Cleavage of 3′-terminal adenosine by archaeal ATP-dependent RNA ligase

Methanothermobacter thermoautotrophicus RNA ligase (MthRnl) catalyzes formation of phosphodiester bonds between the 5′-phosphate and 3′-hydroxyl termini of single-stranded RNAs. It can also react with RNA with a 3′-phosphate end to generate a 2′,3′-cyclic phosphate. Here, we show that MthRnl can additionally remove adenosine from the 3′-terminus of the RNA to produce 3′-deadenylated RNA, RNA(3′-rA). This 3′-deadenylation activity is metal-dependent and requires a 2′-hydroxyl at both the terminal adenosine and the penultimate nucleoside. Residues that contact the ATP/AMP in the MthRnl crystal structures are essential for the 3′-deadenylation activity, suggesting that 3′-adenosine may occupy the ATP-binding pocket. The 3′-end of cleaved RNA(3′-rA) consists of 2′,3′-cyclic phosphate which protects RNA(3′-rA) from ligation and further deadenylation. These findings suggest that ATP-dependent RNA ligase may act on a specific set of 3′-adenylated RNAs to regulate their processing and downstream biological events

HMGA1 variant IVS5-13insC is associated with insulin resistance and type 2 diabetes: an updated meta-analysis

Background: High-mobility group A1 (HMGA1) polymorphism has been suspected as a gene variant associated with type 2 diabetes (T2D). However, conflicting outcomes have been reported. Objective: This meta-analysis aimed to predict the association between the HMGA1 variant IVS5-13insC and T2D. Methods: Statistical analyses were performed using Stata/SE 12.0 software. Results: A total of 11 case-control studies in 6 articles were included. Results suggested that the HMGA1 variant IVS5-13insC was associated with an increased risk of insulin resistance (OR = 0.61, 95% CI 0.56 to 0.66, P < 0.0001), T2D (OR = 0.67, 95% CI 0.61 to 0.73, P < 0.0001), particularly for Caucasians with increased risks of T2D (OR = 0.56, 95% CI 0.49 to 0.65, P < 0.0001) compared with wild-type subjects. Conclusion: This meta-analysis indicated that the HMGA1 variant IVS5-13insC can be a risk factor of T2D development, particularly among Caucasians. Significant risks were also found (Asian: OR = 0.74, 95% CI: 0.63 to 0.86, P < 0.0001, Hispanic-American: OR = 0.81, 95% CI: 0.65 to 1.01, P < 0.0001) in non-Caucasian population. However, ethnical studies should be conducted to reveal whether the HMGA1 variant IVS5-13insC is associated with an increased risk of T2D.Keywords: HMGA1, type 2 diabetes, insulin resistance, variant, meta-analysis

Antioxidant Activities of Plumbagin and Its Cu (II) Complex

Plumbagin and its Cu (II) complex [Cu (plumbagin)2]·H2O have been synthesized, and their antioxidant activities towards the inhibitory effect on DPPH free radical, reducing power, total antioxidant capacity, and inhibition on lipid peroxidation were investigated. Plumbagin and its Cu (II) complex were found to exhibit scavenging activities on DPPH radical with the inhibitory rate of 41% and 24%, respectively. The reducing power of plumbagin was outstanding at the concentrations of 1.0, 1.5, and 2.0 mg/mL, compared to Cu (II) complex and synthetic antioxidant 2,6-di-ter-butyl-4-methylphenol (BHT); the highest level reached 1.333 for plumbagin and 0.581 for Cu (II) complex. Also, the inhibition on lipid peroxidation of plumbagin was higher than that of Cu (II) complex and BHT, 46.4% for plumbagin and 24.5% for Cu (II) complex. The results give a strong impact for designing anticancer drugs, combined with their potential cytotoxic and antioxidant activities, which can be targeted selectively against cancer cells and increase their therapeutic index and additional advantages over other anticancer drugs

Effects of dietary oxidized fish oil on the growth performance, intestinal health, and antioxidant capacity of zebrafish

This study aimed to investigate the effects of oxidized fish oil (OFO) on growth performance, intestinal health, and antioxidant function and to determine the minimum concentration of oxidized fish oil to cause irreversible damage to the intestinal tissue structure of zebrafish. A 30-day feeding trial on zebrafish (average weight 0.054 g) was conducted in triplicate groups of fish fed four test diets containing different concentrations of OFO: 0% OFO (OFF, blank control), 2% OFO (OF1), 4% OFO (OF2), and 6% OFO (OF3). The body weight gain (WG), specific growth rates (SGR), feed conversion ratio (FCR), survival rate (SR), and antioxidant function {glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), catalase (CAT), and malondialdehyde (MDA)} were recorded. The intestinal structure was observed at the end of the trial. After the 14-day experimental period, Final body weight (FBW), WG, and SGR decreased significantly with the increase in the concentration of feed OFO (P < 0.05), while FCR showed a downward trend. The activity of T-SOD decreased significantly, the activities of GSH-PX and CAT, and the MDA content increased significantly with the increase in the concentration of feed OFO (P < 0.05). The intestinal morphological damage score showed an upward trend with the increase in the concentration of OFO, and it was significantly higher in group OF2 and OF3 than in group OF1 (P < 0.05). After the 28-day test period, the experimental indexes and intestinal antioxidant function trends were the same as those on 14 days. The increased OFO concentration significantly increased the intestinal morphological injury score (P < 0.05). These results demonstrated that adding 4% OFO to the feed for 14 days could induce irreversible damage to the intestinal tissue structure, weaken the antioxidant function, and decrease the growth performance of zebrafish

