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1Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro显示文摘Dear Editor,In December 2019,a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan,a city of 11 million people in central China.The initial cases were linked to exposures in a seafood market in Wuhan.1 As of January 27,2020,the Chinese authorities reported 2835 confirmed cases in China's Mainland,including 81 deaths.Additionally,19 confirmed cases were identified in Hong Kong,Macao and Taiwan,and 39 imported cases were identified in Thailand,Japan,South Korea,United States,Vietnam,Singapore,Nepal,France,Australia and Canada.The pathogen was soon identified as a novel coronavirus(2019-nCoV),which is closely related to sever acute respiratory syndrome CoV(SARS-CoV).2 Currently,there is no specific treatment against the new virus.Therefore,identifying effective antiviral agents to combat the disease is urgently needed.Manli Wang Ruiyuan Cao Leike Zhang Xinglou Yang Jia Liu Mingyue Xu Zhengli Shi Zhihong Hu Wu Zhong Gengfu Xiao 2020Cell Research2020,30,3:563
2Pharmacological effects of Astragaloside IV: a literature review显示文摘OBJECTIVE: To review the pharmacological effects and mechanisms of action of Astragaloside IV in Huangqi (Radix Astragali Mongolici). METHODS: Aticles focusing on Astragaloside IV in English and Chinese in databases were collected and reviewed in order to summarize the latest extraction separation, pharmacokinetics, and the pharmacological effects of astrageloside IV. RESULTS: Protective effects of Astrageloside IV on the cardiovascular system, immune, digestive, nervous system were identified, and the action mechanisms were associated with regulation of the calcium balance, anti-oxydant, antiapoptosis, antivirus, and so on. CONCLUSION: Astrageloside IV has broad application prospects, especially in cardiovascular diseases, digestive diseases, cancer and other modern high incidence, high-risk diseases, and could be developed as a medicine.Shuang Ren Hua Zhang Yongping Mu Mingyu Sun Ping Liu 2013Journal of Traditional Chinese Medicine2013,33,3:57
3A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy显示文摘anti-CTLA-4 抗体由阻止 B7-CTLA-4 相互作用接近否定发信号引起肿瘤拒绝,这被假定。在比临床上有效的 dosing 完成的血浆层次更加高的集中,令人惊讶地, anti-CTLA-4 抗体 Ipilimumab 不由 CTLA-4 也不 CTLA-4 绑定堵住任何一 B7 trans-endocytosis 到使不能调动或联系房间的 B7。因而, Ipilimumab 不从人性化的任何一个 CTLA4 基因在树枝状的房间(DC ) 上增加 B7 (Ctla4 h/h ) 或人的 CD34 + 茎重新组成房间的 NSG 老鼠。在 Ctla4 高效地表示人和老鼠 CTLA4 基因,绑在人的 anti-CTLA-4 抗体然而并非老鼠 CTLA-4 的 h/m 老鼠导致 Treg 弄空和 Fc 受体依赖者肿瘤拒绝。堵住的抗体 L3D10 比得上在引起肿瘤拒绝的非阻塞的 Ipilimumab。显著地,输在人类化期间堵住活动的 L3D10 子孙在导致 Treg 弄空和肿瘤拒绝仍然保持充分能干。有效地在淋巴的器官堵住 CD4 T 细胞激活和 de novo CD8 T 细胞 priming 的 Anti-B7 抗体否定地不影响 Ipilimumab 的 immunotherapeutic 效果。因此,临床上有效的 anti-CTLA-4 mAb 由独立于检查点封锁的机制引起肿瘤拒绝但是依赖于主人 Fc 受体。我们为 CTLA-4 检查点的一个重评价的数据电话封锁假设并且为安全、有效的 anti-CTLA-4 mAbs 的下一代提供新卓见。Xuexiang Du Fei Tang Mingyue Liu Juanjuan Su Yan Zhang Wei Wu Martin Devenport Christopher A Lazarski Peng Zhang Xu Wang Peiying Ye Changyu Wang Eugene Hwang Tinghui Zhu Ting Xu Pan Zheng Yang Liu 2018Cell Research2018,28,4:25
4Isolation and characterization of Zika virus imported to China using C6/36 mosquito cells显示文摘Dear Editor,Zika virus(ZIKV)is a mosquito-borne flavivirus that usually causes asymptomatic infections or mild illness in humans.However,the unprecedented epidemics of ZIKV in Latin America since early 2015 have made this flavivirus an international health risk(Liu and Zhang,2016).In particular,the potential association of ZIKV infection with the remarkable increase in the numberChenglin Deng Siqing Liu Qiuyan Zhang Mingyue Xu Honglei Zhang Dayong Gu Lei Shi Jian'an He Gengfu Xiao Bo Zhang 2016Virologica Sinica2016,31,2:12
