Ningxia University

Influenza A virus (IAV) exhibits notable genetic diversity and cross-species transmission capacity, posing a continuous challenge to public health. Elucidating host immune regulatory mechanisms is crucial for identifying new antiviral targets that can overcome viral resistance. Here, using human A549 lung epithelial cells as the primary model, we identify fibroblast growth factor 8 (FGF8) as a crucial host factor whose expression is significantly elevated during infection by various IAV subtypes (including H1N1, H13N2, H9N2, and PR8). Through gain- and loss-of-function assays, we demonstrate that FGF8 specifically enhances viral replication at the post-entry stage by suppressing interferon-beta (IFN-β) and interferon-stimulated genes (ISGs) expression. Mechanistically, FGF8 reduces retinoic acid-inducible gene I (RIG-I) protein stability via K48-linked polyubiquitination without affecting its mRNA levels. Ubiquitination identifies Lysine 258 (K258) on RIG-I as the essential modification site; notably, a K258R mutation prevents RIG-I degradation and restores IFN-β induction. Furthermore, TurboID-based proximity labeling captures the close spatial association of FGF8 with both tripartite motif containing 16 (TRIM16) and RIG-I, revealing that FGF8 acts as a molecular scaffold to recruit the E3 ligase TRIM16 to RIG-I. Consistently, TRIM16 silencing replicates the antiviral effects of FGF8 knockdown. Collectively, our findings demonstrate that FGF8 recruits TRIM16 to degrade RIG-I, thereby facilitating viral immune evasion. Disrupting this interaction offers a potential avenue for anti-influenza A virus intervention.

In aquatic environments, natural and anthropogenic factors commonly reduce dissolved oxygen (DO) and trigger hypoxia, which threatens the health and survival of aquatic organisms. As an important economic fish species in China, pikeperch (Sander lucioperca) is extremely sensitive to hypoxia. However, there are relatively few reports on how hypoxia and reoxygenation affect its intestinal physiology and microbial community. Three treatment groups were set for pikeperch: normoxia (DO = 8.5 ± 0.5 mg/L), 48 h hypoxia (DO = 2.5 ± 0.1 mg/L), and reoxygenation (48 h hypoxia followed by 6 h reoxygenation at normal DO), to evaluate alterations in intestinal histopathology, tight junction gene expression, oxidative stress, hypoxia signaling molecules and intestinal microbiota composition. The results showed that hypoxia significantly decreased muscularis thickness by approximately 32.5% and reduced the expression of tight junction genes (Occludin, Claudin2, and ZO-2). Moreover, hypoxia significantly increased oxidative stress index levels (GSH-Px, CAT, and MDA), markedly upregulated the expression of Bax, Caspase3, and HIF-1α, while significantly downregulating the expression of Bcl-2, Egln1, and Egln2. Notably, reoxygenation elicited partial compensatory effects against these hypoxia-induced changes. 16S rRNA sequencing analysis revealed that hypoxic stress altered the intestinal microbial community composition of pikeperch and increased its diversity. In the hypoxia group, the abundance of the phylum Bacillota, along with the genera Halomonas and Acinetobacter, was significantly elevated, whereas in the reoxygenation group, the genus Lactobacillus increased approximately 180-fold. The results indicated that hypoxia caused intestinal oxidative damage, cell apoptosis, and intestinal microbiota dysbiosis in pikeperch, while short-term reoxygenation achieved partial recovery from these hypoxia-triggered intestinal injuries. The present research provides valuable references for in-depth exploration of the molecular mechanisms behind the response of pikeperch to acute hypoxia and reoxygenation stress, while also offering a novel perspective to understand the mechanism by which hypoxia impacts intestinal health in fish.

This study formulated a whole-plant Lycium blend (LB) to examine its effects and underlying mechanisms in ameliorating Type 2 Diabetes Mellitus (T2DM), aiming to develop safe, multi-targeted therapeutic agents.

UPLC-MS/MS was used to identify the chemical constituents in LB and the bioavailable components in drug-containing serum. The therapeutic effects of LB were evaluated through in vitro and in vivo experiments using an insulin resistance model in HepG2 cells and a T2DM mouse model. Additionally, network pharmacology was employed to analyze targets associated with blood components and elucidate the primary molecular mechanisms by which LB improves T2DM. Western blot analysis was utilized to detect protein expression in relevant signaling pathways.

UPLC-MS/MS identified 22 compounds in LB, while drug-containing serum contained 9 bioavailable active components, primarily flavonoids, organic acids, and glycosides. Without affecting food intake or body weight, in vitro and in vivo studies revealed that LB reduces insulin resistance in HepG2 cells, improves lipid metabolism, decreases hepatic steatosis and adipocyte hypertrophy, and dose-dependently lowers daytime blood glucose levels as well as the area under the oral glucose tolerance test (OGTT) curve in T2DM mice. According to Western blot results, LB regulates glucose and lipid metabolism balance by activating the IRS1/PI3K/AKT signaling axis and the AMPK/GLUT4 pathway, suppressing NF-κB-mediated inflammatory responses, and upregulating the expression levels of PGC1α and PPARγ.

This study provides preclinical experimental evidence endorsing the utilization of LB as a natural functional component for the prevention and supplementary treatment of T2DM.