生物学最新文献

Mycoviruses are increasingly recognized for their potential applications in crop protection, particularly in biocontrol of phytopathogenic fungi and in enhancement of the environmental competence and virulence of entomopathogenic ascomycetes (EA) to optimize their pest control potential. Here, we provide the first evidence of a functional switch between insect-pathogenic and nonpathogenic states in a strain of the EA Beauveria bassiana, driven by a Beauveria bassiana victorivirus 1 (BbVV-1) acting as an essential virulence determinant. The mycovirus-infected wild-type strain (WMI) demonstrated broad-spectrum virulence across insect orders, whereas the isogenic mycovirus-free strain (MFr) was entirely nonpathogenic, exhibiting a complete suppression of cuticle penetration capability, which was restored only through injection of conidia into the hemocoel, bypassing the cuticle barrier. A comprehensive analysis of mycovirus-related inhibition of cuticle penetration revealed that WMI exhibited strong activity in extracellular cuticle-degrading enzymes (ECEs) relevant to virulence, with emphasis on Pr1 protease, whereas ECE secretion, and notably Pr1, were markedly suppressed in MFr. Insect infection by WMI showed a time-dependent increase in the number of pr1 gene copies and quantity of fungal DNA, while neither pr1 expression nor fungal DNA were detected in MFr during the infection cycle. Downregulation of the pr1 gene in MFr suggests a direct effect of mycovirus on fungal transcriptional regulation, highlighting the potential to deploy this BbVV-1 to produce hypervirulent EA strains but also to transition EA from entomopathogens to solely plant-beneficial microorganisms.

Influenza H3N8 viruses have been frequently isolated from chicken farms. However, comprehensive characterization of their virological properties, molecular evolution, virulence, and risk of spillover into mammals remains limited. In particular, little attention has been given to the transmission efficiency of H3N8 avian influenza viruses among chickens and their spillover risk. Here, we systematically characterized H3N8 isolates obtained from asymptomatic chickens through multidisciplinary approaches, including genomic surveillance, receptor binding profiling, and in vivo pathogenicity and transmission assays. All strains showed >98% nucleotide homology with human-infecting strains. Phylogenetic analysis revealed that their internal genes were derived from H9N2, while HA and PB2 genes shared high homology (bootstrap support >98%) with the novel H3N3 virus. All isolates maintained avian-type receptor-binding motifs (HA-Q226/G228) while exhibiting dual α2,3/α2,6-sialic acid binding and robust replication in mammalian cells (peak MDCK titer: 10⁷·⁵ TCID₅₀/mL). ZJ07 demonstrated exceptional thermostability (HA activity persisting >3 hr at 56°C), while JS13 showed 1.8-fold elevated neuraminidase activity versus controls (p < 0.05). In vivo, all strains caused subclinical infections with broad tissue tropism in chickens and mice without adaptation, transmitting efficiently among direct-contact poultry. Strikingly, AH12 achieved 100% airborne transmission in chickens. These findings confirm H3N8's capacity for silent poultry circulation and identify key features conducive to cross-species infection, including dual receptor binding, infection in a mammalian model, and high genetic homology with human strains. The airborne transmissibility of AH12 underscores a heightened spillover risk, necessitating enhanced surveillance and vaccines targeting avian-human interface strains.

Purpose: Neutral cholesterol ester hydrolase 1 (NCEH1), a key enzyme in cellular lipid metabolism, is associated with cancer progression. Its molecular functions in breast cancer remain poorly understood.

Methods: This study evaluated the expression of NCEH1 in breast cancer patients using multiple databases. Functionally, the effects of NCEH1 silencing or overexpression on breast cancer cell growth and motility were investigated. RNA-seq was employed to identify downstream target genes and signalling pathways.

Results: The expression of NCEH1 in breast cancer tissues and cells was significantly higher than that in normal tissues and cells. Silencing NCEH1 suppressed breast cancer cell proliferation and migration. Mechanistically, NCEH1 regulated Neuropilin-1 (NRP1) expression, and both promoted malignant phenotypes in breast cancer by activating the TNF-α/NF-κB signalling pathway.

Conclusion: Our findings demonstrate that NCEH1 accelerates breast cancer progression by modulating NRP1 and activating the TNF-α/NF-κB signalling pathway. Collectively, NCEH1 represents a potential novel biomarker and therapeutic target for breast cancer.

Background: Mitochondria and lysosomes are pivotal in dictating cell survival or death outcomes. While mitochondrial damage and ROS production are key events in mitochondrial cell death, lysosome membrane permeabilization and cathepsin B release mark lysosomal cell death. We aimed to generate a live-cell approach to concurrently monitor mitochondrial redox alterations and lysosomal permeabilization. This would provide mechanistic insight into their dynamic interplay during cell death and enable the discovery of organelle-specific death inducers.

Methods: A dual cell sensor, stably expressing tdTomato-CathepsinB and mitochondria-targeted redox GFP (mt-roGFP), was successfully engineered, and simultaneous imaging of both events by real-time confocal imaging was carried out with selected drugs.

Results: This platform faithfully reported the chronological sequence of organelle-specific events with the progression of cell death, with good temporal and spatial resolution at the single-cell level. Moreover, we have identified and categorised potential lead compounds that predominantly induce lysosomal cell death or mitochondrial cell death, as well as a subset that elicit both events concomitantly.

Conclusion: The study provided evidence that both organelles contribute to cell death in a context-dependent manner, and the temporal analysis of both events is critical in understanding unique organelle-centred cell death.

