Host long non-coding RNAs (lncRNAs) are emerging as critical regulators of influenza A virus (IAV) pathogenesis. Still, the functional landscape of avian host lncRNAs remains largely unexplored. In this study, we identified a novel H9N2induced transcript lncRNA, lncGVRP1, which serves as a conserved positive regulator of IAV replication across H9N2, H1N1, and H3N2 subtypes. In addition, we discovered that lncGVRP1 acts as a functional lncRNA containing a hidden open reading frame (ORF). This ORF encodes a novel 74-amino acid micropeptide, named GVRP1-ORF. Functional rescue experiments demonstrated that the enhancement of viral activity by the lncGVRP1 is strictly dependent on the peptide it encodes. Overexpression of the GVRP1-ORF recapitulated the pro-viral effect achieved by overexpressing the lncRNA. In contrast, an ORF-deleted mutant entirely failed to promote viral replication. Mechanistically, lncGVRP1 facilitates viral propagation by significantly suppressing the host type I interferon (IFN) response and downstream interferon-stimulated genes (ISGs). Furthermore, transcriptome-wide analysis indicated that lncGVRP1 modulates critical cellular machineries, including FoxO signaling and lysosomal trafficking. Collectively, our findings reveal a unique mechanism in which a lncRNA-derived micro-peptide hijacks host immunity to support viral persistence. Moreover, this micro-peptide may serve as a potential therapeutic target against influenza infection.
Dairy farms waste carries multiple bacterial species particularly Escherichia coli, a potential reservoir and disseminator of antimicrobial resistance genes (ARGs) and virulence genes (VGs) through mobilomes. We performed whole-genome sequencing and bioinformatics analysis on 64 multidrug-resistant E. coli isolates from dairy farm waste in Gansu, China, to characterize and predict the co-occurrence of ARGs and VGs on mobilomes. Bioinformatics analysis revealed that key ARGs (sul2, rmtB, blaTEM-1) and VGs (traT, iutA) were predominantly plasmidassociated. Notably, a single Tn2 transposon carrying co-localized blaTEM-1 (ARG) and clpK (VG) is direct evidence of convergence on mobile element. Prophage regions and genomic islands were also rich reservoirs, with ompT (VG) and emrE (ARG) found in 62.5% and 45.3% of isolates, respectively, within the prophage regions. Similarly, fimH (VG) and rsmA (ARG) genes were predominantly identified in 64.1% and 48.4% isolates within the genomic island regions. The convergence of ARGs and VGs associated on diverse mobilomes indicate their potential of dissemination within and between the bacterial pathogens of animal and human significance. Further, our findings highlight the urgent application of integrated One Health policies to mitigate the potential risks.
With the shift toward more ethical and sustainable egg production, the poultry industry is now increasingly shifting towards extended laying cycle. However, extending the production period raises critical concern about the health and welfare of aging laying hens (ALH). A primary challenge is progressive intestinal inflammaging, characterized by compromised barrier integrity, immune dysregulation, and gut microbiota dysbiosis. These changes collectively impair nutrient absorption, reproductive performance, and egg quality. Despite advances in genetics and management, extending production beyond 72 weeks remains challenging. This review concludes that inflammaging in ALH is driven by an agerelated shift in gut homeostasis involving intestinal barrier, immune function, microbiota dysbiosis and short chain fatty acids, and emphasized the mechanisms that promote intestinal inflammaging. Secondly, it also evaluated emerging nutritional interventions over the past decade including polyphenols, probiotics, fermented feed stuff, and enzyme supplementation, which showed promising results in restoring gut health and enhancing production performance. Based on this review we propose that substantial research gaps persist, particularly concerning the temporal dynamics of gut aging beyond 72 weeks and the long-term efficacy of nutritional interventions. Longitudinal studies are essential to clarify these aspects. Furthermore, optimizing nutritional strategies based on a deeper understanding of gut aging mechanisms offers a pathway to extend laying cycles and achieve sustainable, high-quality egg production.
Ostrich leg and toe disease causes substantial morbidity and economic losses; however, its etiology and pathological progression remain poorly understood and inadequately controlled. This study aimed to investigate pathological changes in the cartilage and subchondral bone of the metatarsophalangeal joint in ostriches with leg and toe disease, with particular emphasis on the expression of key inflammatory mediators. Eighteen 30-day-old male ostriches were divided into three groups (n=6 each): H (healthy), D1 (mild disease), and D2 (severe disease). Pathological changes were evaluated using hematoxylin-eosin (HE) and Masson's trichrome staining. The expression of IL-1 beta, MMP-7, LOXL2, and COL2A1 was analyzed at the mRNA level by quantitative reverse-transcription PCR (qRT-PCR) and at the protein level by immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA). Joint effusion volume and metatarsophalangeal circumference were also measured. Compared with the H group, the D1 and D2 groups showed significant increases in joint fluid volume (D1 vs H, P<0.01; D2 vs D1, P<0.01) and joint circumference (D1 vs H, P<0.01; D2 vs D1, P <0.05). Histological examination revealed fragmentation of collagen fibers in the superficial cartilage, a reduction in chondrocytes in the middle layer, and loosely arranged trabeculae in the subchondral bone. IL-1 beta and MMP-7 were progressively upregulated at both mRNA and protein levels with increasing lesion severity (IL-1 beta: P <0.01; MMP-7: P <0.01). In contrast, LOXL2 and COL2A1 were progressively downregulated (LOXL2: P<0.01; COL2A1: D1 vs H, P<0.01; D2 vs D1, P<0.05). These findings demonstrate that the progressive upregulation of IL-1 beta and MMP-7, together with the downregulation of LOXL2 and COL2A1, is closely associated with lesion severity, suggesting that these mediators may play key roles in the pathogenesis of ostrich leg and toe disease and may serve as potential targets for therapeutic intervention.
There are ongoing debates regarding the taxonomy of the E. granulosus Echinococcus granulosus sensu lato (s.l.) complex, with the species status of genotypes G1/G3 (E. granulosus s.s.) and the G6-G10 cluster (E. canadensis) being particularly contested. To solve this challenge, we develop a machine learning (ML)-based k-mer method to predict genotypes of E. granulosus s.l. via the mitochondrial DNA sequence data available in GenBank. We used 7-mer sequences that represent mtDNA to reveal untapped diversity across 948 sequences of seven known genotypes of E. granulosus s.l. We evaluated the utility of varying k-mer lengths, including fixed vs adaptive lengths, for sequence comparisons. Principal component analysis (PCA) identified the most discriminative patterns, addressed the computational challenges posed by high-dimensional features and fed them into 5 distinct ML algorithms, including both conventional (LR, RF and SVM) and DL (1D-CNN and the LSTM) methods. Moreover, crucial insights into performance implications and efficiency improvements have been emphasized via 10-fold cross-validation. Our method attains approximately 95% accuracy in predicting E. granulosus s.l. genotypes. High genetic diversity within G6, G8 and G3 contributes significantly to the controversial taxonomy of the E. canadensis cluster and E. granulosus s.s., respectively. Moreover, ML can potentially compete with BLAST (the NCBI sequence alignment tool) when the BLAST-Similarity-KNN classifier is implemented on the E. granulosus mtDNA data. This study provides a novel approach for classifying E. granulosus s.l. at the species level, thereby supporting disease control activities.
