Increasing the energy band gap under the premise to maintain a large nonlinear optical (NLO) response is a challenging issue for the exploration and molecular design of mid-infrared nonlinear optical...

Nonalcoholic steatohepatitis (NASH) is a key step in the progression of nonalcoholic fatty liver (NAFL) to cirrhosis. However, the molecular mechanisms of the NAFL-to-NASH transition are largely unknown. Here, we identify methyltransferase like 3 (METTL3) as a key negative regulator of NASH pathogenesis. Hepatocyte-specific deletion of Mettl3 drives NAFL-to-NASH progression by increasing CD36-mediated hepatic free fatty acid uptake and CCL2-induced inflammation, which is due to increased chromatin accessibility in the promoter region of Cd36 and Ccl2. Antibody blockade of CD36 and CCL2 ameliorates NASH progression in hepatic Mettl3 knockout mice. Hepatic overexpression of Mettl3 protects against NASH progression by inhibiting the expression of CD36 and CCL2. Mechanistically, METTL3 directly binds to the promoters of the Cd36 and Ccl2 genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in  their promoters, thus suppressing Cd36 and Ccl2 transcription. Furthermore, METTL3 is translocated from the nucleus to the cytosol in NASH, which is associated with CDK9-mediated phosphorylation of METTL3. Our data reveal a mechanism by which METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against NASH progression.

In this work, we design and synthesize a new chalcogenide LiGaGeS on the basis of known infrared (IR) material LiGaS by partially substituting Ga with Ge. This compound possesses very strong nonlinear (NLO) response (2.5 × LiGaS) and large band gap (3.52 eV), manifesting a better balance between band gap and NLO response compared with that for LiGaS. Moreover, LiGaGeS exhibits a much lower melting point (663 °C) than that of LiGaS (1050 °C). This would result in the much smaller vapor pressure of sulfur in the fused quartz vessels used for the crystal growth, and thus, it should be greatly beneficial to obtain the large stoichiometric LiGaGeS single crystal. Our studies demonstrate that LiGaGeS is a good candidate material for IR NLO applications.