The emergence and global spread of antimicrobial resistant (AMR) pathogens represent a critical challenge to global public health security. The ESKAPE pathogens refer to a group of highly troublesome multidrug-resistant bacteria responsible for hospital-acquired infections. Of particular concern are Gram-negative ESKAPE pathogens, which pose a significant threat to patient health and healthcare systems worldwide. Systematic investigation into antimicrobial resistance mechanisms and pathogenicity regulation is therefore imperative for developing effective infection control strategies. Emerging evidence highlights small regulatory RNAs (sRNAs) as pivotal post-transcriptional modulators in bacterial physiology, particularly in governing virulence determinant expression and host-pathogen interactions during infection. This review summarizes recent advances in sRNA-mediated regulatory mechanisms in Gram-negative ESKAPE pathogens, with emphasis on Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. We discuss the classification of sRNAs, their regulatory mechanisms, their roles in modulating virulence factors and pathogenicity, as well as the challenges and opportunities in targeting sRNAs for antimicrobial therapy. Evidence accumulated across the studies reviewed indicates that sRNAs exert their function through base pairing with target mRNAs or other sRNA, through interactions with proteins, or as dual-function sRNA. sRNAs have emerged as essential regulators of virulence in the ESKAPE pathogens, influencing capsular polysaccharide production, iron acquisition, biofilm formation, regulation of catabolic pathway genes, cell adhesion and invasion, as well as host immune responses during infection. This review provides a framework for understanding bacterial adaptive evolution through sRNA-mediated regulation and identifies novel intervention targets against multidrug-resistant pathogens.

Gut microbiota has been considered as a key bridge between phytochemicals and host immunity. Prevotella copri (P. copri) showed a close correlation with inflammation, and protocatechuic acid (PCA) has potential protective effects in our previous studies. To understand the underlying mechanism, a total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly assigned into 3 groups, with 6 replicates and 6 piglets per replicate. The piglets were fed a basal diet, a basal diet containing 1.0 × 10⁸ CFU/kg P. copri or 1.0 × 10⁸ CFU/kg P. copri +400 mg/kg PCA for 28 d. Results showed that P. copri decreased the final body weight and average daily gain (ADG), while increased the feed-to-gain ratio (F/G), with increased serum levels of interleukin (IL)-2 and IL-8 in piglets (p < 0.05), and reduced the expression of intestinal tight junction protein (p < 0.05). Dietary supplementation of PCA increased the ADG by suppressing inflammation and enhancing intestinal integrity. In vitro experiments demonstrated that argininosuccinic acid, indole-3-aldehyde, and N-acetylputrescine are critical metabolites produced by P. copri, which initiated inflammatory responses by upregulating pro-inflammatory cytokines and downregulating tight junction proteins in MODE-K cells. PCA was found to effectively attenuate these effects in a dose-dependent manner. In conclusion, PCA can improve the growth performance in weaned piglets by attenuating inflammation caused by P. copri and its metabolites.

The receptor for advanced glycation end products (RAGE) and its ligands are critical drivers of adipose tissue inflammation. While RAGE expression increases in ageing cells and pathological conditions, its specific role in high-fat diet (HFD)-induced adipose tissue senescence remains to be fully elucidated. In this study, we investigated the function of RAGE in the development of adipose tissue senescence associated with obesity. We observed that HFD-fed RAGE-deficient (RAGE^-/-) mice exhibited significantly reduced body weight and adipocyte hypertrophy compared to wild-type (WT) controls. At the molecular level, RAGE^-/- mice displayed lower mRNA expression of cell cycle regulators and markers of the senescence-associated secretory phenotype. This anti-senescent phenotype was accompanied by decreased reactive oxygen species (ROS) production and elevated expression of anti-oxidant genes. Mechanistically, the lack of RAGE resulted in the upregulation of silent information regulator type 1 (SIRT1) in adipose tissues. Notably, the inhibition of SIRT1 reversed these anti-senescent effects and attenuated anti-oxidant gene expression in RAGE-deficient mice. Furthermore, while antioxidant treatment with N-acetylcysteine (NAC) reduced p53 in WT mice, it failed to fully suppress p16 and p21, whereas NAC treatment in RAGE^-/- mice significantly downregulated all senescence markers, suggesting a synergistic protective effect. In conclusion, our results demonstrated that RAGE deficiency improved anti-oxidant properties and prevents adipocyte senescence via the SIRT1 signalling pathway, highlighting a potential therapeutic target for obesity-associated tissue dysfunction.

Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.

Recent large-scale outbreaks of diarrhea in pigs in China have been attributed to viral pathogens. To investigate the primary viral causes of diarrhea, we collected 1343 fecal samples from 84 pig farms across 20 provinces. PEDV showed the highest positivity rate at 50.90%, with a positive farm rate of 66.67%. PoRVA had a positive rate of 33.80% and a positive farm rate of 40.48%. TGEV and PDCoV exhibited lower positivity rates of 3.10% and 6.00%, respectively, with positive farm rates of 14.29% and 16.67%. Co-infections, primarily involving PEDV and PoRVA, accounted for 19.05% of cases. Additionally, an analysis of the spatiotemporal distribution of viruses from 2022 to 2024 was conducted. This study also included phylogenetic and amino acid analyses focusing on PEDV and PoRVA. Among them, PEDV predominantly belongs to GIIa and GIIc, while PoRVA predominantly belongs to G4, G5 and G9. We analyzed neutralizing epitopes and functional sites of the PEDV S protein, revealing that the SS2 and SS6 epitopes are relatively conserved, while various mutations were observed in other functional sites. Additionally, significant variability in the VP7 protein of PoRVA was noted among different genotypes, with several conserved amino acid sequences identified, primarily located in the loop regions of the VP7 protein. The study helps identify high-risk areas and peak periods, thereby providing guidance for epidemic early warning and resource allocation. Additionally, the study conducted a further analysis of the antigenic epitopes of PEDV and PoRVA, providing important information for vaccine design and the formulation of immunization strategies.