Synapsis, the physical bridging of two broken DNA ends, is a critical step in non-homologous DNA end joining (NHEJ), the primary pathway for repairing DNA double-strand breaks (DSBs) in vertebrates. While NHEJ synapsis has been well characterized using blunt-ended DNA, how diverse DNA end configurations influence synaptic complex formation remains much less clear. Here, using single-molecule FRET, we show that end configurations play a decisive role in synapsis pathway choice, with end pairing compensating for XLF in facilitating synaptic complex transitions. Notably, 3-nucleotide (nt) microhomology at DNA ends significantly enhances close synaptic (CS) complex formation mediated by Ku70-Ku80 (Ku) and XRCC4-Ligase IV (X4L4), even in the absence of XLF. Although XLF is nonessential for synapsis with 3-nt microhomology, it further promotes CS formation when present. The FRET analysis reveals that the single-stranded and double-stranded junctions of the DNA ends are in close contact within the primary CS complex, while the overhangs flip out of the duplex, potentially stabilizing the complex. These findings underscore the pivotal role of DNA end configurations in regulating synapsis and their broader implications for NHEJ repair efficiency and fidelity. DNA double-strand breaks are primarily repaired by non-homologous end joining, which requires synapsis of broken DNA ends. Here, the authors show that DNA end configurations, particularly short microhomologies, dictate synaptic complex formation and can bypass XLF to promote close end joining.

Background The Yangtze finless porpoise (YFP; Neophocaena asiaeorientalis asiaeorientalis) is a critically endangered freshwater cetacean, but little is known about the microbiota and the influencing factors. Here, we performed metatranscriptomic sequencing on fecal samples collected from the YFPs under distinct environments to characterize the gut bacterial and viral communities, which consisted of 43 wild and 3 captive YFPs. Results Our analyses revealed that distinct environments of YFPs resulted in significant divergence in the gut microbiota. The captive adult YFPs inhabiting sanitized, stable environments exhibited consistent intestinal microbiota composition and structure, differing markedly from the wild adult YFPs. Notably, Romboutsia, a potential health-associated genus, was significantly prevalent in captive adult YFPs, whereas wild adult YFPs demonstrated higher relative abundances of known opportunistic pathogens. And the wild YFPs in a complex natural environment exhibited highly inter-individual variation with the absence of an age-specific pattern. High-abundance antibiotic resistance genes were prevalent in both captive and wild YFPs. Besides, less overlap in virus species between captive and wild populations was discovered, with one novel genus and two novel species identified. Conclusion We aimed to comprehensively characterize the intestinal bacterial and viral communities of the YFP and to identify the influencing factors. Lifestyle differences were associated with distinct gut microbial compositions, while the individual specificity observed among the wild population may reflect environmental and host-specific influences.

The genus Henipavirus includes highly lethal zoonotic pathogens such as Nipah virus (NiV) and Hendra virus (HeV), both classified as Risk Group 4 agents and recognized as priority pathogens by the World Health Organization (WHO). Recent International Committee on Taxonomy of Viruses (ICTV) taxonomic revisions restrict the genus to only bat-borne viruses, with multiple novel henipaviruses identified recently. In this mini-review, we synthesize current knowledge on henipavirus distribution, diversity, and biological risk. Eight members of the genus have been identified to date. HeV remains geographically confined to Australia, whereas NiV circulates in several countries across South and Southeast Asia. Except HeV and NiV, all other members have been detected solely in bats. Phylogenetic analysis confirms their common ancestry; however, unlike HeV, NiV exhibits marked geographic structuring in its lineage divergence. To help assess relative risk, we summarize henipavirus infection spectrum, receptor usage patterns, and pathogenicity, along with the current state of prophylactic and therapeutic interventions, thereby providing a foundation for evidence-based risk classification. Critical knowledge gaps persist for recently discovered viruses, including the lack of live virus isolates and corresponding in vivo data from animal models, precluding definitive risk assessment. Given the increasing frequency of spillover events—highlighted by the 2026 Nipah outbreaks in India and Bangladesh—there is an urgent need to enhance surveillance and characterization of henipaviruses within a One Health framework. This review provides a consolidated reference for understanding the biological risks posed by henipaviruses and aims to inform preparedness efforts against future threats posed by these viruses.

