The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
Causative gene mutations have been identified in about 2% of those with amyotrophic lateral sclerosis (ALS), often, but not always, when there is a strong family history. There is an assumption that ...there is a genetic component to all ALS, but genome-wide association studies have yet to produce a robustly replicated result. A definitive estimate of ALS heritability is therefore required to determine whether ongoing efforts to find susceptibility genes are worth while.
The authors performed two twin studies, one population- and one clinic-based. The authors used structural equation modelling to perform a meta-analysis of data from these studies and an existing twin study to estimate ALS heritability, and identified 171 twin pairs in which at least one twin had ALS.
Five monozygotic twin pairs were concordant-affected, and 44 discordant-affected. No dizygotic twin pairs were concordant-affected, and 122 discordant-affected. The heritability of sporadic ALS was estimated as 0.61 (0.38 to 0.78) with the unshared environmental component 0.39 (0.22 to 0.62). ALS has a high heritability, and efforts to find causative genes should continue.
A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent ...assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
γ-aminobutyric acid (GABA) is a non-protein amino acid involved in various physiological processes; it aids in the protection of plants against abiotic stresses, such as drought, heavy metals, and ...salinity. GABA tends to have a protective effect against drought stress in plants by increasing osmolytes and leaf turgor and reducing oxidative damage via antioxidant regulation. Guard cell GABA production is essential, as it may provide the benefits of reducing stomatal opening and transpiration and controlling the release of tonoplast-localized anion transporter, thus resulting in increased water-use efficiency and drought tolerance. We summarized a number of scientific reports on the role and mechanism of GABA-induced drought tolerance in plants. We also discussed existing insights regarding GABA’s metabolic and signaling functions used to increase plant tolerance to drought stress.
Patients with chronic coronary disease were randomly assigned to receive 0.5 mg of colchicine once daily or matching placebo. The incidence of the composite end point of cardiovascular death, ...spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was significantly lower with colchicine than with placebo.
Ozone (O3) is a gaseous environmental pollutant that can enter leaves through stomatal pores and cause damage to foliage. It can induce oxidative stress through the generation of reactive oxygen ...species (ROS) like hydrogen peroxide (H2O2) that can actively participate in stomatal closing or opening in plants. A number of phytohormones, including abscisic acid (ABA), ethylene (ET), salicylic acid (SA), and jasmonic acid (JA) are involved in stomatal regulation in plants. The effects of ozone on these phytohormones’ ability to regulate the guard cells of stomata have been little studied, however, and the goal of this paper is to explore and understand the effects of ozone on stomatal regulation through guard cell signaling by phytohormones. In this review, we updated the existing knowledge by considering several physiological mechanisms related to stomatal regulation after response to ozone. The collected information should deepen our understanding of the molecular pathways associated with response to ozone stress, in particular, how it influences stomatal regulation, mitogen-activated protein kinase (MAPK) activity, and phytohormone signaling. After summarizing the findings and noting the gaps in the literature, we present some ideas for future research on ozone stress in plants
Background
It is gradually accepted that solid bolus swallow needs to be added to the procedure of manometry. The motility differences in the upper esophageal sphincter (UES) and lower esophageal ...sphincter (LES) were not well described. Sierra Scientific Instruments solid‐state high‐resolution manometry (HRM) system, the most popular HRM system in China, lacks the Chinese normative values for both liquid and solid bolus swallow parameters.
Methods
The esophageal HRM data of 88 healthy volunteers were analyzed. The parameters of both sphincters in resting stage were summarized and those during solid and liquid swallows were compared.
Key Results
Normative HRM values of sphincter parameters in solid and liquid bolus swallows in China were established. The UES residual pressure of solid bolus swallows was lower than that of liquid bolus (0.3±5.5 mm Hg vs 4.8±5.9 mm Hg, P=.000). The time parameters of UES relaxation between two types of bolus swallows were similar. In solid bolus swallows, the intrabolus pressure (IBP) (13.8±5.1 mm Hg vs 10.9±5.7 mm Hg, P=.000) and LES relaxation time (11.0±2.1 seconds vs 8.7±1.3 seconds, P=.000) were higher. The 4‐second integrated relaxation pressure between both bolus swallows was similar.
Conclusions & Inferences
The function of the UES and LES between solid and liquid bolus swallows is different. Chinese HRM parameters are different from the Chicago Classification (http://www.chictr.org.cn, Number ChiCTR‐EOC‐15007147).
This study demonstrated the motility differences between solid and liquid bolus swallows for both the UES and LES. It confirms the application of HRM with solid swallows. More importantly, this study provides the normative values for both liquid and solid bolus swallows of Sierra Scientific Instruments solid‐state HRM system for Chinese population.
