Data_Sheet_1_Enterovirus 71 Suppresses miR-17-92 Cluster Through Up-Regulating Methylation of the miRNA Promoter.docx

Enterovirus 71 (EV71), the etiological agent of hand-foot-and-mouth disease, has become an increasing public health challenge worldwide. Accumulating evidence suggests that mammalian microRNAs (miRNAs), a class of non-coding RNAs of 18 to 24 nucleotides (nt) with important regulatory roles in cellular processes, participate in host antiviral defense and studies have suggested roles of miRNAs in EV71 replication and pathogenesis. In the current study, we reported that the expression of hsa-miR-17∼92 cluster was significantly downregulated during EV71 infection. Overexpression of hsa-miR-17∼92 inhibited, while inhibition of endogenous hsa-miR-17∼92 facilitated EV71 replication. We identified two sequences located at nt 3024 to 3038 and nt 2838 to 2862 of the EV71 (strain FY0805) genome as potential targets for hsa-miR-17-5p and miR-19a/b, respectively, which were validated by luciferase reporter assays and Western blot. Meanwhile, we identified DNA methylation as a novel mechanism of hsa-miR-17∼92 regulatory roles. The methylation of the miR-17-92 promoter was significantly increased (50%) upon EV71 infection, which appeared to be caused by the increased expression of DNMT3B but not DNMT1 and DNMT3A. Furthermore, we demonstrated that the members of miR-17-92 cluster were decreased in the sera of EV71 infected patients, suggesting the clinical implication and the potential therapeutic application of miR-17-92.</p

Table_1_Severe Fever With Thrombocytopenia Syndrome Virus-Induced Macrophage Differentiation Is Regulated by miR-146.XLSX

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with a high mortality rate in humans, which is caused by SFTS virus (SFTSV), a novel phlebovirus in the Bunyaviridae family, is tick borne and endemic in Eastern Asia. Previous study found that SFTSV can infect and replicate in macrophages in vivo and in vitro. However, the role of macrophages in virus replication and the potential pathogenic mechanisms of SFTSV in macrophage remain unclear. In this study, we provided evidence that the SFTSV infection drove macrophage differentiation skewed to M2 phenotype, facilitated virus shedding, and resulted in viral spread. We showed evidence that miR-146a and b were significantly upregulated in macrophages during the SFTSV infection, driving the differentiation of macrophages into M2 cells by targeting STAT1. Further analysis revealed that the elevated miR-146b but not miR-146a was responsible for IL-10 stimulation. We also found that SFTSV increased endogenous miR-146b-induced differentiation of macrophages into M2 cells mediated by viral non-structural protein (NSs). The M2 skewed differentiation of macrophages may have important implication to the pathogenesis of SFTS.</p

Mechanistic Insights of Ethanol Steam Reforming over Ni–CeO_<i>x</i>(111): The Importance of Hydroxyl Groups for Suppressing Coke Formation

We have studied the reaction of ethanol and water over Ni–CeO_2‑<i>x</i>(111) model surfaces to elucidate the mechanistic steps associated with the ethanol steam reforming (ESR) reaction. Our results provide insights about the importance of hydroxyl groups to the ESR reaction over Ni-based catalysts. Systematically, we have investigated the reaction of ethanol on Ni–CeO_2‑<i>x</i>(111) at varying Ce³⁺ concentrations (CeO_1.8–2.0) with absence/presence of water using a combination of soft X-ray photoelectron spectroscopy (sXPS) and temperature-programmed desorption (TPD). Consistent with previous reports, upon annealing, metallic Ni formed on reduced ceria while NiO was the main component on fully oxidized ceria. Ni⁰ is the active phase leading to both the C–C and C–H cleavage of ethanol but is also responsible for carbon accumulation or coking. We have identified a Ni₃C phase that formed prior to the formation of coke. At temperatures above 600 K, the lattice oxygen from ceria and the hydroxyl groups from water interact cooperatively in the removal of coke, likely through a strong metal–support interaction between nickel and ceria that facilitates oxygen transfer