Metagenomics insights into gentamicin degradation and the dynamic of antibiotic resistance genes during co-composting of the gentamicin myelial residues with addition of various organic wastes.

Increasing antibiotic mycelial residues (AMRs) and related antibiotic resistance genes (ARGs) pose a significant threat to ecosystems and public health. Composting is a crucial method for recycling AMRs. However, the variation in ARGs and gentamicin degradation in the composting process of gentamicin mycelial residues (GMRs) has received little attention on an actual industrial scale. This research investigated the metabolic pathways and functional genes on the gentamicin and ARGs removal during the co-composting of GMRs with addition of various organic wastes (rice chaff, mushroom residue, etc.) under various C/N ratios (15:1, 25:1, 35:1). The results showed that the removal efficiencies of gentamicin and the total ARGs were 98.23 % and 53.20 %, respectively, with the C/N ratio of 25:1. Moreover, metagenomics and LS-MS/MS analysis demonstrated that the acetylation was the primary pathway for gentamicin biodegradation and the corresponding degrading genes were the categories of aac(3) and aac(6'). However, the relative abundance of aminoglycoside resistance genes (AMGs) were increased after 60 days composting. The partial least squares path modeling analysis demonstrated that the AMG abundance was directly influenced by the predominant mobile gene elements intI1 (p < 0.05) which was closely related to the bacterial community composition. Therefore, the ecological environmental risks should be assessed in the future application of GMRs composting products.

TSMiner: a novel framework for generating time-specific gene regulatory networks from time-series expression profiles.

Time-series gene expression profiles are the primary source of information on complicated biological processes; however, capturing dynamic regulatory events from such data is challenging. Herein, we present a novel analytic tool, time-series miner (TSMiner), that can construct time-specific regulatory networks from time-series expression profiles using two groups of genes: (i) genes encoding transcription factors (TFs) that are activated or repressed at a specific time and (ii) genes associated with biological pathways showing significant mutual interactions with these TFs. Compared with existing methods, TSMiner demonstrated superior sensitivity and accuracy. Additionally, the application of TSMiner to a time-course RNA-seq dataset associated with mouse liver regeneration (LR) identified 389 transcriptional activators and 49 transcriptional repressors that were either activated or repressed across the LR process. TSMiner also predicted 109 and 47 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways significantly interacting with the transcriptional activators and repressors, respectively. These findings revealed the temporal dynamics of multiple critical LR-related biological processes, including cell proliferation, metabolism and the immune response. The series of evaluations and experiments demonstrated that TSMiner provides highly reliable predictions and increases the understanding of rapidly accumulating time-series omics data.

circCCT3 Modulates Vascular Endothelial Growth Factor A and Wnt Signaling to Enhance Colorectal Cancer Metastasis Through Sponging miR-613.

Colorectal cancer (CRC) has been suggested to be one of the leading cancer types all over the world. Till now, the molecular mechanism by which circCCT3 regulates CRC remains to be clarified. To detect mRNA and protein levels of various genes, Reverse Transcription-quantitative PCR and western blot were used in our study. Luciferase reporter assay was utilized to probe direct interaction between genes. We used transwell assay to assess the invasion ability of CRC cells. For apoptosis detection, immunofluorescence of CRC cells by Annexin V staining was performed. We carried out bioinformatic analysis to show higher expression of circCCT3 in human clinical CRC tumors. Low level of circCCT3 was closely associated with higher disease-free survival of CRC patients. Moreover, we found that circCCT3 was linked to advanced stage of CRC. miR-613 is the target of circCCT3 and responsible for circCCT3-modulated invasion and apoptosis of CRC cells. In addition, we identified WNT3 and vascular endothelial growth factor A (VEGFA) as downstream effectors of miR-613 in CRC cells. WNT3 and VEGFA overexpression resulted in partial rescue of miR-613-mediated phenotypes of CRC cells. In conclusion, we propose that circCCT3 contributes to CRC metastasis via miR-613/WNT3 or miR-613/VEGFA, promoting the development of therapeutical approaches for treating CRC.

[Expression of microRNA-10a-5p in laryngeal epithelial premalignant lesions].

OBJECTIVE: To investigate the expression of microRNA-10a-5p (miR-10a) in laryngeal epithelial premalignant lesions (LEPL) and to analyze the correlations of its dysregulation with clinicopathologic parameters of LEPL. METHODS: According to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ ( CIS). The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlated with the clinical and follow-up data of all LEPL patients. RESULTS: miR-10a was down-regulated in LEPL with increasing grade of dysplasia. There was significantly statistical difference between low-risk ( MID + MOD) and high-risk ( SD + CIS) lesion groups (P = 0.03). The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P < 0.05). CONCLUSIONS: Down regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer.