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Mol Cell. 2026 Jun 19:S1097-2765(26)00385-0. doi: 10.1016/j.molcel.2026.06.014. Online ahead of print.

ABSTRACT

Adaptation to fluctuating nutrient supply is essential for organismal survival, but how human cells monitor the abundance of many critical nutrients remains undefined. Characterizing the conditional degradation of CDO1, the critical enzyme responsible for cysteine catabolism, here we identify a Cullin-RING E3 ligase complex defined by the substrate adaptor LRRC58 that is sensitive to cysteine abundance. When cysteine is replete, LRRC58 activity is restrained through ubiquitination and proteasomal degradation. Upon cysteine deprivation, LRRC58 is stabilized to permit CDO1 degradation. Through saturation mutagenesis stability profiling, we systematically validate a structural model of the CDO1-LRRC58 interaction and identify residues at the LRRC58 C terminus required for cysteine-dependent instability. CDO1 degradation prevents ferroptotic cell death upon cysteine scarcity, and CDO1 mutations causing neurodevelopmental defects in humans encode dominant-active proteins refractory to LRRC58 recognition. Altogether, these data reveal the CDO1-LRRC58 axis as a critical regulator of cysteine homeostasis that safeguards neural development.

PMID:42320481 | DOI:10.1016/j.molcel.2026.06.014

Chemistry. 2026 Jun 18:e71280. doi: 10.1002/chem.71280. Online ahead of print.

ABSTRACT

Multi-receptor peptide agonists represent an effective strategy for obesity treatment, extending the success of incretin-based therapies through simultaneous engagement of complementary targets. Their development, however, is synthetically demanding, as each receptor combination typically requires de novo preparation of large fusion peptides. We report a modular polyethylene glycol (PEG)-based scaffold that enables orthogonal attachment of up to three functional components, including therapeutic peptides, half-life-extending units, and other labels, via sequential strain-promoted azide-alkyne cycloaddition (SPAAC) and copper-catalysed azide-alkyne cycloaddition (CuAAC). The scaffold is assembled on solid phase without intermediate purification, providing a readily accessible and versatile linker. Using glucagon-like peptide-1 (GLP-1) and amylin receptor agonists as a proof-of-concept, dual-agonist constructs with tuneable valency and functionality were rapidly generated. Lead conjugates displayed balanced, low-picomolar potency at both receptors in cyclic adenosine monophosphate (cAMP) assays and showed selective receptor-mediated internalisation in GLP-1 receptor-expressing cells. This orthogonal click-based platform enables rapid and modular multi-agonist assembly, facilitating systematic exploration of receptor combinations, valency, and payload effects. Beyond incretin biology, it offers a general route to multifunctional peptide therapeutics and diagnostics.

PMID:42315994 | DOI:10.1002/chem.71280

Emerg Med J. 2026 Jun 18:emermed-2026-215891. doi: 10.1136/emermed-2026-215891. Online ahead of print.

NO ABSTRACT

PMID:42315322 | DOI:10.1136/emermed-2026-215891

Arch Virol. 2026 Jun 18;171(7):215. doi: 10.1007/s00705-026-06672-8.

ABSTRACT

The COVID-19 pandemic highlighted the potential of oral antiseptic agents to reduce viral transmission. Strategies that enhance and sustain antiviral activity in the oral cavity may further support control of respiratory viruses. In this study, we evaluated the virucidal activity of selected antiseptic agents against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), individually and in combination, under controlled in vitro conditions. Cetylpyridinium chloride (CPC), benzethonium chloride (BZT), thymol, and tannic acid were assessed using a quantitative suspension assay in the presence of mucin and representative mucoadhesive polymers. Dynamic light scattering and zeta potential analyses were performed to characterize interactions between active agents and mucin or polymers. CPC, BZT, and thymol exhibited dose-dependent viral inactivation. CPC reduced IAV and SARS-CoV-2 titres by approximately 4 log₁₀ at > 200 µg/mL and 25 µg/mL, respectively, while thymol achieved comparable reductions at 1000 µg/mL and 750 µg/mL. Tannic acid showed minimal virucidal activity. Notably, CPC-thymol and BZT-thymol combinations achieved > 4 log₁₀ reductions at substantially lower concentrations than individual agents, indicating enhanced virucidal activity and improved cytocompatibility. Mucin markedly attenuated the virucidal activity of CPC-thymol combinations; however, selected polymers partially preserved antiviral efficacy under mucin-rich conditions. Physicochemical analyses suggest that electrostatic, hydrophobic, and hydrogen-bonding interactions contribute to these effects. These findings demonstrate the enhanced antiviral activity of quaternary ammonium compound-thymol combinations and highlight the influence of mucosal components and macromolecules interactions in modulating oral antiseptic activity.

