(Z)-4-[(Ethyl­amino)(furan-2-yl)methyl­idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one

In the crystal of the title compound, C17H17N3O2, the mol­ecules exist in the keto–enamine form. The pyrazole ring is oriented at 10.59 (4) and 57.98 (5)° to the phenyl and furyl rings, respectively, and the dihedral angle between phenyl and furyl rings is 73.30 (11)°. An intra­molecular N—H⋯O hydrogen bond occurs between imino and carbonyl groups. In the crystal, weak C—H⋯O hydrogen bonds link the mol­ecules into supra­molecular chains along the b axis

The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish

SMYD4 belongs to a family of lysine methyltransferases. We analyzed the role of smyd4 in zebrafish development by generating a smyd4 mutant zebrafish line (smyd4L544Efs*1) using the CRISPR/Cas9 technology. The maternal and zygotic smyd4L544Efs*1 mutants demonstrated severe cardiac malformations, including defects in left-right patterning and looping and hypoplastic ventricles, suggesting that smyd4 was critical for heart development. Importantly, we identified two rare SMYD4 genetic variants in a 208-patient cohort with congenital heart defects. Both biochemical and functional analyses indicated that SMYD4(G345D) was pathogenic. Our data suggested that smyd4 functions as a histone methyltransferase and, by interacting with HDAC1, also serves as a potential modulator for histone acetylation. Transcriptome and bioinformatics analyses of smyd4L544Efs*1 and wild-type developing hearts suggested that smyd4 is a key epigenetic regulator involved in regulating endoplasmic reticulum-mediated protein processing and several important metabolic pathways in developing zebrafish hearts

Pattern recognition receptors in the development of nonalcoholic fatty liver disease and progression to hepatocellular carcinoma: An emerging therapeutic strategy

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and has become the leading chronic liver disease worldwide. NAFLD is viewed as the hepatic manifestation of metabolic syndrome, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to advanced fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD progression is still not clear. Pattern recognition receptor (PRR)-mediated innate immune responses play a critical role in the initiation of NAFLD and the progression of NAFLD-related HCC. Toll-like receptors (TLRs) and the cyclic GMP-AMP (cGAMP) synthase (cGAS) are the two major PRRs in hepatocytes and resident innate immune cells in the liver. Increasing evidence indicates that the overactivation of TLRs and the cGAS signaling pathways may contribute to the development of liver disorders, including NAFLD progression. However, induction of PRRs is critical for the release of type I interferons (IFN-I) and the maturation of dendritic cells (DCs), which prime systemic antitumor immunity in HCC therapy. In this review, we will summarize the emerging evidence regarding the molecular mechanisms of TLRs and cGAS in the development of NAFLD and HCC. The dysfunction of PRR-mediated innate immune response is a critical determinant of NAFLD pathology; targeting and selectively inhibiting TLRs and cGAS signaling provides therapeutic potential for treating NALF-associated diseases in humans

AFM and Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) Studies on Formation of Air-Stable Supported Lipid Bilayers

Supported lipid bilayers (SLBs) were prepared by deposition of unilamellar vesicles on a silicon substrate. Atomic force microscopy (AFM) and a new Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) developed by us were used to trace the dynamic formation of lipid bilayers on the silicon surfaces. The evolution from deformation of vesicles to formation of bilayers can be distinguished clearly by AFM imaging. MTR-IR provided high quality infrared spectra of ultrathin lipid bilayers with high sensitivity and high signal to noise ratio (SNR). The structural and orientational changes during vesicle’s fusion were monitored with MTR-IR. MTR-IR shows superiority over other infrared approaches for ultrathin films on standard silicon wafers in view of its economy and high sensitivity. Both MTR-IR and AFM results were consistent with each other and they provided more information for understanding the self-assembling procedure of SLBs

Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype. [Abstract copyright: Copyright © 2022 Gao, Rao, Wei, Xia, Huang, Tang, Hide, Zheng, Li, Zhao, Sun and Chen.