Probiotic consumption and hepatic steatosis: results from the NHANES 2011–2016 and Mendelian randomization study

BackgroundRecent research showed that probiotics treatment may reduce insulin resistance, regulate lipid metabolism, raise liver enzyme levels, and ameliorate inflammation in individuals with metabolic associated fatty liver disease (MAFLD). However, the possible effects of probiotic use on the progression of hepatic steatosis (HS) have not been identified. The purpose of this study was to investigate this in a large population database.MethodsThe cross-sectional research was conducted among adults with complete data on probiotic yogurt consumption and HS in the 2011–2016 National Health and Nutrition Examination Survey (NHANES). Probiotic yogurt consumption was assessed using a dietary supplement questionnaire, while HS was evaluated with HS index (HSI). To explore their relationship, weighted univariate regression analysis, subgroup analysis, and interaction analysis were conducted. To evaluate the causal association between yogurt consumption and NAFLD, mendelian randomization analysis (MR) were performed. A restricted cubic spline (RCS) was used to analyze the relationship curve between the leves of yogurt consumption and hepatic steatosis.ResultsA total of 7,891 participants were included in the study represented 146.7 million non-institutionalized residents of the United States, of whom 4,322 (54.77%) were diagnosed with HS. Multivariable logistic regression showed probiotic yogurt consumption had significantly inverse relationship for HS (OR = 0.84, 95% CI: 0.72–0.97, p = 0.02) after adjusting for all covariates. Once more, the independent relationship between probiotic yogurt consumption and HS was verified by subgroup analysis and interaction analysis. The MR analysis results indicate that there is no causal relationship between yogurt consumption and NAFLD. The RCS model demonstrated a robust J-shaped link between yogurt consumption and HS, revealing a significant decrease in risk within the lower range of yogurt consumption, which attained the lowest risk close to 0.4 cup.ConclusionAccording to the NHANES data, the consumption of probiotics and yogurt has a beneficial effect on HS, whereas the MR results indicated it was not related to NAFLD. The RCS analysis indicates a J-shaped relationship between yogurt consumption and HS, which may account for the inconsistency in the results. Based on these findings, we recommend that adults take half a cup of yogurt daily

Archaea ATP-Dependent RNA Ligase

RNA ligases play important roles in repairing and circularizing RNAs post-transcriptionally. In this study, we generated an allelic knockout of ATP-dependent RNA ligase (Rnl) in the hyperthermophilic archaeon Thermococcus kodakarensis to identify its biological targets. A comparative analysis of circular RNA reveals that the Rnl-knockout strain represses circularization of C/D box sRNAs without affecting the circularization of tRNA and rRNA processing intermediates. Recombinant archaeal Rnl could circularize C/D box sRNAs with a mutation in the conserved C/D box sequence element but not when the terminal stem structures were disrupted, suggesting that proximity of the two ends could be critical for intramolecular ligation. Furthermore, T. kodakarensis accumulates aberrant RNA fragments derived from ribosomal RNA in the absence of Rnl. These results suggest that Rnl is responsible for C/D box sRNA circularization and may also play a role in ribosomal RNA processing

HMGA1 variant IVS5-13insC is associated with insulin resistance and type 2 diabetes: an updated meta-analysis

Background: High-mobility group A1 (HMGA1) polymorphism has been suspected as a gene variant associated with type 2 diabetes (T2D). However, conflicting outcomes have been reported. Objective: This meta-analysis aimed to predict the association between the HMGA1 variant IVS5-13insC and T2D. Methods: Statistical analyses were performed using Stata/SE 12.0 software. Results: A total of 11 case-control studies in 6 articles were included. Results suggested that the HMGA1 variant IVS5-13insC was associated with an increased risk of insulin resistance (OR = 0.61, 95% CI 0.56 to 0.66, P &lt; 0.0001), T2D (OR = 0.67, 95% CI 0.61 to 0.73, P &lt; 0.0001), particularly for Caucasians with increased risks of T2D (OR = 0.56, 95% CI 0.49 to 0.65, P &lt; 0.0001) compared with wild-type subjects. Conclusion: This meta-analysis indicated that the HMGA1 variant IVS5-13insC can be a risk factor of T2D development, particularly among Caucasians. Significant risks were also found (Asian: OR = 0.74, 95% CI: 0.63 to 0.86, P &lt; 0.0001, Hispanic-American: OR = 0.81, 95% CI: 0.65 to 1.01, P &lt; 0.0001) in non-Caucasian population. However, ethnical studies should be conducted to reveal whether the HMGA1 variant IVS5-13insC is associated with an increased risk of T2D