5Advanced fabrication for electrospun three-dimensional nanofiber aerogels and scaffolds显示文摘Electrospinning is a versatile strategy for creating nanofiber materials with various structures,which has broad application for a myriad of areas ranging from tissue engineering,energy harvesting,filtration and has become one of the most important academic and technical activities in the field of material science in recent years.In addition to playing a significant role in the construction of two-dimensional(2D)nanomaterials,electrospinning holds great promise as a robust method for producing three-dimensional(3D)aerogels and scaffolds.This article reviews and summarizes the recent advanced methods for fabricating electrospun three-dimensional nanofiber aerogels and scaffolds,including gas foaming,direct electrospinning of 3D nanofibrous scaffold,short nanofibers assembling into 3D aerogels/scaffolds,3D printing,electrospray,origami and cell sheet engineering,centrifugal electrospinning,and other methods.Besides,intriguing formation process,crosslinking pathway,properties,and applications of 3D aerogels and scaffolds are also introduced.Taken together,these aerogels and scaffolds with various excellent features present tremendous potential in various fields.Yujie Chen Muhammad Shafiq Mingyue Liu Yosry Morsi Xiumei Mo 2020Bioactive Materials2020,5,4:12
6Insight-HXMT observations of the first binary neutron star merger GW170817显示文摘Finding the electromagnetic(EM) counterpart of binary compact star merger, especially the binary neutron star(BNS) merger,is critically important for gravitational wave(GW) astronomy, cosmology and fundamental physics. On Aug. 17, 2017,Advanced LIGO and Fermi/GBM independently triggered the first BNS merger, GW170817, and its high energy EM counterpart,GRB 170817 A, respectively, resulting in a global observation campaign covering gamma-ray, X-ray, UV, optical, IR, radio as well as neutrinos. The High Energy X-ray telescope(HE) onboard Insight-HXMT(Hard X-ray Modulation Telescope) is the unique high-energy gamma-ray telescope that monitored the entire GW localization area and especially the optical counterpart(SSS17 a/AT2017 gfo) with very large collection area(~1000 cm^2) and microsecond time resolution in 0.2-5 MeV. In addition,Insight-HXMT quickly implemented a Target of Opportunity(ToO) observation to scan the GW localization area for potential X-ray emission from the GW source. Although Insight-HXMT did not detect any significant high energy(0.2-5 MeV) radiation from GW170817, its observation helped to confirm the unexpected weak and soft nature of GRB 170817 A. Meanwhile,Insight-HXMT/HE provides one of the most stringent constraints(~10^(-7) to 10^(-6) erg/cm^2/s) for both GRB170817 A and any other possible precursor or extended emissions in 0.2-5 MeV, which help us to better understand the properties of EM radiation from this BNS merger. Therefore the observation of Insight-HXMT constitutes an important chapter in the full context of multi-wavelength and multi-messenger observation of this historical GW event.TiPei Li ShaoLin Xiong ShuangNan Zhang FangJun Lu LiMing Song XueLei Cao Zhi Chang Gang Chen Li Chen TianXiang Chen Yong Chen YiBao Chen YuPeng Chen Wei Cui WeiWei Cui JingKang Deng YongWei Dong YuanYuan Du MinXue Fu GuanHua Gao He Gao Min Gao MingYu Ge YuDong Gu Ju Guan ChengCheng Guo DaWei Han Wei Hu Yue Huang Jia Huo ShuMei Jia LuHua Jiang WeiChun Jiang Jing Jin YongJie Jin Bing Li ChengKui Li Gang Li MaoShun Li Wei Li Xian Li XiaoBo Li XuFang Li YanGuo Li ZiJian Li ZhengWei Li XiaoHua Liang JinYuan Liao CongZhan Liu GuoQing Liu HongWei Liu ShaoZhen Liu XiaoJing Liu Yuan Liu YiNong Liu Bo Lu XueFeng Lu Tao Luo Xiang Ma