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| 1 | Status and challenges of global antimicrobial resistance control: A dialogue between Professors Yonghong Xiao and Takeshi Nishijima显示文摘Antimicrobial resistance(AMR)is one of the top 10 public health threats,which is not only related to human health,but also closely related to animal health and environmental health.One health concept and framework are the core strategy to contain AMR.The World Health Organization(WHO)has already issued the Global Action Plan to contain AMR,which includes surveillance,education,stewardship,and innovation of new diagnostics and therapeutics.Western Asia–Pacific region is the most populous area of WHO,and also a region with severe AMR.Here,Dr.Nishijima,a professional officer of AMR control from WHO Regional Office for the Western Pacific discussed with Professor Yonghong Xiao(Zhejiang University)about the epidemiology,socioeconomic impact of AMR globally and in Western Asia–Pacific region(WPRO),and they talked the actions and strategies,achievements and shortcomings in the control of AMR during the past years,introduced the initiative of quadripartite One Health.The outstanding results of China in AMR containment were recognized. | Yonghong Xiao Takeshi Nishijima | 2024 | hLife2024，2，2： | 0 |
| 2 | Mucosal vaccine development for respiratory viral infections显示文摘Mucosal vaccines have risen to prominence in the corona virus disease 2019(COVID-19)pandemic due to their ability to elicit both local antibody and tissue-resident T cell responses,affording a dual-layered defense against infection and transmission at respiratory entry sites.While intramuscular vaccines predominantly focus on systemic immunity,mucosal vaccines offer a more nuanced,site-specific approach.However,the field faces a dearth of mucosal vaccine options for respiratory diseases,starkly contrasting to the extensive array of well-characterized injectable vaccines.The unique features of mucosal surfaces necessitate specialized adjuvants and delivery systems,adding complexity to adapting injectable vaccine technologies for mucosal applications.Here,we review the recent insights into the specificities of respiratory mucosal immunology that provide a foundation for future innovations besides the emerging vaccine platforms,newly discovered adjuvants,and vaccine delivery systems,which may open promising avenues for developing mucosal vaccines targeting respiratory pathogens. | Yifan Lin Zhenxiang Hu Yang-Xin Fu Hua Peng | 2024 | hLife2024，2，2： | 0 |
| 3 | Insights into varicella-zoster virus assembly from the B-and C-capsid at near-atomic resolution structures显示文摘Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen. | Lei Cao Nan Wang Zhe Lv Wenyuan Chen Zhonghao Chen Lifei Song Xueyan Sha Guiqiang Wang Yaling Hu Xiaojun Lian Guoliang Cui Jinyan Fan Yaru Quan Hongrong Liu Hai Hou Xiangxi Wang | 2024 | hLife2024，2，2： | 0 |
| 4 | Lycorine derivative effectively inhibits the replication of coronaviruses both in vitro and in vivo显示文摘The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs. | Liang Shen Jianzhong Zhao Ying Xia Junjie Lu Jiali Sun Jian Tang Hui Xing Lijuan Yin Yang Yang Chunhua Wang | 2024 | hLife2024，2，2： | 0 |
| 5 | Quantitative interactomic of CD40 in primary B cells显示文摘INTRODUCTION Over the past few decades,antibody-based therapies have emerged as an additional tool to treat patients developing cancer and auto-immune diseases.The natural properties of the developed antibodies may lead to agonist or blocking functions for the targeted molecule.Thus,antibodies developed for clinical trials are extensively analyzed in vitro and in vivo for safety and efficacy,yet they are not routinely evaluated for their potential signaling effectiveness. | Jeremy Argenty Emilie Maturin Mylene Camus Valentin Mellado Jeanne Perroteau Benoit Pasquier Guillaume Voisinne Odile Burlet-Schiltz Lih-Ling Lin Anne Gonzalez de Peredo Romain Roncagalli Bernard Malissen | 2024 | hLife2024，2，2： | 0 |
