Additional file 1: Table S1. of Prognostic impact of restored sinus rhythm in patients with sepsis and new-onset atrial fibrillation

Hazard ratio of different AF status for in-hospital mortality. Cox proportional hazard model with time-varying exposure was conducted for the analysis. (DOC 32 kb

Metabolic Engineering-Based Rapid Characterization of a Sesquiterpene Cyclase and the Skeletons of Fusariumdiene and Fusagramineol from <i>Fusarium graminearum</i>

The potential power of sesquiterpene synthase FgJ03939 from <i>Fusarium graminearum</i> was fully exploited in a farnesyl diphosphate-overexpressing <i>Saccharomyces cerevisiae</i> chassis to produce the novel sesquiterpenes fusariumdiene (<b>1</b>), <i>epi</i>-fusagramineol (<b>2</b>), and fusagramineol (<b>3</b>) with 5/7 bicyclic and 5/6/3 tricyclic ring systems, respectively, as well as five known sesquiterpenes (<b>4</b>–<b>8</b>). The structure of the unusual skeletons was characterized, and an absolute configuration was proposed. A mechanism for the biosynthesis of <b>1</b>–<b>8</b> was also proposed

Induction of autophagy by valproic acid enhanced lymphoma cell chemosensitivity through HDAC-independent and IP3-mediated PRKAA activation

<p>Autophagy is closely related to tumor cell sensitivity to anticancer drugs. The HDAC (histone deacetylase) inhibitor valproic acid (VPA) interacted synergistically with chemotherapeutic agents to trigger lymphoma cell autophagy, which resulted from activation of AMPK (AMP-activated protein kinase) and inhibition of downstream MTOR (mechanistic target of rapamycin [serine/threonine kinase]) signaling. In an HDAC-independent manner, VPA potentiated the effect of doxorubicin on lymphoma cell autophagy via reduction of cellular inositol 1,4,5 trisphosphate (IP3), blockade of calcium into mitochondria and modulation of PRKAA1/2-MTOR cascade. In murine xenograft models established with subcutaneous injection of lymphoma cells, dual treatment of VPA and doxorubicin initiated IP3-mediated calcium depletion and PRKAA1/2 activation, induced in situ autophagy and efficiently retarded tumor growth. Aberrant genes involving mitochondrial calcium transfer were frequently observed in primary tumors of lymphoma patients. Collectively, these findings suggested an HDAC-independent chemosensitizing activity of VPA and provided an insight into the clinical application of targeting autophagy in the treatment of lymphoma.</p

MOESM1 of Global transcriptional response of Aspergillus niger in the process of glucoamylase fermentation

Additional file 1: Table S1. All differentially expressed genes in the process of glucoamylase fermentation

Image_1_Enhanced lipid metabolism confers the immunosuppressive tumor microenvironment in CD5-positive non-MYC/BCL2 double expressor lymphoma.tiff

Lymphoma cells expressing CD5 (CD5+) confer inferior outcome of diffuse large B-cell lymphoma (DLBCL), especially in non–MYC/BCL2 double expressor (non-DE) patients. In tumor microenvironment, CD5+ non-DE tumor revealed increased proportion of immunosuppressive M2 macrophages and enhanced pathways related to macrophage activation and migration. In accordance to M2 activation, lipid metabolism was upregulated, including fatty acid uptake and fatty acid oxidation, which supplied energy for M2 macrophage polarization and activation. Meanwhile, CD36 expression was upregulated and strongly correlated to the proportion of M2 macrophages in CD5+ non-DE DLBCL. In vitro, a DLBCL cell line (LY10) overexpressing CD5 significantly increased M2 proportion in comparison with control when cocultured with peripheral blood mononuclear cells (PBMCs). The addition of metformin significantly decreased the M2 proportion and the CD36 expression level in the coculture systems, indicating that metformin could target altered lipid metabolism and decrease M2 macrophages in DLBCL, especially in CD5+ non-DE lymphoma. In conclusion, enhanced lipid metabolism and M2 macrophage activation contributed to the immunosuppressive tumor microenvironment and could be potential therapeutic targets in CD5+ non-DE DLBCL.</p

Image_2_Enhanced lipid metabolism confers the immunosuppressive tumor microenvironment in CD5-positive non-MYC/BCL2 double expressor lymphoma.tiff

Lymphoma cells expressing CD5 (CD5+) confer inferior outcome of diffuse large B-cell lymphoma (DLBCL), especially in non–MYC/BCL2 double expressor (non-DE) patients. In tumor microenvironment, CD5+ non-DE tumor revealed increased proportion of immunosuppressive M2 macrophages and enhanced pathways related to macrophage activation and migration. In accordance to M2 activation, lipid metabolism was upregulated, including fatty acid uptake and fatty acid oxidation, which supplied energy for M2 macrophage polarization and activation. Meanwhile, CD36 expression was upregulated and strongly correlated to the proportion of M2 macrophages in CD5+ non-DE DLBCL. In vitro, a DLBCL cell line (LY10) overexpressing CD5 significantly increased M2 proportion in comparison with control when cocultured with peripheral blood mononuclear cells (PBMCs). The addition of metformin significantly decreased the M2 proportion and the CD36 expression level in the coculture systems, indicating that metformin could target altered lipid metabolism and decrease M2 macrophages in DLBCL, especially in CD5+ non-DE lymphoma. In conclusion, enhanced lipid metabolism and M2 macrophage activation contributed to the immunosuppressive tumor microenvironment and could be potential therapeutic targets in CD5+ non-DE DLBCL.</p