Clinically critical antibiotic-resistant Salmonella enterica (S. enterica) causing bloodstream infections remains a public health challenge. Here, we aim to reveal the emergence and trends of clinically important antibiotic resistance in S. enterica causing bloodstream infections using 833 isolates from six Chinese provincial-level administrative areas during 1994-2023. We identified 48 serovars and 64 sequence types (STs). Overall, 8.52% of 833 isolates were resistant or had decreased susceptibility to ciprofloxacin, 4.32% and 6.84% reported resistance or decreased susceptibility to third- and fourth-generation cephalosporins (3GCs and 4GCs), 1.80% reported resistance to fosfomycin, and 2.16% reported resistance to azithromycin. Across these six regions, azithromycin and fosfomycin resistance is increasing, as is decreased susceptibility or resistance to ciprofloxacin, 3GCs, and 4GCs, especially among younger children and elderly people. Clinically prioritized antibiotic resistance also varies by region, serovar, and age group. S. Paratyphi A genotype 2.3.3 strains are mainly divided into 2 lineages distributed in Guangxi and Shanghai. Within the scope of this passive surveillance dataset, S. Typhi genotype 4.3.1.2.1 was identified as the earliest documented case among the collected isolates. Our retrospective and longitudinal genomic epidemiology study provides critical data for the formulation of treatment guidelines and policies for bloodstream infections and for the monitoring and control of antimicrobial resistance.

Antimicrobial resistance (AMR) in invasive Salmonella infections remains a global public health concern, and enhanced high-quality genomic surveillance is essential to inform guidelines and policies. Here, we aimed to describe clinically key antibiotic resistance trends in invasive Salmonella infections using 7691 isolates derived from national surveillance and publicly available datasets between 1954 and 2024. 29 (37.7%) of 77 countries identified at least one isolate with resistance or decreased susceptibility to ciprofloxacin, 25 (32.5%) and 29 (37.7%) countries resistance or decreased susceptibility to ceftriaxone and cefixime, 8 (10.4%) countries resistance to azithromycin, 15 (19.5%) countries resistance to fosfomycin, 10 (13.0%) countries resistance to colistin. Overall, 7.39% of 7691 isolates were resistant or decreased susceptibility to ciprofloxacin, 7.91% reported resistance or decreased susceptibility to 3GCs, 4.23% reported resistance to fosfomycin, and 0.79% reported resistance to azithromycin. Globally, azithromycin resistance is increasing, as is resistance or decreased susceptibility to ciprofloxacin, 3GCs, and 4GCs. However, surveillance levels remain inadequate in African and South American regions. We generated a global map of clinically key antibiotic resistance genes in invasive Salmonella infections worldwide. This retrospective, global, longitudinal genomic epidemiology study on invasive Salmonella provides evidence-based data for clinical guidelines, genomic surveillance, AMR control, and public health policies. Antimicrobial resistance in invasive Salmonella is an escalating global health threat, yet its global trends and genomic evidence remain poorly understood. Wang and Xu et al. use a state-of-the-art pipeline integrating global genomics to reveal emergence and spatiotemporal patterns of WHO priority antibiotic resistance in invasive Salmonella.

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD-ACE2 complex, play key roles in virus-receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Respiratory diseases pose a significant threat to the health and lives of people. Although current vaccines targeting the respiratory pathogens can decrease disease severity, they mostly fail to effectively prevent infections and transmissions. Clearly identifying the clinical issues related to respiratory diseases, analyzing the important scientific questions surrounding airway mucosal immunity, and developing vaccines and therapeutic interventions based on the regulation of mucosal immune responses are key to addressing the issues of respiratory diseases. Here, we summarize the clinical pathological features of respiratory diseases and their relationship with pulmonary mucosal immunity. We also outline the immune response processes of respiratory mucosa represented by the pulmonary mucosa. On this basis, we reveiw the AI-based design strategies and mucosal delivery techniques for the respiratory diseases. We hope to summarize important clinical, fundamental, and technical issues in the research of respiratory mucosal immunity, thereby facilitating the exploration of new approaches for disease prevention and treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause significant morbidity and mortality despite the end of its pandemic phase. The emergence of highly mutated SARS-CoV-2 variants of concern highlights the requirement of broad-spectrum antiviral countermeasures which possess both prophylactic and therapeutic efficacies. Here, we obtain a macrocyclic peptide, 6L3-3P11K, that effectively inhibits a wide range of SARS-CoV-2 variants and subvariants. Structural studies show that 6L3-3P11K forms homotrimers that lock the spike protein (S) trimer into a “closed” conformation by engaging a conserved non-receptor binding motif (non-RBM) of S. This interaction disrupts the binding between S and ACE2 receptor. Structure-guided modifications result in a thermostable and trypsin-resistant macrocyclic peptide, 6L3-1F3P11hR, that exhibits prophylactic and therapeutic effects against SARS-CoV-2 infection in a male hACE2 transgenic mouse model after intranasal administration. Our results provide a drug candidate for the control and prevention of COVID-19 and may stimulate further research on macrocyclic broad-spectrum anti-coronavirus drug development. Newly emerging SARS-CoV-2 variants underscore the need for broad-spectrum antiviral solutions. This study shows a macrocyclic peptide inhibitor that locks the SARS-CoV-2 spike trimer into a “closed” conformation by engaging a conserved region, and demonstrates that intranasal administration of the peptide inhibitor protects against Omicron variants.

Onychomadesis, characterized by proximal detachment of the nail plate due to temporary arrest of matrix proliferation, has been increasingly recognized as a complication following viral infections. Enterovirus-associated hand-foot-and-mouth disease (HFMD) is the most frequently reported cause. Recent studies demonstrate that some enteroviruses, including Coxsackievirus A10, utilize the host receptor KREMEN1 (KRM1) to impair Wnt/β-catenin signaling and suppress nail stem cell differentiation, thereby providing a molecular basis for infection-induced nail shedding. Additionally, cases of onychomadesis linked to other viral infections, including KRM1-independent enteroviruses, influenza virus, SARS-CoV-2, varicella-zoster virus, and co-infections involving HIV and mpox, have also been documented. Despite growing recognition of the virus-induced onychomadesis, in most cases the exact pathogeneses are yet elusive, thereof lack of approved treatments.Understanding the molecular mechanisms of onychomadesis and other sequelae can enhance diagnostics and therapies, guiding future drug development for virus-induced nail disorders and related complications. A comprehensive literature search was conducted using PubMed up to Dec 2025, including the search terms: onychomadesis, Beau's line, infection or virus, and follow-up. This review aims to explore the molecular pathophysiology of virus-induced onychomadesis and to examine the underlying molecular mechanisms, including the roles of viral receptors and signaling pathways in nail stem cell differentiation. It scrutinizes the currently available literatures of link between viral infections, particularly HFMD, and onychomadesis, focusing on the molecular mechanisms involved, and explores potential therapeutic insights.

This dialogue explores the transformative potential of spatiotemporal omics in reshaping the future of infectious disease research. Experts Zhihua Ou, Ziqing Deng, George Fu Gao, Andrea Cossarizza, Wenhong Zhang, and Aldo Tagliabue discussed the integration of multi-omics technologies to obtain high-resolution, dynamic, and spatiotemporal insights into disease pathogenesis. The conversation highlighted the key technical barriers that must be addressed for the broad application of spatiotemporal omics. Strategic research priorities were outlined, with a focus on diseases with high global burden and an emphasis on a u201COne Healthu201D framework. The dialogue underscored the need to prioritize omics technologies based on specific biological questions and clinical goals. Major challenges in translating basic discoveries into clinical applications, such as data standardization, interdisciplinary collaboration, and ethical considerations, were also examined. Finally, the experts proposed strategies for the newly established SpatioTemporal Omics Consortium (STOC) Infection Working Group to foster international collaboration through cultivating a shared vision, developing interoperable platforms, and securing sustainable funding to effectively integrate global scientific talent and resources for substantive innovations.

Multivalent nanoparticle vaccines elicit potent T cell-dependent (TD) antibody responses, yet how they initiate CD4+ T cell help remains unclear. Here, we show that antigen-specific B cells function as antigen-presenting cells (APCs) for CD4+ T cell priming across distinct nanoparticle platforms, including AP205 and ferritin. Using SARS-CoV-2 RBD and mpox virus A35 antigens, we demonstrate that B cells and dendritic cells (DCs) act redundantly to initiate early CD4+ T cell activation. In hosts lacking MHC class II expression on non-B cells, B cells alone were sufficient to drive naive CD4+ T cell proliferation. Moreover, B cell-mediated antigen presentation was required for inducing TD responses beyond the draining lymph nodes. These findings reveal a general mechanism by which multivalent nanoparticles engage B cells as APCs and highlight a potential strategy to enhance vaccine-induced immunity.

