Erythropoietin-mediated IL-17 F attenuates sepsis-induced gut microbiota dysbiosis and barrier dysfunction.

Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients.

Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis.

OBJECTIVE: Over-proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of RA disease. At the same time, ferroptosis may play a pivotal role in maintaining the balance of proliferation and death of synovium. In this study, we firstly evaluated the ferroptosis level in RA fibroblast-like synoviocytes (FLS) and then explored the role of glycine in ferroptosis. METHODS: Ferroptosis was evaluated in RA synovium and FLS. The therapeutic effect of glycine on RA was evaluated by clinical and histopathological score and cytokine level in a CIA mouse model. The influence of glycine on ferroptosis was evaluated by mitochondrial morphology observation and membrane potential assay in RA FLS. Methylase expression was detected to explore the mechanism behind the effect of glycine on glutathione peroxidase 4 (GPX4) methylation. RESULTS: Compared with healthy controls, ferroptosis decreased in the RA synovium and FLS, with a decrease in Acyl Coenzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1 (FTH1), GPX4 and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in healthy controls, the increase in antioxidation was slightly higher than oxidation. RNA-seq and verification showed that glycine regulated the ferroptosis pathway through increase S-adenosylmethionine (SAM) concentration and decrease the expression of GPX4 and FTH1 by promoting SAM-mediated GPX4 promoter methylation and reducing FTH1 expression in RA FLS. CONCLUSIONS: In summary, we confirmed a decline in ferroptosis in RA and explored that glycine enhanced ferroptosis via SAM-mediated GPX4 promoter methylation and ferritin decrease.

Janus Poly(Vinylidene Fluoride) Membranes with Penetrative Pores for Photothermal Desalination.

Solar-driven desalination has been considered as a promising technology for producing clean water through an abundant and pollution-free energy source. It is a critical challenge to reasonably design the porous morphology and the thermal management of photothermal membranes for enabling efficient energy conversion and water production. In this work, a Janus poly(vinylidene fluoride) membrane was fabricated in combination of penetrative pore structure, asymmetric surface wettability with proper thermal management for high-efficiency solar desalination. Highly open and directly penetrative pores achieved by the two-dimensional solvent freezing strategy are considered to provide direct pathways for water and vapor transportation. The unique feature of hydrophobic upper layer/hydrophilic lower layer enables the photothermal membranes to self-float on the water surface and rapidly pump water from the bulk to the surface. The resulting Janus membrane exhibits a satisfactory light absorbance as high as 97% and a photothermal conversion efficiency of 62.8% under one-sun irradiation in a direct contact mode. The solar-to-vapor efficiency rises up to 90.2% with the assistance of a thermal insulator adopted beneath. Both the Janus membrane and the composite setup are able to work efficiently with a high stability in seawater desalination, and the concentration of ion in condensed water is reduced to below 1 ppm. Therefore, Janus membranes with directly penetrative pores and photothermal surfaces shine a light on the development of high-performance solar evaporators for the practical application in solar seawater desalination.