Bin Meng Yi Nang JianYin Nie Ge OU JinLu Qu Na Sai Liang Sun Yin Tan Lian Tao WenHui Tao YouLi Tuo GuoFeng Wang HuanYu Wang Juan Wang WenShuai Wang YuSa Wang XiangYang Wen BoBing WU Mei Wu GuangCheng Xiao He Xu YuPeng Xu LinLi Yan JiaWei Yang Sheng Yang YanJi Yang AiMei Zhang ChunLei Zhang ChengMo Zhang Fan Zhang HongMei Zhang Juan Zhang Qiang Zhang Shu Zhang Tong Zhang Wei Zhang WanChang Zhang WenZhao Zhang Yi Zhang Yue Zhang YiFei Zhang YongJie Zhang Zhao Zhang ZiLiang Zhang HaiSheng Zhao JianLing Zhao XiaoFan Zhao ShiJie Zheng Yue Zhu YuXuan Zhu ChangLin Zou 2018Science China(Physics,Mechanics & Astronomy)2018,61,3:12
7Selection of optimal window length using STFT for quantitative SNR analysis of LFM signal显示文摘An adaptive approach to select analysis window parameters for linear frequency modulated(LFM) signals is proposed to obtain the optimal 3 dB signal-to-noise ratio(SNR) in the shorttime Fourier transform(STFT) domain.After analyzing the instantaneous frequency and instantaneous bandwidth to deduce the relation between the window length and deviation of the Gaussian window,high-order statistics is used to select the appropriate window length for STFT and get the optimal SNR with the right time-frequency resolution according to the signal characteristic under a fixed sampling rate.Computer simulations have verified the effectiveness of the new method.Qingbo Yin Liran Shen Mingyu Lu Xiangyang Wang Zhi Liu 2013Journal of Systems Engineering and Electronics2013,24,1:11
8The enhanced X-ray Timing and Polarimetry mission—eXTP显示文摘In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment.ShuangNan Zhang Andrea Santangelo Marco Feroci YuPeng Xu FangJun Lu Yong Chen Hua Feng Shu Zhang Sφren Brandt Margarita Hernanz Luca Baldini Enrico Bozzo Riccardo Campana Alessandra De Rosa YongWei Dong Yuri Evangelista Vladimir Karas Norbert Meidinger Aline Meuris Kirpal Nandra Teng Pan Giovanni Pareschi Piotr Orleanski QiuShi Huang Stephane Schanne Giorgia Sironi Daniele Spiga Jiri Svoboda Gianpiero Tagliaferri Christoph Tenzer Andrea Vacchi Silvia Zane Dave Walton ZhanShan Wang Berend Winter Xin Wu Jean J.M.in't Zand Mahdi Ahangarianabhari Giovanni Ambrosi Filippo Ambrosino Marco Barbera Stefano Basso Jörg Bayer Ronaldo Bellazzini Pierluigi Bellutti Bruna Bertucci Giuseppe Bertuccio Giacomo Borghi XueLei Cao Franck Cadoux Francesco Ceraudo TianXiang Chen Yu Peng Chen Jerome Chevenez Marta Civitani Wei Cui WeiWei Cui Thomas Dauser Ettore Del Monte Sergio Di Cosimo Sebastian Diebold Victor Doroshenko Michal Dovciak YuanYuan Du Lorenzo Ducci QingMei Fan Yannick Favre Fabio Fuschino JoséLuis Ga'lvez Min Gao MingYu Ge Olivier Gevin Marco Grassi QuanYing Gu YuDong Gu DaWei Han Bin Hong Wei Hu Long Ji ShuMei Jia WeiChun Jiang Thomas Kennedy Ingo Kreykenbohm Irfan Kuvvetli Claudio Labanti Luca Latronico Gang Li MaoShun Li Xian Li Wei Li ZhengWei Li Olivier Limousin HongWei Liu XiaoJing Liu Bo Lu Tao Luo Daniele Macera Piero Malcovati Adrian Martindale Malgorzata Michalska Bin Meng Massimo Minuti Alfredo Morbidini Fabio Muleri Stephane Paltani Emanuele Perinati Antonino Picciotto Claudio Piemonte JinLu Qu Alexandre Rachevski Irina Rashevskaya Jerome Rodriguez Thomas Schanz ZhengXiang Shen LiZhi Sheng JiangBo Song LiMing Song Carmelo Sgro Liang Sun Ying Tan Phil Uttley Bo Wang DianLong Wang GuoFeng Wang Juan Wang LangPing Wang YuSa Wang Anna L.Watts XiangYang Wen Jörn Wilms ShaoLin Xiong JiaWei Yang Sheng Yang YanJi Yang Nian Yu WenDa Zhang Gianluigi Zampa Nicola Zampa Andrzej A.Zdziarski AiMei Zhang ChengMo Zhang Fan Zhang Long Zhang Tong Zhang Yi Zhang XiaoLi Zhang ZiLiang Zhang BaoSheng Zhao ShiJie Zheng Yu Peng Zhou Nicola Zorzi J.Frans Zwart 2019Science China(Physics,Mechanics & Astronomy)2019,62,2:11
9Effects of Different Land-Use Types on Soil Erosion Under Natural Rainfall in the Loess Plateau, China显示文摘黄土高原,位于中国的干旱、半干旱的区域,由于强烈人的活动和土壤 erodibility 经历重要土壤侵蚀。探索并且识别能控制土壤侵蚀并且完成某些农业生产能力的陆地使用类型或陆地使用模式是必要的。这研究在 Yan'an 的北方与二个斜坡坡度(5 ° 和 15 ° ) 建立了流量阴谋,黄土高原的一个区域,与 3 单身者一起,陆地使用打字(栽培土地, CL;switchgrass, SG;并且放弃了土地, AL ) 并且 2 种合成陆地使用类型(CL-SG 和 CL-AL ) 。从 2006 ~ 2012,我们连续地监视了降雨特征,流量深度,土壤损失,植被范围,和土壤物理性质。结果为 5 种陆地使用类型在流量和土壤损失事件的数字显示了一个一般趋势:CL = CL-SG > CL-AL > SG > AL。为流量深度,土壤损失,他们变化的大小,和降雨流量回归方程的斜坡的一般趋势是 CL > CL-SG > CL-AL > SG > AL,而为流量产生的降雨阀值展出了相反的趋势。nonparametric 的结果关于流量 depth/EI 30 和 EI 30 在 30 min,和关系回归显示了的流量深度土壤损失上是降雨动能和最大的降雨紧张的产品的土壤 loss/EI 30, 测试 CL-AL 的效果类似于 SG 的;SG 类似于 AL;并且 CL-AL, SG,和 AL 比关于土壤和水保存的 CL 优异。显著地作为斜坡坡度增加的流量深度和土壤损失增加了。流量深度和土壤损失显著地分别地与土壤粒子尺寸作文和体积密度被相关。最强壮的重要关联在流量深度和植被范围之间以及在土壤损失和植被范围之间被发现,它证明那篇植被报道是控制土壤侵蚀的主要因素。因此,因为土壤保存和农业生产的某个度在学习区域是必要的,合成陆地使用类型 CL-AL 和人工的草地(SG ) 是适当选择。FENG Qiang ZHAO Wenwu WANG Jun ZHANG Xiao ZHAO Mingyue ZHONG Lina LIU Yuanxin FANG Xuening 2016Pedosphere2016,26,2:11
10Cell multiplication, apoptosis and p-Akt protein expression of bone mesenchymal stem cells of rat under hypoxia environment显示文摘Objective: To elucidate whether cell multiplication, apoptosis, glucose intake and p-Akt protein expression of bone Mesenchy-mal Stem Cells(MSCs) of rats is influenced by a hypoxic environment ex vivo. Methods: Passage 3 of bone marrow MSCs takenfrom Wistar rats, were cultured in a culturing chamber with 94%N2, 1%O2, 5%CO2 at 37℃. At different hypoxia time points, 0, 0.5,1, 4 and 8 h, glucose uptake was assayed by using radiation isotope 3H-G, Apoptotic Rate(AR) and dead rate(DR) were analyzedby flow cytometry(FCM) after Annexin V/PI staining, cell multiplication(by MTT methods) and p-Akt protein by immunocyto-chemistry and western blot. Results: Assay for CD29+, CD44+, CD71+, CD34- , Tn T+(after 5-azacytidine agent inducing) andALP+(after bone differentiation agent inducing) suggested these bone-derived cells were MSCs. The 3H-G intaking ratio(CPM/flask value: 157 ±11, 110 ±11, 107 ±13, 103 ±10, 100 ±9 and 98 ±10) of MSCs at different hypoxia time points, significantlydecreased compared to that of normoxia(P < 0.01) and tended to descend slowly with hypoxia time duration, for which there wasno statistical significance(P > 0.05). The AR(0.09 ±2.03%, 12.9 ±1.72%, 13.7 ±2.26%, 13.8 ±3.01%, 14.1 ±2.78% and 14.7 ±4.01% at 0, 0.5, 1, 4 and 8 h, respectively, P < 0.01) and DR (0.04 ±1.79%, 0.93 ±1.85%, 3.11 ±2.14%, 4.09 ±2.36%, 4.72 ±2.05% and 4.91 ±3.72% at 0, 0.5, 1, 4 and 8 h, respectively, P < 0.05) at different hypoxia time points significantly increasedcompared to those time in normoxia; The AR further went up with time (P < 0.05), however there was no statistical significance(P > 0.05) for the DR. Optical absorption value of MTT methods at different hypoxia time points significantly decreased com-pared to those with a corresponding normoxia time (P < 0.01) and degraded with time (in an hypoxic environment - P < 0.01).IOD of p-Akt protein of MSCs at different hypoxia time points significantly increased (0.367 ±0.031, 0.556 ±0.023, 0.579 ±0.013, 0.660 ±0.024, 0.685 ±0.039 and 0.685 ±0.011, respectively) compared to their equivalents in normoxia (P<0.05), how-ever, there was no statistical significance (P > 0.05) for different hypoxia time points. Hypoxia may result in ultramicrostructurechanges, such as defluvium of Microvilli, apoptotic body, 'margination'and so on and are further aggravated with hypoxia timestretching. Conclusion: Hypoxia may lead to a depression of MSCs intaking glucose, creep of cell multiplication, upregulation ofp-Akt protein and apoptosis of MSCs ex vivo.Hongliang Kong Ningning Liu Xin Huo Bo Wang Haipeng Zhang Mingyu Gao Guoxian Qi 2007Journal of Nanjing Medical University2007,21,4:10
