The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here, we show that glutamate potentiates aminoglycoside antibiotics, resulting in improved elimination of antibiotic-resistant pathogens. When exploring the metabolic flux of glutamate, it was found that the enzymes that link the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway to the TCA cycle were key players in this increased efficacy. Together, the PEP-pyruvate-AcCoA pathway and TCA cycle can be considered the pyruvate cycle (P cycle). Our results show that inhibition or gene depletion of the enzymes in the P cycle shut down the TCA cycle even in the presence of excess carbon sources, and that the P cycle operates routinely as a general mechanism for energy production and regulation in and These findings address metabolic mechanisms of metabolite-induced potentiation and fundamental questions about bacterial biochemistry and energy metabolism.

Circular RNAs, as hopeful diagnosis markers and therapeutic molecules, have been studied, probed and applied into several diseases, such as cardiovascular diseases, systemic lupus erythematosus, leukemia, pulmonary tuberculosis, and cancer especially. Recently, mounting evidence has supported that circRNAs play a key role in the tumorigenesis, progress, invasion and metastasis in lung cancer. Its special structure-3′-5′ covalent loop-allow it to execute several special functions in both normal eukaryotic cells and cancer cells. Our review summaries the latest studies on characteristics and biogenesis of circRNAs, and highlight the regulatory functions about miRNA sponge of lungcancer-related circRNAs. In addition, the interaction of the circRNA-miRNA-mRNA regulatory network will also be elaborated in detail in this review. Therefore, this review can provide a new idea or strategy for further development and application in clinical setting in terms of early-diagnosis and better treatment.

Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistant Escherichia coli , whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system.

Background: The systemic use of corticosteroids for patients in severe community-acquired pneumonia (CAP) remains disputed in clinical practice. We undertook a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with severe CAP. Methods: We searched MEDLINE (1946 to June 2018), EMBASE (1966 to June 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for severe CAP. The endpoints of the study included total mortality, length of intensive care unit (ICU) stay and mechanical ventilation. Results: Nine trials which contained 914 patients were included for final meta-analysis. Of the 488 patients in the corticosteroid group, there were 37 deaths (7.58%) and 56 deaths occurred in 426 patients in the control group (13.1%). Corticosteroid therapy was associated with a lower rate of all-cause mortality compared to control (odd ratio [OR] 0.63, 95% confidence interval [CI] 0.42–0.95, P = .03). Subgroup analysis was conducted to show that the drug type modified the effect of steroids for mortality rate: prednisolone or methylprednisolone therapy (OR 0.37, 95% CI 0.19–0.72) reduced total mortality, whereas hydrocortisone use did not (OR 0.90, 95% CI 0.54–1.49). We found the length of ICU stay was significantly shorter in the steroid group compared to control (MD −2.52 days, 95% CI −4.88 to −0.15; P = .04). And there was a reduction trend in the need for mechanical ventilation in corticosteroid group (OR 0.53, 95% CI 0.28–1.02; P = .06). There was no trend towards more adverse events in the corticosteroid arm compared to control (OR 0.92, 95% CI 0.58–1.47; P = .74). Conclusion: Overall, adjunctive systemic corticosteroids therapy was effective and safe for patients with severe CAP. In addition, the effects of mortality may differ according to the type of corticosteroids.