| 6 | Getting ready for the next inforuses显示文摘With the end of Corona Virus Disease 2019(COVID-19)as a global health emergency in May 2023[1],experts can now meet face-to-face to discuss what people were saying and doing behind the keyboards during our first global‘paninfodemic’,the term used to describe the abundance of information[2],helpful or dangerous,during a disease outbreak. | AndréCosta Lobato | 2024 | hLife2024，2，2： | 0 |
| 7 | Medicine has no borders,health unites us all:Henry Norman Bethune as a pioneer,medical scientist,and internationalist显示文摘BE A BENEVOLENT BEING,BE A GREAT ARMY DOCTORHenry Norman Bethune was a fighter and a pioneering medicalexpert with excellent medical skills.He was a member of theCanadian Communist Party,a great internationalist,and an internationally renowned thoracic surgeon(Figure 1). | Huan Liu Xue Gong Zhaoqi Liu Kunlan Zuo Hao Cheng | 2024 | hLife2024，2，3： | 0 |
| 8 | Phenazines:Natural products for microbial growth control显示文摘The unprecedented problem of antibiotic resistance has become a major challenge for public health,which has contributed to an increase in infections caused by such bacteria.These microbial infections,typically biofilm-related,are alsocoupled to an increase in human mortality and morbidity.However,the demand for new antimicrobial agents hasincreased along with the evolution of microbial resistance mechanisms.Natural products produced by bacteria,such as phenazines,have been recognized as an important source for the development of new antimicrobial agents,through the exploitation of their capacity to increase oxidative stress in other organisms.Phenazines are a large groupof nitrogen-containing heterocyclic compounds and are essential for several cellular processes including iron acquisition,signaling events,enzymatic processes,and biofilm formation.Phenazine-inspired antibiotics(i.e.,2-bromo-1-hydroxyphenazine,2,4-dibromo-1-hydroxyphenazine,bromophenazine-21,phenazine-13,and phenazine-14)are veryactive against a wide range of gram-positive and gram-negative bacteria,including those associated with severe infections.In this study,mechanisms of phenazine-inspired antibiotics in the cellular processes of planktonic and sessilebacteria are reviewed.Moreover,the application of phenazine-inspired antibiotics for the eradication of multidrugresistant planktonic and biofilm bacterial infections is also reviewed. | Cátia A Sousa Marta Ribeiro Francisca Vale Manuel Simões | 2024 | hLife2024，2，3： | 0 |
| 9 | Safety,immunogenicity,and preliminary efficacy of a randomized clinical trial ofomicron XBB.1.5-containing bivalent mRNA vaccine显示文摘Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns. | Xuanjing Yu Wei Yang Wei Li Na Wan Guanghong Yan Zumi Zhou Xiao Zhu Wei Su Yani Li Chenyu Xing Sifan Duan Houze Yu Xinshuai Zhao Chunmei Li Taicheng Zhou Dingyun You Jia Wei Zijie Zhang | 2024 | hLife2024，2，3： | 0 |
| 10 | A human monoclonal antibody neutralizes SARS-CoV-2 Omicron variants bytargeting the upstream region of spikeprotein HR2 motif显示文摘The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019(COVID-19).Neutralizing monoclonal antibody(mAb)that binds to theconserved S2 subunit of the SARS-CoV-2 spike(S)protein alone,or in combination with mAb that binds to the receptor-binding domain(RBD)of S protein,might be effective in eliciting protection from infection by a variety of SARS-CoV2 variants.Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors,we identified a high-affinity S2-specific mAb-39,that could inhibit original SARS-CoV-2 strain,Omicron BA.1,BA.2.86,BA.4,BA.5,and EG.5.1 S protein-mediated membrane fusion,leading to the neutralization of these pseudoviralinfections.Moreover,mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highlyneutralization-resistant Omicron variants.Molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2(HR2)motif of the S2 subunit.Collectively,these findings demonstrate that targeting the conserved upstream region of the HR2 motif(e.g.,using mAbs)provides anovel strategy for preventing the infection of SARS-CoV-2 and its variants. | Hang Su Jun Zhang Zhenfei Yi Sajid Khan Mian Peng Liang Ye Alan Bao Han Zhang Guangli Suo Qian Li Housheng Zheng Dandan Wu Thomas J.Kipps Lanfeng Wang Zhenghong Lin Suping Zhang | 2024 | hLife2024，2，3： | 0 |