PMID:42310234 | DOI:10.1007/s00705-026-06672-8

Sci Transl Med. 2026 Jun 17;18(854):eadx4108. doi: 10.1126/scitranslmed.adx4108. Epub 2026 Jun 17.

ABSTRACT

The expanding global crisis of bacterial infections caused by antimicrobial-resistant pathogens has resulted in an urgent need for therapeutics. Previous efforts to target pathogen surface antigens with monoclonal antibodies (mAbs) have sought to activate the complement system, primarily through the antibody-dependent classical pathway. However, most mAbs have induced insufficient complement activation because pathogen evasion strategies disrupt the complex spatiotemporal requirements for activation of the classical pathway initiation complex C1. To address this, we developed a targeted complement activation therapy (T-CAT), which uses antibodies furnished with the enzymatic capability to initiate complement activation directly on the bacterial surface without involvement of the classical pathway initiation complex. We found that T-CAT mAbs directed against bacterial surface antigens can overcome the strategies that pathogens evolved to escape from classical pathway-mediated clearance by the immune system. We further demonstrated that T-CAT mAbs could safely and effectively be used to treat infectious disease in experimental murine models of sepsis and pneumonia caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Neisseria meningitidis. Together, these data highlight the potential for T-CAT as a next-generation mAb platform with broad applicability against diverse microbial species, including multidrug-resistant pathogens, without promoting drug resistance.

PMID:42308332 | DOI:10.1126/scitranslmed.adx4108

Cell Chem Biol. 2026 Jun 15:S2451-9456(26)00187-X. doi: 10.1016/j.chembiol.2026.05.008. Online ahead of print.

ABSTRACT

Regulated cell death (RCD) plays a central role in host defenses against infection. It is also an important driver of pathology in sepsis. The proteins that regulate RCD in mice and, to a lesser degree, in humans are increasingly well understood. In other species, how RCD, especially pyroptosis, occurs in response to infection is less clear. In this review, we outline what is currently known about genes involved in RCD with a focus on pyroptosis across different species and consider the potential consequences that the genetic diversity might have on the host response to infection.

PMID:42296960 | DOI:10.1016/j.chembiol.2026.05.008

Front Cell Infect Microbiol. 2026 May 29;16:1813484. doi: 10.3389/fcimb.2026.1813484. eCollection 2026.

ABSTRACT

The interferon system, first discovered in chicken embryonated eggs, plays a pivotal role in defending vertebrates against pathogens, yet comprehensive multi-omics analyses of immune responses in avian species remain scarce. In this study, we employed an integrative approach combining RNA-Seq transcriptomics with SILAC-based quantitative proteomics to characterize global changes in gene and protein expression following immune stimulation in DF-1 chicken fibroblasts. Cells were treated with three distinct immune stimuli: chicken type I interferon, the synthetic double-stranded RNA (dsRNA) analog poly(I:C), and Infectious Bursal Disease Virus (IBDV), a birnavirus with a bi-segmented dsRNA genome. Our analysis revealed a core set of over 110 genes consistently upregulated across all conditions, representing conserved components of the antiviral response. Each stimulus also triggered distinct transcriptional programs, with poly(I:C) eliciting the most robust cytokine induction. At the proteomic level, we quantified more than 2,400 proteins, uncovering asymmetric regulatory patterns in which upregulated proteins exhibited greater fold changes than those that were downregulated. Notably, analysis of transcription-translation coupling revealed a moderate overall correlation between mRNA and protein abundance, which was significantly attenuated following poly(I:C) stimulation, likely reflecting PKR-mediated translational arrest. Ontological analysis corroborated the upregulation of interferon-stimulated genes and proteins involved in inhibiting viral genome replication, as expected. Intriguingly, proteins associated with mitochondrial metabolism and protein synthesis were consistently downregulated, suggesting a coordinated suppression of cellular bioenergetic and translational functions during the antiviral response. These findings underscore the critical role of post-transcriptional regulation in shaping the innate immune landscape, as numerous proteins exhibited altered expression without corresponding mRNA changes. Collectively, this study provides a comprehensive resource for dissecting cellular avian immune signaling and demonstrates the power of integrative multi-omics approaches in uncovering the complex regulatory networks governing host defense.

