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| 1 | 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 |
| 2 | Minimum component high frequency Gm-C wavelet filters based on Maclaurin series and multiple loop feedback显示文摘 | ZHAO Wenshan SUN Yichuang HE Yigang | 2010 | Electronics Letters2010，46，1： | 1 |
| 3 | Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy显示文摘Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients.Here,we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells,especially myeloid derived suppressor cells(MDSCs)and CD8^(+)T cells.Then,peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique,and its mutant peptide VS3 was obtained by molecular docking based mutation.Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition,and elicit anti-tumor activity in vivo.The peptide DVS3-Pal was further designed by D-amino acid substitution and fatty acid modification,which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8^(+)T cell function and decreasing MDSCs infiltration.This is the first study to develop peptides to block VISTA/PSGL-1 interaction,which could act as promising candidates for cancer immunotherapy. | Xiaoshuang Niu Menghan Wu Guodong Li Xiuman Zhou Wenpeng Cao Wenjie Zhai Aijun Wu Xiaowen Zhou Shengzhe Jin Guanyu Chen Yanying Li Jiangfeng Du Yahong Wu Lu Qiu Wenshan Zhao Yanfeng Gao | 2023 | Acta Pharmaceutica Sinica B2023，13，11： | 0 |
| 4 | Organic Memristor Based on High Planar Cyanostilbene/Polymer Composite Films显示文摘Organic memristors with low power consumption,fast write/erasure speed,and complementary metal-oxide-semiconductor(CMOS)compatibility have attracted tremendous attention to mimic biological synapses to realize neuromorphic computation in recent years.In this paper,organic resistive switching memory(ORSM)based on(Z)-3-(naphthalen-2-yl)-2-(4-nitrophenyl)acrylonitrile(NNA)and polymer poly(N-vinylcarbazole)(PVK)composite film was prepared by spin-coating method.Device performance based on NNA:PVK composite films with different mass fractions of NNA were systematically investigated.The ORSM based on PVK:40%(mass fraction)NNA composite film exhibited non-volatile and bipolar memory properties with a switching ratio(Ion/Ioff)of 24.1,endurance of 68 times and retention time of 104 s,a“SET”voltage(Vset)of−0.55 V and a“RESET”voltage(Vreset)of 2.35 V.The resistive switching was ascribed to the filling and vacant process of the charge traps induced by NNA and the inherent traps in PVK bulk.The holes trapping and de-trapping process occurred when the device was applied with a negative or positive bias,which caused the transforming of the conductive way of charges,that is the resistive behaviors in the macroscopic.This study provides a promising platform for the fabrication of ORSM with high performance. | ZHAO Jinjin LI Wei WANG Xuechen WEI Xiao ZHU Huiwen QU Wenshan MEN Dandan GAO Zhixiang WEI Bin GAO Hanfei WU Yuchen | 2023 | Chemical Research in Chinese Universities2023，39，1： | 0 |
| 5 | CRYSTALLIZATION OF AMORPHOUS Fe_(62)Co_(15.5)Nd_(4)B_(18.5) ALLOY AND ITS INFLUENCE ON HARD MAGNETIC PROPERTIES显示文摘Magnetic properties and crystallization of amorphous Fe_(62)Co_(15.5)Nd_(4)B_(18.5) alloy are studied.The Curie temperature of the present sample is 127K higher than that of amorphous Fe_(77.5)Nd_(4)B_(18.5) alloy,but their crystallization temperature is compatible with each other.A coercive field of 2.34kOe,a remanence of 12.3kG and an energy product of 11.6MGOe are obtained at room temperature in the Fe_(62)Co_(15.5)Nd_(4)B_(18.5) alloy annealed at 650°C.The 15.5at.%-Co substitution for Fe results in an increase of about 1l0K in Tc of 2:14:1 phase. | SHEN Baogen YANG Linyuan ZHANG Junxian WO Feng NING Taishan ZHAO Jiangao GUO Huiqun ZHAN Wenshan | 1990 | Chinese Physics Letters1990，7，9： | 0 |
| 6 | Overexpression of Hepcidin Alleviates Steatohepatitis and Fibrosis in a Diet-induced Nonalcoholic Steatohepatitis显示文摘Background and Aims:Iron overload can contribute to the progression of nonalcoholic fatty liver disease(NAFLD)to nonalcoholic steatohepatitis(NASH).Hepcidin(Hamp),which is primarily synthesized in hepatocytes,is a key reg-ulator of iron metabolism.However,the role of Hamp in NASH remains unclear.Therefore,we aimed to elucidate the role of Hamp in the pathophysiology of NASH.Methods:Male mice were fed a choline-deficient L-amino acid-defined(CDAA)diet for 16 weeks to establish the mouse NASH model.A choline-supplemented amino acid-defined(CSAA)diet was used as the control diet.Recombinant adeno-asso-ciated virus genome 2 serotype 8 vector expressing Hamp(rAAV2/8-Hamp)or its negative control(rAAV2/8-NC)was administered intravenously at week 8 of either the CDAA or CSAA diet.Results:rAAV2/8-Hamp treatment markedly decreased liver weight and improved hepatic steatosis in the CDAA-fed mice,accompanied by changes in lipogenesis-related genes and adiponectin expression.Compared with the control group,rAAV2/8-Hamp therapy attenuated liver damage,with mice exhibiting reduced histological NAFLD inflammation and fibrosis,as well as lower levels of liver enzymes.Moreover,α-smooth muscle actin-positive acti-vated hepatic stellate cells(HSCs)and CD68-postive mac-rophages increased in number in the CDAA-fed mice,which was reversed by rAAV2/8-Hamp treatment.Consistent with the in vivo findings,overexpression of Hamp increased adi-ponectin expression in hepatocytes and Hamp treatment inhibited HSC activation.Conclusions:Overexpression of Hamp using rAAV2/8-Hamp robustly attenuated liver stea-tohepatitis,inflammation,and fibrosis in an animal model of NASH,suggesting a potential therapeutic role for Hamp. | Hui Chen Wenshan Zhao Xuzhen Yan Tao Huang Aiting Yang | 2022 | Journal of Clinical and Translational Hepatology2022，10，4： | 0 |
