The purpose of this study is to investigate the correlation between single-nucleotide polymorphism (SNP) at the 3' end of the untranslated region (UTR) of Sirtuin 2 (SIRT2) gene and the risk of developing Alzheimer’s disease (AD), and to explore its underlying mechanisms. In total, 260 patients with AD and 260 healthy controls were recruited in this study. The genotype of rs2015 and rs2241703 loci of the SIRT2 gene was analyzed by Sanger sequencing for all participants. Quantitative real-time Polymerase chain reaction (qRT-PCR) was used to analyze microRNAs (miRNAs) and SIRT2 mRNA levels. Western blotting was used to analyze the expression level of SIRT2 protein. The dual luciferase reporter gene assay and cell transfection were performed to examine the role of miRNAs in regulating SIRT2 expression. Carriers of the SIRT2 gene rs2015 locus A allele were 0.69 times less likely to develop AD than the carriers of the C allele (95% confidence interval (CI): 0.59–0.80, p < 0.01). The carriers of the SIRT2 gene rs2241703 locus A allele were 1.43 times more likely to develop AD than the carriers of the G allele (95% CI: 1.23–1.61, p < 0.01). The rs2015 locus single-nucleotide polymorphism (SNP) affected the binding efficiency between miR-376a-5p and miR-8061 and the 3'UTR of the SIRT2 gene, and miR-376a-5p and miR-8061 bound to SIRT2 rs2015 A allele to down-regulate the expression of the SIRT2 protein. The rs2241703 SNP affected the binding efficiency between miR-486-3p and the 3'UTR of SIRT2 gene, and miR-486-3p bound to SIRT2 rs2241703 A allele to down-regulate SIRT2 protein expression. The SIRT2 gene rs2015 and rs2241703 loci SNPs are associated with the risk of AD. The rs2015 locus SNP affects regulation of miR-376a-5p and miR-8061 in SIRT2 expression and the rs2241703 locus SNP affects regulation of miR-486-3p in SIRT2, but further studies are needed to verify this mechanism. 相似文献
Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK‐875, AMG‐837, and LY2881835. Among them, most promising compounds 7 , 14 , and 15 were obtained with EC50 values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK‐875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7 , 14 , and 15 had significant glucose‐lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold. 相似文献
Prior research has indicated that narratives are more persuasive than nonnarrative messages. One of the reasons for this effectiveness is that the narratives’ intention to persuade is often not explicit, thus making them less likely to be disputed. The goal of this research is to examine the moderating role of persuasive intent in narrative persuasion. To do so, we conducted a 2 (Message format: narrative vs. nonnarrative messages) × 2 (Persuasive intent: intent vs. no intent) experiment with a factorial design among 205 participants on the effects of health narrative messages. Results indicated that persuasive intent undermined the effects of health narratives on persuasion by reducing believability and increasing reactance. Both believability and reactance partially mediated the effects of the narrative messages on attitudes and behavioral intention. 相似文献
Elastography ultrasound (EUS) imaging has shown its effectiveness for diagnosis of tumors by providing additional information about tissue stiffness to the conventional B-mode ultrasound (BUS). However, due to the lack of EUS devices and experienced sonologists, EUS is not widely used, especially in rural areas. It is still a challenging task to improve the performance of the single-modal BUS-based computer-aided diagnosis (CAD) for tumors. In this work, we propose a novel transfer learning (TL)–based deep neural network (DNN) algorithm, named CW-PM-DNN, for the BUS-based CAD by transferring diagnosis knowledge from EUS during model training. CW-PM-DNN integrates both the feature-level and classifier-level knowledge transfer into a unified framework. In the feature-level TL, a bichannel DNN is learned by the cross-weight-based multimodal DL (MDL-CW) algorithm to transfer informative features from EUS to BUS. In the classifier-level TL, a projective model (PM)–based classifier is then embedded to the pretrained bichannel DNN to implement the parameter transfer in the classifier model at the second stage. The back-propagation procedure is then applied to optimize the whole CW-PM-DNN to further improve its performance. Experimental results on two bimodal ultrasound tumor datasets demonstrate that the proposed CW-PM-DNN achieves the best classification accuracy, sensitivity, and specificity of 89.02 ± 1.54%, 88.37 ± 4.72%, and 89.63 ± 4.06%, respectively, for the breast ultrasound dataset, and the corresponding values of 80.57 ± 3.41%, 76.67 ± 3.85%, and 83.94 ± 3.95%, respectively, for the prostate ultrasound dataset. The proposed two-stage TL-based CW-PM-DNN algorithm outperforms all the compared algorithms. It is also proved that the performance of the BUS-based CAD can be significantly improved by transferring the knowledge of EUS. It suggests that CW-PM-DNN has the potential for more applications in the field of medical image–based CAD.