PMID:42291312 | PMC:PMC13259848 | DOI:10.3389/fcimb.2026.1813484

BMC Med Res Methodol. 2026 Jun 13. doi: 10.1186/s12874-026-02907-z. Online ahead of print.

ABSTRACT

BACKGROUND: The United Kingdom has a history of world-leading health research, showcased most recently in its response to the Covid pandemic. However, while the UK's performance in academic clinical research remains strong, its global position in the delivery of commercial research has declined. In 2023 Lord O'Shaughnessy reviewed the barriers and drivers to the delivery of commercial trials, identifying 27 recommendations to improve commercial trial performance. Highlighted within the report was the importance of the UK being globally competitive in the delivery of its trials, including study set up and approval times.

METHODS: A dataset from the National Institute for Health and Care Research (NIHR), containing 28,188 site observations from 5,421 unique commercial studies provided data on first recruits to commercial studies spanning a 15-year period from 2010 to 2024. Where there were issues with data quality or reliability, data were cleaned, leaving 23,622 observations from 4,849 studies for analysis. Logistic regression and generalised linear mixed effects models were applied to determine whether sites that recruited their first participant to commercial studies more quickly had a higher probability of recruiting to time and target.

RESULTS: Sites that recruited their first participant more quickly were significantly more likely to recruit to time and target (RTT); (odds ratio per one-month increase in time 0.88, 95% CI 0.87 to 0.89, p < 0.0001). The model suggests that the predicted probability of RTT for a site falls to < 50% if it takes more than 8 months to recruit its first participant. A secondary analysis showed a highly significant increase in probability of a site meeting RTT if they recruited the 'first' Global, European or UK participants onto a study (odds ratio 2.96, 95% CI 2.20 to 4.05, p < 0.0001).

CONCLUSIONS: Sites that recruit first participants more quickly are more likely to recruit to time and target in commercial studies. This is likely to lead to them being selected by sponsors to participate in subsequent studies, increasing research opportunities for their patients and revenue for their organisation. Achieving quicker firsts requires proactive planning and coordination by R&D departments and study teams. Setting up sites in a timely manner is a key determinant of successful study delivery and a key component of the UK government's 10-Year Health Plan for England and Life Sciences Sector Plan.

TRIAL REGISTRATION: Not applicable.

PMID:42288738 | DOI:10.1186/s12874-026-02907-z

Angew Chem Int Ed Engl. 2026 Jun 12:e9595531. doi: 10.1002/anie.9595531. Online ahead of print.

ABSTRACT

Achieving cell-selective targeted protein degradation remains a major challenge for translating proteolysis-targeting chimeras (PROTACs) into therapeutics. Although pancreatic β-cells are well vascularised and readily accessible to circulating peptides, selective receptor-mediated drug delivery remains challenging. Here, we exploit the glucagon-like peptide-1 receptor (GLP-1R) as a β-cell-specific entry route and report, for the first time, a multicomponent stapled glucagon-like peptide-1 (GLP-1) analogue constructed by tryptophan-mediated multicomponent Petasis reaction (TMPR). This modular stapling strategy affords a conformationally stabilised GLP-1 peptide bearing a chemically orthogonal handle for late-stage conjugation, displaying markedly enhanced α-helicity and improved receptor potency, compared with the wild-type peptide. Linking this improved analogue to a bromodomain-containing protein 4 (BRD4)-directed degrader furnishes the first GLP-1-guided PROTAC, which retains GLP-1R agonism and induces selective BRD4 degradation in GLP-1R-positive cells, consistent with receptor-guided uptake and intracellular activation of the degrader payload. Together, these results provide strong proof-of-concept evidence that a TMPR-stapled GLP-1 peptide can serve as a β-cell-directed delivery platform for receptor-defined protein degradation.

PMID:42283322 | DOI:10.1002/anie.9595531

Nutrients. 2026 May 28;18(11):1727. doi: 10.3390/nu18111727.

ABSTRACT

BACKGROUND: Individuals with Down syndrome (DS) are at an increased risk of obesity and, subsequently, its cardiometabolic and cognitive impacts. Caregivers play a critical role in managing health, yet their perceptions and behaviors have been poorly characterized.

METHODS: We performed a cross-sectional online survey of caregivers (n = 764) taking care of 48% females and 52% males with DS, conducted across European populations, predominantly in Spain and France. We assessed perceived obesity, perceived harmfulness of current weight, professional consultation, and confidence in promoting healthy behaviors. Associations were examined using chi-square tests, correlation analysis, and ordinal and logistic regression models.

RESULTS: Around one-third (32%) of caregivers perceived their family member with DS with obesity. Perceived obesity changed with age and was more frequently reported in female family members with DS. Awareness of general metabolic risk factors was high among caregivers, but half of respondents were unaware that abdominal fat affects brain health. Consultation with healthcare professionals was uncommon (57% "Never/Rarely/Sometimes") even among those perceived with obesity.

CONCLUSIONS: Caregivers demonstrate good general awareness about high energy food risks but limited knowledge of the link between obesity and brain health. Enhancing caregiver education and supporting behavioral change could promote healthier lifestyles in families with individuals with DS.

PMID:42280370 | DOI:10.3390/nu18111727

Nutrients. 2026 May 26;18(11):1692. doi: 10.3390/nu18111692.

ABSTRACT

BACKGROUND: Lifestyle factors such as diet and physical activity significantly impact on the risk of obesity in individuals with Down syndrome (DS). However, in the absence of national nutritional guidelines in individuals with DS, further work is needed to understand their dietary and physical activity patterns. In this work we retrieved caregivers' responses on those aspects.

METHODS: We analyzed data from a cross-sectional online survey of caregivers of individuals with DS conducted as part of the GO-DS21 project and reported in the accompanying paper (nutrients-4216283) (n = 764). We explored physical activity patterns, dietary habits, beliefs around weight-loss interventions and caregiver confidence that family members with DS would engage in a healthier lifestyle. Associations were examined using correlation analysis, and cumulative and binary logistic regression models.

RESULTS: Caregivers reported that most individuals with DS exercised 1-3 times per week, with frequency declining with age. Males were more likely to exercise daily than females. Caregiver exercise frequency was positively correlated with that of their DS family member (ρ = 0.521, p < 0.001), suggesting clustering of shared health behaviors within households. In adjusted models, caregivers who exercised regularly had up to thirteen-fold higher odds of having a physically active family member with DS (aOR = 13.02, 95% CI: 7.40-24.06, p < 0.001). Fried food consumption and higher snack frequency were independently associated with perceived obesity status, while sugar-sweetened beverage consumption was not. Caregivers favored exercise as a weight-loss strategy, while anti-obesity drugs were endorsed by only 11% of caregivers primarily and were more likely to be endorsed when obesity was perceived (aOR = 4.21, 95% CI: 2.44-7.39, p < 0.001). Finally, caregiver confidence that their family member with DS would engage in healthier behaviors was associated with perceived obesity status and strongly associated with higher physical activity levels (aOR 14.68, 95% CI: 6.59-33.40, p < 0.001).

