Molecular level insight of thiocyanate degradation by Pseudomonas putida TDB-1 under a high arsenic and alkaline condition.

It is a big challenge to bioremediate thiocyanate pollution in the gold extraction heap leaching tailings and surrounding soils with high contents of arsenic and alkali. Here, a novel thiocyanate-degrading bacterium Pseudomonas putida TDB-1 was successfully applied to completely degrade 1000 mg/L thiocyanate under a high arsenic (400 mg/L) and alkaline condition (pH = 10). It also leached the contents of thiocyanate from 1302.16 to 269.72 mg/kg in the gold extraction heap leaching tailings after 50 h. The maximum transformation rates of S and N in thiocyanate to the two finial products of SO42- and NO3- were 88.98 % and 92.71 %, respectively. Moreover, the genome sequencing confirmed that the biomarker gene of thiocyanate-degrading bacterium, CynS was identified in the strain TDB-1. The bacterial transcriptome revealed that critical genes, such as CynS, CcoNOQP, SoxY, tst, gltBD, arsRBCH and NhaC, etc. in the thiocyanate degradation, S and N metabolisms, and As and alkali resistance were significantly up-regulated in the groups with 300 mg/L SCN- (T300) and with 300 mg/L SCN- and 200 mg/L As (TA300). In addition, the protein-protein interaction network showed that the glutamate synthase encoding by gltB and gltD served as central node to integrate the S and N metabolism pathways with thiocyanate as substrate. The results of our study provide a novel molecular level insight for the dynamic gene expression regulation of thiocyanate degradation by the strain TDB-1 with a severe arsenic and alkaline stress.

Integrative Analysis Reveals Potentially Functional N6-Methylandenosine-Related Long Noncoding RNAs in Colon Adenocarcinoma.

N6-methyladenosine (m6A) is one of the most prevalent RNA modifications in mRNA and non-coding RNA. In this study, we identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs. Moreover, the m6A-related long noncoding RNAs (lncRNAs) could clearly stratify the colon adenocarcinoma (COAD) samples into three subtypes. The subtype 2 had nearly 40% of samples with microsatellite instability (MSI), significantly higher than the two other subtypes. In accordance with this finding, the inflammatory response-related pathways were highly activated in this subtype. The subtype-3 had a shorter overall survival and a higher proportion of patients with advanced stage than subtypes 1 and 2 (p-value < 0.05). Pathway analysis suggested that the energy metabolism-related pathways might be aberrantly activated in subtype 3. In addition, we observed that most of the m6A readers and m6A-related lncRNAs were upregulated in subtype 3, suggesting that the m6A readers and the m6A-related lncRNAs might be associated with metabolic reprogramming and unfavorable outcome in COAD. Among the m6A-related lncRNAs in subtype 3, four were predicted as prognostically relevant. Functional inference suggested that CTD-3184A7.4, RP11-458F8.4, and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs might be involved in energy metabolism-related pathways. In summary, we conducted a systematic data analysis to identify the key m6A regulators and m6A-related lncRNAs, and evaluated their clinical and functional importance in COAD, which may provide important evidences for further m6A-related researches.

Sufentanil postoperative analgesia reduce the increase of T helper 17 (Th17) cells and FoxP3+ regulatory T (Treg) cells in rat hepatocellular carcinoma surgical model: A randomised animal study.