| 11 | hLife:Linking basic research and clinical applications显示文摘Scientific journals are platforms for communication between authors and readers,and also among readers and the wider public.To promote health science and related medical science fields,we are pleased to announce the launch of a transdisciplinary journal named hLife,which combines the ideas of a healthier,happier and harmonious life together.hLife is a peer-reviewed,open-access monthly journal published online,sponsored by the Institute of Microbiology,Chinese Academy of Sciences,in cooperation with the Chinese Society of Biotechnology and the Shanghai Immune Therapy Institute.The editorial board consists of around 60 scientists from 12 countries or regions worldwide,among them two Nobel Laureates.Now,hLife is one of the“high starting point journals”of the Chinese Action Plan for Journal Excellence. | George Fu Gao Chen Dong Jules A Hoffmann | 2023 | hLife2023，1，1： | 0 |
| 12 | The structure of HSV-1 gB bound to a potent neutralizing antibody reveals a conservative antigenic domain across herpesviruses显示文摘Human herpesviruses(HHV),including the alpha,beta,andgamma subfamilies,are enveloped viruses with broad prevalence,establishing life-time latent infections and inducing a variety of diseases[1].Among them,herpes simplex virus(HSV),consists of two HSV-1 and HSV-2 variants,ubiquitouslyaffecting global populations[2].As an enveloped virus,HSV features a repertoire of glycoproteins such as glycoproteins D(gD),glycoproteins H(gH),glycoproteins L(gL),and glycoproteins B(gB),to orchestrate host cell recognition and infection[3,4]. | Cong Sun Jia-Wen Yang Chu Xie Xin-Yan Fang Guo-Long Bu Ge-Xin Zhao Dan-Ling Dai Zheng Liu Mu-Sheng Zeng | 2024 | hLife2024，2，3： | 0 |
| 13 | The discovery of T–B cell lineages:An interview with Professor Max D Cooper显示文摘In the early 1960s,despite a general understanding of antibodies and immunoglobulins,their source and their relationship with anti-infection immunity remained largely enigmatic.However,this changed with the groundbreaking discoveries of Dr.Max D Cooper,professor at Emory University School of Medicine.In the 1960s,Dr.Max D Cooper discovered the existence of two different lymphoid lineages,B and T cells,which are now widely recognized as the cornerstone components of the adaptive immune system.B and T cells are responsible for humoral and cellular immunity,respectively.This discovery served as the foundation of modern immunology.Here,Dr.Max D Cooper shares his inspiring journey,from career choice to research experiences,as well as offering sage advice to aspiring immunologists. | Chen Dong Max D Cooper | 2023 | hLife2023，1，1： | 0 |
| 14 | Fecal microbiota transplantation:A new strategy to delay aging显示文摘The gut microbiota,the community of gut microorganisms that inhabit the gastrointestinal tract,plays a crucial role in modulating host immunity,metabolism,and neurological health,thereby influencing the entire organism.Aging is associated with changes in gut microbiota composition and functionality,often resulting in dysbiosis,an imbalance of gut microbiota and an aging hallmark.Recent studies have suggested that fecal microbiota transplantation(FMT),the transfer of fecal material containing beneficial microbes from a healthy donor to a recipient with a disturbed microbiota,may restore the balance of host gut microbiota and ameliorate some aging-associated impairments in diverse organs.In particular,FMT from young donors has shown more beneficial effects than FMT from aged donors.In this paper,we review recent advances in FMT for its effects on aging and discuss the potential mechanisms and challenges of this novel intervention,highlighting its potential to improve health outcomes in the aging population. | Haoteng Yan Jie Ren Guang-Hui Liu | 2023 | hLife2023，1，1： | 0 |