CONCLUSIONS: In this large European caregiver survey, reported consumption of selected energy-dense foods was generally low, although fried food intake and higher snack frequency were associated with perceived obesity. Physical activity patterns were closely aligned between caregivers and individuals with DS, suggesting shared household health behaviors. These findings highlight the importance of involving caregivers and family environments in lifestyle interventions aimed at supporting physical activity and weight management in individuals with DS.

PMID:42280336 | DOI:10.3390/nu18111692

Chem Sci. 2026 May 29. doi: 10.1039/d6sc02646j. Online ahead of print.

ABSTRACT

Therapeutic peptides constitute a valuable class of drug candidates due to their ability to modulate targets which are often considered 'undruggable' by traditional small molecule drugs. Nevertheless, many peptides suffer from extremely short plasma half-life which limit their therapeutic potential. The fusion of therapeutic peptides to the Fc region of IgG antibodies has emerged as a highly established and effective approach for prolonging the systemic half-life of peptides. These Fc-fusion compounds are produced using recombinant techniques, expressed as a single linear polypeptide chain. However, such recombinant approaches limit incorporation of non-proteinogenic features such as peptides with non-natural amino acids, unnatural cyclic peptides, or pharmaceutical oligonucleotides. These features can increase stability, improve biological activity, and offer unique chemical properties. Therefore, the development of novel methods for the generation of Fc-fusion proteins which allow incorporation of these non-proteinogenic components is desirable. This work reports a semi-synthetic strategy for generating Fc-peptide conjugates through the design, synthesis, and bioconjugation of functionalised disulfide re-bridging linkers. Using this approach, an Fc-peptide conjugate was generated displaying retained biological activity in vitro and prolonged circulation in vivo. This methodology allows the simple and efficient generation of Fc-peptide conjugates.

PMID:42266899 | PMC:PMC13244299 | DOI:10.1039/d6sc02646j

Nat Protoc. 2026 Jun 9. doi: 10.1038/s41596-026-01376-4. Online ahead of print.

ABSTRACT

Antibody conjugates represent key advances in targeted biotherapeutics, combining the precision of antibodies with a range of functional payloads, including cytotoxic small molecules, enzymes and peptides, to achieve high selectivity, reduced off-target effects and an improved therapeutic window compared with conventional small-molecule drugs. Here we present a protocol for the solid-phase synthesis of tetra-divinylpyrimidine (tetraDVP) linkers, a modular and scalable strategy for generating cysteine-reactive linkers used in site-selective bioconjugation, enabling the rapid production of diverse antibody conjugates. This protocol describes a multistep synthetic workflow involving solution-phase intermediate synthesis, solid-phase assembly on resin, polyethylene glycol elongation, installation of divinylpyrimidine warheads, and mild cleavage conditions, enabling reproducible production of the final linker scaffold. TetraDVP linkers are designed to simultaneously rebridge all four interchain disulfide bonds of native IgG1 and IgG4 antibodies with a single molecule, enabling the controlled installation of functional payloads such as peptides, drugs or protein tags with controlled payload-to-antibody ratio. This approach provides the only reported strategy for conjugating a single payload to a native antibody without the need for chromatographic purification or genetic/glycan engineering. Compared with previous solution-phase routes, this solid-phase protocol improves yield, scalability and reproducibility while enabling rapid diversification of linker architecture. The complete procedure can be performed in ~2 weeks and provides a versatile platform for accessing tetraDVP linkers bearing a variety of functional handles for antibody conjugation.

PMID:42265460 | DOI:10.1038/s41596-026-01376-4

Microbiology (Reading). 2026 Jun;172(6). doi: 10.1099/mic.0.001713.

