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| 1 | SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade显示文摘Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy. | Mingxia Zhao Wenjie Guo Yuanyuan Wu Chenxi Yang Liang Zhong Guoliang Deng Yuyu Zhu Wen Liu Yanhong Gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 18 |
| 2 | Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics显示文摘Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy. | Jian Gao Zhigui Wu Mingxia Zhao Rui Zhang Manru Li Dongdong Sun Haibo Cheng Xianjia Qi Yuxian Shen Qiang Xu Hongqi Chen Dijun Chen Yang Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 5 |
| 3 | Blocking of the PD-1/PD-L1 interaction by a novel cyclic peptide inhibitor for cancer immunotherapy显示文摘The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance.Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherapy.Here,we developed a cyclic peptide C8 by using Ph.D.-C7 C phage display technology.C8 showed high binding affinity with h PD-1 and could effectively interfere the interaction of PD-1/PD-L1.Furthermore,C8 could stimulate CD8^(+)T cell activation in human peripheral blood mononuclear cells(PBMCs).We also observed that C8 could suppress tumor growth in CT26 and B16-OVA,as well as anti-PD-1 antibody resistant B16 mouse model.CD8^(+)T cells infiltration significantly increased in tumor microenvironment,and IFN-γsecretion by CD8^(+)T cells in draining lymph nodes also increased.Simultaneously,we exploited T cells depletion models and confirmed that C8 exerted anti-tumor effects via activating CD8^(+)T cells dependent manner.The interaction model of C8 with h PD-1 was simulated and confirmed by alanine scanning.In conclusion,C8 shows anti-tumor capability by blockade of PD-1/PD-L1 interaction,and C8 may provide an alternative candidate for cancer immunotherapy. | Wenjie Zhai Xiuman Zhou Mingxia Zhai Wanqiong Li Yunhui Ran Yixuan Sun Jiangfeng Du Wenshan Zhao Lingxiao Xing Yuanming Qi Yanfeng Gao | 2021 | Science China(Life Sciences)2021，64，4： | 5 |
| 4 | Rejection of insulin therapy among patients with type 2 diabetes in China: reasons and recommendations显示文摘 | Xiong Zhenzhen Yuan Li Guo Xiaohui Lou Qingqing Zhao Fang Shen Li Zhang Mingxia Sun Zilin | 2014 | Chinese Medical Journal2014，，20： | 4 |
| 5 | Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis显示文摘Impairment of glucose(Glu)uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases.Heterogeneous nuclear ribonucleoprotein A1(hnRNP Al)is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions.The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis.Our results showed that conditional deletion of hnRNP Al in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet(HFD).Conditional knockout mice fed a HFD showed exacerbated obesity,insulin resistance,and hepatic steatosis.In vitro interference of hnRNP Al in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake,whereas hnRNP Al overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin.The expression and stability of glycogen synthase(gysl)mRNA were also decreased in the absence of hnRNP A l.Mechanistically,hnRNP Al interacted with gys l and stabilized its mRNA,thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue.Taken together,our findings are the first to show that reduced expression of hnRNP Al in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis. | Mingxia Zhao Lihong Shen Zijun Ouyang Manru Li Guoliang Deng Chenxi Yang Wei Zheng Lingdong Kong Xuefeng Wu Xudong Wu Wenjie Guo Ye Yin Qiang Xu Yang Sun | 2020 | Journal of Molecular Cell Biology2020，12，4： | 2 |
| 6 | Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer显示文摘 | Wei Liu Mingxia Zhai Zongyin Wu Yuanming Qi Yahong Wu Chao Dai Meng Sun Lu Li Yanfeng Gao | 2012 | Amino Acids2012，，： | 1 |
| 7 | Low-temperature synthesis of photocatalytic TiO2 thin film from aqueous anatase precursor sols显示文摘 | Lei Ge Mingxia Xu Ming Sun Haibo Fang | 2006 | Journal of Sol - Gel Science and Technology2006，，1： | 1 |
| 8 | Functional reorganization associated with outcome in hand function after stroke revealed by regional homogeneity显示文摘 | Dazhi Yin Yanli Luo Fan Song Dongrong Xu Bradley S. Peterson Limin Sun Weiwei Men Xu Yan Mingxia Fan | 2013 | Neuroradiology2013，，6： | 1 |
| 9 | Preparation of TiO2 thin films from autoclaved sol containing needle-like anatase crystals显示文摘 | Lei Ge Mingxia Xu Haibo Fang Ming Sun | 2006 | J Applied Surface Science2006，253，： | 1 |
| 10 | Progress on deuterated potassium dihydrogen phosphate(DKDP)crystals for high power laser system application显示文摘In this review,we introduce the progress in the growth of large-aperture DKDP crystals and some aspects of crystal quality including determination of deuterium content,homogeneity of deuterium distribution,residual strains,nonlinear absorption,and laser-induced damage resistance for its application in high power laser system.Large-aperture high-quality DKDP crystal with deuteration level of 70%has been successfully grown by the traditional method,which can fabricate the large single-crystal optics with the size exceeding 400 mm.Neutron diffraction technique is an efficient method to research the deuterium content and 3D residual strains in single crystals.More efforts have been paid in the processes of purity of raw materials,continuous filtration technology,thermal annealing and laser conditioning for increasing the laser-induced damage threshold(LIDT)and these processes enable the currently grown crystals to meet the specifications of the laser system for inertial confinement fusion(ICF),although the laser damage mechanism and laser conditioning mechanism are still not well understood.The advancements on growth of large-aperture high-quality DKDP crystal would support the development of ICF in China. | Mingxia Xu Baoan Liu Lisong Zhang Hongkai Ren Qingtian Gu Xun Sun Shenglai Wang Xinguang Xu | 2022 | Light(Science & Applications)2022，11，9： | 1 |
| 11 | Identification of serum metabolites enhancing inflammatory responses in COVID-19显示文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is characterized by a strong production of inflammatory cytokines such as TNF and IL-6,which underlie the severity of the disease.However,the molecular mechanisms responsible for such a strong immune response remains unclear.Here,utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages,we identified that 611 metabolites(of 1,039)were significantly altered in COVID-19 patients.Among them,two metabolites,agmatine and putrescine,were prominently elevated in the serum of patients;and 2-quinolinecarboxylate was changed in a biphasic manner,elevated during early COVID-19 infection but levelled off.When tested in mouse embryonic fibroblasts(MEFs)and macrophages,these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production.Importantly,these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice,but not in the mice lacking NF-κB.Intriguingly,these metabolites have little effects on the activation of interferon regulatory factors(IRFs)for the production of type I interferons(IFNs)for antiviral defenses.These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses,exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons.Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients. | Chen-Song Zhang Bingchang Zhang Mengqi Li Xiaoyan Wei Kai Gong Zhiyong Li Xiangyang Yao Jianfeng Wu Cixiong Zhang Mingxia Zhu Lei Zhang Xiufeng Sun Yi-Hong Zhan Zhengye Jiang Wenpeng Zhao Wei Zhong Xinguo Zhuang Dawang Zhou Hai-Long Piao Sheng-Cai Lin Zhanxiang Wang | 2022 | Science China(Life Sciences)2022，65，10： | 1 |
| 12 | Low-temperature synthesis of photocatalytic TiO2 thin film from aqueous anatase precursor sols显示文摘 | GE Lei XU Mingxia SUN Ming | 2006 | J Sol-Gel Sci Techn2006，，38： | 1 |
