Design, synthesis and anti-NASH effect evaluation of novel GFT505 derivatives in vitro and in vivo.

Non-alcoholic fatty liver disease (NAFLD) is emerging as the largest burden of chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a progressive form of NAFLD that can progress to cirrhosis and hepatocellular carcinoma. Unfortunately, current treatment options for NASH are very limited. Among the multiple pathways of NASH, peroxisome proliferators-activated receptors (PPARS) are recognized as an important and effective target. GFT 505 is a dual excitement agent for the treatment of PPAR-α/δ for the treatment of NASH. However, its activity and toxicity need to be further improved. Therefore, here we would like to report the design, synthesis and biological evaluation of 11 GFT 505 derivatives. The initial cytotoxicity through proliferation activity of HepG2 cells and in vitro anti-NASH activity evaluation demonstrated that under the same concentration, the compound 3d possess significantly lower cytotoxicity and better anti-NASH activity than that of GFT 505. Moreover, Molecular docking also shows that 3d and PPAR-α/δ can form a stable hydrogen bond and have the lowest binding energy. Therefore this novel molecule 3d was selected to go further in vivo investigation. Methionine-choline deficiency (MCD) induced C57BL/6J NASH model mice was used for the in vivo biological experiments and the compound 3d demostrated lower liver toxicity than that of GFT 505 in the body at the same dose, and it did more effectively improve hyperlipidemia, liver fat degeneration and liver inflammation as well as significantly enhance the content of the GSH which is inportant for the liver protection. This study suggested that the compound 3d is a very promising lead compound for the treatment of NASH.

ZIF-67 Derivative Decorated MXene for a Highly Integrated Flexible Self-Powered Photodetector.

The rapid development of portable and wearable electronics has promoted the integration of multifunction techniques. Although flexible energy storage systems have been successfully investigated, the compact configuration with photodetector and energy storage components has received less attention. As a new member of the 2D material class, MXene exhibits remarkable electronic and optical properties. Here, through the intentional introduction of ZIF-67 derivatives deposited on the Mo2CTx nanosheets, the synthesized Co-CoOx/NC/Mo2CTx heterostructure not only provided a straightforward pathway for photogenerated electrons to transport but also enhanced the structural stability of Mo2CTx, leading to a high responsivity and short rise/decay time under the illumination of simulated light in the photoelectrochemical (PEC) configuration. The integrated flexible device based on a zinc ion battery and Co-CoOx/NC/Mo2CTx heterostructure shows outstanding photodetection function and retains the intrinsic charge/discharge behaviors, which could monitor 1 day sunlight changes in real time. The paradigm presented here paves the way for realizing the development of miniaturization and multifunction toward next-generation portable and wearable technologies.