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| 1 | The function and clinical application of extracellular vesicles in innate immune regulation显示文摘The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications. | Xiaoxue Zhou Feng Xie Lin Wang Long Zhang Suping Zhang Meiyu Fang Fangfang Zhou | 2020 | Cellular & Molecular Immunology2020，17，4： | 6 |
| 2 | Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer显示文摘Histone acetylation is a critical process in the regulation of chromatin structure and gene expression.Histone deacetylases(HDACs)remove the acetyl group,leading to chromatin condensation and transcriptional repression.HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects.This paper describes our work on the structural determination and structure-activity relationship(SAR)optimization of tetrahydroisoquinoline compounds as HDAC inhibitors.These compounds were tested for their ability to inhibit HDAC 1,3,6 and for their ability to inhibit the proliferation of a panel of cancer cell lines.Among these,compound 82 showed the greatest inhibitory activity toward HDAC 1,3,6 and strongly inhibited growth of the cancer cell lines,with results clearly superior to those of the reference compound,vorinostat(SAHA).Compound 82 increased the acetylation of histones H3,H4 and tubulin in a concentration-dependent manner,suggesting that it is a broad inhibitor of HDACs. | Danqi Chen Aijun Shen Guanghua Fang Hongchun Liu Minmin Zhang Shuai Tang Bing Xiong Lanping Ma Meiyu Geng Jingkang Shen | 2016 | Acta Pharmaceutica Sinica B2016，6，1： | 4 |
| 3 | Detection of faviviruses by reverse transcriptase-polymerase chain reaction with the universal primer set 显示文摘 | Fang Meiyu Chen Huosheng Chen Cuihua | 1997 | Microbiol Immunol1997，41，： | 1 |
| 4 | Light-modulated vertical heterojunction phototransistors with distinct logical photocurrents显示文摘The intriguing carrier dynamics in graphene heterojunctions have stimulated great interest in modulating the optoelectronic features to realize high-performance photodetectors.However,for most phototransistors,the photoresponse characteristics are modulated with an electrical gate or a static field.In this paper,we demonstrate a graphene/C_(60)/pentacene vertical phototransistor to tune both the photoresponse time and photocurrent based on light modulation.By exploiting the power-dependent multiple states of the photocurrent,remarkable logical photocurrent switching under infrared light modulation occurs in a thick C_(60) layer(11 nm)device,which implies competition of the photogenerated carriers between graphene/C_(60) and C_(60)/pentacene.Meanwhile,we observe a complete positive-negative alternating process under continuous 405 nm irradiation.Furthermore,infrared light modulation of a thin C_(60)(5 nm)device results in a photoresponsivity improvement from 3425 A/W up to 7673 A/W,and we clearly probe the primary reason for the distinct modulation results between the 5 and 11 nm C_(60) devices.In addition,the tuneable bandwidth of the infrared response from 10 to 3×10^(3) Hz under visible light modulation is explored.Such distinct types of optical modulation phenomena and logical photocurrent inversion characteristics pave the way for future tuneable logical photocurrent switching devices and high-performance phototransistors with vertical graphene heterojunction structures. | Jiayue Han Meiyu He Ming Yang Qi Han Fang Wang Fang Zhong Mengjian Xu Qing Li He Zhu Chongxin Shan Weida Hu Xiaoqing Chen Xinran Wang Jun Gou Zhiming Wu Jun Wang | 2020 | Light(Science & Applications)2020，9，1： | 1 |
| 5 | Knockdown of hepatocyte Perilipin-3 mitigates hepatic steatosis and steatohepatitis caused by hepatocyte CGI-58 deletion in mice显示文摘Comparative gene identification-58(CGI-58),also known asα/βhydrolase domain containing 5,is the co-activator of adipose triglyceride lipase that hydrolyzes triglycerides stored in the cytosolic lipid droplets.Mutations in CGI-58 gene cause Chanarin-Dorfman syndrome(CDS),an autosomal recessive neutral lipid storage disease with ichthyosis.The liver pathology of CDS manifests as steatosis and steatohepatitis,which currently has no effective treatments.Perilipin-3(Plin3)is a member of the Perilipin-ADRP-TIP47 protein family that is essential for lipid droplet biogenesis.The objective of this study was to test a hypothesis that deletion of a major lipid droplet protein alleviates fatty liver pathogenesis caused by CGI-58 deficiency in hepatocytes.Adult CGI-58-floxed mice were injected with adeno-associated vectors simultaneously expressing the Cre recombinase and microRNA against Plin3 under the control of a hepatocyte-specific promoter,followed by high-fat diet feeding for 6 weeks.Liver and blood samples were then collected from these animals for histological and biochemical analysis.Plin3 knockdown in hepatocytes prevented steatosis,steatohepatitis,and necroptosis caused by hepatocyte CGI-58 deficiency.Our work is the first to show that inhibiting Plin3 in hepatocytes is sufficient to mitigate hepatocyte CGI-58 deficiency-induced hepatic steatosis and steatohepatitis in mice. | Xinyu Bao Xiaogen Ma Rongfeng Huang Jianghui Chen Haoran Xin Meiyu Zhou Lihua Li Shifei Tong Qian Zhang Guanghou Shui Fang Deng Liqing Yu Min-Dian Li Zhihui Zhang | 2022 | Journal of Molecular Cell Biology2022，14，8： | 0 |
