Synthesis of 5,6-dihydro-2H-pyran-2-ones (microreview)

[Figure not available: see fulltext.][Figure not available: see fulltext.] 5,6-Dihydro-2H-pyran-2-ones constitute an important class of heterocyclic compounds which also may be considered as α,β-unsaturated δ-lactones. These types of heterocycles have shown a wide range of biological and pharmacological activities including human antitumor,1,2 antifungal,3,5 antimicrobial,4 anti-inflammatory,4 antistress,4 antibiotic,5antituberculosis,6 antiparasitic,6 antiviral;7 5,6-dihydro-2Hpyran-2-ones are also known as the inducer of a colony stimulating factor in bone marrow stromal cells.5 All this made 5,6-dihydro-2H-pyran-2-ones more attractive both for chemists and pharmacologists. For example, (R)-rugulactone which was firstly reported in 2009 by Cardellina and coworkers possess interesting anticancer properties.2 In addition, 5,6-dihydro-2H-pyran-2-ones as chemical intermediates have widely been applied to the synthesis of numerous organic compounds including heterocycles.8 Nowadays, there are several synthetic routes to the preparation of these heterocycles including intramolecular cyclization, N-heterocyclic carbeneprecatalyst (NHC-precatalyst) reaction of enals and ketones, dicobaltoctacarbonyl-mediated tandem (5+1)/(4+2) cycloaddition, ring-closing metathesis of dienes containing carboxylate group by Grubbs II catalyst, (3+2) cycloaddition reaction, condensation reaction, and biosynthesis pathway.[Figure not available: see fulltext.] © 2016, Springer Science+Business Media New York

Canola traits and some soil biological parameters in response to fertilization and tillage management

This study describes the effects of fertilization and tillage methods on soil microbial community and canola traits. A field experiment was carried out in 2009 to 2010 growing season. Experiments were arranged in a split plot based on randomized complete block design with three replications. Main plots consisted of no tillage (T1), minimum tillage (T2) and conventional tillage (T3). Six strategies for obtaining the basal fertilizer requirement including (N1): farmyard manure; (N2): compost; (N3):chemical fertilizers; (N4): farmyard manure + compost; (N5): farmyard manure + compost + chemical fertilizers and (N6): control, were arranged in sub plots. Results show that the activities of all enzymes were generally higher in the N4 treatment than in the unfertilized and chemical fertilizer treatments. The phosphatase, catalase and urease activities in the N3 treatment were significantly lower than in the farm yard manure (FYM) and compost treatments (CT). The activity of all enzyme activity tended to be higher in the NT treatment. The highest leaf N, P and K containing grain and grain yield was obtained from N5 treatment. Applying CT system caused to a reduction in grain yield as compared with chisel plowing.Key words: Enzyme activity, compost, farmyard manure, tillage

Prognostic value of mean platelet volume in patients undergoing elective percutaneous coronary intervention

Objective: We sought to determine the role of mean platelet volume (MPV) for predicting long-term outcomes of elective percutaneous coronary intervention (PCI). Methods: On the basis of retrospective cohort study, we collected characteristics of 680 patients undergoing elective PCI from October 2005 to August 2010. The patients who had preoperative MPV were assessed for developing major adverse cardiac events (MACE) during 1-year follow- up. They were categorized into two groups including MPV <9.6 fL (n=89) and MPV �9.6 fL (n=92). Data were analyzed using t-test, chi-square test, Pearson correlation, receiver operating characteristic (ROC) curve and logistic regression. Results: One-hundred eighty one patients (26.6) met inclusion criteria. The MACE was observed in 29 patients (16); and its rate in low- and high-MPV groups was 11.2 and 20.7, respectively (p=0.084). MPV was significantly higher in the patients with left ventricular ejection fraction (LVEF) <40 compared with that of �40 (p<0.001). There were a significant and negative correlation between MPV and platelet count (r=-0.305, p<0.001), and significant and positive correlations between MPV and platelet distribution width (PDW) and platelet large cell ratio (P-LCR) (r=0.615, p<0.001 and r=0.913, p<0.001; respectively). The best MPV cut-off point was 9.25 fL; the sensitivity and specificity were 79 and 38, respectively. Elevated MPV was the best predictor of MACE at 1-year follow-up (OR=11.359, 95 CI 2.481-51.994, p=0.002). Conclusion: The results indicate that preoperative MPV is an independent predictor of the MACE at 1-year follow-up in the patients undergoing elective PCI. Moreover, it may be useful for risk stratification in such cases. © 2015 by Turkish Society of Cardiology

