Introduction: Sporotrichosis is a fungal disease caused by a complex of Sporothrix schenckii, leading to chronic infections of the epidermis and subcutaneous tissue in both humans and animals.Methods: Through virtual screening targeting the key gene abaA to screen out the small-molecule drugs to treat Sporotrichosis. To further validate the antifungal activity of small-molecule drugs, growth curves, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) for Sporothrix globosa (S. globosa) and Sporothrix schenckii (S. schenckii) were measured. In addition, we have done animal experiments to explore the function of the drugs. At the same time, qRT-PCR and transcriptome were used to verify the important role of abaA gene in Sporothrix.Results: Azelastine and Mefloquine effectively inhibit S. globosa and S. schenckii. MBC, and MIC for S. globosa and S. schenckii confirmed that both Azelastine and Mefloquine inhibited the growth of S. globosa and S. schenckii. Additionally, animal experiments demonstrated that Azelastine and Mefloquine reduced skin lesions in mice; post-treatment observations revealed improvements in inflammatory infiltration and granuloma formation. Through transcriptome analysis and qRT-PCR for validation, our findings demonstrate that the abaA gene plays a crucial role in regulating the attachment of the Sporothrix cell wall to the host matrix and in melanin regulation. Notably, when the abaA gene was inhibited, there was a marked increase in the expression of repair genes. These results emphasize the significance of the abaA gene in the biology of Sporothrix.Discussion: Two small-molecule drugs exhibit the ability to inhibit Sporothrix and treat sporotrichosis both in vitro and in murine models, suggesting their potential for development as therapeutic agents for sporotrichosis. And qRT-PCR and transcriptome results underscore the significance of the abaA gene in Sporothrix. Our results lay the foundation for the search for new treatments for other mycosis.

RNA viruses, such as respiratory syncytial virus and SARS-CoV-2, can generate viral circular RNAs (circRNAs), which may play important roles during viral infection. However, whether influenza A viruses have this ability to generate viral circRNAs remains unknown. In this study, we discovered that the negative-strand RNA of the H1N1 nucleoprotein (NP) gene can generate a circRNA, designated circNP37. Furthermore, we demonstrated that circNP37 positively regulated viral replication by competitively sponging host miR-361-5p which inhibited polymerase basic protein 2 (PB2) expression. These results were confirmed using in vivo experiments. Compared with wild-type virus, infection with circNP37 knockout virus resulted in a reduced viral load in the lungs. This study demonstrates, for the first time, the existence and biological function of H1N1-derived circNP37. These findings help us better understand the mechanisms of influenza virus replication and pathogenicity. Highlights Negative-strand RNA of the H1N1 nucleoprotein gene can generate a circRNA CircNP37 plays important roles in viral replication and viral-host interactions CircNP37 positively regulates replication by competitively sponging host miR-361-5p eTOC Blurb In this study, we found that influenza A virus H1N1 infection can generate virus-derived circRNA, circNP37. We also demonstrated that circNP37 positively regulate viral PB2 gene expression and viral replication via sponge host miR-361-5p during viral infection.

Sporothrix schenckii (S. schenckii) is a dimorphic fungus that produces lymphocutaneous lesions. The signature characteristic of S. schenckii is a temperature-induced phase transition. Silent information regulator (Sir) has been proven to be involved in phenotypic switching in Saccharomyces cerevisiae (S. cerevisiae) and Candida albicans (C. albicans) by organizing chromatin structure. In this study, we isolated and characterized a Sir homologue gene, designated as SsSir2, from the yeast form of S. schenckii. The full-length SsSir2 cDNA sequence is 1753 bp in size and contains an open reading frame of 1329 bp encoding 442 amino acids. The predicted molecular mass of SsSir2 is 48.1 kDa with an estimated theoretical isoelectric point of 4.6. The SsSir2 kinase domain shows a 78% identity with that of Hst2, a Sir2 Ib gene from S. cerevisiae. Three exons and two introns were identified within the 1472-bp SsSir2 genomic DNA sequence of S. schenckii. A three-dimensional model of SsSir2 was constructed using a homology modeling method, and its reliability was evaluated. The active site of SsSir2 was identified by docking simulation, which indicated that several important residues, such as Asn127 and Asp129, play an important role in the histone deacetylase activity of Sir2 family proteins. The differential expression of the SsSir2 in two stages was demonstrated by real-time RT-PCR. The expression of SsSir2 was higher in the yeast stage compared with that in the mycelial one, which indicated that SsSir2 may be involved in the phenotypic switching and morphogenesis of the yeast phase in S. schenckii.

Coastal wetlands are critical components of blue carbon ecosystems, yet the functional roles of benthic shellfish species in regulating sediment carbon dynamics are not yet fully elucidated. To address this knowledge gap, we investigated the effects of different shellfish zones—gastropods (Bullacta exarata, Umbonium thomasi) and bivalves (Mactra veneriformis, Meretrix meretrix, Potamocorbula laevis)—on sediment carbon fractions and microbial communities in representative intertidal wetlands of Liaodong Bay, China. We analyzed dissolved organic carbon (DOC), particulate organic carbon (POC), microbial biomass carbon (MBC), enzyme activities, and microbial genomic profiles, with particular emphasis on carbon fixation gene abundance within the top 0–10 cm of sediment. The results showed that POC and MBC levels in gastropod zones were 56.11% and 99.83% higher, respectively, than in bivalve zones, while carbon fixation gene abundance was 14.54% lower. Structural equation modeling (SEM) further revealed that shellfish type had a significant direct effect on MBC (λ = 0.824, p < 0.001). This study provides novel evidence that shellfish community composition regulates blue carbon storage through both biogeochemical and microbial pathways, highlighting the importance of species-specific management in shellfish aquaculture to enhance carbon sequestration. These findings offer a theoretical foundation for future assessments of coastal wetland carbon sinks and ecosystem service valuation.

To investigate the effects and underlying molecular mechanisms of the interaction between nonstructural protein (NS1) and nucleolar and coiled-body phosphoprotein 1 (NOLC1) on rRNA synthesis via nucleolar telomeric repeat-binding factor 2 (TRF2) under nucleolar stress in avian influenza A virus infection. The analysis of TRF2 ties into the exploration of ribosomal protein L11 (RPL11) and mouse double minute 2 (MDM2) because TRF2 has been found to interact with NOLC1, and the RPL11-MDM2 pathway plays an important role in nucleolar regulation and cellular processes. Both human embryonic kidney 293T cells and human lung adenocarcinoma A549 cells were transfected with the plasmids pCAGGS-HA and pCAGGS-HA-NS1, respectively. In addition, A549 cells were transfected with the plasmids pEGFP-N1, pEGFP-N1-NS1 and pDsRed2-N1-TRF2. The cell cycle was detected by flow cytometry, and coimmunoprecipitation was applied to examine the interactions between different proteins. The effect of NS1 on TRF2 was detected by immunoprecipitation, and the colocalization of NOLC1 and TRF2 or NS1 and TRF2 was visualized by immunofluorescence. Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression of the TRF2 and p21. There is a strong interaction between NOLC1 and TRF2, and the colocalization of NOLC1 and TRF2 in the nucleus. The protein expression of NOLC1 in A549-HA-NS1 cells was lower than that in A549-HA cells, which was accompanied by the upregulated protein expression of p53 in A549-HA-NS1 cells (all P<0.05). TRF2 was scattered throughout the nucleus without clear nucleolar aggregation. RPL11 specifically interacted with MDM2 in the NS1 group, and expression of the p21 gene was significantly increased in the HA-NS1 group compared with the HA group (P<0.01). NS1 protein can lead to the reduced aggregation of TRF2 in the nucleolus, inhibition of rRNA expression, and cell cycle blockade by interfering with the NOLC1 protein and generating nucleolar stress.