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CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

null

《医学前沿（英文）》 2017年第11卷第4期页码 554-562 doi: 10.1007/s11684-017-0543-6

摘要：

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

关键词： CAR-T CRISPR-Cas9 LAG-3

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Dynamic behavior of superheated steam and ways of control

LI Xu

《能源前沿（英文）》 2008年第2卷第1期页码 25-30 doi: 10.1007/s11708-008-0014-5

摘要： A simple way of calculating the dynamic behavior of a superheater is presented. A comparison of the measured data with the calculated result verifies the accuracy of this simple method. It is the first time that a phase compensation for real roots, i.e., the twin lead/lag loop which is facile for engineering applications, is used in superheated steam temperature control. Numerous simulation results show that both the response time lapse and maximal dynamic deviation are greatly reduced. Moreover, a formula to calculate the setting parameters is presented, together with a practical example of its engineering application in superheated steam temperature control with single-stage attemperation in a power plant boiler. This method can remarkably improve the control performance of superheated steam temperature and makes it possible for one stage attemperation to be sufficient for the superheater of power plant boilers, thus simplifying the superheater system and reducing investment. Because the control performance is remarkably raised, the set values of the steam temperature control system can be raised above rated values and also the operational economy, without impairing the operation safety.

关键词： engineering investment Numerous simulation lead/lag temperature

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变距/摆振耦合对直升机空中共振稳定性的影响

薛海峰,向锦武,张晓谷,李书强

《中国工程科学》 2007年第9卷第9期页码 58-62

摘要：

采用多桨叶坐标转换和复数坐标变换等方法，研究了变距/摆振耦合对直升机空中共振的影响；推导出完全引入变距/ 摆振耦合的直升机空中共振分析公式，建立了相应的分析模型和计算程序。利用系统的特征值研究了直升机空中共振的动不稳定性，得出变距/摆振耦合对直升机空中共振的影响；通过系统的特征向量与各自由度之间的相互作用（能量关系）的研究，揭示了空中共振机理，以某型直升机为例进行了计算分析。研究表明：正的变距/摆振耦合可以抑制旋翼/机体耦合系统的动不稳定性，在同时存在挥舞/摆振耦合和正的变距/摆振耦合时，直升机的旋翼/机体耦合系统为绝对稳定。

关键词：直升机动不稳定性直升机空中共振变距/摆振耦合

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循环双谱及在周期平稳类故障中的应用

苏中元,贾民平,许飞云,胡建中

《中国工程科学》 2006年第8卷第9期页码 57-60

摘要：

论述了未知循环频率的周期平稳信号循环双谱的估计方法；研究了在循环双谱的循环累积量计算中涉及变量的简化存储方法，提出了该变量矩阵是对称阵，通过算法可以三角阵的元素来表述，克服了循环双谱传统估计方法计算量较大的缺陷，提高了运算效率；提出了循环双谱对调相故障信号的分析能力，以及对加性噪声的处理能力，仿真并验证了该方法的有效性，并将其应用于旋转机械状态分析。

关键词：周期平稳循环双谱滞后积

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continuous girder with variable cross-sections in considering effect of large deflection and shear lag

Yuji CHEN, Qizhi LUO,

《结构与土木工程前沿（英文）》 2009年第3卷第4期页码 352-356 doi: 10.1007/s11709-009-0057-7

摘要： In order to study the mechanics behavior of a thin-walled box continuous girder with variable cross-sections, using potential variation theories, considering the effect of shear lag of flange’s stress and the nonlinear geometry of vertical displacement, and evolving five generalized displacements with the spline function, the large deflection problem of the thin-walled box continuous girder with variable cross-section was transformed to a nonlinear algebraic equation, which was solved using the Newton-Raphon iterative method. The results of the calculation show that different shear lag warp functions to the cantilever, top and bottom plate should be taken to analyze the mechanics behavior of the thin-walled box continuous girder reliably. The thin-walled box continuous girder with variable cross-sections has more reasonable stress state and is more adaptable for the longitudinal change of internal forces than that with equal cross-sections. The effect of large deflection on the stress and displacement of the thin-walled box continuous girder with variable cross-sections depends on the values of the load.

关键词： thin-walled box girder with variable cross-sections potential variational theory shear lag large deflection problem

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虞晓含：中医话健康，食补改善免疫力（2020年3月1日）

2022年04月18日

关键词：营养健康

Synthesis of copolymers of 3-acryloyloxymethyl-3′-methyloxetane and 3-(2-(2-(2-Methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane and their ionic conductivity properties

