Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

[Identification of keystone predators in Haizhou Bay food web based on the revised SURF index]. / 基于改进的SURFæŒ‡æ•°ç”„é€‰æµ·å·žæ¹¾é±¼ç±»ç¾¤è½çš„å ³é”®æ•é£Ÿè€ .

Keystone predator species play an important role in regulating the number, richness and distribution of prey species. Based on the bottom trawl surveys in Haizhou Bay, keystone predator species in fish communities were identified by the revised SURF (supportive role to fishery ecosystems) index. Conger myriaster, Saurida elongata, Hexagrammos otakii, Chelidonichthys spinosus, and Larimichthys polyactis were the keystone predators in the fish community. They had high number of nodes degree, and were also the main predators of many species. Further, they had strong ability of clustering. The fluctuations of their density would have great impacts on ecosystem energy flow and food web structure. The method not only considered the feeding ratio between species, but also took the amount of catch and abundance of species as important factors in the identification of keystone predators. Compared with the traditional method, this method had great improvement and provided a new one for the identification of key predators. Our results showed that the strong inter-specific interactions played an important role in maintaining the structure and function of food webs. Protection of key predators would benefit the stability of biological communities and species diversity. Therefore, ecosystem-based fisheries management (EBFM) should give priority to the protection of key species. The important economic fish species, C. myriaster and L. polyactis, should be protected with high priority as they suffered from higher fishing pressure.