Hybrid graded element model for nonlinear functionally graded materials

A hybrid graded element model is developed in this article for solving the heat conduction problem of nonlinear functionally graded materials (FGMs), whose material properties not only vary spatially but also are temperature dependent. In the proposed approach, both Kirchhoff transformation and iterative method are introduced to deal with the nonlinear term in the heat conduction equation of nonlinear FGMs. Then, the graded element is formulated based on two sets of independent temperature fields. One is the intra-element temperature field, which is defined within the element domain and constructed by a linear combination of fundamental solutions; the other is the frame field, which is defined on the element boundary only and used as the boundary interpolation functions of the element to ensure the field continuity over the inter-element boundary. This model can simulate the graded material properties naturally due to the inherent properties of fundamental solutions, which are employed in constructing the graded element. Moreover, a multi-subdomain method is developed to deal with the problem with different materials. Finally, the performance of the proposed method is assessed by several benchmark examples. The results are in excellent agreement with the analytical solutions

Rutin prevents retinal ganglion cell death and exerts protective effects by regulating transforming growth factor-β2/Smad2/3Akt/PTEN signaling in experimental rat glaucoma

Purpose: To investigate the protective effect of rutin against glaucoma in a rat model, and the mechanisms involved. Methods: Sprague-Dawley rats were injected hypertonic saline in the limbal vein for elevation of intraocular pressure (IOP). Rats in the treatment group were administered rutin at doses of 12.5, 25 or 50 mg/kg orally and daily for 21 days. Results: Rutin markedly (p < 0.05) reduced IOP and prevented loss of retinal ganglion cells (RGCs). The expression of apoptotic pathway proteins, i.e., Bcl-xL, Bcl-2, Bad and Bax were significantly (p < 0.05) regulated by rutin. Moreover, rutin caused a substantial decrease in TGF-β2 expression, and also down-regulated p-Smad2 and p-Smad3 dose-dependently (p < 0.05). Raised levels of collagen I, fibronectin and elastin were effectively down-regulated. Rutin substantially up-regulated the Akt pathway involved in cell survival, and markedly improved the survival of RGCs subjected to hypoxia in vitro (p < 0.05). Conclusion: These results reveal that rutin exerts protective effect against glaucoma in a rat model via a mechanism involving regulation of the TGF-β2/Smad2/3Akt/PTEN signaling pathways. Thus, rutin has potentials for use in the management of glaucoma

Properties and Proanthocyanidin-Loading Capacity of Acid-Induced Micellar Casein-Sodium Alginate Emulsion Gels

In this work, oil-in-water (O/W) emulsion gels with 70% oil phase were prepared using micellar casein (MC) and sodium alginate (SA) as substrates with the addition of gluconate-δ-lactone (GDL) as acidifying agent. The effects of GDL addition on the microstructure, stability and rheological properties of emulsion gels were studied, and the release characteristics of emulsion gels loaded with proanthocyanidins (PC) were analyzed. The results showed that with increasing GDL concentration, the average size of oil droplets in emulsion gels decreased, and it gradually decreased during the storage period. GDL acidification improved the apparent viscosity and storage modulus of emulsion gels, and this effect increased with GDL concentration. The microstructure of emulsion gels did not change significantly after heat treatment at 65 or 80 ℃ for 30 min. Meanwhile, the emulsion gels were stable to acidic and basic conditions as well as storage. In addition, the release rate of PC-loaded emulsion gels was higher than that of free PC during simulated intestinal digestion, and the cumulative release rate at 10 h increased with GDL concentration. The results of this study could provide a reference for the preparation of emulsion gels based on MC and the improvement of PC stability

Tumor grade-associated genomic mutations in Chinese patients with non-small cell lung cancer