| 15 | A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites IV and V of the viral fusion glycoprotein显示文摘Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation. | Lianpan Dai Jian Song Lili Xu Zhao Gao Senyu Xu Yan Chai Liang Wang Mi Yang Tong Ma Qihui Wang Sushan Cao Junming Yie Gang Zou Zhengde Xie Jim Zhen Wu George Fu Gao | 2023 | hLife2023，1，1： | 0 |
| 16 | Distinctive serotypes of SARS-related coronaviruses defined by convalescent sera from unvaccinated individuals显示文摘Multiple Omicron sub-lineages have emerged,with Omicron XBB and XBB.1.5 subvariants becoming the dominant variants globally at the time of this study.The key feature of new variants is their ability to escape humoral immunity despite the fact that there are limited genetic changes from their preceding variants.This raises the question of whether Omicron should be regarded as a separate serotype from viruses serologically clustered with the ancestral severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.Here,we present cross-neutralization data based on a pseudovirus neutralization test using convalescent sera from naïve individuals who had recovered from primary infection by SARS-CoV-1 and SARS-CoV-2 strains/variants including the ancestral virus and variants Beta,Delta,Omicron BA.1,Omicron BA.2 and Omicron BA.5.The results revealed no significant cross-neutralization in any of the three-way testing for SARS-CoV-1,ancestral SARS-CoV-2 and SARS-CoV-2 Omicron subvariants.The data argue for the assignment of three distinct serotypes for the currently known human-infecting SARS-related coronaviruses. | Chee Wah Tan Feng Zhu Wan Ni Chia #Barnaby EYoung Aileen Ying Yan Yeoh Thomas Althaus Chee Fu Yung Wee Chee Yap Beng Lee Lim Mark I-C Chen Jinyan Zhang Yun Yan Mah Eric Voiglio Alex Sigal Jianxin Huo Shengli Xu Yee Joo Tan Kong-Peng Lam David Lye Lin-Fa Wang | 2023 | hLife2023，1，1： | 0 |
| 17 | Mouse model for pangolin-origin coronavirus GX/P2V/2017 infection and cross-protection from COVID-19 ZF2001 subunit vaccine显示文摘Many severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)–related coronaviruses have been discovered,constituting potential threats to human health.However,it remains unclear whether the currently available vaccines are effective against these coronaviruses.Here,we constructed a wild-type mouse model to evaluate pathogenicity of the SARS-CoV-2-related pangolin coronavirus GX/P2V/2017 and neutralization efficacy of the approved tandemrepeat SARS-CoV-2 spike receptor-binding domain(RBD)vaccine ZF2001.We found that ZF2001-induced cross-reactive and cross-neutralizing antibodies against GX/P2V/2017,and the vaccination alleviated the pathological lung damage caused by GX/P2V/2017 in mice.These results indicate that RBD may work as a promising candidate for pan-coronavirus vaccine development. | Xiao Qu Yunfei Jia Na Jia Huahao Fan Anqi Zheng Luoyuan Xia Zhenfei Wang Di Tian Sheng Niu Yu Hu Wenxia Tian Zhihai Chen Yigang Tong Yuwei Gao Wuchun Cao Qihui Wang George Fu Gao | 2023 | hLife2023，1，1： | 0 |
