LB100 ameliorates nonalcoholic fatty liver disease via the AMPK/Sirt1 pathway

BACKGROUND It is well known that nonalcoholic fatty liver disease(NAFLD)is associated with insulin resistance(IR).LB100,a serine/threonine protein phosphatase 2A(PP2A)inhibitor,is closely related to IR.However,there is little data regarding its direct influence on NAFLD.AIM To elucidate the effect and underlying mechanism of LB100 in NAFLD.METHODS After 10 wk of high fat diet(HFD)feeding,male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk(three times a week).The L02 cell line was treated with LB100 and free fatty acids(FFAs)for 24 h.Hematoxylin and eosin and oil red O staining were performed for histological examination.Western blot analysis was used to detect the protein expression of Sirtuin 1(Sirt1),total and phosphorylated AMP-activated protein kinaseα(AMPKα),and the proteins involved in lipogenesis and fatty acid oxidation.The mRNA levels were determined by qPCR.Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD.RESULTS LB100 significantly ameliorated HFD-induced obesity,hepatic lipid accumulation and hepatic injury in mice.In addition,LB100 significantly downregulated the protein levels of acetyl-CoA carboxylase,sterol regulatory element-binding protein 1 and its lipogenesis target genes,including stearoyl-CoA desaturase-1 and fatty acid synthase,and upregulated the levels of proteins involved in fatty acidβ-oxidation,such as peroxisome proliferator-activated receptorα(PPARα),peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α),carnitine palmitoyltransferase 1α,acyl-CoA oxidase 1 and uncoupling protein 2,as well as the upstream mediators Sirt1 and AMPKαin the livers of HFD-fed mice.In vitro,LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway.Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKαin L02 cells.CONCLUSION PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway.LB100 may be a potential therapeutic agent for NAFLD.

Snow algal blooms in Antarctic King George Island in 2017-2022 and their future trend based on CMIP6 projection

Snow algal blooms have a remarkable climatic or environmental effect through influencing the snow-albedo feedback,accelerating the melting of surface snow,and amplifying global warming.Snow algal blooms occurred frequently on King George Island,Antarctic,during the recent six austral summers(December to next February)through 2017-2022.Based on an assessment of satellite images,this study found that the range and amount of snow algal blooms in the summers of 2018,2020,2021 and 2022 are relatively larger than in the summers of 2017 and 2019.Whether meteorological conditions have shaped the year-to-year variation of algal bloom intensities is analyzed through observational composite.The results suggest that during the strong bloom summers there exist prevailing northerly or northwesterly wind anomalies which advect warm and humid airmass from the southern ocean into the island,increasing surface air temperature and humidity;the warmer and more humid surface favors melting of snow and an increase of low cloud cover,subsequently enhancing the atmospheric downward long-wave radiation and amplifying surface warmth;the increased low cloud cover reflects more ultraviolet rays back to space and weakens the short-wave radiation reaching the surface.All these factors together favor to a stronger bloom.In comparison,during 2017 and 2019 there exist weak southerly wind anomalies which induce the northward advection of cold and dry air from the Antarctic Continent and favor the cooler surface.Consequently,it is unfavorable for the snow algal bloom.Based on these results,a snow algal bloom potential index(API)integrating the meteorological conditions is constructed,and its future trend is projected based on the EC-Earth3 run attending the CMIP6 under SSP245 and SSP585.A significant increasing trend is projected especially under SSP585.Thus snow algal bloom on King George Island will become more frequent and stronger in future.This implies a potential accelerate melting of ice shelf over Antarctic Peninsula.

Fully Biodegradable Poly(lactic acid)/Poly(propylene carbonate)Shape Memory Materials with Low Recovery Temperature Based on in situ Compatibilization by Dicumyl Peroxide

Fully biodegradable blends with low shape memory recovery temperature were obtained based on poly（lactic acid）（PLA） and poly（propylene carbonate）（PPC）. By virtue of their similar chemical structures, in situ cross-linking reaction initiated by dicumyl peroxide（DCP） between PLA and PPC chains was realized in PLA/PPC blends. Therefore, the compatibility between PLA and PPC was increased, which obviously changed the phase structures and increased the elongation at break of the blends. The compatibilized blends had a recovery performance at 45 °C. Combining the changes of phase structures, the mechanism of the shape memory was discussed. It was demonstrated that in situ compatibilization by dicumyl peroxide was effective to obtain eco-friendly PLA/PPC blends with good mechanical and shape memory properties.