Abstract Clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) continue to circulate worldwide, posing zoonotic threats, especially with recent cattle outbreaks. The mechanisms by which these viruses adapt to mammalian hosts while maintaining a broad avian tropism remain poorly understood. Here, we demonstrate that two naturally occurring mutations (K222Q and S227R) in the hemagglutinin (HA) of a human-infecting H5N8 strain, first identified in 2020, enhance binding affinity for both α2-6-linked and Sialyl Lewis X (SLe X ) glycans, which may underlie the broad tissue binding and cross-species potential. Structural analyses reveal that these mutations expand receptor specificity for these glycans, which are abundant in the human respiratory tract and duck trachea, providing a possible molecular basis for cross-species transmission. Our findings suggest that clade 2.3.4.4b H5Ny viruses evolved dual receptor specificity as early as the 2020 Russian H5N8 strain, potentially contributing to sporadic human infections and widespread dissemination among birds and mammals.

Plant-based biomanufacturing is emerging as a promising alternative in biopharmaceutical production, providing distinct advantages in biosafety, rapid scalability, and cost efficiency. Unlike mammalian cell systems, plant bioreactors eliminate the risk of human pathogen contamination and can be cultivated under simple, low-cost conditions using light, water, and basic nutrients. Compared to prokaryotic systems, plant bioreactors maintain essential post-translational modifications, with certain plant-derived glycosylation patterns even exhibiting intrinsic adjuvant properties. The development of highly efficient transient expression systems, particularly those mediated by Agrobacterium tumefaciens, has further accelerated the use of plant-based production. These systems enable recombinant protein expression within days instead of months, making them especially suitable for rapid response to emerging infectious diseases or other public health emergencies. Plant hosts provide significant flexibility, encompassing a wide range of species from model organisms, such as tobacco and Arabidopsis to crops, such as rice and maize. Furthermore, diverse cultivation formats are available, including whole plants, hairy roots, callus cultures, and suspension cell systems. This dual diversity in both species and cultivation approaches provides customizable solutions tailored to different product types and production scales. Several commercial and clinical-stage products reveal the practical viability of plant molecular farming. Notable examples include the tobacco-derived virus-like particle (VLP) coronavirus of 2019 (COVID-19) vaccine, a carrot cell-based recombinant enzyme for the treatment of Gaucher disease, and rice endosperm-produced recombinant human serum albumin. These cases show the applicability of plant systems across multiple therapeutic categories, from prophylactic vaccines to replacement enzymes and plasma protein substitutes. Despite these advances, several technical and regulatory difficulties persist. Protein expression levels in plants are often limited by large cell sizes and low cell densities per culture volume. Correct folding and assembly of complex proteins remain challenging, and downstream purification is complicated by the release of host cell proteins and secondary metabolites during extraction, a process that can account for up to 90% of total production costs. Immunogenic plant-specific glycans may require glycoengineering to minimize undesired immune responses. Moreover, achieving batch-to-batch consistency and addressing environmental biosafety concerns, such as pollen pollution in field-grown crops, are critical for industrial scale-up. Finally, the absence of globally harmonized regulatory pathways further complicates market entry and commercial adoption. Looking ahead, the advancement of plant-based bioproduction should focus on multiple interrelated objectives. Expression yields could be improved through refined vector design, optimized expression cassettes, and strategic co-expression of molecular chaperones. Downstream processing may be simplified by adopting secretion-based strategies, self-aggregating fusion tags, and more efficient purification workflows. The development of genetically uniform and highly dispersible suspension cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)-mediated editing will further support scalable manufacturing. Concurrently, establishing plant-specific good manufacturing practice guidelines is essential to ensure consistent product quality and safety. By integrating innovations in synthetic biology, process engineering, and regulatory frameworks, plant-based systems are positioned to mature into a reliable and adaptable production platform, thereby contributing to a more resilient and diversified supply chain for biologics, vaccines, and high-value plant metabolites.

This year marks the 50th anniversary of the Ebola virus identification, but the 2026 outbreak of Bundibugyo ebolavirus disease has exposed important limitations in Ebola preparedness strategies that remain largely focused on Zaire ebolavirus. Although major advances in diagnostics, vaccines, and therapeutics have followed the 2014–2016 West African Ebola epidemic, most licensed countermeasures were developed against Zaire ebolavirus and may provide limited protection against other ebolavirus species, including Bundibugyo ebolavirus. Herein, we examine the epidemiological significance of Bundibugyo ebolavirus and review current and emerging diagnostics, vaccines, antibody therapies, and antiviral strategies, with emphasis on their species coverage and limitations. We further discuss how diagnostic blind spots and limited species-inclusive countermeasures contributed to challenges during the current outbreak. Future Ebola preparedness should adopt a broader framework encompassing multiple ebolavirus species with epidemic potential.