Value of contrast-enhanced CT based radiomic machine learning algorithm in differentiating gastrointestinal stromal tumors with KIT exon 11 mutation: a two-center study

PURPOSEKnowing the genetic phenotype of gastrointestinal stromal tumors (GISTs) is essential for patients who receive therapy with tyrosine kinase inhibitors. The aim of this study was to develop a radiomic algorithm for predicting GISTs with KIT exon 11 mutation.METHODSWe enrolled 106 patients (80 in the training set, 26 in the validation set) with clinicopathologically confirmed GISTs from two centers. Preoperative and postoperative clinical characteristics were selected and analyzed to construct the clinical model. Arterial phase, venous phase, delayed phase, and tri-phase combined radiomics algorithms were generated from the training set based on contrast-enhanced computed tomography (CE-CT) images. Various radiomics feature selection methods were used, namely least absolute shrinkage and selection operator (LASSO); minimum redundancy maximum relevance (mRMR); and generalized linear model (GLM) as a machine-learning classifier. Independent predictive factors were determined to construct preoperative and postoperative radiomics nomograms by multivariate logistic regression analysis. The performances of the clinical model, radiomics algorithm, and radiomics nomogram in distinguishing GISTs with the KIT exon 11 mutation were evaluated by area under the curve (AUC) of the receiver operating characteristics.RESULTSOf 106 patients who underwent genetic analysis, 61 had the KIT exon 11 mutation. The combined radiomics algorithm was found to be the best prediction model for differentiating the expression status of the KIT exon 11 mutation (AUC = 0.836; 95% confidence interval [CI], 0.640-0.951) in the validation set. The clinical model, and preoperative and postoperative radiomics nomograms had AUCs of 0.606 (95% CI, 0.397-0.790), 0.715 (95% CI, 0.506-0.873), and 0.679 (95% CI, 0.468-0.847), respectively, with the validation set.CONCLUSIONThe radiomics algorithm could distinguish GISTs with the KIT exon 11 mutation based on CE-CT images and could potentially be used for selective genetic analysis to support the precision medicine of GISTs

Knowledge and risk behaviors related to HIV/AIDS, and their association with information resource among men who have sex with men in Heilongjiang province, China

<p>Abstract</p> <p>Backgroud</p> <p>In Heilongjiang province, the HIV prevalence in men who have sex with men (MSM) is generally lower than other part of China. However, the official perception for their risk of HIV/AIDS infection has been increasing in the province over the years. Moreover, little information on HIV/AIDS was provided to the communities so that we have disadvantage of controlling HIV/AIDS epidemic in the region. The purpose of this study is to investigate the prevalence of HIV among MSM in Heilongjiang province, to assess their knowledge levels and risk behaviors related to HIV/AIDS, and to explore their associations with information resources.</p> <p>Methods</p> <p>A cross-sectional study using a standardized questionnaire and blood test was administered in 2008 by local interviewers to a sample (1353) of MSM in four cities in Heilongjiang province.</p> <p>Results</p> <p>Among 1353 MSM, 2.3% were identified with HIV infection. About 48.7% of the subjects had multiple male sexual partners and only 37.3% of the subjects had consistent condom use (use every time) in the past 6 months. Most had a fair level of knowledge on HIV/AIDS, with the highest mean knowledge score among the MSM from Jiamusi, those with income 2000-3000 RMB/month, those searching sexual partners via internet and those performed HIV testing over 1 year ago). However, some myths regarding viral transmission (e.g., via mosquito bites or sharing kitchen utensils) also existed. Resources of information from which knowledge and risk behaviors related to HIV/AIDS was most available were television (58.6%) among MSM, followed by sexual partner (51.6%), publicity material (51.0%) and internet (48.7%). Significantly statistical differences of mean knowledge score were revealed in favor of book (<it>P </it>= 0.0002), medical staff (<it>P </it>= 0.0007), publicity material (<it>P </it>= 0.005) and sexual partner (<it>P </it>= 0.02). Press (<it>P </it>= 0.04) and book (<it>P </it>= 0.0003) were contributory to the most frequent condom use (condom use every time), while medical staff (<it>P </it>= 0.005) and publicity material (<it>P </it>= 0.04) is associated with moderate rate of condom use (condom use often).</p> <p>Conclusions</p> <p>Although the prevalence of HIV infection is low among MSM in Heilongjiang province, the situation that the risk behaviors were frequent in the population is alarming. The study suggests that some strategies like condom use and education intervention are practical approaches and need to be strengthened.</p