11Artificial intelligence in drug design显示文摘Thanks to the fast improvement of the computing power and the rapid development of the computational chemistry and biology,the computer-aided drug design techniques have been successfully applied in almost every stage of the drug discovery and development pipeline to speed up the process of research and reduce the cost and risk related to preclinical and clinical trials.Owing to the development of machine learning theory and the accumulation of pharmacological data, the artificial intelligence(AI) technology, as a powerful data mining tool, has cut a figure in various fields of the drug design, such as virtual screening,activity scoring, quantitative structure-activity relationship(QSAR) analysis, de novo drug design, and in silico evaluation of absorption, distribution, metabolism, excretion and toxicity(ADME/T) properties. Although it is still challenging to provide a physical explanation of the AI-based models, it indeed has been acting as a great power to help manipulating the drug discovery through the versatile frameworks. Recently, due to the strong generalization ability and powerful feature extraction capability,deep learning methods have been employed in predicting the molecular properties as well as generating the desired molecules,which will further promote the application of AI technologies in the field of drug design.Feisheng Zhong Jing Xing Xutong Li Xiaohong Liu Zunyun Fu Zhaoping Xiong Dong Lu Xiaolong Wu Jihui Zhao Xiaoqin Tan Fei Li Xiaomin Luo Zhaojun Li Kaixian Chen Mingyue Zheng Hualiang Jiang 2018Science China(Life Sciences)2018,61,10:10
12Degree of Brine Evaporation and Origin of the Mengyejing Potash Deposit:Evidence from Fluid Inclusions in Halite显示文摘The Mengyejing potash deposit is located in the southern port of the Simao Basin, Yunnan Province, and is hosted in mid-Cretaceous strata. The chemical compositions of fluid inclusions in halite crystals, collected from the level-610 adit in the deposit, were analysed by laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS). The results show that the brine is of the Na-K-Mg-Ca-Cl type and has K concentrations that are distinctly higher than those of Mg and Ca, unlike normal brines associated with Cretaceous halite. The high K concentrations indicate that the degree of evaporation of the ancient Mengyejing saline lake was very high, reaching the sylvite deposition stage but rarely reaching the carnallite deposition stage. The trajectory of the H and O isotopic compositions of the brines in the halite-hosted fluid inclusions corresponds to intense evaporation, indicating that the net evaporation exceeded the net inflow of brines. These brine compositions in halite-hosted fluid inclusions were likely formed by the dissolution of previously deposited K-bearing minerals by fresh continental and/or seawater, forming a type of modified seawater, with deep hydrothermal fluids potentially supplying additional potassium. The basin likely experienced multiple seawater incursion, dissolution and redeposition events in a high-temperature environment with high evaporation rates.SHEN Lijian LIU Chenglin WANG Licheng HU Yufei HU Mingyue FENG Yuexing 2017Acta Geologica Sinica(English Edition)2017,91,1:9
