Search

Glutamine synthetase (GS) catalyzes de novo synthesis of glutamine that facilitates cancer cell growth. In the liver, GS functions next to the urea cycle to remove ammonia waste. As a dysregulated urea cycle is implicated in cancer development, the impact of GS's ammonia clearance function has not been explored in cancer. Here, we show that oncogenic activation of β-catenin (encoded by CTNNB1) led to a decreased urea cycle and elevated ammonia waste burden. While β-catenin induced the expression of GS, which is thought to be cancer promoting, surprisingly, genetic ablation of hepatic GS accelerated the onset of liver tumors in several mouse models that involved β-catenin activation. Mechanistically, GS ablation exacerbated hyperammonemia and facilitated the production of glutamate-derived nonessential amino acids, which subsequently stimulated mechanistic target of rapamycin complex 1 (mTORC1). Pharmacological and genetic inhibition of mTORC1 and glutamic transaminases suppressed tumorigenesis facilitated by GS ablation. While patients with hepatocellular carcinoma, especially those with CTNNB1 mutations, have an overall defective urea cycle and increased expression of GS, there exists a subset of patients with low GS expression that is associated with mTORC1 hyperactivation. Therefore, GS-mediated ammonia clearance serves as a tumor-suppressing mechanism in livers that harbor β-catenin activation mutations and a compromised urea cycle.

In this paper, semantic segmentation based on a convolutional neural network is used to guide the image color restoration process. In order to avoid the problem of content mismatch, higher-order features are first extracted from the basic dimensions of the input image, and the convolutional operation is done on the feature map by the excitation function. Then the network parameters are optimized and updated by the backpropagation algorithm to minimize the error between the prediction result and the real result. Finally, in image processing, the dilated convolution technique is introduced to perform noise reduction on the semantic segmented image pixels to optimize the restoration quality. In order to prove the effectiveness of the method in this paper, an experimental analysis of the method is conducted. The experimental results show that the peak signal-to-noise ratio of the model proposed in this paper is higher than 42.986db on average, the structural similarity reaches 0.8%, and the fit is around 0.75. And its color difference can reach at least 11.2% with the increase of iterations. It indicates that the reduction algorithm of semantic segmentation and convolutional neural network greatly improves the accuracy of color reduction results and can obtain printmaking images with higher color quality.

Clinical practice guidelines are an important basis for clinical decision-making, but there are still many factors that prevent physicians from following the guidelines. One of the problems, the limited external validity of the guidelines, ultimately prevents the guidelines from providing an adequate basis for clinical decision-making, thus forming the gap between the guidelines and clinical decisions. Real-world research can enhance the external validity of the guidelines, provide a basis for clinical decision-making, and offer localized evidence for the guidelines, evidence of cost-effectiveness and other evidence for the guidelines. It can also monitor the implementation of the guidelines and help to make up for the lack of evidence in the formulation of traditional guidelines. Therefore, high-quality real-world studies and real-world evidence may be considered in the guideline development process to facilitate guideline optimization and serve as an aid to guideline quality improvement.

In this study, the influence of two distinct reactive aggregate dosages on the alkali–silica reaction (ASR) of concrete was investigated. The expansion ratio, axial compressive strength, splitting tensile strength, and relative dynamic elastic modulus (RDEM) of concrete were considered as the main parameters to study the failure criteria of concrete induced by ASR at 40°C. Microscopic experiments, such as scanning electron microscopy and X-ray computed microtomography, were applied to analyze the damage induced by ASR on the concrete prisms and the propagation of internal cracks of the reactive aggregates in nanospace. The results showed that the two ranges can be used as the failure criteria produced by the ASR of concrete containing 3 and 6% dosages of reactive aggregates at 40°C, respectively, when the RDEM of concrete was reduced to 70‒75% and 85‒90%. Additionally, the results of CT indicated that microcracks tended to extend from the initial defects of aggregate to the cement slurry. Meanwhile, ASR gel packed with the pores, which reduced the porosity. It was noteworthy that the adhesive force between the ASR gel and the cement matrix after filling pores could not make up for the loss of the mechanical properties of concrete.

Background/Aim. Macroangiopathy is the major cause of death and disability in type 2 diabetic patients. Studies have shown that liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, can protect cardiovascular system by inhibiting chronic inflammation of diabetes. However, a study about the effects of liraglutide on peripheral blood vessels and peripheral blood leukocytes has not been reported yet. The aim of this study was to determine vasculoprotective effect, vascular protection and mechanism of action of liraglutide in addition to its hypoglycemic effect. Methods. A total of 60 hospitalized patients with type 2 diabetes were recruited from December 2013 to December 2014 at the First Affiliated Hospital of Dalian Medical University, PR China. Before the treatment with liraglutide, height and weight were measured to calculate body mass index (BMI). Blood urea nitrogen (BUN) and so on were detected. Homeostasis model assessment of insulin resistance (HOMA-IR) and islet β cell function (HOMA-β) were computed. After applying liraglutide for three months, all indexes were measured again. The effects of liraglutide on these indexes were analyzed by paired sample t-test. Results. After the treatment with liraglutide, values of glycosylated hemoglobin ‒ HbA1c (8.46 ± 1.62 vs. 7.26 ± 1.40%) and 2h postprandial blood glucose ‒ 2hPBG (11.95 vs. 9.6 mmol/L) decreased significantly (p < 0.05). Body weight (87.3 vs. 82.5 kg) and BMI (30.37 vs. 28.63 kg/m2) decreased by 5.5% and 5.7%, respectively (p < 0.05). Also, levels of triglycerides (TG) (2.57 ± 1.54 vs. 1.81 ± 0.70 mmol/L) and LDL-cholesterol (2.92 ± 0.78 vs. 1.89 ± 0.66 mmol/L) reduced significantly (p < 0.05). Ankle-brachial index (ABI) decreased from 1.24 ± 0.10 to 1.14 ± 0.06 cm/s by 8%, while brachial-ankle pulse wave velocity (ba-PWV) decreased from 1,442.15 ± 196.26 to 1,316.85 ± 146.63 cm/s by 8.7%, and both differences were statistically significant (p < 0.001). Conclusion. Liraglutide, with a good hypoglycemic effect, can significantly reduce postprandial blood glucose and HbA1c, but cannot significantly improve fasting plasma glucose, insulin resistance and islet β cell function. It also considerably decreased body weight, BMI and TG. Liraglutide can significantly lower ba-PWV and ABI to protect peripheral blood vessels.

Based on MnO2/carbon cloth (CC) composite materials, an Ag-doped MnO2 nanowire, self-assembled, urchin-like structure was synthesized in situ on the surface of CC using a simple method, and a novel and efficient flexible electrode material for supercapacitors was developed. The morphology, structure, elemental distribution, and pore distribution of the material were analyzed using SEM, TEM, XRD, XPS, and BET. The electrochemical performance was tested using cyclic voltammetry (CV) and galvanostatic charge/discharge (GCD). In the three-electrode system, GCD testing showed that the specific capacitance of the material reached 520.8 F/g at 0.5 A/g. After 2000 cycles at a current density of 1 A/g, the capacitance retention rate was 90.6%, demonstrating its enormous potential in the application of supercapacitor electrode materials. [ABSTRACT FROM AUTHOR]