| 18 | Emergence of hypervirulent Pseudomonas aeruginosa pathotypically armed with co-expressed T3SS effectors ExoS and ExoU显示文摘Pseudomonas aeruginosa is a significant pathogen mainly causing healthcare-associated infections(HAIs).Newly emerging high-risk clones of P.aeruginosa with elevated virulence profiles furtherly cause severe community-acquired infections(CAIs).Usually,it is not common for P.aeruginosa to co-carry exoU and exoS genes,encoding two type III secretion system(T3SS)effectors.The pathogenicity mechanism of exoS+/exoU+strains of P.aeruginosa remains unclear.Here,we provide detailed evidence for a subset of hypervirulent P.aeruginosa strains,which abundantly co-express and secrete the T3SS effectors ExoS and ExoU.The exoS+/exoU+P.aeruginosa strains were available to cause both HAIs and CAIs.The CAI-associated strains could elicit severe inflammation and hemorrhage,leading to higher death rates in a murine acute pneumonia model,and had great virulence potential in establishing chronic infections,demonstrating hypervirulence when compared to PAO1(exoS+/exoU-)and PA14(exoS-/exoU+).Both ExoS and ExoU were co-expressed and co-secreted in abundance in exoS+/exoU+strains.Their abundant protein secretion could boost exoS+/exoU+strains’potentials for cytotoxicity in vitro and pathogenicity in vivo.Genomic evidence indicates that exoU acquisition is likely mediated by horizontal gene transfer(HGT)of the pathogenicity island PAPI-2,while deletion of exoU was sufficient to mitigate virulence in the exoS+/exoU+strains.Furthermore,bioinformatics analysis showed that such exoS+/exoU+P.aeruginosa strains turned out to be widely distributed across the globe.Overall,the research provide detailed evidence for the high virulence and epidemicity of exoS+/exoU+strains of P.aeruginosa,highlighting an urgent need for surveillance against these high-risk hypervirulent strains. | Yuqin Song Yongqi Mu Nai-Kei Wong Zhuo Yue Juan Li Min Yuan Xiong Zhu Jinshu Hu Gang Zhang Dawei Wei Chao Wang Weihui Wu Fang Bai Jie Feng | 2023 | hLife2023，1，1： | 0 |
| 19 | T cell cross-reactivity in autoimmune-like hepatitis triggered by COVID-19显示文摘Over 1000 cases of pediatric hepatitis of unknown etiology have been reported worldwide since the first case was reported in the UK.To date,the etiology of pediatric hepatitis remains unknown and controversial.Adenovirus was first suspected to be the cause as it was present in the blood samples of the majority of cases.Partial cases have also been tested positive for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].However,it is still unclear how these viruses contribute to pediatric hepatitis.In the case of a pediatric patient with SARS-CoV-2 infection,the liver biopsy showed acute submassive hepatocyte necrosis,accompanied by a significant increase in T cell infiltration[2].Furthermore,CD8+T cell dominant hepatitis induced by coronavirus disease 2019(COVID-19)vaccination has also been recently reported[3].Although it is known that T cell receptors(TCRs)can discriminate between self-and non-self-antigens,it is now well-accepted that TCRs exhibit cross-reactivity toward similar and even distinct antigen peptides[4].Thus,we hypothesized that following SARS-CoV-2 infection or vaccination,T cells carrying TCRs that recognize self-antigens undergo clonal expansion,which could eventually result in the onset of autoimmune-like hepatitis(Figure 1A). | Yisu Liu Yuqian Wang Zhiqiang Peng Guideng Li Jianwei Wang | 2023 | hLife2023，1，1： | 0 |
| 20 | George Fu Gao,Professor Jules A Hoffmann,Professor Chris Walzer and Professor Jiahai Lu显示文摘Four heavyweight guests in the field of public health gathered together.No-bel Laureate Jules A Hoffmann,Academician George Fu Gao,Professor Chris Walzer and Professor Jiahai Lu discussed how to deal with global public health crises,such as the recent coronavirus disease 2019(COVID-19)pandemic,as well as the role of international organizations.The concept of“One Health”emerged as the latest approach to disease prevention and control.This concept emphasizes the intertwined health of humans,animals and the environment.The experts shared their thoughts and insights on how humanity can address emerging global public health crises through international cooperation. | George Fu Gao Jules A Hoffmann Chris Walzer Jiahai Lu | 2023 | hLife2023，1，2： | 0 |
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