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| 1 | A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein显示文摘最新新兴的中东呼吸症候群 coronavirus (MERS-CoV ) 能在人引起严重、致命的急性呼吸疾病。尽管有全球努力,潜力为一联系在未来流行不能被排除。有效相对的措施的发展是迫切的。MERS-CoV-specific 抗病毒的药或疫苗是还没可得到的。使用 MERS-CoV (MERS-RBD ) 的尖铁受体绑定领域使老鼠免疫,我们识别了二抵销 monoclonal 抗体(mAbs ) 4C2 和 2E6。两 mAbs potently 与高功效在 vitro 绑在 MERS-RBD 和块病毒入口。我们进一步由使在 Fab 碎片和 RBD 之间的建筑群结晶调查了他们中立化的机制,并且解决了 4C2 Fab/MERS-RBD 建筑群的结构。结构证明 4C2 认出部分重叠的 epitope 在 MERS-RBD 的受体绑定脚印,从而由位的阻碍者和接口残余竞争防碍病毒 / 受体相互作用。2E6 也堵住受体绑定,并且为绑定与 4C2 竞争到 MERS-RBD。基于结构,我们进一步由保存仅仅 paratope 残余并且从人的免疫球蛋白与对应物代替留下的氨基酸使 4C2 人性化。人性化的 4C2 (4C2h ) 抗体支撑了类似的抵销的活动和生物化学的特征到父母老鼠抗体。最后,我们证明 4C2h 能显著地在感染 MERS-CoV 的 Ad5-hCD26-transduced 鼠标的肺消除病毒 titers,因此在临床的设置为预防和治疗代表一个有希望的代理人。 | Yan Li YuhuaWan Peipei Liu Jincun Zhao Guangwen Lu Jianxun Qi Qihui Wang Xuancheng LU Ying Wu Weniun Liu Buchang Zhang Kwok-Yung Yuen Stanley Perlman George F Gao Jinghua Yan | 2015 | Cell Research2015,25,11: | 14 |
| 2 | SARS-like virus in the Middle East:A truly bat-related coronavirus causing human diseases显示文摘On September 23rd,the United Kingdom Health Protection Agency(HPA)reported the diagnostic confirmation of a human infection case by a new type of coronavirus(http://www.hpa.org.uk/NewsCentre/NationalPressReleases/2012PressReleases/120923acuterespiratoryillnessidentified/).The patient is a 49-year-old Qatari who suffered from an acute,serious respiratory illness. | Guangwen Lu Di Liu | 2012 | Protein & Cell2012,3,11: | 8 |
| 3 | An octamer of enolase from Streptococcus suis显示文摘Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic cells.The enzyme can also locate on the cell surface and bind to plasminogen,via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host cells.The functions of the eukaryotic enzymes on the cell surface expression(including T cells,B cells,neutrophils,monocytoes,neuronal cells and epithelial cells)are not known.Streptococcus suis serotype 2(S.suis 2,SS2)is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome(STSS)never seen before in human sufferers.We recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal S.suis 2 infection.In this study,a 2.4-angstrom structure of the SS2 enolase is solved,revealing an octameric arrangement in the crystal.We further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation assay.These results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as well.This is,to our knowledge,the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically,and the second octamer enolase structure in addition to that of Streptococcus pneumoniae.We also investigated the plasminogen binding property of the SS2 enzyme. | Qiong Lu Hao Lu Jianxun Qi Guangwen Lu George F Gao | 2012 | Protein & Cell2012,3,10: | 4 |
| 4 | An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamaseⅡfrom Erythrobacter litoralis显示文摘NDM-1(New Delhi metallo-beta-lactamase)gene encodes a metallo-beta-lactamase(MBL)with high carbapenemase activity,which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern.Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis,a marine microbial isolate.We have further expressed these two mature proteins in E.coli cells,both of which present as a monomer with a molecular mass of 25 kDa.Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline.The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance,Zn2+-bound NDM-1,adopts at least some stable tertiary structure in contrast to the metal-free protein.Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic,challenging the antimicrobial resistance monitoring. | Beiwen Zheng Shuguang Tan Jia Gao Huiming Han Jun Liu Guangwen Lu Di Liu Yong Yi Baoli Zhu George F.Gao | 2011 | Protein & Cell2011,2,3: | 2 |
| 5 | Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells显示文摘Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model.The histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein.Moreover,histones enhance cell-cell fusion.Finally,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model.These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19. | Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang Guobo Shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song Lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei | 2022 | Cellular & Molecular Immunology2022,19,5: | 2 |