Type I interferons augment regulatory T cell polarization in concert with ancillary cytokine signals

In the transplant community, research efforts exploring endogenous alternatives to inducing tolerogenic allo-specific immune responses are much needed. In this regard, CD4 + FoxP3+ regulatory T cells (Tregs) are appealing candidates due to their intrinsic natural immunosuppressive qualities. To date, various homeostatic factors that dictate Treg survival and fitness have been elucidated, particularly the non-redundant roles of antigenic CD3ζ/T-cell-receptor, co-stimulatory CD28, and cytokine interleukin (IL-)2 dependent signaling. Many of the additional biological signals that affect Tregs remain to be elucidated, however, especially in the transplant context. Previously, we demonstrated an unexpected link between type I interferons (IFNs) and Tregs in models of multiple myeloma (MM)—where MM plasmacytes escaped immunological surveillance by enhancing type I IFN signaling and precipitating upregulated Treg responses that could be overturned with specific knockdown of type I IFN signaling. Here, we elaborated on these findings by assessing the role of type I IFN signaling (IFN-α and -β) on Treg homeostasis within an alloimmune context. Specifically, we studied the induction of Tregs from naïve CD4 T cells. Using in vitro and in vivo models of murine skin allotransplantation, we found that type I IFN indeed spatiotemporally enhanced the polarization of naïve CD4 T cells into FoxP3+ Tregs. Notably, however, this effect was not independent of, and rather co-dependent on, ancillary cytokine signals including IL-2. These findings provide evidence for the relevance of type I IFN pathway in modulating FoxP3+ Treg responses and, by extension, stipulate an additional means of facilitating Treg fitness via type I IFNs

Thrombolysis in Stroke With Unknown Onset Based on Non-Contrast Computerized Tomography (TRUST CT).

Background Intravenous thrombolysis (IVT) in wake-up stroke (WUS) or stroke with unknown onset (SUO) has been recently proven to be safe and effective using advanced neuroimaging (magnetic resonance imaging or computerized tomography-perfusion) for patient selection. However, in most of the thrombolyzing centers advanced neuroimaging is not instantly available. We hypothesize that pragmatic non-contrast computed tomography-based IVT in WUS/SUO may be feasible and safe. Methods and Results TRUST-CT (Thrombolysis in Stroke With Unknown Onset Based on Non-Contrast Computerized Tomography) is an international multicenter registry-based study. WUS/SUO patients undergoing non-contrast computed tomography-based IVT with National Institute of Health Stroke Scale ≥4 and initial Alberta Stroke Program Early Computerized Tomography score ≥7 were included and compared with propensity score matched non-thrombolyzed WUS/SUO controls. Primary end point was the incidence of symptomatic intracranial hemorrhage; secondary end points included 24-hour National Institute of Health Stroke Scale improvement of ≥4 and modified Rankin Scale at 90 days. One hundred and seventeen WUS/SUO patients treated with non-contrast computed tomography-based IVT were included. As compared with 112 controls, the median admission National Institute of Health Stroke Scale was 10 and the median Alberta Stroke Program Early Computerized Tomography score was 10 in both groups. Four (3.4%) IVT patients and one control patient (0.9%) suffered symptomatic intracranial hemorrhage (adjusted odds ratio 7.9, 95% CI 0.65-96, P=0.1). A decrease of ≥4 National Institute of Health Stroke Scale points was observed in 67 (57.3%) of IVT patients as compared with 25 (22.3%) in controls (adjusted odds ratio 5.8, CI 3.0-11.2, P&lt;0.001). A months, 39 (33.3%) IVT patients reached a modified Rankin Scale score of 0 or 1 versus 23 (20.5%) controls (adjusted odds ratio 1.94, CI 1.0-3.76, P=0.05). Conclusions Non-contrast computed tomography-based thrombolysis in WUS/SUO seems feasible and safe and may be effective. Randomized prospective comparisons are warranted. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03634748

A Machine Learning based approach to predict road rutting considering uncertainty

