Spatial multi-omics characterizes GPR35-relevant lipid metabolism signatures across liver zonation in MASLD

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a metabolic disease that can progress to metabolic dysfunction-associated steatohepatitis(MASH),cirrhosis,and cancer.The zonal distribution of biomolecules in the liver is implicated in mediat-ing the disease progression.Recently,G-protein-coupled receptor 35(GPR35)has been highlighted to play a role in MASLD,but the precise mechanism is not fully understood,particularly,in a liver-zonal manner.Here,we aimed to identify spatially distributed specific genes and metabolites in different liver zonation that are regulated by GPR35 in MASLD,by combining lipid metabolomics,spatial transcriptomics(ST),and spatial metabolomics(SM).We found that GPR35 influenced lipid accumulation,inflammatory and metabolism-related factors in specific regions,notably affecting the anti-inflammation factor ELF4(E74 like E-twenty six(ETS)tran-scription factor 4),lipid homeostasis key factor CIDEA(cell death-inducing DNA fragmentation factor alpha(DFFA)-like effector A),and the injury response-related genes SAA1/2/3(serum amyloid A1/2/3),thereby impacting MASLD progression.Furthermore,SM elucidated specific metabolite distributions across different liver regions,such as C10H11N4O7P(3ʹ,5ʹ-cyclic inosine monophosphate(3ʹ,5ʹ-IMP))for the central vein,and this metabolite significantly decreased in the liver zones of GPR35-deficient mice during MASLD progression.Taken together,GPR35 regulates hepatocyte damage repair,controls inflammation,and prevents MASLD progression by influencing phospholipid homeostasis and gene expression in a zonal manner.

Electrochemical Determination of Salivary N-Acetylneuraminic Acid by Miniaturized Capillary Electrophoresis Coupled with Sample Stacking

Due to their important biological role as markers for different pathologies, sialic acid （SA） analyses are important for clinical research. In this work, a miniaturized capillary electrophoresis with amperometrie detection （mini-CE-AD） was developed for the determination of N-aeetylneuraminic acid （NANA）, which is the most widespread form of SAs. NANA was first oxidized by periodic acid in an acidic solution, and then the oxidation product β-formyl pyruvic acid was derivatized with electroactive 2-thiobarbituric acid （TBA） to form an electroactive NANA-TBA adduct, which could be readily determined by mini-CE-AD. The limit of detection （LOD） of NANA-TBA could achieve 0.50 μg/mL （1.6 μmol·L-1, S/N=3） based on an online enrichment approach of moving chemical reaction boundary. The proposed method was successfully applied to the analysis of NANA in human saliva, and the recoveries were in the range of 91.8%-109% with RSDs of 1.8%-3.9%. Due to its simple design and construction, low cost and portability, the mini-CE-AD device will possess more practicability in more field work as an alternative to conventional and microchip CE approaches.