Background: primary sclerosing cholangitis (PSC) is a chronic cholestatic disease characterized by inflammation and fibrosis of the bile ducts. Cholestasis may lead to hepatic inflammation and fibrosis, and amelioration of cholestasis may allow recovery from inflammatory and fibrotic pathological damage. Prevotella copri (P. copri) intervention have been reported could significantly improve cholestasis and liver fibrosis in DDC-induced PSC mice model. Despite alone P. copri treatment could not recover DDC-induced inflammation, it increased the abundance of Lactobacillus murinus (L. murinus) compared to DDC treatment, which has been reported to have anti-inflammatory effects. The abundance of L. murinus still not recover to normal level may underlie hepatic inflammation in P. copri+DDC mice. Method: alone or in combination interventions of P. copri and L. murinus were used to investigate the molecular mechanism of improvement of PSC inflammation and fibrosis. Results: P. copri and L. murinus significantly reduced the hepatic inflammatory cell aggregation and inflammatory factor expression, as well as the hepatic collagen content and fibrin factor expression in PSC mice. Further analysis of phosphorylation and dephosphorylation levels revealed that P. copri and L. murinus combined intervention in PSC mice inhibited the activity of DDC-activated TGF-β1/Smad pathway, thereby reducing liver inflammation and fibrosis. Conclusion: combination of P. copri and L. murinus inhibits the TGF-β1/Smad pathway and reduces inflammation and fibrosis in PSC.

Improving plant nitrogen use efficiency (NUE) is important for many crops, especially in hybrid breeding. Reducing nitrogen inputs is key for achieving sustainable rice production and decreasing environmental problems. Here, we analyzed the transcriptomic and physiological changes in two indica restorer lines (Nanhui511 and Minghui23) under high (HN) and low nitrogen (LN) conditions. Nanhui511 (NH511) was more sensitive to different nitrogen supplies and exhibited higher nitrogen uptake and NUE under HN conditions by increasing lateral root and tiller numbers in the seedling and maturation stages, respectively. It also exhibited a lower survival rate than that of MH23 when planted in chlorate-containing hydroponic solution, indicating its high nitrogen uptake ability under different nitrogen supply conditions. When transferred from LN to HN conditions, NH511 had 2456 differentially expressed genes, whereas MH23 had only 266. Furthermore, genes related to nitrogen utilization showed differential expression in NH511 under HN conditions, while the opposite was observed in MH23. These results will help decrease certain limitations of hybrid rice breeding and provide novel data for high-NUE hybrid rice cultivation.