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| 1 | Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies显示文摘Neutralizing monoclonal antibodies(nAbs)to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represent promising candidates for clinical intervention against coronavirus disease 2019(COVID-19).We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain(RBD)of the viral spike(S)protein and the receptor angiotensin converting enzyme 2(ACE2).However,the structural basis for their potent neutralizing activity remains unclear.Here,we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2.The bivalent binding of the full-length IgG is found to associate with more RBDs in the“up”conformation than the monovalent binding of Fab,perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein.Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities.This work provides a structural basis for further understanding the mechanism of nAbs,especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit. | Renhong Yan Ruoke Wang Bin Ju Jinfang Yu Yuanyuan Zhang Nan Liu Jia Wang Qi Zhang Peng Chen Bing Zhou Yaning Li Yaping Shen Shuyuan Zhang Long Tian Yingying Guo Lu Xia Xinyue Zhong Lin Cheng Xiangyang Ge Juanjuan Zhao Hong-Wei Wang Xinquan Wang Zheng Zhang Linqi Zhang Qiang Zhou | 2021 | Cell Research2021，31，5： | 4 |
| 2 | A cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans显示文摘Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle control generally determines their life cycles, either in the environment or during infections.Thus, cell cycle components can potentially serve as important targets for the development of antifungal strategy against fungal infections. Here, in Cryptococcus neoformans, the most common cause of fatal fungal meningitis, we show that a previously uncharacterized B-type cyclin named Cbc1 is essential for both its infectious and sexual cycles. We reveal that Cbc1 coordinates various sexual differentiation and molecular processes, including meiosis. Especially, the absence of Cbc1 abolishes formation of sexual spores in C. neoformans, which are presumed infectious particles. Cbc1 is also required for the major Cryptococcus pathogenic attributes. Virulence assessment using the murine model of cryptococcosis revealed that the cbc1 mutant is avirulent.Together, our results provide an important insight into how C. neoformans employs shared cell cycle regulation to coordinate its infectious and sexual cycles, which are considered crucial for virulence evolution and the production of infectious spores. | Pengjie Hu Linxia Liu Weixin Ke Xiuyun Tian Linqi Wang | 2021 | Science China(Life Sciences)2021，64，8： | 1 |
| 3 | Recent advances and future challenges in the use of nanoparticles for the dispersal of infectious biofilms显示文摘Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation.We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy.Deoxyribonuclease(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal.Also,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as dispersants.On their own,dispersants do not inhibit bacterial growth or kill bacterial pathogens.Both natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like p H-responsive micelles,liposomes or hydrogels.Depending on their composition,nanoparticles can also possess intrinsic dispersant properties.Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells.However,this sudden increase in bacterial concentration can also cause sepsis.Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat.Importantly,biofilm remaining after dispersant administration appears more susceptible to existing antibiotics.Being part of the natural biofilm life-cycle,no signs of'dispersant-resistance'have been observed.Dispersants are therewith promising for the control of infectious biofilms. | Shuang Tian Henny C.van der Mei Yijin Ren Henk J.Busscher Linqi Shi | 2021 | Journal of Materials Science & Technology2021，，25： | 1 |
| 4 | Contribution of human alpha-defensin 1,2 and 3 to the anti-HIV-1 activity of CD8 antiviral factor显示文摘 | Zhang Linqi Tu Wenjie He Tian | 2002 | Science2002，298，5595： | 1 |
| 5 | In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms显示文摘Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections. | Guang Yang Da-Yuan Wang Yong Liu Fan Huang Shuang Tian Yijin Ren Jianfeng Liu Yingli An Henny C.van der Mei Henk J.Busscher Linqi Shi | 2022 | Bioactive Materials2022，7，8： | 0 |
| 6 | Effects of previous drying of sediment on root functional traits and rhizoperformance of emerged macrophytes显示文摘Purpose of the current study was to investigate the effects of constantly wet and dried-rewetted sediments on root functional traits of emerged macrophytes and their nutrients removal abilities.It is based on the hypothesis that root characteristics and nutrients removal abilities of plants will be altered in the course of sediment desiccation.Four emerged macrophytes including two fibrous-root plants(Canna indica and Acorus calamus)and two thick-root plants(Alocasia cucullata and Aglaonema commutatum)were investigated for their root functional traits and rhizoperformance in both wet and dried-rewetted sediments.Results showed that sediment desiccation followed by rewetting substantially altered the root functional traits(root surface area,radial oxygen loss,and root activity)of plants due to adverse changes in morphological characteristics(porosity,bulk density,particle density)of dried-rewetted sediments than by wet sediments.Consequently,limited plants growth and removal of nitrogen(N),phosphorus(P)and dissolved organic carbon(DOC)were recorded in driedrewetted sediments and their pore water than in wet sediments.Radial oxygen loss from plant roots correlated positively with root functional traits,plants growth,and removal of N,P and DOC from pore water and sediment in both sediment types.Among the macrophyte species,the fibrous-root plants having advantages root functional traits,greatly influenced the rhizospheric conditions(pH,dissolved oxygen and redox potential),and demonstrated higher N,P and DOC reduction from both sediment types.While,the thick-rooted plants with thick diameter roots(D>1 mm)and higher rhizome exhibited longer life-span in both sediment types. | Farasat Ali Ghulam Jilani Leilei Bai Chunliu Wang Linqi Tian Helong Jiang | 2021 | Frontiers of Environmental Science & Engineering2021，15，6： | 0 |
| 7 | A forkhead transcription factor contributes to the regulatory differences of pathogenicity in closely related fungal pathogens显示文摘Cryptococcus neoformans and its sister species Cryptococcus deuterogattii are important human fungal pathogens.Despite their phylogenetically close relationship,these two Cryptococcus pathogens are greatly different in their clinical characteristics.However,the determinants underlying the regulatory differences of their pathogenicity remain largely unknown.Here,we show that the forkhead transcription factor Hcm1 promotes infection in C.neoformans but not in C.deuterogattii.Monitoring in vitro and in vivo fitness outcomes of multiple clinical isolates from the two pathogens indicates that Hcm1 mediates pathogenicity in C.neoformans through its key involvement in oxidative stress defense.By comparison,Hcm1 is not critical for antioxidation in C.deuterogattii.Furthermore,we identified SRX1,which encodes the antioxidant sulfiredoxin,as a conserved target of Hcm1 in two Cryptococcus pathogens.Like HCM1,SRX1 had a greater role in antioxidation in C.neoformans than in C.deuterogattii.Significantly,overexpression of SRX1 can largely rescue the defective pathogenicity caused by the absence of Hcm1 in C.neoformans.Conversely,Srx1 is dispensable for virulence in C.deuterogattii.Overall,our findings demonstrate that the difference in the contribution of the antioxidant sulfiredoxin to oxidative stress defense underlies the Hcm1-mediated regulatory differences of pathogenicity in two closely related pathogens. | Weixin Ke Yuyan Xie Yue Hu Hao Ding Xin Fan Jingjing Huang Xiuyun Tian Baokun Zhang Yingchun Xu Xiao Liu Ying Yang Linqi Wang | 2022 | mLife2022，1，1： | 0 |
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