Migratory birds play an important role in the spread of antimicrobial resistance (AMR); however, gaps in surveillance data from vital regions along migratory flyways across China limit the detection of emergent threats. Here, we assembled 340 metagenomes from 52 bird species covering 11 provincial administrative districts in China, presenting a specialized migratory microbial genome and gene catalog to archive the genomic and functional diversity of gut microbiomes in wild birds. This comprehensive migratory bird microbial genome and gene (MBGG) catalog includes 5823 metagenome-assembled genomes (MAGs), 13 072 plasmid sequences, and 44 974 viral genomes, which represent 1709 candidate species spanning 36 phyla. The catalog also contains over 20 million non-redundant protein-encoding genes, the use of which is confirmed by the mining of 15 678 secondary metabolite biosynthetic gene clusters, 1814 known antibiotic resistance genes, and 7219 virulence factors. The number of clinically critical ARGs identified in Grus japonensis was the highest, followed by Cygnus cygnus and Sibirionetta formosa, which indicated that these species are hotspot species of clinically critical AMR dissemination. Moreover, we mapped the profile of bacterial zoonotic/opportunistic pathogens carried by wild birds and evaluated their associations with publicly available genomes. Finally, the precise migratory movements for 10 bird species using a global positioning system tracking system help to assess the movement of microorganisms and AMR risk. Collectively, this valuable resource provides the basis for the integration and unification of global wild bird microbiomes, timely sharing, and assessing the uncertainty of migratory microbiomes in the future.

Most neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 target the receptor-binding domain (RBD). However, due to high immune pressure, the RBD accumulates mutations, thus significantly reducing antibody efficacy against emerging variants/subvariants. Although some RBD-targeting antibodies bind conserved epitopes, they usually exhibit weak-to-moderate neutralization. Similarly, antibodies against the N-terminal domain (NTD) or S2 subunit often retain broad binding but generally lack potent neutralization. To address this, we initially identified the broadly reactive nanobody, N103, which exhibited weak neutralizing potency. Structural and functional analyses revealed that N103 targets a conserved NTD epitope and triggers S1 subunit shedding, thereby destabilizing the spike trimer through an allosteric mechanism. Leveraging this insight, we engineered a trispecific antibody combining N103 with antibodies targeting the conserved RBD and S2 epitopes. This design synergistically integrated their distinct binding profiles and mechanisms, achieving potent and broad neutralization against both pseudoviruses and authentic viruses, including the immune-evasive BA.2.86 subvariant. Furthermore, challenge studies in human angiotensin-converting enzyme 2 knockin mice demonstrated robust in vivo protection. Our findings highlight a cooperative multi-target strategy in which antibodies with limited individual potency can collectively achieve broad and potent neutralization through rational design. This approach provides a promising framework for next-generation antibody therapeutics.

Background:Continuous SARS-CoV-2 Omicron emergence poses challenges to immune protection from the previous infection/vaccination in the population. While neutralizing antibodies serve as a key immune protection indicator, their cross-protective effect against novel variants remains limited. However, T cell immunity may confer more durable and broad-spectrum protection. Methods:We evaluated immune dynamics in four Chinese cohorts comprising BF.7/BA.5.2, XBB, and JN.1 convalescents, plus tetravalent recombinant protein vaccine recipients. Neutralizing antibodies were assessed against nine variants spanning the emerging evolutionary spectrum. T cell responses were characterized using variant-specific peptide pools. Antigenic relationships were analyzed through multidimensional scaling-based cartography. Results:BF.7/BA.5.2 convalescents exhibited progressive antibody evasion, with fold-changes against heterologous variants increasing from 4-12-fold initially to > 20-fold at 6 months. XBB convalescents maintained stable short-term responses, while JN.1 convalescents showed superior cross-reactivity against descendant lineages. BA.3.2 demonstrated maximal immune evasion across all groups, occupying the most distant antigenic position. In contrast, T cell immunity exhibited remarkable stability and cross-reactivity, maintaining elevated levels at 6 months with balanced responses against all tested variants. The tetravalent vaccine induced broad-spectrum T cell responses comparable to natural infection, and elicited cross-neutralizing antibody responses against different Omicron variants. Discussion:Our study reveals SARS-CoV-2 variant-specific antibody escape compensated by stable cross-reactive T cell responses. In the context of continued viral evolution, stimulating robust T cell immune responses may be critical to achieve a high population immune barrier against future coronaviruses/variants. These findings emphasize the necessity of comprehensive immune evaluation integrating both humoral and cellular components and provide scientific foundations for optimizing vaccine strategies and immune surveillance systems to address emerging viruses and their variants.

Radiotherapy (RT) is a cornerstone of cancer treatment; however, its efficacy is frequently hampered by its adverse effects on normal tissues. By studying the effects of high-dose radiotherapy (HDRT) and low-dose radiotherapy (LDRT), we found that cancer cells adapt distinct responses to these doses to reduce cytotoxicity. Upon HDRT, cancThese authors contributed equally to this worker cells initiate a strong DNA damage response (DDR) to gain resistance through rapid production and/or activation of proteins for cell cycle arrest and DNA damage repair. In contrast, LDRT has a milder effect on the DDR and promotes resistance by triggering the synthesis of new proteins, including those essential for DNA repair and protein damage clearance. We showed that the inhibition of proteasome activity using a proteasome inhibitor (PI) result in the accumulation of damage to both proteins and DNA, leading to the profound death of cancer cells. Mechanistically, LDRT enhances protein synthesis through both increased mTOR signaling and 80S ribosome assembly. On the basis of these findings, we designed a chemoradiotherapy strategy that combines LDTR with PI to treat cancer while minimizing non-targeted toxicity.

With an unexpected increase of human metapneumovirus (hMPV) cases in northern China since late 2024, concerns arose whether novel hMPV variants triggered this epidemic. Utilizing the Beijing Respiratory Pathogen Surveillance System (RPSS), we conducted a genomic evolutionary analysis spanning 2014-2024 and revealed genetic information for the strains that caused the high rates of hMPV outbreaks during this period. To clarify the epidemic drivers and evolutionary characteristics of the hMPV strains circulating in Beijing, phylogenetic, population dynamic and mutation analyses were performed using high-quality complete sequences from both this study and publicly available data. A total of 348 high-quality hMPV genomes were obtained by next-generation sequencing (NGS), all of which belonged to four known clades: A2b1, A2b2, B1, and B2. Before 2024, A2b2 predominated in Beijing; however, a shift to clade B2 was observed starting in late 2024. In addition, a phylogenetically independent lineage Ⅰ was identified in this study, accounting for 93.1% of B2 genomes collected since late 2024. Furthermore, we identified several unique nonsynonymous mutations in viruses within lineage I that may have phenotypic implications. Our findings indicate that lineage I of clade B2 was the major cause of the unusual increase in hMPV outbreaks in Beijing in late 2024, with no evidence of an emerging novel variant. Although our data were only restricted to samples from Beijing, the findings are likely representative of the hMPV surge across northern China in 2024, given city's high population density and mobility.

The major route of COVID-19 vaccination currently is via intramuscular injection. Data from clinical trials and real-world studies have demonstrated its effectiveness in preventing severe illness and death caused by SARS-CoV-2 infection. However, its protective efficacy against SARS-CoV-2 infection and transmission in situ remains relatively low. Given that SARS-CoV-2, especially the Omicron variant and its sub-variants, primarily infects and replicates in the human upper respiratory tract, mucosal immune responses are crucial for preventing viral infection. Therefore, we constructed a chimpanzee adenovirus (AdC68)-vectored vaccine expressing the Delta-XBB receptor-binding domain (RBD)-dimer and comprehensively compared the immune responses induced by intramuscular injection, intranasal administration, or aerosol inhalation. Our results revealed that aerosol inhalation of the recombinant AdC68 vaccine induced robust systemic and mucosal immune responses and immune memory, particularly activating memory T cells in the lungs with a long duration in the mouse model. Additionally, we assessed long-term protection against a SARS-CoV-2 XBB.1 challenge after ~6 months following a booster vaccination with AdC68-Delta-XBB via different immunization routes. We found that, compared with the intramuscular route, aerosol inhalation provided significantly better protection, without detectable replicating virus in the nasal tissue. This study demonstrates that the AdC68-Delta-XBB vaccine induces robust mucosal immune responses via aerosol inhalation vaccination and prevents SARS-CoV-2 infection in mucosa.IMPORTANCEImmunity induced by first-generation COVID-19 vaccines administered by intramuscular injection is highly effective against severe disease and death but is limited in its ability to prevent viral infection and transmission. A more cost-effective and practical vaccine delivered by the respiratory route is needed to better understand mucosal immune responses and to assess protective efficacy. This study evaluated the immune responses and protective efficacy elicited by intramuscular injection, intranasal administration, or aerosol inhalation of AdC68-Delta-XBB in a mouse model and demonstrated that the aerosol inhalation approach is particularly advantageous for robustly stimulating both systemic and mucosal immune responses. These findings will help guide future clinical development and provide a basis for developing vaccines against other respiratory pathogens.