ABSTRACT

Bacterial pathogens can increase transmission opportunities by surviving in the external environment, but despite wide variation in this ability, the drivers of such differences remain poorly understood. Here, we comparatively analysed data from 47 studies on 29 bacterial pathogens to investigate how phylogeny, structural traits (cell wall structure), life history (transmission mode, lifestyle, generation time) and abiotic conditions (temperature, humidity and surface material) influence persistence following deposition on inert surfaces. Our results showed that bacterial species differ consistently in persistence, but not in a way predicted by phylogeny. Of the bacterial traits, cell wall structure had a significant effect, with Gram-positive bacteria showing longer survival times. In contrast, transmission mode, lifestyle and generation time had no consistent effect on persistence. Bacteria also survived longer on inorganic surfaces, but with no significant effect of temperature or humidity. These findings indicate that both bacterial structural traits and abiotic conditions may play crucial roles in shaping bacterial persistence in the environment, likely through effects on resistance to hypoosmotic stress. How the benefits of persisting in dry external environments, for instance, by harbouring a Gram-positive cell wall, trade off with survival in hyperosmotic conditions or in the face of immune defences, however, remain to be determined.

PMID:42258372 | DOI:10.1099/mic.0.001713

bioRxiv [Preprint]. 2026 May 26:2026.05.24.727525. doi: 10.64898/2026.05.24.727525.

ABSTRACT

BA.3.2, a variant of SARS-CoV-2 containing ~40 mutations in its spike protein compared to its nearest ancestor, has spread globally since its first detection in South Africa in November 2024. Here, we report antigenic characterization of BA.3.2 viruses in three naive animal models, and visualize its antigenic phenotype in the context of SARS-CoV-2 evolution using antigenic cartography. We find that: (1) BA.3.2 is substantially antigenically divergent from existing SARS-CoV-2 variants; (2) infection with BA.3.2 in hamster and mouse animal models produces sera with lower homologous titer than infection with other variants. Both of these results may have implications for the selection of vaccine antigens.

PMID:42244675 | PMC:PMC13232355 | DOI:10.64898/2026.05.24.727525

PLoS Biol. 2026 Jun 5;24(6):e3003834. doi: 10.1371/journal.pbio.3003834. Online ahead of print.

ABSTRACT

All bacterial biofilms contain an extracellular matrix rich in filamentous molecules that self-associate, conferring emergent properties to bacteria, including antibiotic tolerance. Pseudomonas aeruginosa is a human pathogen that forms biofilms in diverse infectious settings, where the upregulation of a filamentous bacteriophage Pf4, has been shown to be a key virulence factor that protects bacteria from antibiotics. Here, we modeled biophysical characteristics of biofilm-linked liquid crystalline droplets formed by Pf4, which predicted that sub-stoichiometric phage binders had the ability to disrupt liquid crystals by changing the surface properties of the phage. We tested this prediction by developing nanobodies targeting the outer surface of the Pf4 phage, which disrupted in vitro reconstituted droplets, promoted antibiotic diffusion into bacteria, disrupted P. aeruginosa biofilm formation under a variety of conditions, and abolished antibiotic tolerance of biofilms. The inhibition strategy illustrated in this study could be extended to biofilms of other pathogenic bacteria, where filamentous molecules are pervasive in the extracellular matrix. Furthermore, our findings exemplify how targeting a biophysical mechanism, rather than a defined biochemical target, is a promising avenue for intervention, with the potential of applying this concept to other disease-related contexts.

PMID:42247470 | DOI:10.1371/journal.pbio.3003834

bioRxiv [Preprint]. 2026 May 22:2026.05.21.726960. doi: 10.64898/2026.05.21.726960.

ABSTRACT

RNA design has been hindered by the limited accuracy of 3D structure prediction. Here, we show that intricate RNA structures can be generated with current deep learning tools through accurate de novo design of pseudoknot secondary structures. In an Eterna competition involving 57 pseudoknots, generative AI methods matched experienced human designers in solving most blind challenges, evaluated by single-nucleotide-resolution chemical mapping, compensatory mutagenesis, and cryogenic electron microscopy. Unexpectedly, AI-generated molecules with accurate secondary structures formed well-ordered 3D folds stabilized by noncanonical tertiary interactions not modeled during design. Success was guided by a RNet foundation model trained on prior chemical mapping data, suggesting that some difficult RNA design tasks may be tractable without first solving RNA 3D structure prediction.