The explosive growth of digital data is overwhelming conventional storage media, creating an urgent need for more efficient solutions. DNA, with its ultra-high density and long-term stability, emerges as a promising medium; however, most current implementations remain static and archival, limiting practical utility. To address this limitation, a modular DNA data storage system built upon dynamic DNA bytes (DynaBytes)-pre-fabricated DNA segments that can be ligated into reconfigurable information units-is presented. Within this DynaByte system, core, functional, and control DynaBytes are organized to implement a molecular file system, enabling the storage of 210,776 bits (26,347 bytes) of digital information with demonstrated CRUD (Create-Read-Update-Delete)-like operations, hierarchical access, and nanopore-based real-time retrieval. Robust data recovery is achieved under ∼100x error-prone sequencing through streamlined error correction and fuzzy decoding. By relying on in vitro ligation of standardized components, the DynaByte system reduces cost, scales efficiently, and supports interactive, rewritable data storage. These features advance DNA storage beyond passive archiving toward a reconfigurable framework, opening new possibilities for dynamic, practical, and large-scale DNA-based data systems.

RNA viruses represent an integral component of human-associated environments and human health. However, the ecology of environmental RNA viruses remains largely unexplored. Here, we analyzed 2922 metatranscriptomic samples collected from urban and surrounding environments-including human-dense settings (e.g., transit hubs, hospitals, banks), alongside peri-urban settings - across 102 cities in 31 countries and constructed the Urban & Peri-urban RNA Virus Atlas (UPVAtlas), comprising 54,945 RNA viruses, 77% of which had not been previously observed. Phylogenetic reconstruction based on RNA-dependent RNA polymerases from UPVAtlas greatly expanded the evolutionary diversity of RNA viruses, leading to the identification of two potential candidate phyla, one candidate class, and several unclassified clades. Host association analyses further revealed the ecological complexity of environmental RNA viruses, with the diversity of vertebrate-related and ESKAPE pathogen-related viruses underscoring the importance of continued monitoring of urban environments for tracking RNA viral prevalence and dynamics, with direct relevance to future public health.

Respiratory infections are a leading cause of hospitalization and mortality in children, and the pediatric intensive care unit (PICU) is a critical setting for managing severe cases. However, the epidemiological patterns of respiratory pathogens in the PICU remain insufficiently characterized. In this retrospective study, we analyzed respiratory pathogen testing results from 2126 pediatric patients admitted to the PICU of Wuhan Children’s Hospital between 2019 and 2024. The pathogen spectrum and epidemiological characteristics were evaluated across age groups and seasons. Respiratory syncytial virus (RSV, 18.06%) was the most frequently detected viral pathogen, while Streptococcus pneumoniae (6.96%) was the predominant non-viral pathogen. The overall infection burden was highest in children aged ≤ 1 year (53.75%) and 3 < age ≤ 6 years (54.70%), indicating that early childhood represents a high-risk period for severe respiratory infections requiring intensive care. Pathogen distribution varied significantly across age groups. Distinct seasonal patterns were observed for several respiratory pathogens, particularly among viral pathogens, whereas non-viral pathogens showed more variable seasonal distributions. Furthermore, screening for 10 common pathogens accounted for 75% of PICU respiratory infections, highlighting the clinical utility of multiplex molecular detection. This study delineates the pathogen spectrum of respiratory tract infections in the PICU and characterizes their age- and season-specific epidemiological patterns. This study defines the pathogen spectrum and age- and season-specific patterns of respiratory infections in the PICU, providing evidence to support targeted pathogen surveillance, optimized multiplex diagnostics, and risk-informed infection control strategies in pediatric critical care.

