Increased METTL3 expression and m6A RNA methylation may contribute to the development of dry eye in primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder defined by xerostomia and keratoconjunctivitis sicca, and its etiology remains unknown. N6-methyladenosine (m6A) is the predominant posttranscriptional modification in eukaryotic mRNAs and is dynamically regulated by m6A regulators. Dysregulation of m6A modification is closely associated with several autoimmune disorders, but the role of m6A modification in pSS remains unknown. This study investigated the potential role of m6A and m6A-related regulators in pSS patients with dry eye. METHODS: This cross-sectional study included forty-eight pSS patients with dry eye and forty healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) were isolated, and the level of m6A in total RNA was measured. The expression of m6A regulators was determined utilizing real-time PCR and western blotting. The serological indicators detected included autoantibodies, immunoglobulins (Igs), complement factors (Cs), and inflammatory indicators. Dry eye symptoms and signs were measured, including the ocular surface disease index, Schirmer's test (ST), corneal fluorescein staining score (CFS), and tear break-up time. Spearman's correlation coefficient was employed to assess the associations of m6A and m6A-related regulator expression with clinical characteristics. RESULTS: The expression level of m6A was markedly increased in the PBMCs of pSS patients with dry eye compared to HCs (P value<0.001). The relative mRNA and protein expression levels of the m6A regulators methyltransferase-like 3 (METTL3) and YT521-B homology domains 1 were markedly elevated in pSS patients with dry eye (both P value<0.01). The m6A RNA level was found to be positively related to METTL3 expression in pSS patients (r = 0.793, P value<0.001). Both the m6A RNA level and METTL3 mRNA expression correlated with the anti-SSB antibody, IgG, ST, and CFS (all P values < 0.05). The m6A RNA level was associated with C4 (r = -0.432, P value = 0.002), while METTL3 mRNA expression was associated with C3 (r = -0.313, P value = 0.030). CONCLUSIONS: Our work revealed that the upregulation of m6A and METTL3 was associated with the performance of serological indicators and dry eye signs in pSS patients with dry eye. METTL3 may contribute to the pathogenesis of dry eye related to pSS.

Effect of interaction between Pd and Fe in modified red mud on catalytic decomposition of toluene.

As an industrial solid waste produced by alumina industry, red mud was modified as support of Pd catalysts for toluene catalytic oxidation in this paper. The xPd/MRM catalysts had high activity for toluene catalytic oxidation, and the 0.3Pd/MRM catalyst showed the best catalytic performance (T50 = 175 °C and T100 = 200 °C). The results indicated that the prepared 0.3Pd/MRM catalyst had more ratio of surface-adsorbed oxygen and Fe3+, rather than MRM and RM, which benefitted to the toluene oxidation. The excessive Pd species and the growth of the PdO nanoparticles negatively affected the catalytic efficiency of toluene. 0.4Pd/MRM activity decreased because of PdO aggregation in the catalyst, which could be confirmed by TEM analysis. The results of XPS, H2-TPR, FT-IR, O2-TPD, and Raman examination revealed that the formation of Pd-O-Fe under the interaction between Fe in MRM and Pd (Pd2+ + Fe 2+ → Pd0 + Fe3+) increased the electron transfer and raised the mobility of surface-adsorbed oxygen. Furthermore, in situ DRIFTS and GC-MS were used to detect intermediate products of catalytic reactions, and the reaction mechanism of catalysts was also studied. The catalytic oxidation of toluene on 0.3Pd/MRM catalyst might have two reaction paths simultaneously. The first reaction path would be toluene → species benzyl → benzaldehyde → benzoic acid → long-chain aldehydes or carboxylic acids → CO2 and H2O. The second reaction path would be toluene → benzene → phenol → long-chain aldehydes or carboxylic acids → CO2 and H2O.