The gut microbiota is known to be associated with a variety of human metabolic diseases, including metabolic dysfunction–associated steatohepatitis (MASH). Fungi are increasingly recognized as important members of this community; however, the role of fungal symbionts in metabolic diseases is unknown. We have systematically isolated and characterized gut fungi, identifying Fusarium foetens as an intestinal symbiotic filamentous fungus in mice. F. foetens reverses MASH progression in mouse models through an intestinal ceramide synthetase 6 (CerS6)–ceramide axis. Moreover, we identified FF-C1, a secondary metabolite from F. foetens , as a CerS6 inhibitor that has an endogenous protective effect on MASH progression.

To reveal the effects of water stress on the decline in introduced Mongolian pine (Pinus sylvestris var. mongolica) plantations, radial growth (basal area increment, BAI) and tree-ring cellulose δ¹³C (carbon isotope composition) were compared in an introduced Mongolian pine plantation and a natural Mongolian pine forest during 1965–2009. Results showed that the BAI of plantation trees increased until 1990, followed by an abrupt decline from 1990 to 1996 and maintained a stable level thereafter. In contrast, no sign of decreased growth was found for natural trees. Tree-ring δ¹³C_corr of plantation trees, corrected for atmospheric changes in δ¹³C, significantly increased before and after 1990. However, no significant variations in tree-ring δ¹³C_corr for natural trees before and after 1990 indicated no obviously water stress. Intrinsic water-use efficiency (iWUE, calculated from tree-ring δ¹³C) significantly increased before and after 1990 for both forests. Significant negative relationship between BAI and δ¹³C_corr or iWUE was found for plantation trees after 1990 when precipitation, Palmer Drought Severity Index (PDSI) and groundwater level decreased, suggesting water stress impact on growth. For plantation trees, PDSI was positively and negatively correlated with BAI and δ¹³C_corr, respectively, after 1990. For natural trees, BAI had no relationship with PDSI after 1990. These findings suggested that a decrease in PDSI (e.g. decreased precipitation and higher temperature) and groundwater level had made plantation trees face a more serious water stress compared with that of natural trees, which decreased tree growth. However, other stressors such as nutrient limitation may also contribute to growth decline.

Three new dibenzo-α-pyrone derivatives, alternolides A–C (1–3), and seven known congeners (4–10) were isolated from the marine-derived fungus of Alternaria alternata LW37 assisted by the one strain-many compounds (OSMAC) strategy. The structures of 1–3 were established by extensive spectroscopic analyses, and their absolute configurations were determined by modified Snatzke′s method and electronic circular dichroism (ECD) calculations. Compounds 6 and 7 showed good 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant scavenging activities with IC₅₀ values of 83.94 ± 4.14 and 23.60 ± 1.23 µM, respectively. Additionally, 2, 3 and 7 exhibited inhibitory effects against α-glucosidase with IC₅₀ values of 725.85 ± 4.75, 451.25 ± 6.95 and 6.27 ± 0.68 µM, respectively. The enzyme kinetics study indicated 2 and 3 were mixed-type inhibitors of α-glucosidase with K_i values of 347.0 and 108.5 µM, respectively. Furthermore, the interactions of 2, 3 and 7 with α-glucosidase were investigated by molecular docking.

Two new sulfur-containing benzofurans, talarobenzofurans A and B (1 and 2), one new benzofuran talarobenzofuran C (3) and two new α-pyrones talaropyrones A and B (5 and 6), along with five known compounds eurothiocin A (4), nodulisporipyrone A (7), peniazaphilin B (8), ramulosin (9) and 6-hydroxyramulosin (10) were isolated and identified from the culture extract of the mangrove-derived fungus Talaromyces sp. WHUF0341 guided by OSMAC (one strain-many compounds) strategy. Their structures were established by extensive spectroscopic data analysis, the modified Mosher’s method and electronic circular dichroism (ECD) calculations. Structurally, compounds 1 and 2 possesed the unique thioester moiety derived from benzofuran and 2-hydroxy-3-mercaptopropionic acid, which was rarely-observed in natural products. The α-glucosidase inhibitory and antibacterial activities of the isolated compounds were evaluated. Compounds 3 and 4 exhibited inhibitory effects against α-glucosidase activity with IC₅₀ values of 48.9 ± 2.16 and 8.8 ± 1.08 µM, respectively. The inhibitory type of 3 on α-glucosidase was determined as non-competitive-type inhibition with K_i value of 242.3 μM by using Lineweaver-Burk double reciprocal and Dixon single reciprocal plots. Meanwhile, the binding model of 3 and 4 with α-glucosidase was determined by molecular docking assay. The biosynthetic pathways of compounds 1−4 were also proposed. This study suggested that benzofurans 3 and 4 could be potential lead compounds for the hypoglycemic drugs.