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| 1 | Age-related rhesus macaque models of COVID-19显示文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection. | Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song Yajin Qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin | 2020 | Animal Models and Experimental Medicine2020，3，1： | 22 |
| 2 | Existence of Qiongnan suture zone on the north margin of South China Sea显示文摘This paper aims to explore whether paleo-suture zone exists in the pre-Cenozoic basement of South China Sea (SCS). By taking advantage of integrated geophysical surveying data, including multi-channel reflection seismicity, oceanic bottom seismicity, gravity and magnetic data as well as paleomagnetism and drilling information, a comprehensive analysis on sedimentary stratigraphy, seismic stratigraphy, magmatic and metamorphic petrology, geochemistry, gravity study, magnetics, paleogeomagnetics as well as geotectonics was carried out, and the results clearly indicate that a pre-Cenozoic suture zone, i.e. “Qiongnan (south Hainan Island) suture zone”, does exist on the north margin of SCS. This suture zone starts in the west from the Jiusuo-Lingshui fault zone in the south of Hainan Island, extends eastward across the continental slope to the north of SCS, and links with Shoufeng fault in Taiwan. It is inferred that the Qiongnan suture zone was sutured approximately in Indosinian (Triassic) Epoch and is actually the vestige of “Qiongnan ocean basin”, the extension of the main paleo-Tethys ocean basin in SCS. The formation of Qiongnan suture zone marked the collision-accretion of the Qiongnan Block toward the Qiongzhong Block. The Qiongnan suture zone is linked to the west with the southward extension of the principal suture zone of the Paleo-Tethys at Bitu-Changning-Menglian-Bentong-Raub, across the southern segment of the Red River-East Vietnam-Wanna strike-slip fault zone, and connected to the east with the suture zone emplaced into the south margin of the Oki-Hida Pre-Jurassic terranes in southwest Japan, across the northerni2 e segment of the Manila trench fault zone in the northeast side of Taiwan Island. The discovery of this suture zone is believed to be potentially significant toward study of the pre-Cenozoic geotectonic pattern of SCS, the temporal and spatial distribution of the east paleo-Tethys structural domain in SCS and the relationship of recombination and superimposition between the east paleo-Tethys structural domain and the west Pacific structural domain, in addition to the oil/gas geological potentials in the pre-Cenozoic marine vestige-superimposed basin in the study area. | LIU Hailing YAN Pin LIU Yingchun DENG Hui | 2006 | Chinese Science Bulletin2006，51，B12： | 12 |
| 3 | Sequential infection with H1N1 and SARS-CoV-2 aggravated COVID-19 pathogenesis in a mammalian model, and covaccination as an effective method of prevention of COVID-19 and influenza显示文摘Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus,leading to more serious respiratory diseases during this winter.However,the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear.Using a mammalian model,sequential infection was performed in ferrets and in K18-MCE2 mice,with SARS-CoV-2 infection following H1N1.We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19,and enhanced pulmonary damage,but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets.Moreover,mortality was increased in sequentially infected mice compared with single-infection mice.Compared with singlevaccine inoculation,co-inoculation of PiCoVacc(a SARS-CoV-2 vaccine)and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses.Combined immunization effectively protected K18-MCE2 mice against both H1N1 and SARS-CoV-2 infection.Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2,which together notably enhanced pneumonia in ferrets and mice,as well as demonstrated that simultaneous vaccination against HINT and SARS-CoV-2 may be an effective prevention strategy for the coming winter. | Linlin Bao Wei Deng Feifei Qi Qi Lv Zhiqi Song Jiangning Liu Hong Gao Qiang Wei Pin Yu Yanfeng Xu Yajin Qu Fengdi Li Jing Xue Shuran Gong Mingya Liu Guanpeng Wang Shunyi Wang Binbin Zhao Bin Cong Chuan Qin | 2021 | Signal Transduction and Targeted Therapy2021，6，6： | 4 |
| 4 | Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients显示文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many countries.However,the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown.Here,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune systems.The viral protein partially co-localized with activated Mac-2+macrophages throughout the body.Moreover,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal COVID-19.Particularly,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune dysregulation.Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation.Melatonin,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted medicine.Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers. | Zhiqi Song Linlin Bao Wei Deng Jiangning Liu Erjun Ren Qi Lv Mingya Liu Feifei Qi Ting Chen Ran Deng Fengdi Li Yunpeng Liu Qiang Wei Hong Gao Pin Yu Yunlin Han Wenjie Zhao Junjun Zheng Xujian Liang Fuhe Yang Chuan Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 2 |