BACKGROUND: Surgery-related pain and opioids might exacerbate immune defenses in immunocompromised cancer patients which might affect postoperativd overall survival. Sufentanil is a good postoperative pain control drug,the present study aimed to figure out whether it effect T cell immunity in rat hepatocellular carcinoma surgical model. METHODS: A rat hepatocellular carcinoma (HCC) models was established by N-nitrosodiethylamine. Forty-eight of them were randomly divided into 3 equal groups: surgery without postoperative analgesia (Group C), surgery with morphine postoperative analgesia (Group M), surgery with sufentanil postoperative analgesia (Group S). Each animal underwent a standard left hepatolobectomy, and intraperitoneally implanted with osmotic minipumps filled with sufentanil, morphine or normal saline according to the different group. The food and water consumptions, body weight changes, locomotor activity and mechanical pain threshold (MPT) were observed. The ratio of CD4+/CD8+, proportions of Th1, Th2, Th17 and Treg cells in blood were detected using flow cytometry. The liver function and the rats' survival situation of each group were observed. RESULTS: The food and water consumption, locomotor activity and MPT of group C declined than those of group S and M on d1, d2, d3 (P < 0.05). The CD4+/CD8+ ratio and the proportion of Th1 cells were significantly higher while the proportion of Th2, Th17 and Treg cells were significantly lower in group S and group M compared with group C. The rats of group S have higher CD4+/CD8+ ratio on d3, while lower proportion of Treg cells on d7 compared with group M. The plasma ALT and AST values in group C were significantly higher than that of group S and group M on both d3 and d7. There were not significant differences in mortality rate between 3 groups. CONCLUSIONS: Sufentanil and morphine postoperative analgesia in HCC rats accepted hepatectomy could relieve postoperative pain, promote the recovery of liver function after surgery, alleviate the immunosuppressive effect of pain. Furthermore, Compared to morphine, sufentanil might have a slighter effect on CD4+/CD8+ ratio and Treg frequencies. Therefore, sufentanil postoperative analgesia is better than morphine in HCC hepatectomy rats.

Frontline Science: Low regulatory T cells predict perioperative major adverse cardiovascular and cerebrovascular events after noncardiac surgery.

Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis-generating post hoc analysis of the LeukoCAPE-1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart disease patients for association with MACCE (composite of cardiac death, myocardial infarction, myocardial ischemia, myocardial injury after noncardiac surgery, thromboembolic stroke) within 30 d after surgery. Regulatory T cells (Tregs) were the only leukocyte subgroup associated with MACCE. We found reduced Tregs in patients experiencing MACCE versus no-MACCE (0.02 [0.01; 0.03] vs. 0.04 [0.03; 0.05] Tregs nl-1 , P = 0.002). Using Youden index, we derived the optimal threshold value for association with MACCE to be 0.027 Tregs nl-1 . Subsequently, we recruited 233 coronary heart disease patients for the prospective, observational LeukoCAPE-2 study and independently validated this Treg cutoff for prediction of MACCE within 30 d after noncardiac surgery. After multivariate logistic regression, Tregs < 0.027 cells nl-1 remained an independent predictor for MACCE (OR = 2.54 [1.22; 5.23], P = 0.012). Tregs improved risk discrimination of the revised cardiac risk index based on ΔAUC (area under the curve; ΔAUC = 0.09, P = 0.02), NRI (0.26), and IDI (0.06). Preoperative Treg levels below 0.027 cells nl-1 predicted perioperative MACCE and can be measured to increase accuracy of established preoperative cardiac risk stratification in coronary heart disease patients undergoing noncardiac surgery.

"Testing is Healthy" TimePlay campaign: Evaluation of sexual health promotion gamification intervention targeting young adults.

OBJECTIVES: The objectives of the study were to 1) describe the implementation of the "Testing is Healthy" campaign in four locations in British Columbia (BC) and 2) report process evaluation indicators for the campaign. PARTICIPANTS: Young adults ages 20-29 years, the age group with the highest reported rates of chlamydia and gonorrhea in BC. SETTINGS: Movie theatres located in Langley, Burnaby, Coquitlam and Surrey, which are communities served by the Fraser Health Authority (FHA) in BC. INTERVENTION: The FHA launched the campaign in 2014 and 2015 to bring down the prevalence of sexually transmitted infections (STIs) and HIV in the region. The campaign used the Cineplex TimePlay platform to engage moviegoers in answering STI/HIV-related questions, and to connect them to a clinic finder on the BC Centre for Disease Control Sex Smart Resource (SSR) website. TimePlay includes elements of gaming, is technology-based, and has been a successful advertisement platform for consumer products and services. However, this is the first time it has been used for sexual health promotion. The campaign was evaluated for 1) reach, based on theatre attendance and TimePlay participation, and 2) the effectiveness of connecting people to sexual health information using SSR web analytics. OUTCOMES: In total, the campaign received 548 410 views and 77 149 plays. SSR web analytics showed a significant increase in unique page views of the Clinic Finder page between the first and the second campaign. IMPLICATIONS: The campaign reached a large population at a low cost and was correlated with spikes in the unique page views for the Clinic Finder page.

Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy.

Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR.