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Interestingly, deletion of one sequence, encompassing amino acids 505-527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515-519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective walls rich in long chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with wild-type bacteria. These findings indicate that MtrP and TmaT have non-redundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in Corynebacterineae. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 μM (yeast PGK1) and 6.86 μM (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 μM (yeast PGK1) and 186 μM (human PGK1). The Vmax of the forward reaction was about 3.5- and 5.8-fold higher than that of the reverse reaction for the human and yeast enzymes, respectively. Consistently, the intracellular steady-state concentrations of 3-PG were between 180 and 550 μM in cancer cells, providing a basis for glycolysis to shuttle 3-PG to the serine synthesis pathway. Using siRNA-mediated PGK1-specific knockdown in five cancer cell lines derived from different tissues, along with titration of PGK1 in a cell-free glycolysis system, we found that the perturbation of PGK1 had no or only marginal effects on the glucose consumption and lactate generation. The PGK1 knockdown increased the concentrations of fructose 1,6-bisphosphate (FBP), dihydroxyacetone phosphate (DHAP), glyceraldehyde 3-phosphate (GA3P), and 1,3-BPG in nearly equal proportions, controlled by the kinetic and thermodynamic states of glycolysis. We conclude that perturbation of PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Thyroid cancer (TC) is the most common endocrine malignancy, and miR-574 is significantly up-regulated in TC. However, the role and underlying mechanism of miR-574 in TC development are poorly understood. In this study, we showed that NF-κB/p65 signaling pathway was activated and miR-574 was up-regulated in TC cells. p65 directly bound to the promoter of miR-574 and activated miR-574 transcription. Functionally, miR-574 inhibited apoptosis, promoted proliferation and migration of TC cells, and stimulated TC-induced tube formation of endothelial cells. On the molecular level, miR-574 inhibited the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) by binding to 3′-UTR of BNIP3. miR-574 also down-regulated the expression of apoptosis-inducing factor (AIF), while elevated the levels of MMP2, MMP9, and VEGFA. In vivo, miR-574 promoted xenograft growth, which was associated with reduced apoptosis and enhanced angiogenesis. NF-B/miR-574 signaling presents multiple oncogenic activities on TC development by directly regulating the BNIP3/AIF pathway. Therefore, targeting NF-B/miR-574 signaling may reduce the aggressiveness of TC. Implications miR-574, directly regulated by NF-κB/p65, promotes tumorigenesis of thyroid cancer via inhibiting BNIP3/AIF pathway. Copyright ©2020, American Association for Cancer Research.INTRODUCTION It is uncertain whether treatment by recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) can promote healing of deep second-degree burns. This meta-analysis aimed to systematically review and assess randomised controlled trials (RCTs) that investigated the efficacy and safety of rhGM-CSF for treating deep second-degree burns. METHODS This meta-analysis conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. The PubMed, Cochrane Library, Medline and Embase databases and relevant references were systematically searched for RCTs (published up to November 2019). selleck chemical Main outcome measures included the wound healing rate, wound healing time and average optical densities of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). We performed a meta-analysis using fixed or random effects models. RESULTS Seven RCTs comprising 982 patients with 1184 burns (652 patients received rhGM-CSF vs 532 controls) were included. Compared with standard wound care alone, the use of rhGM-CSF significantly reduced wound healing time by 4.