METTL16-mediated translation of CIDEA promotes non-alcoholic fatty liver disease progression via m6A-dependent manner.

Background: As the most prevalent chemical modifications on eukaryotic mRNAs, N6-methyladenosine (m6A) methylation was reported to participate in the regulation of various metabolic diseases. This study aimed to investigate the roles of m6A methylation and methyltransferase-like16 (METTL16) in non-alcoholic fatty liver disease (NAFLD). Methods: In this study, we used a model of diet-induced NAFLD, maintaining six male C57BL/6J mice on high-fat diet (HFD) to generate hepatic steatosis. The high-throughput sequencing and RNA sequencing were performed to identify the m6A methylation patterns and differentially expressed mRNAs in HFD mice livers. Furthermore, we detected the expression levels of m6A modify enzymes by qRT-PCR in liver tissues, and further investigated the potential role of METTL16 in NAFLD through constructing overexpression and a knockdown model of METTL16 in HepG2 cells. Results: In total, we confirmed 15,999 m6A recurrent peaks in HFD mice and 12,322 in the control. Genes with differentially methylated m6A peaks were significantly associated with the dysregulated glucolipid metabolism and aggravated hepatic inflammatory response. In addition, we identified five genes (CIDEA, THRSP, OSBPL3, GDF15 and LGALS1) that played important roles in NAFLD progression after analyzing the differentially expressed genes containing differentially methylated m6A peaks. Intriguingly, we found that the expression levels of METTL16 were substantially increased in the NAFLD model in vivo and in vitro, and further confirmed that METTL16 upregulated the expression level of lipogenic genes CIDEA in HepG2 cells. Conclusions: These results indicate the critical roles of m6A methylation and METTL16 in HFD-induced mice and cell NAFLD models, which broaden people's perspectives on potential m6A-related treatments and biomarkers for NAFLD.

Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 inflammasome and the nuclear factor-κB pathway after Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae (MP) can infect both the upper and lower respiratory tracts. Polydatin (PD), a traditional Chinese medicine, is known to have anti-inflammation and antifibrosis properties. However, the protective effects of PD against MP pneumonia (MPP) remain unclear. So, the aim of this study was to describe the therapeutic effects and underlying mechanisms of PD against MPP. BALB/c mice were assigned to three groups: a normal control group, MP infection group, or PD-treated MP infection group. BEAS-2B cells transfected with or without NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 (NLRP3) were used to confirm the protective mechanisms of PD. Immunohistochemical analysis, Western blot analysis, enzyme-linked immunosorbent assay, and flow cytometry were used in this study. The results showed that PD treatment suppressed MP-induced lung injury in mice by suppressing the expression of inflammatory factors and inhibiting the development of pulmonary fibrosis. Meanwhile, PD treatment inhibited activation of the NLRP3 inflammasome and nuclear factor κB (NF-κB) pathway. Overexpression of NLRP3 reversed the protective effect of PD against MP-induced injury of BEAS-2B cells. Taken together, these results indicate that PD treatment suppressed the inflammatory response and the development of pulmonary fibrosis by inhibiting the NLRP3 inflammasome and NF-κB pathway after MP infection.

Slow magnetic relaxation and field-induced metamagnetism in nitronyl nitroxide-Dy(III) magnetic chains.

The combination of lanthanide ions and nitronyl nitroxide radicals resulted in four new Ln-radical one-dimensional compounds, namely, [Ln(hfac)3{NIT-Ph(OMe)2}]n(Ln(III) = Sm (1), Eu (2), Gd (3), Dy (4); hfac = hexafluoroacetylacetonate; NIT-Ph(OMe)2 = 2-(2',4'-dimethoxyphenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxyl-3-oxide). The four complexes were found to be isomorphous and exhibit nitronyl nitroxide radicals-bridged lanthanides linear chains. DC magnetic susceptibilities show that the directly bonded nitronyl nitroxide interacts ferromagnetically with Gd and Dy ions. The Dy complex exhibits three-step metamagnetism and frequency-dependent ac magnetic susceptibilities, indicating single-chain magnet behavior. This work shows that the magnetic behaviors of one-dimensional Ln-nitronyl nitroxide chains can be fine tuned by the substituents of the radicals.

Construction of nitronyl nitroxide-based 3d-4f clusters: structure and magnetism.

Three unprecedented nitronyl nitroxide radical-bridged 3d-4f clusters, [Ln2 Cu2 (hfac)10 (NIT-3py)2 (H2 O)2 ](Ln(III) =Y, Gd, Dy), have been obtained from the self-assembly of Ln(hfac)3 , Cu(hfac)2 , and the radical ligand. The Dy complex shows a slow relaxation of magnetization, representing the first nitronyl nitroxide radical-based 3d-4f cluster with single-molecule magnet behavior.

Hetero-tri-spin [2p-3d-4f] chain compounds based on nitronyl nitroxide lanthanide metallo-ligands: synthesis, structure, and magnetic properties.

Employing nitronyl nitroxide lanthanide(III) complexes as metallo-ligands allowed the efficient and highly selective preparation of three series of unprecedented hetero-tri-spin (Cu-Ln-radical) one-dimensional compounds. These 2p-3d-4f spin systems, namely [Ln3Cu(hfac)11(NitPhOAll)4] (Ln(III) = Gd 1Gd, Tb 1Tb, Dy 1Dy; NitPhOAll = 2-(4'-allyloxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), [Ln3Cu(hfac)11(NitPhOPr)4] (Ln(III) = Gd 2Gd, Tb 2Tb, Dy 2Dy, Ho 2Ho, Yb 2Yb; NitPhOPr = 2-(4'-propoxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) and [Ln3Cu(hfac)11(NitPhOBz)4] (Ln(III) = Gd 3Gd, Tb 3Tb, Dy 3Dy; NitPhOBz=2-(4'-benzyloxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) involve O-bound nitronyl nitroxide radicals as bridging ligands in chain structures with a [Cu-Nit-Ln-Nit-Ln-Nit-Ln-Nit] repeating unit. The dc magnetic studies show that ferromagnetic metal-radical interactions take place in these hetero-tri-spin chain complexes, these and the next-neighbor interactions have been quantified for the Gd derivatives. Complexes 1Tb and 2Tb exhibit frequency dependence of ac magnetic susceptibilities, indicating single-chain magnet behavior.

Unprecedented nitronyl nitroxide bridged 3d-4f complexes: structure and magnetic properties.

Two novel 2p-3d-4f compounds, {Ln(hfac)3[Cu(hfac)2]3(NITPhPyrim)2} [Ln = Gd (1), Dy (2)], have been obtained by reacting phenyl pyrimidyl nitronyl nitroxide with Cu(hfac)2 and Ln(hfac)3. These two compounds are the first examples of two-dimensional 3d-4f complexes bridged by nitronyl nitroxide radicals. Overall ferromagnetic behaviors were observed in both compounds.