| 5 | Sequential immunizations confer cross-protection against variants of SARS-CoV-2,including Omicron in Rhesus macaques显示文摘Variants of concern(VOCs)like Delta and Omicron,harbor a high number of mutations,which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies(NAbs).In this study,Rhesus macaques immunized with 2-dose inactivated vaccines(Coronavac)were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine,or a bivalent inactivated vaccine(Beta and Delta)to determine the effectiveness of sequential immunization.The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type. | Wei Deng Qi Lv Fengdi Li Jiangning Liu Zhiqi Song Feifei Qi Qiang Wei Pin Yu Mingya Liu Shasha Zhou Yaqing Zhang Hong Gao Nan Wang Zijing Jia Kai Gao Jiayi Liu Chong Xiao Haiquan Shang Xiangxi Wang Linlin Bao Chuan Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 2 |
| 6 | Cellular Chain Complex of Small Covers with Integer Coefficients and Its Application显示文摘 | Deng Pin LIU | 2018 | Acta Mathematica Sinica,English Series2018，34，11： | 2 |
| 7 | Therapeutic efficacy of Pudilan Xiaoyan Oral Liquid(PDL)for COVID-19 in vitro and in vivo显示文摘Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed cases.Until now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 infection.Existing medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection. | Wei Deng Yanfeng Xu Qi Kong Jing Xue Pin Yu Jiangning Liu Qi Lv Fengdi Li Qiang Wei Linlin Bao | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 8 | ACE2 expression is regulated by AhR in SARS-CoV-2-infected macaques显示文摘During the current outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),more than 115 million people have been infected,and 2.5 million have died.1,2 Despite such great harm to human health,the pathogenesis of COVID-19 remains unclear.As the first step in the pathogenetic process,viral entry is mediated by the binding of the SARS-CoV-2 surface spike(S)protein to angiotensin-converting enzyme 2(ACE2)on host cells,such as lung epithelial cells.As an alternative to S protein-blocking strategies,manipulating host cell ACE2 expression may exert an inhibitory effect on SARS-CoV-2 infection.However,the molecular mechanism regulating ACE2 expression remains unclear. | Jiadi Lv Pin Yu Zhenfeng Wang Wei Deng Linlin Bao Jiangning Liu Fengli Li Qiangqiang Zhu Nannan Zhou Qi Lv Guanpeng Wang Shunyi Wang Yabo Zhou Jiangping Song Wei-Min Tong Yuying Liu Chuan Qin Bo Huang | 2021 | Cellular & Molecular Immunology2021，18，5： | 1 |
| 9 | Potential Antiviral Target for SARS-CoV-2:A Key Early Responsive Kinase during Viral Entry显示文摘Currently,there is no effective antiviral medication for coronavirus disease 2019(COVID-19)and the knowledge on the potential therapeutic target is in great need.Guided by a time-course transmission electron microscope(TEM)imaging,we analyzed early phosphorylation dynamics within the first 15 min during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral entry.Based on alterations in the phosphorylation events,we found that kinase activities such as protein kinase C(PKC),interleukin-1 receptor-associated kinase 4(IRAK4),MAP/microtubule affinity-regulating kinase 3(MARK3),and TANK-binding kinase 1(TBK1)were affected within 15 min of infection.Application of the corresponding kinase inhibitors of PKC,IRAK4,and p38 showed significant inhibition of SARS-CoV-2 replication.Additionally,proinflammatory cytokine production was reduced by applying PKC and p38 inhibitors.By an acquisition of a combined image data using positiveand negative-sense RNA probes,as well as pseudovirus entry assay,we demonstrated that PKC contributed to viral entry into the host cell,and therefore,could be a potential COVID-19 therapeutic target. | Siwen Liu Lin Zhu Guangshan Xie Bobo Wing-Yee Mok Zhu Yang Shaofeng Deng Siu-Ying Lau Pin Chen Pui Wang Honglin Chen Zongwei Cai | 2022 | CCS Chemistry2022，4，1： | 1 |
| 10 | The temporal and spatial distribution of volcanism in the South China Sea region显示文摘 | Yan Pin Deng Hui Liu Hailing | 2006 | Jour nal of Asian Earth Sciences2006，27，5： | 1 |
| 11 | SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterolincreased endosomal pH of alveolar macrophages显示文摘Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy.Here,we show that ACE2-overexpressing A549 cell-derived microparticles(AO-MPs)are a potential therapeutic agent against SARS-CoV-2 infection.Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages(AMs).Then,AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs,thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation.This pH regulation is attributable to oxidized cholesterol,which is enriched in AO-MPs and translocated to endosomal membranes,thus interfering with proton pumps and impairing endosomal acidification.In addition to promoting viral degradation,AO-MPs also inhibit the proinflammatory phenotype of AMs,leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects.These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future. | Zhenfeng Wang Jiadi Lv Pin Yu Yajin Qu Yabo Zhou Li Zhou Qiangqiang Zhu Shunshun Li Jiangping Song Wei Deng Ran Gao Yuying Liu Jiangning Liu Wei-Min Tong Chuan Qin Bo Huang | 2022 | Cellular & Molecular Immunology2022，19，2： | 1 |