13Classification of the Gut Microbiota of Patients in Intensive Care Units During Development of Sepsis and Septic Shock显示文摘The gut microbiota of intensive care unit(ICU)patients displays extreme dysbiosis associated with increased susceptibility to organ failure,sepsis,and septic shock.However,such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota.We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis.We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions.During the development of sepsis or septic shock and during various medical treatments,the ICU patients always exhibited two dysbiotic microbiota patterns,or ICU-enterotypes,which could not be explained by host properties such as age,sex,and body mass index,or external stressors such as infection site and antibiotic use.ICU-enterotype I(ICU E1)comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae,while ICU-enterotype II(ICU E2)comprised predominantly Enterococcus.Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II(APACHE II)scores>18,septic shock was more likely to occur with ICU E1(P=0.041).Additionally,ICU E1 was correlated with high serum lactate levels(P=0.007).Therefore,different patterns of dysbiosis were correlated with different clinical outcomes,suggesting that ICU-enterotypes should be diagnosed as independent clinical indices.Thus,the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients.This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.Wanglin Liu Mingyue Cheng Jinman Li Peng Zhang Hang Fan Qinghe Hu Maozhen Han Longxiang Su Huaiwu He Yigang Tong Kang Ning Yun Long 2020Genomics, Proteomics & Bioinformatics2020,18,6:7
14Uncoupling therapeutic from effects for safer and effective CTLA4 humanized mice immunotherapy-related adverse anti-CTLA-4 antibodies in显示文摘Xuexiang Du Mingyue Liu Juanjuan Su Peng Zhang Fei Tang Peiying Ye Martin Devenport Xu Wang Yan Zhang Yang Liu Pan Zheng 2018Cell Research2018,28,4:6
15Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy显示文摘It remains unclear why the clinically used anti-CTLA-4 antibodies, popularly called checkpoint inhibitors, have severe immunotherapy-related adverse effects (irAEs) and yet suboptimal cancer immunotherapeutic effects (CITE). Here we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface by the LRBA-dependent mechanism. Disrupting CTLA-4 recycling results in robust CTLA-4 downregulation by all anti-CTLA-4 antibodies and confers toxicity to a non-irAE-prone anti-CTLA-4 mAb. Conversely, increasing the pH sensitivity of TremeIgG1 by introducing designed tyrosine-to-histidine mutations prevents antibody-triggered lysosomal CTLA-4 downregulation and dramatically attenuates irAE. Surprisingly, by avoiding CTLA-4 downregulation and due to their increased bioavailability, pH-sensitive anti-CTLA-4 antibodies are more effective in intratumor regulatory T-cell depletion and rejection of large established tumors. Our data establish a new paradigm for cancer research that allows for abrogating irAE while increasing CITE of anti-CTLA-4 antibodies.Yan Zhang Xuexiang Du Mingyue Liu Fei Tang Peng Zhang Chunxia Ai James K. Fields Eric J. Sundberg Olga S. Latinovic Martin Devenport Pan Zheng Yang Liu 2019Cell Research2019,29,8:6
16Hydrolyzed seawater pearl tablet modulates the immunity via attenuating Th1/Th2 imbalance in an immunosuppressed mouse model显示文摘OBJECTIVE: To investigate whether Hydrolyzed Seawater Pearl tablet(HSPT) could modulate the Th1/Th2 imbalance in an immunosuppressed mouse model with Th1 to Th2 shift induced by Cyclosporine A(Cs A) which can be used in the clinical treatment of Th2 to Th1 shift diseases, and explore the possible mechanism for the adjuvant therapeutic efficacy of HSPT on recurrent respiratory infections(RRI) and acquired immune deficiency syndrome(AIDS).METHODS: The mice were randomly divided into six groups of five animals each, namely normal group, model group, lentinan polysaccharide tablet(LPT) group and three HPST treated groups. HPST treated groups were administered with