Abstract Aims To compare the performance of volumetric-modulated arc radiotherapy (VMAT) by dual arc with fixed beam intensity-modulated radiotherapies (IMRTs) and single arc VMAT on nasopharyngeal ...carcinomas (NPC). Materials and methods Twenty NPC cases were re-planned using the planning system of the Pinnacle3® SmartArc (SA) module to compare the performance of the following four techniques: seven-field (7F) and 18-field (18F) fixed beam IMRT, and single (SA1 ) and dual arc VMAT (SA2 ). The plan was delivered on an Elekta Synergy™ Linac equipped with an 80-leaf 1 cm multileaf collimator. Three dose levels of planning target volumes (PTVs) with 70/59.4/54.0 Gy in 33 fractions were prescribed and delivered as a simultaneous integrated boost. The conformity index and homogeneity index of the PTVs, the comprehensive quality index (CQI), the normal tissue complication probability for the organs at risk (OARs), and the planning time, delivery efficiency and accuracy were analysed. Results A significantly inferior conformity index at the three dose levels of PTV and homogeneity index of PTV70 were observed in SA1 compared with the other techniques. Comparable conformity index and homogeneity index of the PTV were observed among 7F/18F IMRT and SA2 . Based on the CQI of the 11 OARs, the most efficient dose reduction was observed in 18F IMRT followed in order by SA2 , 7F IMRT and SA1 . The planning time was on average 13.2/24.9/40.1/42.8 min for 7F/18F IMRT/SA1 /SA2 , respectively. With regards to the delivery efficiency compared with 7F IMRT, a 51 and 41% reduction in delivery time was achieved by SA1 and SA2 , respectively. All techniques presented a high quality assurance pass rate (>98%) of the Γ3mm,3% criterion. Conclusion In NPC cases, SA2 gave superior results in terms of PTV coverage and OAR sparing compared with SA1 and approached the performance achieved by 18F IMRT, but without sacrificing the delivery efficiency.
Bariatric surgery is known to reduce leptin and increase adiponectin levels, but the influence of sleeve gastrectomy on the leptin: adiponectin ratio (LAR), a measure of insulin sensitivity and ...cardiovascular risk, has not previously been described. We sought to determine the influence of sleeve gastrectomy on LAR in adults with severe obesity.In a single centre prospective cohort study of adults undergoing laparoscopic sleeve gastrectomy over a four-month period in our unit, we measured LAR preoperatively and 12 months after surgery. Of 22 patients undergoing sleeve gastrectomy, 17 (12 females, 12 with type 2 diabetes) had follow-up LAR measured at 12.1 ± 1 months. Mean body weight decreased from 130.6 ± 30.8 kg to 97.6 ± 21.6 kg, body mass index (BMI) from 46.9 ± 7.8 to 35.3 ± 7.2 kg m
and excess body weight from 87.5 ± 31.3 to 41.3 ± 28.8% (all p < 0.001). The reduction in leptin from 40.7 ± 24.9 to 30.9 ± 30.5 ng/ml was not significant (p = 0.11), but adiponectin increased from 4.49 ± 1.6 to 8.93 ± 6.36 µg/ml (p = 0.005) and LAR decreased from 8.89 ± 4.8 to 5.26 ± 6.52 ng/µg (p = 0.001), equivalent to a 70.9% increase in insulin sensitivity. The correlation with the amount of weight lost was stronger for LAR than it was for leptin or adiponectin alone. In this single-centre, interventional prospective cohort, patients undergoing laparoscopic sleeve gastrectomy had a substantial reduction in their LAR after 12 months which was proportional to the amount of weight lost. This may indicate an improvement in insulin sensitivity and a reduction in cardiovascular risk.
The response surface methodology (RSM), which typically uses quadratic polynomials, is predominantly used for metamodeling in crashworthiness optimization because of the high computational cost of ...vehicle crash simulations. Research shows, however, that RSM may not be suitable for modeling highly nonlinear responses that can often be found in impact related problems, especially when using limited quantity of response samples. The radial basis functions (RBF) have been shown to be promising for highly nonlinear problems, but no application to crashworthiness problems has been found in the literature. In this study, metamodels by RSM and RBF are used for multiobjective optimization of a vehicle body in frontal collision, with validations by finite element simulations using the full-scale vehicle model. The results show that RSM is able to produce good approximation models for energy absorption, and the model appropriateness can be well predicted by ANOVA. However, in the case of peak acceleration, RBF is found to generate better models than RSM based on the same number of response samples, with the multiquadric function identified to be the most stable RBF. Although RBF models are computationally more expensive, the optimization results of RBF models are found to be more accurate.
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