PMID:42239184 | PMC:PMC13228335 | DOI:10.64898/2026.05.21.726960

EMBO J. 2026 Jun 3. doi: 10.1038/s44318-026-00825-w. Online ahead of print.

ABSTRACT

Interferons (IFN) are cytokines that regulate the expression of hundreds of genes during viral infections to generate a broadly antiviral environment in the stimulated cell. Antiviral breadth is provided by the concurrent expression of many individual IFN-stimulated genes (ISG), each encoding a protein with often exquisite antiviral specificity. Here, we identify mechanistic plasticity at a single genetic locus as a novel mechanism to diversify the antiviral profile of human cells. Through alternative splicing, the OAS2 gene encodes two antiviral molecules with distinct target specificities. The shorter OAS2 p69 isoform restricts seasonal human coronavirus OC43 (HCoV-OC43), whereas the longer p71 isoform restricts picornavirus Cardiovirus A (EMCV). The restriction profile is determined by the variable length OAS2 C-terminal tails. Notably, these antiviral activities differ in their dependence on RNase L, suggesting that alternative splicing separates canonical restriction and virus sensing functions across two distinct OAS2 polypeptides. Together, these findings show how alternative splicing expands antiviral diversity at the human OAS2 locus.

PMID:42236548 | DOI:10.1038/s44318-026-00825-w

QJM. 2026 May 29:hcag138. doi: 10.1093/qjmed/hcag138. Online ahead of print.

ABSTRACT

Avian influenza continues to evolve as a zoonotic threat with important implications for clinical practice and global health preparedness. Sustained circulation in wild birds, repeated spillover into poultry, and an increasing number of infections across diverse mammalian hosts have reshaped exposure pathways and broadened the risk landscape for human infection. For clinicians, this evolving ecology translates into atypical presentations and increased diagnostic uncertainty. Recent global activity has been characterised by widespread animal outbreaks and the emergence of new transmission interfaces, including occupational exposures and livestock-associated events. Human infections remain largely zoonotic and geographically heterogeneous, with patterns influenced by surveillance intensity, exposure context, and healthcare access. We synthesise current evidence on the virology, transmission, global epidemiology, clinical manifestations, diagnosis, treatment, and prevention of avian influenza in humans. We highlight evolving mammalian adaptation and changing risk interfaces that complicate risk assessment. Improved clinician awareness, early diagnosis, and integrated One Health surveillance remain central to strengthening preparedness for future influenza threats.

PMID:42213088 | DOI:10.1093/qjmed/hcag138

Philos Trans R Soc Lond B Biol Sci. 2026 May 28;381(1951):20250110. doi: 10.1098/rstb.2025.0110.

ABSTRACT

Plant diseases occurring across wild and crop plants present modelling and management challenges. Wild plant and crop pathosystems differ in ecological structure, evolutionary dynamics and responsiveness to human intervention. At the interface, pathogens may spill over, spill back, persist or evolve, shaped by host diversity, dispersal processes and landscape connectivity. The potential importance of factors including pathogen dispersal, host life history and spatial configuration are examined through a qualitative comparison of case studies: Puccinia graminis, Phakopsora pachyrhizi, Xylella fastidiosa, Pyricularia oryzae Triticum lineage and Austropuccinia psidii. These examples illustrate how wild hosts may function as reservoirs, recombination partners or spillover targets, and how their role influences management efficacy and evolutionary risk. We explore the consequences of this wild-crop interface through two central questions: (i) how should plant diseases involving wild and cultivated pathosystems be managed, and (ii) what proportion of management effort should be allocated to each system? We show the principles underpinning answers to these questions via a conceptual framework based on a generic compartmental model incorporating asymmetric transmission and system-specific interventions, thereby accounting for key aspects of pathogen spread within and between wild host and crop populations. Finally, we identify critical data needs and modelling directions to better inform disease management on the wild plant-crop interface and argue for a more integrative approach bridging ecological and anthropogenic drivers of epidemics. This article is part of the theme issue 'Wild plant pathosystems'.

PMID:42206329 | DOI:10.1098/rstb.2025.0110