Yuyue Qin

Vibrio alginolyticus, a prevalent marine Gram-negative pathogenic bacterium, can cause vibriosis in aquaculture and pose potential threats to human health. The excessive abuse of antibiotics has aggravated the multidrug resistance of bacteria, driving researchers to explore natural antibacterial substances from mangrove endophytic fungi. In this study, four known indole-diterpenoids, 7α-hydroxypaxilline (1), paspaline (2), paspalinine (3), 4a-demethylpaspaline-4a-carboxylic acid (4), were isolated the marine-derived fungus Penicillium janthinellum D131. Among them, compound 1 exhibited superior inhibitory activity against Vibrio alginolyticus, with a minimum inhibitory concentration (MIC) of 0.781 μg/mL, which was superior to chloramphenicol (1.56 μg/mL). A series of phenotypic experiments confirmed the potent bactericidal activity of this compound. The results of multi-omics analysis and Western blot assays demonstrated that the compound disrupts the 50S ribosome-mediated translation process in bacteria. Molecular docking analysis and kinetic simulation were further performed to identify the target site, and the results revealed that the compound interacts with 23S ribosomal RNA (23S rRNA). In vitro translation assays further verified that the compound blocks bacterial protein synthesis by targeting 23S rRNA. This study reports the excellent anti-vibrio activity of 1, which is superior to chloramphenicol, and clarifies its ribosome-targeting mechanism of action. These findings provide a theoretical basis for the research and development of novel antibacterial drugs for aquaculture and broaden the potential applications of lead compounds.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammation of the colonic mucosa, and there is currently a lack of safe and effective treatment drugs. Resorcylic acid lactones (RALs) are a natural product that have been reported to have anti-inflammatory effects. However, the mechanism of whether RALs can treat UC and their anti-inflammatory effects remains underexplored. In this study, three new RAL derivatives, Penicillactones A–C (1–3), along with seven known analogs (4–10), were isolated from the marine fungus Penicillium sp. HN20. The structures of compounds 1–3 were elucidated by spectroscopic methods, ¹³C NMR theoretical calculations, and ECD analysis. Among these, compound 4 exhibited potent anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages. In a dextran sulfate sodium (DSS)-induced UC model, compound 4 alleviated body weight loss, disease activity, colon shortening, and spleen enlargement, and protected intestinal epithelial integrity. Mechanistic studies revealed that compound 4 primarily exerts its effects by downregulating the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling pathway, inhibiting pro-inflammatory cytokine production. Collectively, these findings provide the first evidence that marine-derived RAL derivatives exert anti-inflammatory effects by inhibiting the MAPK/ERK pathway, highlighting compound 4 as a promising therapeutic candidate for inflammation and UC.

The Sanniang Bay (SNB) and Dafeng River Estuary (DFR) in the Northern Beibu Gulf, China, are critical habitats for the Indo-Pacific humpback dolphin (Sousa chinensis). However, whether and how the decreased dissolved oxygen (DO) has happened in bottom seawater remains poorly understood. This study investigated DO depletion and microbial community responses using a multidisciplinary approach. High-resolution spatiotemporal sampling (16 stations across four seasons) was combined with functional annotation of prokaryotic taxa (FAPROTAX) to characterize anaerobic metabolic pathways and quantitative PCR (qPCR) targeting dsrA and dsrB genes to quantify sulfate-reducing bacteria. Partial least-squares path modeling (PLS-PM) was employed to statistically link environmental variables (seawater properties and nutrients) to microbial community structure. Results revealed pronounced bottom DO declining to 5.44 and 7.09 mg L⁻¹, a level approaching sub-optimal state (4.0–4.8 mg L⁻¹) in September. Elevated chlorophyll-a (Chl-a) near the SDH coincided with anaerobic microbial enrichment, including sulfate reducers (dsrA/dsrB abundance: SNB > DFR). PLS-PM identified seawater properties (turbidity, DO, pH) and nitrogen as key drivers of anaerobic taxa distribution. Co-occurrence network analysis further demonstrated distinct microbial modules in SNB (phytoplankton-associated denitrifiers) and DFR (autotrophic sulfur oxidizers, nitrogen fixation, and denitrification). These findings highlight how environmental factors drive decreased DO, reshaping microbial networks and threatening coastal ecosystems. This work underscores the need for regulating aquaculture/agricultural runoff to limit eutrophication-driven hypoxia and temporarily restrict human activities in SNB during peak hypoxia (September–October).