Roads as vital public assets are the backbone for transportation systems and support constant societal development. Recently, data-driven technologies such as digital twins and especially machine learning have shown great potential to maintain the service level of the existing road infrastructure by accurate future condition modelling and optimal maintenance treatment recommendations. However, the pavement community suffers from inadequate data and errors experienced in data collection, which unavoidably limits machine learning performance. In addition, focusing solely on data without considering the underlying physical behaviour remains as a challenge for the practical implementation of machine learning. To this end, this study provides a machine learning based approach to predict road rutting taking into account the machine learning uncertainties. The US Long-Term Pavement Performance public database has been used as the main data source while supplementary synthetic data was added using Finite Element simulations based on physics. The obtained results indicate that adding extra simulation data improved the model’s short-term prediction accuracy by 4.4% and reduced the long-term prediction uncertainty by 6.76%. The approach could potentially mitigate the issue of lack of data and the uncertainties around the data collected, by integrating existing understanding of pavement physical behaviour into the machine learning modelling pipeline

Reproduction and feeding biology of madagascar meager (Argyrosomus hololepidotus) from Khuzestan coastal waters

Biological attributes of Madagascar Meager (Argyrosomus hololepidotus) was studied from October 2008 to September 2009 in coastal waters of Khuzestan province. Average maximum length was 128.4±7.50 in October and average minimum length was 104.86±12.47 in May. The maximum weight was 27500g, the minimum weight was 5700g and mean weight for males and females were 15.222±4.40 and 16.942±5.09, respectively. Reproductive studies showed that peak maturity season occurred in July. The length­ weight relationship were calculated as W=0.042L 2 70 for males and W=0.06L2 61for females. The male-female sex ratio was calculated as 1:1.07 and chi-square analysis showed no significant difference (P>0.05) between the two sexes. The average absolute and relative fecundity were estimated to be 4054045±37265 and 179.19±50.41, respectively Madagascar Meager is carnivore and we found the diet of the species consisted of fish (75%), crustaceans (20%) and mollusks (5%). Analysis of monthly variation in the condition factor (CF) indicated a fluctuation throughout the year, with a high level during May. Vacuity index indicated a higher feeding rate in males compared to females. We also found that the species continues feeding in the spawning season

Could a defective epithelial sodium channel lead to bronchiectasis

<p>Abstract</p> <p>Background</p> <p>Bronchiectasis is defined as a permanent dilation of the airways arising from chronic bronchial inflammation/infection. In 50% of cases, no etiology can be identified. Recently, the role of the epithelial sodium channel ENaC has been pointed out in the pathophysiology of cystic fibrosis, a disease due to mutations in the <it>CFTR </it>gene and causing bronchiectasis in the airways. Moreover, it was found that transgenic mice overexpressing <it>ENaCβ </it>present cystic fibrosis-like lung disease symptoms. Our aim was to evaluate if a defective ENaC protein could be involved in the development of bronchiectasis.</p> <p>Methods</p> <p>We extensively analysed <it>ENaCβ </it>and <it>γ </it>genes in 55 patients with idiopathic bronchiectasis and without two mutations in the coding regions of <it>CFTR</it>. Thirty-eight patients presented functional abnormalities suggesting impaired sodium transport (abnormal sweat chloride concentration or nasal potential difference measurement), and 17 had no such evidence.</p> <p>Results</p> <p>Sequencing of the exons and flanking introns of the <it>ENaCβ </it>and <it>γ </it>gene identified five different amino-acid changes (p.Ser82Cys, p.Pro369Thr, p.Asn288Ser in <it>ENaCβ </it>; and p.Gly183Ser, p.Glu197Lys in <it>ENaCγ</it>) in heterozygous state in 8 patients. The p.Ser82Cys amino-acid change was found in 3 unrelated patients who were also heterozygous for a <it>CFTR </it>mutation or variant (1 p.F508del, 1 IVS8-5T, and 1 IVS8-5T:1716G>A (p.E528E)). The other mutations were found in patients without <it>CFTR </it>mutation, the p.Glu197Lys mutation in 2 patients and the other variants in single patients. Among the 8 patients bearing an <it>ENaC </it>mutation, 5 had functional abnormalities suggesting impaired sodium transport.</p> <p>Conclusion</p> <p>Our results suggest that several variants in <it>ENaCβ </it>and <it>γ </it>genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for <it>ENaCβ/CFTR </it>mutations or variants.</p