| 7 | Numerical study of elbow erosion due to sand particles under annular flow considering liquid entrainment显示文摘Sand particle erosion is always a challenge in natural gas production.In particular,the erosion in gas-liquid-solid annular flow is more complicated.In this study,a three-phase flow numerical model that couples the volume of fluid multiphase flow model and the discrete phase model was developed for prediction of erosion in annular flow.The ability of the numerical model to simulate the gas-liquid annular flow is validated through comparison with the experimental data.On the basis of the above numerical model,the phase distribution in the pipe was analyzed.The liquid entrainment behavior was reasonably simulated through the numerical model,which guaranteed the accuracy of predicting the particle erosion.Additionally,four erosion prediction models were used for the erosion calculation,among them,the Zhang et al.erosion model predicted the realistic results.Through the analysis of the particle trajectory and the particle impact behavior on the elbow,the cushion effect of the liquid film on the particles and the erosion morphology generation at the elbow were revealed. | Xiangyang Zhao Xuewen Cao Hengguang Cao Jun Zhang Jianing Zhang Wenshan Peng Jiang Bian | 2023 | Particuology2023，，5： | 0 |
| 8 | Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy显示文摘Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower cost.Lymphocyte-activation gene 3(LAG-3)is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1(FGL1).Here,we found that LAG-3 expression was higher than programmed cell death protein 1(PD-1)in multiple human cancers by TCGA databases,and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning,which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II.Subsequently,D-amino acids were introduced to substitute the N-and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1,which restores T cell function in vitro and inhibits tumor growth in vivo.Further,a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1blocking peptide OPBP-1(8-12),which activates T cell with enhanced proliferation and IFN-γ production.More importantly,LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response.In conclusion,we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function,and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response. | Yuzhen Qian Yixuan Sun Peishang Shi Xiuman Zhou Qiongqiong Zhang Qingyu Dong Shengzhe Jin Lu Qiu Xiaoshuang Niu Xiaowen Zhou Wenshan Zhao Yahong Wu Wenjie Zhai Yanfeng Gao | 2024 | Acta Pharmaceutica Sinica B2024，14，3： | 0 |
| 9 | Regression Analysis of Misclassified Current Status Data with Informative Observation Times显示文摘Misclassified current status data arises if each study subject can only be observed once and the observation status is determined by a diagnostic test with imperfect sensitivity and specificity.For the situation,another issue that may occur is that the observation time may be correlated with the interested failure time,which is often referred to as informative censoring or observation times.It is well-known that in the presence of informative censoring,the analysis that ignores it could yield biased or even misleading results.In this paper,the authors consider such data and propose a frailty-based inference procedure.In particular,an EM algorithm based on Poisson latent variables is developed and the asymptotic properties of the resulting estimators are established.The numerical results show that the proposed method works well in practice and an application to a set of real data is provided. | WANG Wenshan XU Da ZHAO Shishun SUN Jianguo | 2023 | Journal of Systems Science & Complexity2023，36，3： | 0 |
| 10 | Computational study of transition metal single-atom catalysts supported on nitrogenated carbon nanotubes for electrocatalytic nitrogen reduction显示文摘Developing efficient and stable catalysts for the electrocatalytic N_(2)reduction reaction(NRR)shows promise in nitrogen fixation.Here,we proposed active and stable single-atom catalysts(SACs)toward NRR,where transition metals are anchored on nitrogenated carbon nanotubes(NCNTs).Among the screened nine common transition metals(Ti,V,Cr,Mn,Fe,Mo,Ru,Rh,and Ag)on(4,4)NCNTs,we found Mo-NCNT possesses the most excellent NRR catalytic activity and selectivity with a low overpotential of 0.29 V.Then,the NRR performance of Mo-NCNT was further engineered by controlling the nanotube diameter,where the lowest overpotential is 0.18 V at a diameter of 9.6Å.In addition,we found a linear scaling relation between*NNH and*NH_(2)on the studied catalysts with the exception of(2,2)and(3,3)Mo-NCNTs,owing to their extremely unstable structures.We attribute the outstanding NRR performance of Mo-NCNT to the moderate adsorption of N_(2)due to the slightly low d-band center of Mo,and the charge donating and accepting capacity of NCNTs.This work has provided a deeper insight into designing highefficiency and stable NRR SACs supported by NCNTs. | Yanyang Qin Yan Li Wenshan Zhao Shenghua Chen Tiantian Wu Yaqiong Su | 2023 | Nano Research2023，16，1： | 0 |
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