The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA-binding domain, known ...as 'forkhead box' domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals. Of the FoxO family, FoxO6 is the least characterized member and is shown to play pivotal roles in the liver, skeletal muscle and brain. Altered FoxO6 expression is associated with the pathogenesis of insulin resistance, dietary obesity and type 2 diabetes and risk of neurodegeneration disease. FoxO6 is evolutionally divergent from other FoxO isoforms. FoxO6 mediates insulin action on target genes in a mechanism that is fundamentally different from other FoxO members. Here, we focus our review on the role of FoxO6, in contrast with other FoxO isoforms, in health and disease. We review the distinctive mechanism by which FoxO6 integrates insulin signaling to hepatic glucose and lipid metabolism. We highlight the importance of FoxO6 dysregulation in the dual pathogenesis of fasting hyperglycemia and hyperlipidemia in diabetes. We review the role of FoxO6 in memory consolidation and its contribution to neurodegeneration disease and aging. We discuss the potential therapeutic option of pharmacological FoxO6 inhibition for improving glucose and lipid metabolism in diabetes.
In this review, we survey the latest advances in theoretical understanding of bimolecular reaction dynamics in the past decade. The remarkable recent progress in this field has been driven by more ...accurate and efficient ab initio electronic structure theory, effective potential-energy surface fitting techniques, and novel quantum scattering algorithms. Quantum mechanical characterization of bimolecular reactions continues to uncover interesting dynamical phenomena in atom-diatom reactions and beyond, reaching an unprecedented level of sophistication. In tandem with experimental explorations, these theoretical developments have greatly advanced our understanding of key issues in reaction dynamics, such as microscopic reaction mechanisms, mode specificity, product energy disposal, influence of reactive resonances, and nonadiabatic effects.
To investigate the risk factors associated with the development of thrombocytopenia, and define the thresholds of efficacy and safety in critically ill patients who received linezolid therapy. A ...retrospective study was performed in critically ill patients treated with linezolid. Risk factors associated with thrombocytopenia were identified via medical records and trough levels (C
min
) measured during linezolid treatment. By establishing a logistic model, the risks were predicted by the receiver operating characteristic (ROC) curve and the thresholds of efficacy and safety were identified in the patients. Logistic analysis showed that, weight (OR = 0.906; 95 % CI, 0.839–0.978;
P
= 0.011), baseline platelet count (OR = 0.989; 95 % CI, 0.977–1.000;
P
= 0.049), C
min
(OR = 1.545; 95 % CI, 1.203–1.983;
P
= 0.001), and APACHE II score (OR = 1.130; 95 % CI, 1.003–1.273;
P
= 0.044) were significant factors for linezolid-associated thrombocytopenia. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was the maximum, the best optimal cut-off point was 205.6 on the ROC curve; when C
min
≥ 2 mg/L, the probability of bacterial eradication was more than 80 %; when C
min
≥ 6.3 mg/L, the probability of thrombocytopenia was more than 50 %. In clinical practice, when the calculating results of the combined predictor ≤205.6, the risk of the development of thrombocytopenia may be higher. Furthermore, maintenance of C
min
between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.
Recently, crack segmentation studies have been investigated using deep convolutional neural networks. However, significant deficiencies remain in the preparation of ground truth data, consideration ...of complex scenes, development of an object-specific network for crack segmentation, and use of an evaluation method, among other issues. In this paper, a novel semantic transformer representation network (STRNet) is developed for crack segmentation at the pixel level in complex scenes in a real-time manner. STRNet is composed of a squeeze and excitation attention-based encoder, a multi head attention-based decoder, coarse upsampling, a focal-Tversky loss function, and a learnable swish activation function to design the network concisely by keeping its fast-processing speed. A method for evaluating the level of complexity of image scenes was also proposed. The proposed network is trained with 1203 images with further extensive synthesis-based augmentation, and it is investigated with 545 testing images (1280 × 720, 1024 × 512); it achieves 91.7%, 92.7%, 92.2%, and 92.6% in terms of precision, recall, F1 score, and mIoU (mean intersection over union), respectively. Its performance is compared with those of recently developed advanced networks (Attention U-net, CrackSegNet, Deeplab V3+, FPHBN, and Unet++), with STRNet showing the best performance in the evaluation metrics-it achieves the fastest processing at 49.2 frames per second.
The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria ...and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of invading plasmids and viruses. Here, we studied the effects of the CRISPR/CRISPR-associated Cas9 system that was targeted to the surface antigen (HBsAg)-encoding region of HBV, both in a cell culture system and in vivo. The HBsAg levels in the media of the cells and in the sera of mice were analyzed by a quantitative enzyme-linked immunosorbent assay. The HBV DNA levels were assessed by quantitative PCR and HBsAg expression in mouse livers was assessed by an immunohistochemical assay. The amount of HBsAg secreted in the cell culture and mouse serum was reduced by CRISPR/Cas9 treatment. Immunohistochemistry analyses showed almost no HBsAg-positive cells in the liver tissue of CRISPR/Cas9-S1+X3-treated mice. The CRISPR/Cas9 system efficiently produced mutations in HBV DNA. Thus, CRISPR/Cas9 inhibits HBV replication and expression in vitro and in vivo and may constitute a new therapeutic strategy for HBV infection.
In this paper, we report on the design, modeling, and experimental testing of a piezoelectric-driven microgripper making use of both an integrated gripping force sensor and an integrated tip ...displacement sensor. In the developed microgripper, a stack piezoelectric ceramic actuator is used to simultaneously obtain the tip displacement and the gripping force. A novel monolithic compliant mechanism is proposed to act as the microdisplacement transmission mechanism to obtain the large tip displacement and to provide the possibility of integrating both the gripping force sensor and the tip displacement sensor into the microgripper. The relationship between the gripping force, tip displacement, input force, and input displacement of the piezoelectric-driven microgripper and the dynamic model are established using the pseudorigid-body-model method. The characteristics of the developed microgripper are tested and the case of gripping an optical fiber is presented. The experimental results indicate that: 1) the theoretical model for the developed microgripper matched well with the measured results; 2) the integrated gripping force sensor and tip displacement sensor could accurately measure the gripping force and tip displacement; 3) the developed microgripper could achieve a displacement magnification of 16.0 × with respect to the stack piezoelectric ceramic actuator to realize the large tip displacement with high resolution but is also able to possess the parallel movement of its gripping jaws and the constant displacement magnification.
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