ABSTRACT Biomolecular condensates, formed via liquid–liquid phase separation (LLPS), play crucial roles in a range of cellular processes. Dysregulated or aberrant condensates are closely associated with diseases including neurodegeneration, cancer, metabolic disorders, and viral infections. Accumulating evidence demonstrates that LLPS is highly amenable to chemical regulation. Diverse chemical agents can modulate phase separation by directly or indirectly perturbing the weak, multivalent interactions that govern condensate formation, dissolution, size, material properties, and maturation. The identification of LLPS‐modulating chemical regulators not only provides powerful probes for dissecting the physicochemical principles underlying condensate behavior, but also highlights emerging opportunities for the development of condensate‐targeting strategies of potential therapeutic relevance. In this review, we summarize recent advances in the chemical regulation of LLPS, organizing regulatory strategies according to their dominant mechanistic level of action. We highlight how chemical perturbations reshape phase behavior by altering conformational ensembles, effective interaction valency, electrostatic and metabolic environments, or bulk solvent properties, thereby shifting phase boundaries or biasing pathological liquid‐to‐solid transitions. Finally, we discuss emerging opportunities and remaining challenges in the rational discovery of selective, mechanism‐informed LLPS regulators.

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infancy and exhibits pronounced age-dependent clinical heterogeneity. Fever becomes increasingly prevalent with age, yet whether febrile representation reflects a uniform inflammatory and immune phenotype across infancy remains unclear. In this prospective cohort of infants hospitalized with RSV bronchiolitis, we performed an integrated analysis of clinical features, pharyngeal microbiome composition, host transcriptomic profiles, and host-microbe interaction networks, with particular attention to age-related variation in fever-associated patterns. Clinically, fever prevalence exhibited a strong age-dependent increase across infancy. Correspondingly, canonical correspondence analysis identified age and fever as dominant gradients related to variation in both pharyngeal microbiome composition and host gene expression. Although no significant age-dependent correlations were observed at the global microbial and host transcriptomic levels in the fever-age interaction model, distinct patterns of microbial and host responses related to fever were observed across different age groups. Specifically, ranked gene set enrichment analysis indicated that febrile infants in early infancy showed relative attenuation of host defense-related programs, whereas older infants showed stronger enrichment of antiviral and inflammatory effector pathways, with more selective regulatory and signaling-associated patterns in late infancy. Integrated host-microbe network analysis further delineated a coherent developmental trajectory of fever-associated interaction architectures, evolving from densely interconnected regulatory networks in early infancy to modular, selectively coupled, host-centered configurations with advancing age. Together, febrile responses in RSV bronchiolitis should not be interpreted as a uniform biological phenotype across infancy and support age-aware interpretation of fever in pediatric RSV infection.

Human rhinovirus (HRV) is one of the most common causes of acute low respiratory tract infections (ALRTIs) in children and adults resulting in significant alterations in host gene expression and respiratory tract microbiome composition. We sought to clarify HRV prevalence features in children in Wuhan, and investigate interactions between HRV and host in pharynx microenvironment. A total of 1,790 samples were collected from children with ALRTI between September 2021 and September 2023 and screened for HRV infections using qPCR and targeted next-generation sequencing (tNGS). Among all samples, 47 positive samples, 29 healthy control and 27 HRV-negative ALRTI samples were analyzed by meta-transcriptomic sequencing to compare the microbiota dynamics, gene expression and antimicrobial resistance genes (ARGs) profile of infected and healthy individuals. The analysis revealed an HRV positive rate of 13.8%, with HRV-A and HRV-C strains being more dominant than HRV-B in Wuhan. Microbial diversity was significantly higher in HRV-positive samples, with specific genera such as Haemophilus, Neisseria, and Streptococcus being more abundant. There were 22,321 differentially expressed genes (DEGs) identified in the HRV patients. Enrichment analysis showed that these DEGs were associated with alterations in host responses, including modulations in immune activation and cellular processes. The identified ARGs conferred resistance to 18 distinct classes of antibiotics, with these ARGs being more prevalent in healthy individuals compared to those infected with HRV. Procrustes analysis demonstrated significant concordance between pharyngeal microbial community composition and ARG profiles, while co-occurrence network analysis identified strong associations between Pseudomonadota and ARGs conferring resistance to multiple antibiotic classes. HRV infection was associated with distinct shifts in pharyngeal microbial communities and host transcriptional responses. Collectively, these findings suggest that variation in the pharyngeal microbiome is closely linked to variation in resistome composition.