YE Lin, ZHAO Yumei, FENG Zengguo, BAI Ying, WU Feng

《化学科学与工程前沿（英文）》 2007年第1卷第4期页码 343-348 doi: 10.1007/s11705-007-0062-0

摘要： An oxetane-derived monomer, 3-acryloyloxymethyl-3′-methyloxetane (AMO) was prepared from the reaction of 3-hydromethyl-3-methyloxetane with acryloyl chloride. The cationic ring-opening copolymerization of AMO with another oxetane-derived monomer, 3-(2-(2-(2-methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane (MEMO) was conducted in CHCl solution using BF3 ·OEt/1, 4-butanediol as a co-initiator. The resulting copolymers were characterized by FTIR, H NMR and Gel Permeation Chromatography (GPC) analyses, and it was found that the enchained ratio of AMO in the copolymers is far lower than its feed ratio. They were crosslinked via the radical polymerization of the vinyl group initiated by BPO after doping with lithium trifluoromethanesulfonimide (LiTFSI) to give rise to tough polymeric electrolyte films. The ionic conductivity was measured at varying content of AMO and different concentration of lithium salt LiTFSI by AC impedance, and a maximum ion conductivity of 1.44×10 S/cm at 30°C or 1.25×10 S/cm at 80°C was attained in the sample PAM 33 at the mole ratio of O : Li = 20. The DSC results indicated that decreases with the increase of the proportion of AMO in the copolymer, well consistent with the ion conductivity trend. The TGA (thermogravimetric analysis) measurement revealed that this kind of copolymer electrolytes is more thermostable than their liquid counterparts.

关键词： 4-butanediol 2-methoxyethylenoxy consistent oxetane-derived copolymer

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Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

《医学前沿（英文）》 2008年第2卷第1期页码 95-99 doi: 10.1007/s11684-008-0017-y

摘要： Schistosomiasis japonica, a zoonosis caused by , is endemic to the Philippines and China. Several vaccine candidates have been identified and tested in different animal models, but it is still unclear which will be optimal for testing in the field. Therefore, new antigens and strategies are necessary for vaccine development against schistosomiasis japonica. The Sj14-3-3 gene was amplified and subcloned into the expression vector pPICZ?-B and transformed into X-33 by electroporation. Three transformants were induced with methanol. The cultural supernatant was collected and tested by SDS-PAGE and Western blotting. The protein of rSj14-3-3 was prepared and purified and BALB/c mice were immunized which was followed by a challenging infection. The immuno-protection was then evaluated. The Sj14-3-3 gene was expressed and secreted into the medium and its molecular weight was about 35000 as determined by SDS-PAGE. Western blotting showed that the protein had a high specificity against mouse-anti-Sj14-3-3 monoclonal antibody and rSj14-3-3 had a promising immune reactivity. The results of the immuno-protective experiments revealed that the worm reduction was 26.0%, 32.2%, and 36.8%, respectively. The number of eggs in liver tissue was reduced by 36.8%, 43.2%, and 46.1%, respectively. The recombinant Sj14-3-3 of eukaryotic expression in was successfully harvested. The molecular vaccine of Sj14-3-3 could partially induce resistance to the infection with in BALB/c mice. The recombinant protein Sj14-3-3 has promising immunological potentials for further approach to the diagnosis and development of molecular vaccine.

关键词： development challenging rSj14-3-3 resistance cultural supernatant

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第四届高性能编译、计算和通信国际会议(HP3C 2020)

会议日期： 2020年03月12日

会议地点：广东广州

主办单位： HP3C 2020

作为免疫疗法靶点的FOXP3及其辅因子 Review

Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang

《工程（英文）》 2019年第5卷第1期页码 115-121 doi: 10.1016/j.eng.2019.01.001

摘要：

叉头框蛋白P3（FOXP3）是调节性T细胞（Tregs）的一个主要调节因子，调节性T细胞是能抑制抗原特异性免疫反应的T 细胞亚群，在增强宿主耐受性和维持免疫平衡方面发挥着重要作用。众所周知，FOXP3 与多种蛋白质形成复合物，并能通过乙酰化、磷酸化、泛素化和甲基化等各种翻译后修饰（PTM）进行调节。因此，翻译后修饰可改变FOXP3 的稳定性及其调节基因表达的能力，并最终影响调节性T细胞活性。虽然FOXP3 自身并非理想的药物靶点，但脱乙酰酶、乙酰转移酶、激酶和其他可调节FOXP3 的翻译后修饰的酶均为调控FOXP3 和调节性T细胞活性的潜在靶点。但FOXP3 并非这些酶的唯一底物；因此，当使用相关抑制剂时，必须考虑是否存在有害的“FOXP3脱靶”副作用。

关键词：调节性T细胞叉头框蛋白P3（FOXP3）翻译后修饰自体免疫癌症

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Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

《医学前沿（英文）》 doi: 10.1007/s11684-023-1003-0

摘要： Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

关键词： Lipin3 Lipin1 hypertriglyceridemia obesity mitochondrial dysfunction

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关于3D打印技术在医学模具以及再生组织和器官方面的应用综述

Kan Wang, Chia-Che Ho, Chuck Zhang, Ben Wang

《工程（英文）》 2017年第3卷第5期页码 653-662 doi: 10.1016/J.ENG.2017.05.013

摘要：随着三维（3D）打印和3D 生物打印技术的快速发展，许多研究人员已经开始使用增材制造技术来生产具有多种功能的医学模具。本文综述了3D 打印和3D 生物打印技术在制作功能性医学模具和生物结构方面的应用。特别讨论了3D 打印功能性医学模具（即组织模拟医学模具、放射性医学模具和生理医学模具）及被用于再生组织和器官的3D 生物打印模具的制备（即混合模式支架材料、可转换支架和集成传感器）工艺、发展现状以及未来发展趋势