| 12 | The temporal and spatial distribution of volcanism in the South China Searegion显示文摘 | YAN Pin DENG Hui LIU Hailing | 2006 | Journal of Asian Earth Sciences2006，27，5： | 1 |
| 13 | Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71显示文摘Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to death.Currently,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are available.Here,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in cells.The cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of VP1.In a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic treatment.In particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment. | Zhe Chen Linlin Bao Bin Zhu Hua Fu Shuangli Zhu Tianjiao Ji Ying Xue Chuan Liu Xurong Wang Fengdi Li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo Xu Chuan Qin Hongrong Liu Qi Jin | 2022 | Science China(Life Sciences)2022，65，12： | 0 |
| 14 | The Partial Quotients of Moment-angle Manifolds over a Polygon显示文摘In this paper, we generalize the conception of characteristic function in toric topology and construct many new smooth manifolds by using it. As an application, we classify the Moment-Angle manifolds and the partial quotients manifolds of them over a polygon. In the appendix we give a simple new proof for Orlik–Raymond's theorem in terms of characteristic function which gives the classification for quasitoric manifolds of dimension 4. | Deng Pin LIU | 2015 | Acta Mathematica Sinica,English Series2015，31，2： | 0 |
| 15 | Determination of laser entrance hole size for ignition-scale octahedral spherical hohlraums显示文摘A recently proposed octahedral spherical hohlraum with six laser entrance holes(LEHs)is an attractive concept for an upgraded laser facility aiming at a predictable and reproducible fusion gain with a simple target design.However,with the laser energies available at present,LEH size can be a critical issue.Owing to the uncertainties in simulation results,the LEH size should be determined on the basis of experimental evidence.However,determination of LEH size of an ignition target at a small-scale laser facility poses difficulties.In this paper,we propose to use the prepulse of an ignition pulse to determine the LEH size for ignition-scale hohlraums via LEH closure behavior,and we present convincing evidence from multiple diagnostics at the SGIII facility with ignition-scale hohlraum,laser prepulse,and laser beam size.The LEH closure observed in our experiment is in agreement with data from the National Ignition Facility.The total LEH area of the octahedral hohlraum is found to be very close to that of a cylindrical hohlraum,thus successfully demonstrating the feasibility of the octahedral hohlraum in terms of laser energy,which is crucially important for sizing an ignition-scale octahedrally configured laser system.This work provides a novel way to determine the LEH size of an ignition target at a small-scale laser facility,and it can be applied to other hohlraum configurations for the indirect drive approach. | Yao-Hua Chen Zhichao Li Hui Cao Kaiqiang Pan Sanwei Li Xufei Xie Bo Deng Qiangqiang Wang Zhurong Cao Lifei Hou Xingsen Che Pin Yang Yingjie Li Xiaoan He Tao Xu Yonggang Liu Yulong Li Xiangming Liu Haijun Zhang Wei Zhang Baibin Jiang Jun Xie Wei Zhou Xiaoxia Huang Wen Yi Huo Guoli Ren Kai Li Xudeng Hang Shu Li Chuanlei Zhai Jie Liu Shiyang Zou Yongkun Ding Ke Lan | 2022 | Matter and Radiation at Extremes2022，7，6： | 0 |
| 16 | Space-confined microwave synthesis of ternary-layered BiOCl crystals with high-performance ultraviolet photodetection显示文摘In recent years,two-dimensional(2D)ternary materials have attracted wide attention due to their novel properties which can be achieved by regulating their chemical composition with a very great degree of freedom and adjustable space.However,as for the precise synthesis of 2D ternary materials,great challenges still lie ahead that hinder their further development.In this work,we demonstrated a simple and reliable approach to synthesize 2D ternary-layered BiOCl crystals through a microwave-assisted space-confined process in a short time(<3 minutes).Their ultraviolet(UV)detection performance was analyzed systematically.The photodetectors based on the as-obtained BiOCl platelets demonstrate high sensitivity to 266-nm laser illumination.The responsivity is calculated to be8 A/W and the response time is up to be18 ps.On the other hand,the device is quite stable after being exposed in the ambient air within 3 weeks and the response is almost unchanged during the measurement.The facile and fast synthesis of single crystalline BiOCl platelets and its high sensitivity to UV light irradiation indicate the potential optoelectronic applications of 2D BiOCl photodetectors. | Lixing Kang Xuechao Yu Xiaoxu Zhao Qingling Ouyang Jun Di Manzhang Xu Dan Tian Weiliang Gan Calvin CIAng Shoucong Ning Qundong Fu Jiadong Zhou R.G.Kutty Ya Deng Pin Song Qingsheng Zeng Stephen J.Pennycook Jun Shen Ken-T.Yong Zheng Liu | 2020 | InfoMat2020，2，3： | 0 |
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