MLO (Mildew Resistance Locus O) genes encode seven-transmembrane proteins that function as critical regulators of powdery mildew resistance and abiotic stress responses. Despite their established importance, the MLO gene family in Gossypium hirsutum L. has not been systematically investigated under salt stress conditions. Here, we performed genome-wide identification of 46 GhMLO members using Hidden Markov Model and BLAST searches based on the latest cotton genome assembly. Phylogenetic analysis classified these genes into four distinct subfamilies. Transmembrane topology and conserved domain analyses revealed that all GhMLO proteins contain typical MLO domains and transmembrane structures, maintaining high structural similarity with dicotyledonous model plants. Synteny analysis demonstrated that the expansion of the GhMLO family was primarily driven by segmental and tandem duplications. Integration of transcriptomic data from the COTTONOMICS database revealed tissue-specific expression patterns, with higher transcript abundance in receptacles, stems, and roots, but lower levels in stamens and petals. Salt, drought, and cold stress treatments induced upregulation of GhMLO family members, with most genes showing increased expression over time. RT-qPCR analysis validated that five candidate GhMLO genes were significantly upregulated under salt stress. In summary, this study provides a comprehensive genome-wide characterization of the GhMLO gene family, elucidating their phylogenetic relationships and expression dynamics, which establishes a theoretical basis for identifying key regulatory genes involved in abiotic stress responses and offers novel genetic resources for improving stress tolerance in cotton molecular breeding.

Stanford type A aortic dissection (AAD) is a life-threatening cardiovascular disease characterized by tearing in the aortic wall. Using spatial transcriptomics and multiplex immunofluorescence, we comprehensively analyzed ascending aortas from eight AAD patients across different severities and segments. We demonstrate that SPP1-driven inflammatory signaling intensifies with AAD severity, identifying a nine-gene, layer-anchored severity scale: MYL6/CALD1/MYH9 (mild); CCL2/CP/COL4A1 (moderate); and TMSB4X/ATP5F1E/PKM (severe). Importantly, the collagen-remodeling triad COL1A1/COL3A1/MMP2 is concurrently up-regulated in the brachiocephalic, left subclavian, and left common carotid arteries, often before the ascending aorta meets surgical diameter thresholds. These molecular signatures provide a critical foundation for non-invasive biomarker discovery, risk stratification, and precision pharmacotherapy targeting the SPP1-inflammatory axis, ultimately offering new insights into AAD mechanisms and therapeutic targets.

Growth Regulating Factors (GRFs) are plant-specific transcription factors that play crucial roles in regulating growth and development throughout the plant life cycle. A total of 34 Gossypium hirsutum GRF family genes were identified at the genome-wide level, which were unevenly distributed on 19 chromosomes, and were predicted to be mainly localized in the nucleus and plasma membrane. The number of GRF family genes varied greatly among different species, and they were categorized into four subfamilies (I-IV) according to their phylogenetic relationships. The G. hirsutum GRF genes possessed specific highly conserved structural domains, Trp-Arg-Cys motif (WRC) and Gln, Leu, Gln motif (QLQ), and structural analysis of the genes revealed that they contained 1-23 exons, and most of them contained UTRs. Intraspecies covariance analysis revealed that the GRF genes expanded in G. hirsutum by segmental duplication. The promoter region of the G. hirsutum GRF gene contained a large number of adversity stress response elements, as well as a small number of hormone response elements and growth and development-related response elements. Transcriptome data showed that the expression of G. hirsutum GRF genes was significantly higher in leaves than in other tissues, and some GRF genes responded to a variety of abiotic stresses. Additionally, transcriptomic sequencing revealed significantly higher expression levels of GhGRFs (e.g., GhGRF13/14/18) in embryonic callus (EC) compared to non-embryonic callus (NEC). This differential expression was validated by RT-qPCR, which confirmed that GhGRF13/14/16/20 were significantly upregulated in EC relative to NEC. These findings provide valuable candidate genes and molecular insights for improving G. hirsutum regeneration efficiency and yield-related traits through genetic manipulation, thereby accelerating the molecular breeding of elite G. hirsutum varieties.