HPST(0.51,1.02, 2.04 g/kg) via intragastric gavage(i.g) for 30 consecutive days. LPT used as reference drug for positive control, LPT group was administered with LPT(8.2 mg/kg) for 30 consecutive days. Normal group and model group were received distilled water. The animals in model group, LPT group and HPST treated groups were injected intraperitoneally with Cs A(50 mg/kg) to establish the immunosuppressed mice model with Th1 to Th2 shift on the20 th, 22 nd and 24 th day, one hour after the administration of the respective treatment. Animals were sacrificed one hour after the last administration to collect blood and splenic tissue. The proportion of T cells including CD8+ and CD4+ T cells, Th1 and Th2 in peripheral blood of experimental mice were measured by flow cytometric. The protein level in serum and m RNA level in splenic tissue of experimental mice for interleukin(IL)-2, IL-12, interferon-γ(IFN-γ), IL-4, IL-6, IL-10 and IL-13 were measured by enzyme linked immunosorbent assay and fluorescence quantitative polymerase chain reaction respectively.RESULTS: HSPT elevated the proportion of T cells including both CD8+ and CD4+ T cells, in which the proportion of Th1 and Th2 cells increased, while the ratio of Th1/Th2 cells decreased in peripheral blood of the immunosuppressed mouse model with Th1 to Th2 shift induced by Cs A. Furthermore,HSPT elevated both protein and m RNA level of Th1-type cytokines IL-2 and IFN-γ, while had no significant effect on protein and m RNA level of Th1-type cytokine IL-12 and Th2-type cytokines IL-4, IL-6, IL-10, IL-13 in mouse model.CONCLUSION: Our findings suggest that HSPT can increase proportion of T cells including both CD8+and CD4+T cells and induce Th2 to Th1 shift in both cells and cytokines, which probably was the mechanism to account for the adjuvant therapeutic efficacy of HSPT on RRI and AIDS.LAN Taijin LUO Xuefei MO Mingyue CHEN Zhenxing LUO Fei HAN Siyin LIU Peng LIANG Zhongxiu ZHANG Ting LI Tianyi YAN Qiangqiang LIN Yong LIN Jiang 2021Journal of Traditional Chinese Medicine2021,41,3:6
17Shaking table test and numerical simulation of an isolated cylindrical latticed shell under multiple-support excitations显示文摘In order to study the infl uence of the ground motion spatial eff ect on the seismic response of large span spatial structures with isolation bearings, a single-layer cylindrical latticed shell scale model with a similarity ratio of 1/10 was constructed. An earthquake simulation shaking table test on the response under multiple-support excitations was performed with the high-position seismic isolation method using high damping rubber (HDR) bearings. Small-amplitude sinusoidal waves and seismic wave records with various spectral characteristics were applied to the model. The dynamic characteristics of the model and the seismic isolation eff ect on it were analyzed at varying apparent wave velocities, namely infi nitely great, 1000 m/s, 500 m/s and 250 m/s. Besides, numerical simulations were carried out by Matlab software. According to the comparison results, the numerical results agreed well with the experimental data. Moreover, the results showed that the latticed shell roof exhibited a translational motion as a rigid body after the installation of the HDR bearings with a much lower natural frequency, higher damping ratio and only 1/2~1/8 of the acceleration response peak values. Meanwhile, the structural responses and the bearing deformations at the output end of the seismic waves were greatly increased under multiple-support excitations.Xue Suduo Shan Mingyue Li Xiongyan Liang Shuanzhu Huang Fuyun Liu Yi 2019Earthquake Engineering and Engineering Vibration2019,18,3:5
