Cardiovascular diseases (CVDs) represent the largest contributor to mortality worldwide. Identification of novel therapeutic targets and biomarkers for CVDs is urgently needed. Circular RNAs (circRNAs) are endogenous, abundant, and stable non-coding RNAs formed by back-splicing events. Their role as regulators of gene expression has been increasingly reported. Notably, circRNAs mediate essential physiological and pathological processes in the cardiovascular system. Our first aim, therefore, is to summarize recent advances in the role of circRNAs in cardiac development as well as in pathogenesis of various CVDs. Because circRNAs are stable in circulation and their dynamic changes may reflect different disease stages, they are considered ideal biomarkers. Therefore, our second aim is to review studies that have identified circulating circRNAs as biomarkers for CVDs. Finally, we discuss the shortage of functional studies and the limitations of available clinical studies and provide future perspectives.
Tigecycline is one of the last-resort antibiotics to treat severe infections. Recently, tigecycline resistance has sporadically emerged with an increasing trend, and Tet(X) family represents a new resistance mechanism of tigecycline. In this study, a novel chromosome-encoded tigecycline resistance gene, tet(X14), was identified in a tigecycline-resistant and colistinresistant Empedobacter stercoris strain ES183 recovered from a pig fecal sample in China. Tet(X14) shows 67.14-96.39% sequence identity to the other variants [Tet(X) to Tet(X13)]. Overexpression of Tet(X14) in Escherichia coli confers 16fold increase in tigecycline MIC (from 0.125 to 2 mg/L), which is lower than that of Tet(X3), Tet(X4) and Tet(X6). Structural modelling predicted that Tet(X14) shared a high homology with the other 12 variants with RMSD value from 0.003 to 0.055, and Tet(X14) can interact with tetracyclines by a similar pattern as the other Tet(X)s. tet(X14) and two copies of tet(X2) were identified on a genome island with abnormal GC content carried by the chromosome of ES183, and no mobile genetic elements were found surrounding, suggesting that tet(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome of Riemerella anatipestifer, mainly encoded on antimicrobial resistance islands. E. stercoris and R. anatipestifer belong to the family Flavobacteriaceae, suggesting that the members of Flavobacteriaceae maybe the major reservoir of tet(X14). Our study reports a novel chromosome-encoded tigecycline resistance gene tet(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance for tet(X)-mediated tigecycline resistance.
Summary Scheduling multiple parallel workflows, which arrive at different instants on heterogeneous distributed computing systems, is a great challenge because of the different requirements of resource providers and users. Overall scheduling length is the main concern of resource providers, whereas deadlines of workflows are the major requirements of users. Most algorithms use fairness‐based strategies to reduce the overall scheduling length. However, these algorithms cause obvious unfairness to longer‐makespan workflows or shorter‐makespan workflows. Furthermore, the systems cannot meet the deadlines of all workflows, particularly on large‐scale resource‐constrained computational grids. Gaining a reasonable balance between the overall scheduling length and the deadlines of workflows is a desirable goal. In this study, we first propose a fairness‐based scheduling algorithm called fairness‐based dynamic multiple heterogeneous selection value to achieve high performance of systems compared with existing works. Then, to meet the deadlines of partial higher‐priority workflows, we present a priority‐based scheduling algorithm called priority‐based dynamic multiple heterogeneous selection value. Finally, combining fairness‐based dynamic multiple heterogeneous selection value and priority‐based dynamic multiple heterogeneous selection value, we present the tradeoff‐based scheduling algorithm to meet the deadlines of more higher‐priority workflows while still allowing the lower‐priority workflows to be processed actively for better performance of systems. Both example and extensive experimental evaluations demonstrate significant improvement of our proposed algorithms. Copyright © 2016 John Wiley & Sons, Ltd.
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