Despite the persistent global threat of seasonal influenza viruses such as A(H1N1)pdm09 and A/H3N2, their epidemiological and genetic characteristics in China following the implementation of COVID-19 non-pharmaceutical interventions (NPIs) remain poorly characterized. Between September 2020 and December 2023, we conducted an integrated epidemiological and genomic analysis of influenza A viruses in children in Wuhan. The overall positivity rate for influenza A virus was markedly low at 3.43% (109/3171), reflecting a profound suppression of circulation during the pandemic. Among genotyped positives, H1N1pdm09 was predominant (52.3%), followed by H3N2 (16.5%) and untypeable strains (32.1%). Preschool children showed the highest susceptibility. Phylogenetic analysis revealed that the circulating H1N1 strains (90%) belonged to clade 6B.1A.5a.2, clustering with viruses from Hong Kong and Pakistan. In contrast, H3N2 strains (76.92%) primarily fell into clade 3C.2a1b.2a.2b, closely related to contemporary strains from Europe and North America. Notably, we identified key hemagglutinin mutations associated with antigenic drift (e.g., R240Q in H1N1; E78G, R158G in H3N2) and neuraminidase mutations potentially conferring antiviral resistance (e.g., S247N in H1N1; S245N, a putative novel glycosylation site, in H3N2). Evidence of reassortment events was also detected, underscoring the continued genomic evolution of these viruses despite their low prevalence. Our findings demonstrate that genetically diverse and antigenically drifted influenza A viruses continued to circulate and evolve in Wuhan during the COVID-19 pandemic, albeit at dramatically reduced levels. This highlights the critical need for sustained genomic surveillance and timely updates of vaccine compositions to pre-empt the resurgence of influenza in the post-pandemic era.

The isotopic composition of atmospheric species provides fundamental insights into their sources, sinks, and chemical processes. Conventional end-member mixing models, however, cannot capture progressive isotopic evolution in open systems where mixing and reaction proceed simultaneously. This limitation hinders a comprehensive understanding of the isotope effect and its atmospheric applications. Here, we develop an isotope-enabled chemical transport model (CTM) that tracks four sulfur isotopologues (32SO2, 34SO2, 32SO42−, 34SO42−) through emissions, transport, chemistry, and deposition. An iterative time-splitting method reduces the numerical bias from applying the Rayleigh equation in the open atmosphere. The model reproduces the 34S enrichment of sulfate relative to SO2 and captures the spatial and seasonal patterns of the sulfur isotope effect across eastern China (simulated Δδ34S_SO42− / SO2=6.11 ‰ ±1.85 ‰; observed =3.43 ‰ ±1.11 ‰). Further, the agreement between simulated (with δ34S_SO2=0 ‰ emission assumption) and observed sulfate isotopic compositions, combined with the documented higher δ34S values of coal at 1 ‰–10 ‰ across eastern China, implies a systematic 34S depletion in emitted SO2 relative to fuels. This highlights the importance of considering isotopic fractionation during combustion, flue gas desulfurization and chemical processes for accurate source apportionment. The isotope-enabled model provides a new approach for constraining the sulfur budget.

Supplementary Figure S4 shows subgroup analyses for the association between glucosamine use and incidence of breast cancer in female participants.

Supplementary Figure S8 shows subgroup analyses for the association between glucosamine use and incidence of melanoma cancer.