BackgroundLung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism.MethodsChinese patients with lung cancer were enrolled. The tumor samples were collected by surgery or puncture and applied for next-generation sequencing. A panel of pan-cancer genes was targeted, and the sequencing depth was set to over 1,000 to improve the sensitivity of detecting mutations. Short-length mutations (substitution, insertion, and deletion), copy number variation, and gene fusion were called. Gene mutations were compared between low-grade, middle-grade, and high-grade tumors using Fisher’s exact test. The enriched pathways in each grade of tumors were also inferred.ResultsThe study included 173 Chinese patients with non-small cell lung cancer, of whom 98 (56.6%) patients were female and 75 (43.4%) were male, with a mean age of 56.8 years. All patients were microsatellite stable; 66.4% were at the early stages (Stages 0, I, and II) with a tumor mutational burden of approximately 2.5 (confidence interval = [0, 48.3]). Compared to low-grade tumors, high-grade tumors had a significantly higher percentage of mutations in TP53 (75.9% vs 34.4%, p = 1.86e-3) and PIK3CA (24.1% vs. 0%, p = 3.58e-3). Pathway analysis found that high-grade tumors were enriched with mutations in bacterial invasion of epithelial cells (31% vs. 0%, p = 5.8e-4), Epstein–Barr virus infection (79.3% vs. 37.5%, p = 1.72e-3), and the Wnt signaling pathway (75.9% vs. 34.4%, p = 1.91e-3). High-grade tumors had a significantly higher tumor mutational burden than low-grade tumors (p-value = 0.0017). However, actionable mutations with high-level evidence were lower in high-grade tumors.ConclusionPatients with high-grade tumors from lung cancer may be more affected by bacteria and Epstein–Barr virus than low-grade tumors. High-grade tumors were specially mutated in TP53 and PIK3CA and may benefit more from immunotherapy. Further research on the underlying mechanism of high-grade lung cancer is necessary to develop new therapeutic options. Lung cancer, tumor grade, genomic mutations, Epstein–Barr virus, pathway analysi

A new score system for predicting response to cardiac resynchronization therapy

Background: The aim of this study was to establish a score system derived from clinical, echocardiographic and electrocardiographic indexes and evaluate its clinical value for cardiac resynchronization therapy (CRT) patient selection. Methods: Ninety-three patients receiving CRT were enrolled. A patient selection score system was generated by the clinical, echocardiographic and electrocardiographic parameters achieving a significant level by univariate and multivariate Cox regression model. The positive response to CRT was a left ventricular end systolic volume decrease of ≥ 15% and not reaching primary clinical endpoint (death or re-hospitalization for heart failure) at the end of follow-up. Results: Thirty-nine patients were CRT non-responders (41.94%) and 54 were responders (58.06%). A 4-point score system was generated based on tricuspid annular plane systolic ex­cursion (TAPSE), longitudinal strain (LS), and complete left bundle branch block (CLBBB) combined with a wide QRS duration (QRSd). The sensitivity and specificity for prediction of a positive response to CRT at a score > 2 were 0.823 and 0.850, respectively (AUC: 0.92295% CI 0.691–0.916, p< 0.001). Conclusions: A patient selection score system based on the integration of TAPSE, LS and CLBBB combined with a wide QRSd can help to predict positive response to CRT effectively and reliably

Transgenic CHD1L Expression in Mouse Induces Spontaneous Tumors

Background: Amplification of 1q21 is the most frequent genetic alteration in hepatocellular carcinoma (HCC), which was detected in 58-78% of primary HCC cases by comparative genomic hybridization (CGH). Using chromosome microdissection/ hybrid selection approach we recently isolated a candidate oncogene CHD1L from 1q21 region. Our previous study has demonstrated that CHD1L had strong oncogenic ability, which could be effectively suppressed by siRNA against CHD1L. The molecular mechanism of CHD1L in tumorigenesis has been associated with its role in promoting cell proliferation. Methodology/Principal Findings: To further investigate the in vivo oncogenic role of CHD1L, CHD1L ubiquitous-expression transgenic mouse model was generated. Spontaneous tumor formations were found in 10/41 (24.4%) transgenic mice, including 4 HCCs, but not in their 39 wild-type littermates. In addition, alcohol intoxication was used to induce hepatocyte pathological lesions and results found that overexpression of CHD1L in hepatocytes could promote tumor susceptibility in CHD1L-transgenic mice. To address the mechanism of CHD1L in promoting cell proliferation, DNA content between CHD1Ltransgenic and wildtype mouse embryo fibroblasts (MEFs) was compared by flow cytometry. Flow cytometry results found that CHD1L could facilitate DNA synthesis and G1/ S transition through the up-regulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, and CDK4, and down-regulation of Rb, p27Kip1, and p53. Conclusion/Significance: Taken together, our data strongly support that CHD1L is a novel oncogene and plays an important role in HCC pathogenesis. © 2009 Chen et al.published_or_final_versio