18The Medium Energy X-ray telescope (ME) onboard the Insight-HXMT astronomy satellite显示文摘The Medium Energy X-ray telescope(ME) is one of the three main telescopes on board the Insight hard X-ray modulation telescope(Insight-HXMT) astronomy satellite. ME contains 1728 pixels of Si-PIN detectors sensitive in 5-30 ke V with a total geometrical area of 952 cm^2. The application specific integrated circuit(ASIC) chip, VA32TA6, is used to achieve low power consumption and low readout noise. The collimators define three kinds of field of views(FOVs) for the telescope, 1°×4°, 4°×4°,and blocked ones. Combination of such FOVs can be used to estimate the in-orbit X-ray and particle background components.The energy resolution of ME is ~3 ke V at 17.8 ke V(FWHM) and the time resolution is 255 μs. In this paper, we introduce the design and performance of ME.XueLei Cao WeiChun Jiang Bin Meng WanChang Zhang Tao Luo Sheng Yang ChunLei Zhang YuDong Gu Liang Sun XiaoJing Liu JiaWei Yang Xian Li Ying Tan ShaoZhen Liu YuanYuan Du FangJun Lu YuPeng Xu Ju Guan ShuangNan Zhang HuanYu Wang TiPei Li ChengMo Zhang XiangYang Wen JinLu Qu LiMing Song XiaoBo Li MingYu Ge YuPeng Zhou ShaoLin Xiong Shu Zhang YongJie Zhang ZeHao Cheng Fei Zhang MaoShun Li XiaoHua Liang Min Gao EnBo Yang XiaoHang Liu HongWei Liu YiJung Yang Fan Zhang 2020Science China(Physics,Mechanics & Astronomy)2020,63,4:5
19White-light emitting single-phase phosphor La_3Si_6N_(11):Dy^(3+),Tb^(3+):Color tunable emission, thermal stability and energy transfer process显示文摘A novel white-light emitting single-phase phosphor La_3 Si_6 N_(11):Dy^(3+),exhibiting two emission peaks centering at 475 and 575 nm, was prepared via conventional solid-state reactions. The structure and morphology of La_3 Si_6 N_(11):Dy^(3+)/Tb^(3+) were investigated by X-ray diffraction(XRD) and scanning electron microscopy(SEM). The emission colors can be tuned from white to yellow-green through increasing the Tb^(3+) concentration in La_3 Si_6 N_(11):Dy^(3+),Tb^(3+), The mechanism of energy transfer(ET) from Dy^(3+) to Tb^(3+) is confirmed according to the excitation,emission spectra and decay lifetimes curve. The temperaturedependent luminescence measurements of La_(2.83)Si_6 N_(11):0.1 Dy^(3+),0.07 Tb^(3+) were also performed, and a good thermal stability is shown, suggesting superior properties for the application as white lightemitting diodes(w-LEDs) phosphor.Yuanhong Liu Yuan Xue Ronghui Liu Mingyue Chen Guantong Chen Chunpei Yan Xia Zhang Yu'nan Zhou Wei Gao Xiaole Ma 2019Journal of Rare Earths2019,37,4:5
20Measurements of ^(134)Cs and ^(137)Cs in urine and estimation of the internal dose of an adult exposed to the Chernobyl Accident显示文摘To estimate the internal dose of a Chinese visiting scholar internally contaminated because of the Cherno- byl Accident, the contents of 134Cs and 137Cs in urine were measured using a Ge(Li) γ-spectrometer. The internal doses were calculated based on data from the ICRP Publications. The effective doses from 134Cs and 137Cs were estimated to be 61 μSv and 98 μ Sv, respectively. The sum of 159 μSv was lower than the total effective dose (310 μSv), from the inhalation and ingestion of natural radionuclides. The dose of 131I was also reviewed referring to the UNSCEAR 2000 Report. The equivalent effective dose of 131I was estimated to be 2.9 mSv, 18 times more than the amount of 134Cs and 137Cs. Therefore, it is considered that the earlier estimation of internal doses of 131I is important in evaluating radiation injuries from a nuclear reactor accident.ZHAO Shuquan HUANG Shibin LIU Shiming HU Heping WU Mingyu XIANG Xiqiao ZHU Guoying 2007Nuclear Science and Techniques2007,18,2:5
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