关键词： 3D打印 3D生物打印医学模具再生组织/器官支架

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2020第四届环境与能源工程国际会议(IC3E 2020)

会议日期： 2020年03月12日

会议地点：海南海口三亚

主办单位： APISE

Influence and related mechanism of Retn gene expression on glucose uptake in 3T3-L1 cells

LI Yahui, DONG Shiyuan, YU Chao, JIANG Yu, LI Huaixing, SUN Shuhan

《医学前沿（英文）》 2007年第1卷第3期页码 269-273 doi: 10.1007/s11684-007-0051-1

摘要： The aim of this article was to investigate the influence and the related mechanism of the gene on glucose uptake and insulin resistance in 3T3-L1 cells. Radioimmunoassay was used to determine glucose uptake in 3T3-L1 cells with different gene expression levels, whether cells were stimulated by insulin or not. RT-PCR and real-time RT-PCR analysis were used to determine the mRNA levels of several glucose transport proteins in 3T3-L1 cells with different gene expression levels, including insulin receptor substrate-1(IRS-1), phosphatidylinositol 3-kinase (PI-3K), AKT-2, glucose transporter-4 (GLUT-4), p38 mitogen-activated protein kinase (p38MAPK) and glycogen synthase kinase-3b (GSK-3). The glucose uptake decreased with the increase in gene expression in 3T3-L1 cells, which was independent of whether the cells were stimulated by insulin or not. The mRNA expression of two signal proteins PI-3K and AKT-2 decreased and the other two signal proteins, GSK-3 and p38MAPK, increased with overexpression in 3T3-L1 cells. Resistin could induce insulin resistance in adipocytes, which might be related to the changes of some proteins in PI-3K and Ras pathways.

关键词： 3T3-L1 influence resistance receptor substrate-1 transport

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Combustion and emissions of RP-3 jet fuel and diesel fuel in a single-cylinder diesel engine

《能源前沿（英文）》 2023年第17卷第5期页码 664-677 doi: 10.1007/s11708-021-0787-3

摘要： The combustion characteristics and emission behaviors of RP-3 jet fuel were studied and compared to commercial diesel fuel in a single-cylinder compression ignition (CI) engine. Engine operational parameters, including engine load (0.6, 0.7, and 0.8 MPa indicating the mean effective pressure (IMEP)), the exhaust gas recirculation (EGR) rate (0%, 10%, 20%, and 30%), and the fuel injection timing (−20, −15, −10, and −5 ° crank angle (CA) after top dead center (ATDC)) were adjusted to evaluate the engine performances of RP-3 jet fuel under changed operation conditions. In comparison to diesel fuel, RP-3 jet fuel shows a retarded heat release and lagged combustion phase, which is more obvious under heavy EGR rate conditions. In addition, the higher premixed combustion fraction of RP-3 jet fuel leads to a higher first-stage heat release peak than diesel fuel under all testing conditions. As a result, RP-3 jet fuel features a longer ignition delay (ID) time, a shorter combustion duration (CD), and an earlier CA50 than diesel fuel. The experimental results manifest that RP-3 jet fuel has a slightly lower indicated thermal efficiency (ITE) compared to diesel fuel, but the ITE difference becomes less noticeable under large EGR rate conditions. Compared with diesel fuel, the nitrogen oxides (NO_x) emissions of RP-3 jet fuel are higher while its soot emissions are lower. The NO_x emissions of RP-3 can be effectively reduced with the increased EGR rate and delayed injection timing.

关键词： RP-3 jet fuel diesel engine combustion emissions

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标题作者时间类型操作

CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

null

期刊论文

Dynamic behavior of superheated steam and ways of control

LI Xu

期刊论文

变距/摆振耦合对直升机空中共振稳定性的影响

薛海峰,向锦武,张晓谷,李书强

期刊论文

循环双谱及在周期平稳类故障中的应用

苏中元,贾民平,许飞云,胡建中

期刊论文

continuous girder with variable cross-sections in considering effect of large deflection and shear lag

Yuji CHEN, Qizhi LUO,

期刊论文

虞晓含：中医话健康，食补改善免疫力（2020年3月1日）

2022年04月18日

会议视频

Synthesis of copolymers of 3-acryloyloxymethyl-3′-methyloxetane and 3-(2-(2-(2-Methoxyethylenoxy)ethylenoxy)ethylenoxy)-3′-methyloxetane and their ionic conductivity properties

YE Lin, ZHAO Yumei, FENG Zengguo, BAI Ying, WU Feng

期刊论文

Heterologous expression of signal protein 14-3-3 in and the subsequent immune response in mice

ZHENG Meijuan, SHEN Jilong, LUO Qingli, XU Yuanhong

期刊论文

第四届高性能编译、计算和通信国际会议(HP3C 2020)

2020年03月12日

会议信息

作为免疫疗法靶点的FOXP3及其辅因子

Yasuhiro Nagai,Lian Lam,Mark I. Greene,Hongtao Zhang

期刊论文

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and