Association between Long-Term Changes in Dietary Percentage of Energy from Fat and Obesity: Evidence from over 20 Years of Longitudinal Data

Objectives: This study assessed the associations between long-term trajectories of percentage of energy from fat (PEF) and obesity among Chinese adults. Methods: Longitudinal data collected by the China Health and Nutrition Survey from 1991 to 2015 were analyzed. A body mass index ≥28.0 was defined as general obesity. Participants’ baseline PEF levels were categorized as lower than the recommendation of the Chinese Dietary Guideline (20%), meeting the recommendation (20−30%), and higher than the recommendation (>30%). Patterns of PEF trajectories were identified by latent class trajectory analysis for overall participants and participants in different baseline PEF groups, respectively. Cox proportional hazards regression models with shared frailty were used to estimate associations between PEF and obesity. Results: Data on 13,025 participants with 72,191 visits were analyzed. Four patterns of PEF trajectory were identified for overall participants and participants in three different baseline PEF groups, respectively. Among overall participants, compared with “Baseline Low then Increase Pattern” (from 12% to 20%), participants with “Baseline Normal-Low then Increase-to-High Pattern” (from 20% to 32%) had a higher hazard of obesity (hazard ratio (HR) and 95% confident interval (CI) at 1.18 (1.01−1.37)). Compared with the “Stable Pattern” group (stable at around 18% and 22%, respectively), participants with “Sudden-Increase Pattern” (from 18% to 30%) in the baseline group whose PEF levels were lower than the recommendation and those with “Sudden-Increase then Decrease Pattern” (rapidly increased from 25% to 40%, and then decreased) in the baseline group who met the recommendation had higher hazards of obesity (HRs and 95% CIs being 1.65 (1.13−2.41) and 1.59 (1.03−2.46), respectively). Conclusions: Adults with a trajectory that involved a sudden increase to a high-level PEF had a higher risk of general obesity. People should avoid increasing PEF suddenly

RNA methylomes reveal the m(6)A-mediated regulation of DNA demethylase gene SlDML2 in tomato fruit ripening

Background Methylation of nucleotides, notably in the forms of 5-methylcytosine (5mC) in DNA and N-6-methyladenosine (m(6)A) in mRNA, carries important information for gene regulation. 5mC has been elucidated to participate in the regulation of fruit ripening, whereas the function of m(6)A in this process and the interplay between 5mC and m(6)A remain uncharacterized. Results Here, we show that mRNA m(6)A methylation exhibits dynamic changes similar to DNA methylation during tomato fruit ripening. RNA methylome analysis reveals that m(6)A methylation is a prevalent modification in the mRNA of tomato fruit, and the m(6)A sites are enriched around the stop codons and within the 3 ' untranslated regions. In the fruit of the ripening-deficient epimutant Colorless non-ripening (Cnr) which harbors DNA hypermethylation, over 1100 transcripts display increased m(6)A levels, while only 134 transcripts show decreased m(6)A enrichment, suggesting a global increase in m(6)A. The m(6)A deposition is generally negatively correlated with transcript abundance. Further analysis demonstrates that the overall increase in m(6)A methylation in Cnr mutant fruit is associated with the decreased expression of RNA demethylase gene SlALKBH2, which is regulated by DNA methylation. Interestingly, SlALKBH2 has the ability to bind the transcript of SlDML2, a DNA demethylase gene required for tomato fruit ripening, and modulates its stability via m(6)A demethylation. Mutation of SlALKBH2 decreases the abundance of SlDML2 mRNA and delays fruit ripening. Conclusions Our study identifies a novel layer of gene regulation for key ripening genes and establishes an essential molecular link between DNA methylation and mRNA m(6)A methylation during fruit ripening