| 6 | Low rank approximation in G0W0 calculations显示文摘The single particle energies obtained in a Kohn-Sham density functional theory(DFT) calculation are generally known to be poor approximations to electron excitation energies that are measured in transport,tunneling and spectroscopic experiments such as photo-emission spectroscopy. The correction to these energies can be obtained from the poles of a single particle Green's function derived from a many-body perturbation theory. From a computational perspective, the accuracy and efficiency of such an approach depends on how a self energy term that properly accounts for dynamic screening of electrons is approximated. The G_0W_0 approximation is a widely used technique in which the self energy is expressed as the convolution of a noninteracting Green's function(G_0) and a screened Coulomb interaction(W_0) in the frequency domain. The computational cost associated with such a convolution is high due to the high complexity of evaluating W_0 at multiple frequencies. In this paper, we discuss how the cost of G_0W_0 calculation can be reduced by constructing a low rank approximation to the frequency dependent part of W_0. In particular, we examine the effect of such a low rank approximation on the accuracy of the G_0W_0 approximation. We also discuss how the numerical convolution of G_0 and W_0 can be evaluated efficiently and accurately by using a contour deformation technique with an appropriate choice of the contour. | SHAO MeiYue LIN Lin YANG Chao LIU Fang DA JORNADA Felipe H. DESLIPPE Jack LOUIE Steven G. | 2016 | Science China Mathematics2016，59，8： | 0 |
| 7 | Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma显示文摘Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment.Therefore,this study developed a novel and selective inhibitor of CSFIR and VEGFR,SYHA1813,possessing potent antitumor activity against GBM.SYHA1813 inhibited VEGFR and CSFIR kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo.SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models,including temozolomide(TMZ)insensitive tumors.Notably,SYHA1813 could penetrate the blood-brain barrier(BBB)and prolong the survival time of mice bearing intracranial GBM xenografts.Moreover,SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody.As a clinical proof of concept,SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial.The data of this study support the rationale for an ongoing phase I clinical study(ChiCTR2100045380). | Yingqiang Liu Zhengsheng Zhan Zhuang Kang Mengyuan Li Yongcong Lv Shenglan Li Linjiang Tong Fang Feng Yan Li Mengge Zhang Yaping Xue Yi Chen Tao Zhang Peiran Song Yi Su Yanyan Shen Yiming Sun Xinying Yang Yi Chen Shanyan Yao Hanyu Yang Caixia Wang Meiyu Geng Wenbin Li Wenhu Duan Hua Xie Jian Ding | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 0 |
| 8 | Structure-based drug discovery of novel fusedpyrazolone carboxamide derivatives as potent and selective AXL inhibitors显示文摘a novel and promising antitumor target,AXL plays an important role in tumor growth,metastasis,immunosuppression and drug resistance of various malignancies,which has attracted extensive research interest in recent years.In this study,by employing the structure-based drug design and bioisosterism strategies,we designed and synthesized in total 54 novel AXL inhibitors featuring a fusedpyrazolone carboxamide scaffold,of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions.Notably,compound 59 showed a desirable AXL kinase inhibitory activity(IC_(50):3.5 nmol/L)as well as good kinase selectivity,and it effectively blocked the cellular AXL signaling.In turn,compound 59 could potently inhibit BaF3/TEL-AXL cell viability(IC_(50):1.5 nmol/L)and significantly suppress GAS6/AXL-mediated cancer cell invasion,migration and wound healing at the nanomolar level.More importantly,compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency,in which we observed significant AXL phosphorylation suppression,and its antitumor efficacy at 20 mg/kg(qd)was comparable to that of BGB324 at 50 mg/kg(bid),the most advanced AXL inhibitor.Taken together,this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. | Feifei Fang Yang Dai Hao Wang Yinchun Ji Xuewu Liang Xia Peng Jiyuan Li Yangrong Zhao Chunpu Li Danyi Wangh Yazhou Li Dong Zhang Dan Zhang Meiyu Geng Hong Liu Jing Ai Yu Zhou | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 0 |
| 9 | A novel strategy for treating oncogene-mutated tumors by targeting tumor microenvironment and synergistically enhancing anti-PD-1 immunotherapy显示文摘Oncogenes are critical factors in tumorigenesis of diverse cancer types and play essential roles in tumor immune escape.Mutations in Kirsten rat sarcoma viral oncogene homolog(KRAS)and epidermal growth factor receptor(EGFR)are among the most frequent gain-of-function alterations[1].After many years of in-depth research,inhibitors targeting EGFR or KRAS mutations have been successfully developed,however,their clinical benefit is relatively limited,and they will inevitably encounter the challenge of drug resistance.The emergence of resistance is attributed to secondary mutations in driver genes and other complicated factors. | Yingqiang Liu Linjiang Tong Mengge Zhang Qi Zhang Qiupei Liu Fang Feng Yan Li Mengzhen Lai Haotian Tang Yi Chen Meiyu Geng Wenhu Duan Jian Ding Hua Xie | 2024 | Cancer Communications2024，44，3： | 0 |
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