To better understand the transcriptional regulation of high molecular weight glutenin subunit (HMW-GS) expression, we isolated four Glu-1Bx promoters from six wheat cultivars exhibiting diverse protein expression levels. The activities of the diverse Glu-1Bx promoters were tested and compared with β-glucuronidase (GUS) reporter fusions. Although all the full-length Glu-1Bx promoters showed endosperm-specific activities, the strongest GUS activity was observed with the 1Bx7OE promoter in both transient expression assays and stable transgenic rice lines. A 43 bp insertion in the 1Bx7OE promoter, which is absent in the 1Bx7 promoter, led to enhanced expression. Analysis of promoter deletion constructs confirmed that a 185 bp MITE (miniature inverted-repeat transposable element) in the 1Bx14 promoter had a weak positive effect on Glu-1Bx expression, and a 54 bp deletion in the 1Bx13 promoter reduced endosperm-specific activity. To investigate the effect of the 43 bp insertion in the 1Bx7OE promoter, a functional marker was developed to screen 505 Chinese varieties and 160 European varieties, and only 1Bx7-type varieties harboring the 43 bp insertion in their promoters showed similar overexpression patterns. Hence, the 1Bx7OE promoter should be important tool in crop genetic engineering as well as in molecular assisted breeding.

Sildenafil, a phosphodiesterase-5 inhibitor, and simvastatin, a cholesterol lowering drug, both have therapeutic effects on PAH; however, the combination of these drugs has not been tested in the treatment of PAH. The purpose of this study was to determine whether the combination of sildenafil and simvastatin is superior to each drug alone in the prevention of MCT-induced PAH. Phosphorylated Smad levels were decreased in lung tissue in MCT-injected rats, whereas ERK protein levels were increased. This indicates a possible role for an increase in mitogenic ERK activity in addition to decreased proapoptotic Smad signaling in the MCT model of PAH. Combination sildenafil and simvastatin treatment prevented the MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH), exerted an antiproliferative effect on pulmonary artery smooth muscle cells (PASMC). Our results indicate that combination therapy with sildenafil and simvastatin attenuated the development of pulmonary hypertension more than either treatment alone.

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Background: To assess the usefulness of the neutrophil/lymphocyte ratio (NLR), a marker of inflammation and/or stress, for predicting weaning failure in patients receiving invasive mechanical ventilation (IMV), compared to levels of leukocytes and C-reactive protein (CRP). Methods: This observational prospective cohort study was conducted from July 2013 to December 2016 in an intensive care unit in China, enrolling 269 consecutive patients receiving IMV. Patients underwent a spontaneous breathing trial (SBT) if they were ready to wean, and underwent extubation if they passed the SBT. The evaluated markers were measured immediately prior to SBT, and compared between weaningfailure and weaning-success patients. Receiver-operating characteristic (ROC) curve and logistic regression analyses were used to evaluate the ability of these markers to predict weaning failure. Results: In all, 94 (34.9%) patients failed the weaning process (66 failed SBT and 28 presented with postextubation respiratory distress). NLR was a better predictor of failure (area under the ROC curve, 0.69; 95% CI, 0.62-0.76) than leukocyte levels (0.60, 0.53-0.67) and CRP values (0.58, 0.51-0.65). NLR >11, leukocyte counts >10.5×10 9 /L, and CRP >58 mg/L prior to weaning had the best combination of sensitivity (73%, 64%, and 63%, respectively), specificity (59%, 55%, and 63%), positive predictive value (49%, 43%, and 48%), negative predictive value (81%, 74%, and 76%), and diagnostic accuracy (64%, 58%, and 63%) for predicting weaning failure. However, only NLR >11 (odds ratio, 5.91; 95% CI, 3.08-11.33; P<0.001) was an independent predictor of weaning failure in the adjusted logistic regression model. Conclusions: NLR may be a useful marker for predicting weaning failure, and weaning at NLR >11 might be considered with caution. Further study with a larger sample size and with weaning outcome as a variable of concern is warranted. Trial registration: ClinicalTrials.gov identifier: NCT02981589.