Jin Yang

Abstract Sodium-glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i) is a novel class of anti-diabetic drug, which has displayed a promising benefit for non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of SGLT2i against NAFLD and the underlying mechanisms. The db/db mice and western diet-induced NAFLD mice were treated with dapagliflozin (1 mg·kg −1 ·d −1 , i.g.) or canagliflozin (10 mg·kg −1 ·d −1 , i.g.) for 8 weeks. We showed that the SGLT2i significantly improved NAFLD-associated metabolic indexes, and attenuated hepatic steatosis and fibrosis. Notably, SGLT2i reduced the levels of pro-inflammatory cytokines and chemokines, downregulated M1 macrophage marker expression and upregulated M2 macrophage marker expression in liver tissues. In cultured mouse bone marrow-derived macrophages and human peripheral blood mononuclear cell-derived macrophages, the SGLT2i (10, 20 and 40 μmol/L) significantly promoted macrophage polarization from M1 to M2 phenotype. RNA sequencing, Seahorse analysis and liquid chromatography-tandem mass spectrometry analysis revealed that the SGLT2i suppressed glycolysis and triggered metabolic reprogramming in macrophages. By using genetic manipulation and pharmacological inhibition, we identified that the SGLT2i targeted PFKFB3, a key enzyme of glycolysis, to modulate the macrophage polarization of M1 to M2 phenotype. Using a co-culture of macrophages with hepatocytes, we demonstrated that the SGLT2i inhibited lipogenesis in hepatocytes via crosstalk with macrophages. In conclusion, this study highlights a potential therapeutic application for repurposing SGLT2i and identifying a potential target PFKFB3 for NAFLD treatment.

Microelectronics packaging technology has evolved from through-hole and bulk configuration to surface-mount and small-profile ones. In surface mount packaging, such as flip chips, chip scale packages, and ball grid arrays, chips/packages are attached to the substrates/printed wiring board (PWB) using solder bump interconnections. Solder bumps hidden between the chips/packages and the substrate/board are no longer visible for inspection. A novel solder bump inspection system has been developed using laser ultrasound and interferometer techniques. This system has been successfully applied to detect solder bump defects including missing, misaligned, open, and cracked solder bumps in flip chip packages, chip scale packages and land grid arrays. The system uses a pulsed Nd:YAG laser to induce ultrasound in the thermoelastic regime and the transient out-of-plane displacement response in nanometer scale on the package surface is measured using the interferometer technique. In this paper, wavelet analysis of laser ultrasound signals is presented and compared to previous signal processing methods, such as error ratio and correlation coefficient. The results show that wavelet analysis increases measurement sensitivity for inspecting solder bumps in electronic packages. Laser ultrasound inspection results are also compared to X-ray results. In particular, this paper discusses defect detection for a 6.35 mm × 6.35 mm × 0.6 mm PB18 flip chip package and flip chip package (¿SiMAF¿) with 24 lead-free solder bumps. These two types of flip chip specimens are both nonunderfilled.