low out-of-plane flexural capacity;the critical failure intensity index IDV value is approximately 7.5 m2/s. The structure cannot withstand debris flows with an intensity index IDV greater than 16 m2/s, and it is recommended that the peak impact force should not exceed 2100 k N. The impact damage ability of debris flow on buildings mostly originates from the impact force of the frontal debris flow, with the impact force of the debris flow body being approximately 42% lower than that of the debris flow head. Finally, a five-level classification system for evaluating the damage status of buildings is proposed based on the numerical simulation and investigation results of the disaster site.

关键词： SPH–FEM method Debris flow Buildings The intensity index Dynamic response

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Theoretical analysis of the double-differential cross-sections of neutron,proton,deuteron,^(3)He,andαfor the p+^(6) Li reaction

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Nuclear Science and Techniques 2024年第3期35卷 181-197页

作者： Fang-Lei Zou Xiao-Jun Sun Jing-Shang Zhang Hai-rui Guo Yin-Lu Han rui-rui Xu Xi Tao Ji-Min Wang Xiao-Dong Sun Yuan tian Tao Ye Yong-Li Xu Chun-tian Liang College of Physics Guangxi Normal University541004 GuilinChina Guangxi Key Laboratory of Nuclear Physics and Nuclear Technology 541004 GuilinChina China Institute of Atomic Energy P.O.Box 275(41)102413 BeijingChina Institute of Applied Physics and Computational Mathematics 10094 BeijingChina College of Physics and Electronic Shanxi Datong University037009 DatongChina School of Science Tianjin Chengjian University300384 TianjinChina

Based on the unified Hauser–Feshbach and exciton model,which can describe the particle emission processes between discrete energy levels with energy,angular momentum,and parity conservations,a statistical theory of light nucleus reaction(STLN)is developed to calculate the double-differential cross-sections of the outgoing neutron and light charged particles for the proton-induced^(6) Li reaction.A significant difference is observed between the p+^(6) Li and p+^(7) Li reactions owing to the discrepancies in the energy-level structures of the targets.The reaction channels,including sequential and simultaneous emission processes,are analyzed in detail.Taking the double-differential cross-sections of the outgoing proton as an example,the influence of contaminations(such as^(1) H,^(7)Li,^(12)C,and^(16)O)on the target is identified in terms of the kinetic energy of the first emitted particles.The optical potential parameters of the proton are obtained by fitting the elastic scattering differential cross-sections.The calculated total double-differential cross-sections of the outgoing proton and deuteron at E_(p)=14 MeV agree well with the experimental data for different outgoing angles.Simultaneously,the mixed double differential cross-sections of^(3) He andαare in good agreement with the measurements.The agreement between the measured data and calculated results indicates that the two-body and three-body breakup reactions need to be considered,and the pre-equilibrium reaction mechanism dominates the reaction processes.Based on the STLN model,a PLUNF code for the p+^(6) Li reaction is developed to obtain an ENDF-6-formatted file of the double-differential cross-sections of the nucleon and light composite charged particles.

关键词： Statistical theory of light nucleus reaction p+^(6)Li reaction Light composite charged particle Double-differential cross-sections Two-body breakup Three-body breakup

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