Oxalate regulates crystal-cell adhesion and macrophage metabolism via JPT2/PI3K/AKT signaling to promote the progression of kidney stones

Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter microtubule associated homolog 2(JPT2)is a critical molecule in Ca^(2+)mobilization,and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca^(2+)mobilization.Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.

Fish Skin-Inspired Janus Hydrogel Coating for Drag Reduction

Comprehensive Summary,In nature,fishes have evolved functional skins with effective hydrodynamic performance and anti-fouling,facilitating predation and escaping from predators.Although a large number of fish scale-inspired structured surfaces have been explored,the incorporation of mucus on the structured surfaces has been largely ignored.Inspired by the skin of Osteichthyes fishes,a Janus hydrogel coating(JHC)is successfully prepared by a two-step UV light irradiation at room temperature.The bottom side of JHC(STH)achieves a shear adhesive strength of 103.3±17.5 kPa and can strongly adhere to a large variety of surfaces,including metals,ceramic and polymers.The top surface of JHC(SLH)replicates the structure of cycloid scales,while the nature of hydrogel mimics the mucus on fish skin.SLH possesses prominent mechanical,anti-swelling,anti-fouling and drag reduction properties.The design strategy for JHC has potential applications in numerous fields,like,pipeline transportation,bioengineering,and shipping industry.