| 13 | Synthesis and characterization of TiO2 thin films prepared from refluxed PTA sols显示文摘 | GE Lei XU Mingxia SUN Ming | 2005 | Mater Lett2005，60，2： | 1 |
| 14 | Extract of okra lowers blood glucose and serum lipids in high-fat diet induced obese C57BL/6 mice显示文摘 | Shengjie Fan Yu Zhang Qinhu Sun Lijing Yu Mingxia Li Bin Zheng Ximin Wu Baican Yang Yiming Li Cheng Huang | 2014 | The Journal of Nutritional Biochemistry2014，，： | 1 |
| 15 | Synthesis and gas sensing characteristics of SnO2 ' dandelions' 显示文摘 | Sun Peng Fu Wuyou Yang Haibin Liu Shikai Luo Bao-min Sui Yongming Zhang Yanyan Yuan Mingxia Ma Dong | 2010 | Materials Chemistry and Physics2010，119，： | 1 |
| 16 | Synthesis and characterization of TiO2 thin films prepared from refluxed PTA sols显示文摘 | GE Lei XU Mingxia SUN Ming | 2005 | Mater Lett2005，60，2： | 1 |
| 17 | Sub-sleeve gastrectomy achieves good diabetes control without weight loss in a non-obese diabetic rat model显示文摘 | Dong Sun Shaozhuang Liu Guangyong Zhang Punsiri Colonne Chunxiao Hu Haifeng Han Mingxia Li Sanyuan Hu | 2014 | Surgical Endoscopy2014，，3： | 1 |
| 18 | Posterior Lamellar Eyelid Reconstruction With Acellular Dermis Allograft in Severe Cicatricial Entropion显示文摘 | Jianjun Gu Zheng Wang Mingxia Sun Jin Yuan Jiaqi Chen | 2009 | Annals of Plastic Surgery2009，，3： | 1 |
| 19 | A study of emissions and marker gases from smouldering combustion in Larix gmelinii plantations of the Daxing'an Mountains显示文摘Underground fires are characterized by smouldering combustion with a slow rate of spread rate and without flames.Although smouldering combustion releases large amounts of gaseous pollutants,it is difficult to discover by today's forest fire monitoring technologies.Carbon monoxide(CO),nitrogen oxides(NO_(x))and sulfur dioxide(SO_(2))were identified as high concentration marker gases of smouldering combustion-easily-be monitored.According to a two-way ANOVA,combustion time had a significant impact on CO and NO_(x) emissions;smoldering-depth also had a significant impact on NO_(x) emissions but not on CO emissions.Gas emission equations were established by multiple linear regression,C_(co)=156.989-16.626 t and C_(NOx)=3.637-0.252 t-0.039 h. | Shuyuan Tang Sainan Yin Yanlong Shan Bo Gao Long Sun Xiyue Han Mingxia Wang Mingyu Wang Zongshi Chen | 2022 | Journal of Forestry Research2022，33，1： | 1 |
| 20 | Epitaxial interface stabilizing iridium dioxide toward the oxygen evolution reaction under high working potentials显示文摘Proton exchange membrane water electrolyzer(PEMWE)driven by renewable electricity is a promising technique toward green hydrogen production,but the corrosive environment and high working potential pose severe challenges for developing advanced electrocatalysts for the oxygen evolution reaction(OER).Although Ir-based materials possess relatively balanced activity and stability for the OER,their dissolution behavior cannot be neglected,in particular under high working potentials.In this work,iridium dioxide(IrO_(2))nanoparticles(NPs)were anchored on the surface of exfoliated h-boron nitride(BN)nanosheets(NSs)toward the OER reaction in acid media.Highly active Ir(V)species were stabilized by the epitaxial interface between IrO_(2)and h-BN,and therefore the IrO_(2)/BN delivered stable performance at increased working potentials,while the activity of bare IrO_(2)NPs without h-BN support decreased rapidly.Also,the smaller lattice spacing of h-BN induced compressive strain for IrO_(2),resulting in improved activity.Our results demonstrate the feasibility of stabilizing highly active Ir(V)species for the OER in acid media by constructing robust interface and provide new possibilities toward designing advanced heterostructured electrocatalysts. | Guoqiang Zhao Zhouxin Luo Baohua Zhang Yaping Chen Xiangzhi Cui Jian Chen Yongfeng Liu Mingxia Gao Hongge Pan Wenping Sun | 2023 | Nano Research2023，16，4： | 1 |
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