| 6 | Three-dimensional electrical resistivity structure beneath the Cuonadong dome in the Northern Himalayas revealed by magnetotelluric data and its implication显示文摘The North Himalayan gneiss domes(NHGD),as one of the extensional structures widely distributed across the southern Tibetan Plateau,are an important window for studying post-collisional diastrophism and magmation as well as polymetallic mineralization.However,the deep mechanism for the formation of NHGD remains controversial.The magnetotelluric(MT)method was adopted to study the deep structure of the Cuonadong dome in the Northern Himalayas.The characteristics of the dome were explored by using the MT sounding curves and phase tensors.Three-dimensional(3D)MT inversion was performed to determine the electrical resistivity structure beneath the Cuonadong dome.The preferred 3D electrical resistivity model shows that an obvious low-resistivity anomaly develops beneath the Cuonadong dome which is overlaid by a high-resistivity body and surrounded by an apparent subcircular zone of low-resistivity anomalies.The integrated conductivity(longitudinal conductance)from depths of 1-20 km indicates that the average longitudinal conductance at the core of the Cuonadong dome is about 10,000 S.The high-conductivity anomaly at the core is found to be analogous to that of lava,mainly resulting from the crustal partial melting,and the estimated melt content is 11.0-17.3%.The high conductance surrounding the dome reaches 20,000 S on average,which is mainly attributed to saline fluids.MT results in this study support that the Cuonadong dome experienced magmatic diapirism.Taken together with previous geological and geochemical studies,we suggest that under the east-west(E-W)extensional tectonic setting in southern Tibet,deep crustal partial melting constantly accumulated beneath the dome,and therefore the magmatic diapirism resulted in the formation of the Cuonadong dome.In addition,the MT results also indicate that the development of the Cuonadong dome provides abundant mineralizing fluids and the space for migration of metallogenic fluids for(rare-metal)polymetallic mineralization. | Shuai XUE Zhanwu LU Wenhui LI Hongda LIANG Guangwen WANG Haiyan WANG Hongqiang LI Xin LI | 2022 | Science China Earth Sciences2022,65,8: | 1 |
| 7 | Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection显示文摘The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection. | Jingyun Yang Weiqi Hong Hong Lei Cai He Wenwen Lei Yanan Zhou Tingmei Zhao Aqu Alu Xuelei Ma Jiong Li Li Yang Zhenling Wang Wei Wang Guangwen Lu Guobo Shen Shuaiyao Lu Guizhen Wu Huashan Shi Xiawei Wei | 2023 | Signal Transduction and Targeted Therapy2023,8,7: | 1 |
| 8 | A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants显示文摘There are currently approximately 4000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide.Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic.Here,we described a novel self-assembling universal mRNA vaccine containing a heterologous receptorbinding domain(HRBD)-based dodecamer(HRBD^(dodecamer))against SARS-CoV-2 variants,including Alpha(B.1.1.7),Beta(B.1.351),Gamma(B.1.1.28.1),Delta(B.1.617.2)and Omicron(B.1.1.529).HRBD containing four heterologous RBD(Delta,Beta,Gamma,and Wild-type)can form a stable dodecameric conformation under T4 trimerization tag(Flodon,FD).The HRBD^(dodecamer)-encoding mRNA was then encapsulated into the newly-constructed LNPs consisting of a novel ionizable lipid(4N4T).The obtained universal mRNA vaccine(4N4T-HRBD^(dodecamer))presented higher efficiency in mRNA transfection and expression than the approved ALC-0315 LNPs,initiating potent immune protection against the immune escape of SARS-CoV-2 caused by evolutionary mutation.These findings demonstrated the first evidence that structure-based antigen design and mRNA delivery carrier optimization may facilitate the development of effective universal mRNA vaccines to tackle SARS-CoV-2 variants pandemic. | Shugang Qin Hai Huang Wen Xiao Kepan Chen Xi He Xiaoshan Tang Zhiying Huang Yupei Zhang Xing Duan Na Fan Qian Zheng Min Wu Guangwen Lu Yuquan Wei Xiawei Wei Xiangrong Song | 2023 | Acta Pharmaceutica Sinica B2023,13,10: | 1 |
| 9 | hNUDT16:a universal decapping enzyme for small nucleolar RNA and cytoplasmic mRNA显示文摘Human NUDT16(hNUDT16)is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29.As a metalloenzyme,hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m7 GDP and m227GDP from RNAs.Metal also determines substrate specificity of the enzyme.So far,only U8 small nucleolar RNA(snoRNA)has been identified as the substrate of hNUDT16 in the presence of Mg2+.Here we demonstrate that besides U8,hNUDT16 can also actively cleave the m7 GDP cap from mRNAs in the presence of Mg2+or Mn2+.We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays.In addition,our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis.Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus.These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA,demonstrating the pleiotropic decapping activity of hNUDT16. | Guangwen Lu Jie Zhang Yan Li Zhixin Li Na Zhang Xiang Xu Tingting Wang Zhenhong Guan George F.Gao Jinghua Yan | 2011 | Protein & Cell2011,2,1: | 1 |
| 10 | Structure and Cleavage Specificity of the Chymotrypsin-Like Serine Protease (3CLSP/nsp4) of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)显示文摘 | Xinsheng Tian Guangwen Lu Feng Gao Hao Peng Youjun Feng Guangpeng Ma Mark Bartlam Kegong Tian Jinghua Yan Rolf Hilgenfeld George F. Gao | 2009 | Journal of Molecular Biology2009,,4: | 1 |
| 11 | Application of active-source surface waves in urban underground space detection: A case study of Rongcheng County, Hebei, China显示文摘Active-source surface wave exploration is advantageous because it has high imaging accuracy,is not affected by high-speed layers,and has a low cost;thus,it has unique advantages for investigating shallow surface structures.For the development and utilization of urban underground space,two parameters in the shallow surface are important,namely,the shear wave velocity(V_(S))and the predominant period of the site,which determine the elevation and aseismic grade of the building design.The traditional method is mainly to obtain the two above-mentioned parameters through testing and measuring drilling samples.However,this method is extremely expensive and time consuming.Therefore,in this research,we used the multichannel surface wave acquisition method to extract the fundamental dispersion curve of single-shot data by using the phase shift method and obtain the V_(S) characteristics in the uppermost 40 m by inversion.We arrived at the following two conclusions based on the V_(S) profile.First,the study area can be roughly divided into five layers,among which the layers 0−8 m,14−20 m,and 20−30 m are low-velocity layers,corresponding to miscellaneous fill,a water-bearing sand layer,and a sand layer;therefore,the V_(S) is relatively low.In contrast,the layers at 8−14 m and 30−40 m are high-velocity layers that are mainly composed of clay,with a relatively better compactness and relatively high V_(S) values.In addition,a low-speed anomaly appears abruptly in the high-speed area at 20−40 m.This anomaly,when combined with geological data,suggests that it is an ancient river channel.Second,from the V_(S) value,the V_(Se)(equivalent shear wave velocity)was calculated.The construction site soil was categorized as class III,with good conditions for engineering geology.In addition,we calculated the predominant period of the site to be 0.56-0.77 s based on the V_(S).Therefore,in the overall structural design of the foundation engineering,the natural vibration period of the structure should be strictly controlled to avoid the predominant period of the site. | GuangWen Wang HaiYan Wang HongQiang Li ZhanWu Lu WenHui Li TaiRan Xu | 2022 | Earth and Planetary Physics2022,6,4: | 1 |
| 12 | Nanopores/Nanochannels Based on Electrical and Optical Dual Signal Response for Application in Biological Detection显示文摘Cancers and chronic diseases have always been global health problems. The occurrence and development of such diseases are closely related to the abnormalities of proteins, nucleic acids, ions or small molecules in the body. Nowadays, nanopores/nanochannels have emerged as a powerful platform for detecting these biomolecules based on the electrical signal variation caused by biomolecules passing. However, detection relied on the electrical signal easily suffered from the clogging defects, low throughput, and strong background signals. Fortunately, the emergence of designing nanopores/nanochannels based on electrical and optical dual signal response has brought innovative impetus to biological detection, which can also identify the chemical compositions and conformations of the biomolecules. In this review, we summarize the reasonable preparation of nanopores/nanochannels with electrical and optical dual signal response and their application in biological detection. According to different biomolecules, we divide the targets into four types, including nucleic acids, small molecules, ions and proteins. In each section, the design of representative examples and the principle of dual signal generation are introduced and discussed. Finally, the prospects and challenges of nanopores/nanochannels based on electrical and optical dual signal response are also discussed. | Guangwen Lu Niya Lin Zhaojun Chen Wenlian Jiang Jing-Jing Hu Fan Xia Xiaoding Lou | 2023 | Chinese Journal of Chemistry2023,41,11: | 1 |
| 13 | Crystal structure of SARS-CoV-2 nsp10/nsp162′-O-methylase and its implication on antiviral drug design显示文摘Dear Editor,The unexpected outbreak of a novel human coronavirus infection has imposed great threat to public health.Thus far,this newly-identified virus has spread to 215 countries and territories,infected more than 3.5 million people,and caused over 240,000 deaths worldwide.1 Although intensified countermeasures have been implemented globally to control the virus infection,the pandemic is still surging with a daily increase in infection case of over 65,000 ever since April 1st 2020.1 No prophylactic vaccines or clinical drugs are currently available to prevent or treat the disease,namely coronavirus disease 2019(COVID-19). | Sheng Lin Hua Chen Fei Ye Zimin Chen Fanli Yang Yue Zheng Yu Cao Jingxin Qiao Shengyong Yang Guangwen Lu | 2020 | Signal Transduction and Targeted Therapy2020,5,1: | 1 |
| 14 | In vitro Transcriptome Analysis of Two Chinese Isolates of Streptococcus suis Serotype 2显示文摘The Streptococcus suis serotype 2(S. suis 2) isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two Chinese isolates with that of a reference strain(P1/7). In the89 K genomic island that is specific to these Chinese isolates, a toxin–antitoxin system showed relatively high levels of transcription among the S. suis. The known virulence factors with high transcriptional activity in these two highly-pathogenic strains are mainly involved in adhesion, biofilm formation, hemolysis and the synthesis and transport of the outer membrane protein. Furthermore,our analysis of novel transcripts identified over 50 protein-coding genes with one of them encoding a toxin protein. We also predicted over 30 small RNAs(s RNAs) in each strain, and most of them are involved in riboswitches. We found that six s RNA candidates that are related to bacterial virulence, including csp A and rli38, are specific to Chinese isolates. These results provide insight into the factors responsible for the difference in virulence among the different S. suis 2 isolates. | Dake Zhang Nan Du Sufang Ma Qingtao Hu Guangwen Lu Wei Chen Changqing Zeng | 2014 | Genomics, Proteomics & Bioinformatics2014,12,6: | 1 |
| 15 | Intranasal administration of a recombinant RBD vaccine induces long-term immunity against Omicron-included SARS-CoV-2 variants显示文摘The outbreak of coronavirus disease 2019(COVID-19)has posed great threats to global health and economy.Several effective vaccines are available now,but additional booster immunization is required to retain or increase the immune responses owing to waning immunity and the emergency of new variant strains.The deficiency of intramuscularly delivered vaccines to induce mucosal immunity urged the development of mucosal vaccines.Here,we developed an adjuvanted intranasal RBD vaccine and monitored its long-term immunogenicity against both wild-type and mutant strains of severe acute respiratory syndrome coronavirus-2(SARSCoV-2),including Omicron variants,in mice.Three-dose intranasal immunization with this vaccine induced and maintained high levels of neutralizing IgG antibodies in the sera for at least 1 year.Strong mucosal immunity was also provoked,including mucosal secretory IgA and lung-resident memory T cells(TRM).We also demonstrated that the long-term persistence of lung TRM cells is a consequence of local T-cell proliferation,rather than T-cell migration from lymph nodes.Our data suggested that the adjuvanted intranasal RBD vaccine is a promising vaccine candidate to establish robust,long-lasting,and broad protective immunity against SARS-CoV-2 both systemically and locally. | Hong Lei Aqu Alu Jingyun Yang Wenyan Ren Cai He Tianxia Lan Xuemei He Li Yang Jiong Li Zhenling Wang Xiangrong Song Wei Wang Guangwen Lu Xiawei Wei | 2022 | Signal Transduction and Targeted Therapy2022,7,6: | 1 |
| 16 | Synthesis and Catalytic Properties of Amorphous Ni-P Alloy Hollow Microspheres显示文摘 | Xie Guangwen Lu Zhiguo Wang Zhaobo | 2008 | Catal Commun2008,9,8: | 1 |
| 17 | Cationic nanocarriers as potent adjuvants for recombinant S-RBD vaccine of SARS-CoV-2显示文摘Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.Therefore,to improve the efficacy of the vaccine and seek a novel adjuvant that can stimulate both humoral and cellular immunity,we investigated the potential of series of cationic nanocarriers as adjuvants of the recombinant S-RBD vaccine for SARS-CoV-2.As the surface charge of a nanocarrier might dramatically affect the immunogenicity of a vaccine and enhance and/or shape antigen-specific immune responses,we also used anionic nanocarriers and neutral nanocarriers as controls(Supplementary Table S1).S-RBD vaccines with adjuvant candidates were administered intranasally or intramuscularly in the present study. | Hong Lei Aqu Alu Jingyun Yang Cai He Weiqi Hong Zesheng Cheng Li Yang Jiong Li Zhenling Wang Wei Wang Guangwen Lu Xiawei Wei | 2020 | Signal Transduction and Targeted Therapy2020,5,1: | 0 |
| 18 | Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines显示文摘The ongoing global pandemic of coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),has caused devastating impacts on the public health and the global economy.Rapid viral antigenic evolution has led to the continual generation of new variants.Of special note is the recently expanding Omicron subvariants that are capable of immune evasion from most of the existing neutralizing antibodies(nAbs).This has posed new challenges for the prevention and treatment of COVID-19.Therefore,exploring broad-spectrum antiviral agents to combat the emerging variants is imperative.In sharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain(RBD),the S2 fusion subunit has remained highly conserved among variants.Hence,S2-based therapeutics may provide effective cross-protection against new SARS-CoV-2 variants.Here,we summarize the most recently developed broad-spectrum fusion inhibitors(e.g.,nAbs,peptides,proteins,and small-molecule compounds)and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2 subunit.The main focus includes all the targetable S2 elements,namely,the fusion peptide,stem helix,and heptad repeats 1 and 2(HR1-HR2)bundle.Moreover,we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-reactive fusion inhibitors,which should guide and promote future design of S2-based inhibitors and vaccines against new coronaviruses. | Liyan Guo Sheng Lin Zimin Chen Yu Cao Bin He Guangwen Lu | 2023 | Signal Transduction and Targeted Therapy2023,8,6: | 0 |
| 19 | Quality influencing factors of dispersion curves from short period dense arrays based on a convolutional neural network across the north section of the Xiaojiang fault area显示文摘The number of dispersion curves increases significantly when the scale of a short-period dense array increases.Owing to a substantial increase in data volume,it is important to quickly evaluate dispersion curve quality as well as select the available dispersion curve.Accordingly,this study quantitatively evaluated dispersion curve quality by training a convolutional neural network model for ambient noise tomography using a short-period dense array.The model can select high-quality dispersion curves that exhibit a≤10%difference between the results of manual screening and the proposed model.In addition,this study established a dispersion curve loss function by analyzing the quality of the dispersion curve and the corresponding influencing factors,thereby estimating the number of available dispersion curves for the existing observation systems.Furthermore,a Monte Carlo simulation experiment is used to illustrates the station-pair interval distance probability density function,which is independent of station number in the observational system with randomly deployed stations.The results suggested that the straight-line length should exceed 15 km to ensure that loss rate of dispersion curves remains<0.5,while maintaining the threshold ambient noise tomography accuracy within the study area. | Si Chen Rui Gao Zhanwu Lu Yao Liang Wei Cai Lifu Cao Zilong Chen Guangwen Wang | 2023 | Earthquake Science2023,36,3: | 0 |
| 20 | S19W,T27W,and N33OY mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis显示文摘SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate infection.Ecto-domain protein of ACE2 can therefore function as a decoy.Here we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually unbeneficial.The structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and Y330.While Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in compatibility.Finally,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses.Taken together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19. | Fei Ye Xi Lin Zimin Che Fanli Yang Sheng Lin Jing Yang Hua Chen Honglu Sun Lingling Wang Ao Wen Xindan Zhang Yushan Dai Yu Cao Jingyun Yang Guobo Shen Li Yang Jiong Li Zhenling Wang Wei Wang Xiawei Wei Guangwen Lu | 2021 | Signal Transduction and Targeted Therapy2021,6,10: | 0 |