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| 1 | Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors显示文摘Programmed cell death protein-1(PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T(CAR-T)cells in solid tumors.We generated PD-1 and T cell receptor(TCR)deficient mesothelin-specific CAR-T(MPTK-CAR-T)cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study.A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion.No dose-limiting toxicity or unexpected adverse events were observed in any of the 15 patients.The best overall response was stable disease(2/15 patients).Circulating MPTK-CAR-T cells peaked at days 7–14 and became undetectable beyond 1 month.TCR-positive CAR-T cells rather than TCR-negative CAR-T cells were predominantly detected in effusion or peripheral blood from three patients after infusion.We further confirmed the reduced persistence of TCR-deficient CAR-T cells in animal models.Our results establish the preliminary feasibility and safety of CRISPR-engineered CAR-T cells with PD-1 disruption and suggest that the natural TCR plays an important role in the persistence of CAR-T cells when treating solid tumors. | Zhenguang Wang Na Li Kaichao Feng Meixia Chen Yan Zhang Yang Liu Qingming Yang Jing Nie Na Tang Xingying Zhang Chen Cheng Lianjun Shen Jiaping He Xun Ye Wei Cao Haoyi Wang Weidong Han | 2021 | Cellular & Molecular Immunology2021，18，9： | 7 |
| 2 | THE GLASS TRANSITION TEMPERATURE AND MICROSTRUCTURE OF POLYURETHANE/EPOXY RESIN INTERPENETRATING POLYMER NETWORKS NANOCOMPOSITES显示文摘Nanocomposites with various contents of organophilic montmorillonite (oMMT) have been prepared by adding oMMT to interpenetrating poly- mer networks (IPNs) of polyurethane and epoxy resin (PU/EP) which had been prepared by a sequential polymeric technique. DSC experiment indicates a novel phenomenon that the glass transition tem- perature (Tg) of the nanocomposites increases with the oMMT content up to 3 %, then decreases with further increasing oMMT content. In order to explain this phenomenon, crosslink density, hydrogen bond- ing in the hard segments, crystallization of the nanocomposites and the exfoliation degree of oMMT in the nanocomposites have been investigated by swelling method, FT-IR, XRD, SEM and TEM, re- spectively. The results indicate that the crosslink density and the hydrogen bonding index of the nanocomposites increase, but the crystallization de- gree of the nanocomposites decreases with increas- ing oMMT content. In addition, oMMT improves the network structure of PU/EP. | JIA Qingming ZHENG Maosheng SHEN Renjie CHEN Hongxiang | 2006 | Chinese Science Bulletin2006，51，3： | 7 |
| 3 | Flexible,video-rate,and aberration-compensated axial dual-line scanning imaging with field-of-view jointing and stepped remote focusing显示文摘Parallel dual-plane imaging with a large axial interval enables the simultaneous observation of biological structures and activities in different views of interest.However,the inflexibility in adjusting the field-of-view(FOV)positions in three dimensions and optical sectioning effects,as well as the relatively small effective axial range limited by spherical aberration,have hindered the application of parallel dual-plane imaging.Herein,we propose a flexible,video-rate,and defocus-aberration-compensated axial dual-line scanning imaging method.We used a stepped mirror to remotely generate and detect dual axial lines with compensation for spherical aberration and FOV-jointing to rearrange into a head-to-head line for high-speed optical sectioning acquisition.The lateral and axial positions of the two FOVs could be flexibly adjusted before and during imaging,respectively.The method also allows the adjustment of optical sectioning effects according to specific experimental requirements.We experimentally verified the consistent imaging performance over an axial range of 300μm.We demonstrated high throughput by simultaneously imaging Brownian motions in two 250μm×250μm FOVs with axial and lateral intervals of 150μm and 240μm,respectively,at 24.5 Hz.We also showed potential application in functional imaging by simultaneously acquiring neural activities in the optic tectum and hindbrain of a zebrafish brain.The proposed method is,thus,advantageous compared to existing parallel dual-plane imaging and potentially facilitates intravital biological study in large axial range. | RUI JIN YALAN YU DAN SHEN QINGMING LUO HUI GONG JING YUAN | 2021 | Photonics Research2021，9，8： | 2 |
| 4 | Fabrication of Protein-conjugated Silver Sulfide Nanorods in the Bovine Se- rum Albumin Solution显示文摘 | Yang Lin Xing Ruimin Shen Qingming | 2006 | J Phys Chem B2006，110，10： | 1 |
| 5 | Adaptive segmentation of weld defects based on flooding显示文摘 | SHEN Qingming GAO Jianmin LI Cheng | 2009 | Insight-Non-Destructive Testing and Condition Moni-toring2009，51，10： | 1 |
| 6 | Automat-ic classification of weld defects in radiographic images显示文摘 | SHEN Qingming GAO Jianmin LI Cheng | 2010 | Insight-Non-Destructive Testing and Condition Monitoring2010，52，3： | 1 |
| 7 | Synthesis,Characterization and Properties of Organoclay-modified Polyurethane/epoxy Interpenetrating Polymer Network Nanocomposites显示文摘 | Jia Qingming Zheng Maosheng Shen Renjie | 2006 | Polymer International2006，55，3： | 1 |
| 8 | Carbon monoxide releasing molecule?2 attenuated ischemia/reperfusion?inducedapoptosis in cardiomyocytes via a mitochondrial pathway显示文摘 | Shen Zhao Qingming Lin Heng Li Yumin He Xiangshao Fang Feng Chen Changwei Chen Zitong Huang | 2014 | Molecular Medicine Reports2014，，2： | 1 |
| 9 | Morphologies and properties of polyurethane/epoxy resin inter penetrating network nanocomposites modified with organoclay显示文摘 | Qingming Jia Maosheng Zheng Hongxiang Chen Renjie Shen | | 0，，： | 1 |
| 10 | Adaptive segmentation of weld defects based on flooding 显示文摘 | SHEN Qingming GAO Jianmin LI Cheng | 2009 | Insight-Non-Destructive Testing and Condition Moni- toring2009，51，10： | 1 |
| 11 | Nanocellulosic materials:research/production activities and applications显示文摘Nanocelluloses have emerged as novel materials and attracted significant interest from both academia and industry.Nanocelluloses can now be produced at pilot plant and pre-commercial scales,and even at commercial scales in some regions in the world.Successful commercial applications of nanocelluloses have entered commercial stages though their full potentials are yet to be developed.In this short communication,the applications of these nanomaterials are high-lighted,including high-volume applications(e.g.,paper,textiles),high-value applications(e.g.,aerogels and structure materials for aerospace),and novel/emerging applications(e.g.,organic light emitting diodes,photonic films).Close collaboration between industries and the academic world would facilitate the development of commercial markets for using nanocelluloses in existing/new areas. | Xingye An Dong Cheng Jing Shen Qingming Jia Zhibin He Linqiang Zheng Avik Khan Bo Sun Bitao Xiong Yonghao Ni | 2017 | Journal of Bioresources and Bioproducts2017，2，2： | 0 |
| 12 | CircRNA DICAR as a novel endogenous regulator for diabetic cardiomyopathy and diabetic pyroptosis of cardiomyocytes显示文摘In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM. | Qiong Yuan Yunwei Sun Fan Yang Dan Yan Meihua Shen Zhigang Jin Lin Zhan Guangqi Liu Ling Yang Qianyi Zhou Zhijun Yu Xiangyu Zhou Yang Yu Yong Xu Qingming Wu Jianfang Luo Xiamin Hu Chunxiang Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 0 |
| 13 | A live attenuated RHΔompdcΔuprt mutant of Toxoplasma gondii induces strong protective immunity against toxoplasmosis in mice and cats显示文摘Background Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis.It is essential to develop an effective anti-T.gondii vaccine for the control of toxoplasmosis,and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats.Methods First,theompdc anduprt genes of T.gondii were deleted through the CRISPR-Cas9 system.Then,the intracellular proliferation and virulence of this mutant strain were evaluated.Subsequently,the immune responses induced by this mutant in mice and cats were detected,including antibody titers,cytokine levels,and subsets of T lymphocytes.Finally,the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats.Furthermore,to discover the effective immune element against toxoplasmosis,passive immunizations were carried out.GraphPad Prism software was used to conduct the log-rank(Mantel–Cox)test,Student’st test and one-way ANOVA.Results The RHΔompdcΔuprt were constructed by the CRISPR-Cas9 system.Compared with the wild-type strain,the mutant notably reduced proliferation(P<0.05).In addition,the mutant exhibited virulence attenuation in both murine(BALB/c and BALB/c-nu)and cat models.Notably,limited pathological changes were found in tissues from RHΔompdcΔuprt-injected mice.Furthermore,compared with nonimmunized group,high levels of IgG(IgG1 and IgG2a)antibodies and cytokines(IFN-γ,IL-4,IL-10,IL-2 and IL-12)in mice were detected by the mutant(P<0.05).Remarkably,all RHΔompdcΔuprt-vaccinated mice survived a lethal challenge with RHΔku80 and ME49 and WH6 strains.The immunized sera and splenocytes,especially CD8^(+)T cells,could significantly extend(P<0.05)the survival time of mice challenged with the RHΔku80 strain compared with naïve mice.In addition,compared with nonimmunized cats,cats immunized with the mutant produced high levels of antibodies and cytokines(P<0.05),and notably decreased the shedding numbers of oocysts in feces(95.3%).Conclusions The avirulent RHΔompdcΔuprt strain can provide strong anti-T.gondii immune responses,and is a promising candidate for developing a safe and effective live attenuated vaccine. | Yu Shen Bin Zheng Hao Sun Songrui Wu Jiyuan Fan Jianzu Ding Meng Gao Qingming Kong Di Lou Haojie Ding Xunhui Zhuo Shaohong Lu | 2023 | Infectious Diseases of Poverty2023，12，3： | 0 |
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