A Common SMAD7 Variant Is Associated with Risk of Colorectal Cancer: Evidence from a Case-Control Study and a Meta-Analysis

<div><h3>Background</h3><p>A common genetic variant, rs4939827, located in <em>SMAD7</em>, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.</p> <h3>Method and Findings</h3><p>We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19–1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all <em>P</em> for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.</p> <h3>Conclusion</h3><p>Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.</p> </div

Lactate-Mediated Epigenetic Reprogramming Regulates Formation of Human Pancreatic Cancer-Associated Fibroblasts

Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with overexpression of various inflammatory transcripts including CXCR4. Co-culture of neoplastic cells with CAFs led to increased invasiveness that was abrogated by inhibition of CXCR4. Metabolite tracing revealed that lactate produced by neoplastic cells leads to increased production of alpha-ketoglutarate (aKG) within mesenchymal stem cells (MSCs). In turn, aKG mediated activation of the demethylase TET enzyme led to decreased cytosine methylation and increased hydroxymethylation during de novo differentiation of MSCs to CAF. Co-injection of neoplastic cells with TET-deficient MSCs inhibited tumor growth in vivo. Thus, in PDAC, a tumor-mediated lactate flux is associated with widespread epigenomic reprogramming that is seen during CAF formation

Agricultural Location and Crop Choices in China: A Revisitation on Von Thünen Model

Growing populations and rapid urbanization have put tremendous pressure on the food supply. The rural hinterland around cities is an important source of the urban food supply chain. Facing the constraints of China’s land stock, reasonable use of land space and optimization of agricultural crop structure is crucial to meet the food demand. Von Thünen Model, which is fronted by a 19th-century German economist, outlines a rural landscape of commercial farmers growing agricultural products for local markets while proposing basic patterns and principles of land use in agriculture. Using data from China’s OVOP (“One village, One product”), this paper analyzes the agricultural location and crop choices around two levels of cities (provincial capital cities, and county-level cities) by using Thünen’s theory. The results showed that crop density did decrease as the distance to urban increased. Crop rings are present in the vicinity of both metropolitan and county-level cities, distributed according to crop intensity. Evidence from China suggests that agricultural location and crop selection still follow the basic principles of the Thünen model. Planners and policymakers should refocus on the Von Thünen model to utilize land space and optimize agricultural production scientifically and efficiently

Agricultural Location and Crop Choices in China: A Revisitation on Von Th&uuml;nen Model

Growing populations and rapid urbanization have put tremendous pressure on the food supply. The rural hinterland around cities is an important source of the urban food supply chain. Facing the constraints of China&rsquo;s land stock, reasonable use of land space and optimization of agricultural crop structure is crucial to meet the food demand. Von Th&uuml;nen Model, which is fronted by a 19th-century German economist, outlines a rural landscape of commercial farmers growing agricultural products for local markets while proposing basic patterns and principles of land use in agriculture. Using data from China&rsquo;s OVOP (&ldquo;One village, One product&rdquo;), this paper analyzes the agricultural location and crop choices around two levels of cities (provincial capital cities, and county-level cities) by using Th&uuml;nen&rsquo;s theory. The results showed that crop density did decrease as the distance to urban increased. Crop rings are present in the vicinity of both metropolitan and county-level cities, distributed according to crop intensity. Evidence from China suggests that agricultural location and crop selection still follow the basic principles of the Th&uuml;nen model. Planners and policymakers should refocus on the Von Th&uuml;nen model to utilize land space and optimize agricultural production scientifically and efficiently

Metamorphic Testing of Relation Extraction Models

Relation extraction (RE) is a fundamental NLP task that aims to identify relations between some entities regarding a given text. RE forms the basis for many advanced NLP tasks, such as question answering and text summarization, and thus its quality is critical to the relevant downstream applications. However, evaluating the quality of RE models is non-trivial. On the one hand, obtaining ground truth labels for individual test inputs is tedious and even difficult. On the other hand, there is an increasing need to understand the characteristics of RE models in terms of various aspects. To mitigate these issues, this study proposes evaluating RE models by applying metamorphic testing (MT). A total of eight metamorphic relations (MRs) are identified based on three categories of transformation operations, namely replacement, swap, and combination. These MRs encode some expected properties of different aspects of RE. We further apply MT to three popular RE models. Our experiments reveal a large number of prediction failures in the subject RE models, confirming that MT is effective for evaluating RE models. Further analysis of the experimental results reveals the advantages and disadvantages of our subject models and also uncovers some typical issues of RE models

Independent Association between Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: a Systematic Review and Meta-Analysis

Nonalcoholic fatty liver disease (NAFLD) is closely correlated with insulin resistance and several metabolic syndrome features, but whether it could increase the risk of cardiovascular disease remains undefined. To assess the association between NAFLD and the risk of cardiovascular outcomes, we systematically searched the MEDLINE, Embase, and the Cochrane Library database (1947 to October 2012) by using Medical Subject Heading search terms and a standardized protocol. Randomized controlled trials, casecontrol, and prospective studies carried out in human adults, in which the unadjusted and multivariate adjusted odds ratios with corresponding 95% confidence interval (CI) for cardiovascular disease with NAFLD were reported. The search yielded 4 crosssectional studies and 2 prospective cohort studies including 7,042 participants. The pooled effects estimate showed that NAFLD was a predictor of cardiovascular disease (odds ratio 1.88, 95% CI, 1.68 to 2.01; &lt; 0.001). The random effects summary estimate indicated that NAFLD retained a significant association with cardiovascular outcomes independent of conventional risk factors after adjustment for established cardiovascular risk factors (odds ratio 1.50, 95% CI, 1.21 to 1.87; &lt; 0.001). These results indicate that NAFLD is a strong independent predictor of cardiovascular disease and may play a central role in the cardiovascular risk of metabolic syndrome

Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation

Background. Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process. Methods. Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue. Results. We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1β in BALF. Conclusion. Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model

Effects of Ca-Compounds on the Gases Formation Behavior during Molten Salts Thermal Treatment of Bio-Waste

Bio-waste utilization is essential, and pyrolysis is a prominent way for its effective utilization. However, the gradual accumulation of ash compounds in the intermediate products probably affects the thermal conversion characteristics of bio-waste. In the present study, beech wood and disposable chopsticks were selected as bio-waste samples. The effects of typical ash components (Ca-compounds) on volatile formation behavior were investigated during the molten salts thermal treatment of bio-waste. Results demonstrated that about 80% mass of initial bio-waste was gasified into the volatiles at 300 °C. The introduction of Ca-compounds in the molten salts slightly decreased the total yield of gaseous products. More specifically, Ca2+ could improve the generation of CO2 and suppress the generation of other gases (CO, H2, and CH4), and this is accompanied by a reduction in the low heating value (LHV) of the gases. The possible reason is that Ca2+ might act on the -OH bonds, phenyl C-C bond, methoxy bond and carboxylic acid -COOH bonds of the bio-waste to promote CO2 release. In contrast, the introduction of CO32− and OH- tended to relieve the inhibition effect of Ca2+ on the generation of H-containing gases. Meanwhile, the introduction of Ca2+ can promote the conversion of bio-waste into liquid products as well as increase the saturation level of liquid products. Moreover, as a vital form of carbon storage, CO2 was found to be abundant in the pyrolysis gases from molten salts thermal treatment of bio-waste, and the concentration of CO2 was much higher than that of direct-combustion or co-combustion with coal. It’s a promising way for bio-waste energy conversion as well as synchronized CO2 capture by using molten salts thermal treatment, while the introduction of small amounts of Ca-compounds was found to have no significant effect on the change of CO2 concentration

Hydrophobic Surface Array Structure Based on Laser-Induced Graphene for Deicing and Anti-Icing Applications

The exceptional performance of graphene has driven the advancement of its preparation techniques and applications. Laser-induced graphene (LIG), as a novel graphene preparation technique, has been applied in various fields. Graphene periodic structures created by the LIG technique exhibit superhydrophobic characteristics and can be used for deicing and anti-icing applications, which are significantly influenced by the laser parameters. The laser surface treatment process was simulated by a finite element software analysis (COMSOL Multiphysics) to optimize the scanning parameter range, and the linear array surface structure was subsequently fabricated by the LIG technique. The generation of graphene was confirmed by Raman spectroscopy and energy-dispersive X-ray spectroscopy. The periodic linear array structure was observed by scanning electron microscopy (SEM) and confocal laser imaging (CLSM). In addition, CLSM testings, contact angle measurements, and delayed icing experiments were systematically performed to investigate the effect of scanning speed on surface hydrophobicity. The results show that high-quality and uniform graphene can be achieved using the laser scanning speed of 125 mm/s. The periodic linear array structures can obviously increase the contact angle and suppress delayed icing. Furthermore, these structures have the enhanced ability of the electric heating deicing, which can reach 100 °C and 240 °C within 15 s and within 60 s under the DC voltage power supply ranging from 3 to 7 V, respectively. These results indicate that the LIG technique can be developed to provide an efficient, economical, and convenient approach for preparing graphene and that the hydrophobic surface array structure based on LIG has considerable potential for deicing and anti-icing applications

Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P=0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P<0.05). Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P<0.05). From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM