Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes. A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold overlength HBV genome (pHBV1.3) via the tail vein. Coculture experiments with HBV-expressing hepatoma cells and Jurkat T cells were established in vitro. We observed significant decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and increase in β-catenin/PD-L1 expression in liver tissues from patients with chronic hepatitis B and mice subjected to pHBV1.3 hydrodynamic injection. Mechanistically, decrease in PTEN enhanced β-catenin/c-Myc signaling and PD-L1 expression in HBV-expressing hepatoma cells, which in turn augmented PD-1 expression, lowered IL-2 secretion, and induced T cell apoptosis. However, β-catenin disruption inhibited PTEN-mediated PD-L1 expression, which was accompanied by decreased PD-1 expression, and increased IL-2 production in T cells. Luciferase reporter assays revealed that c-Myc stimulated transcriptional activity of PD-L1. In addition, HBV X protein (HBx) and HBV polymerase (HBp) contributed to PTEN downregulation and β-catenin/PD-L1 upregulation. Strikingly, PTEN overexpression in hepatocytes inhibited β-catenin/PD-L1 signaling and promoted HBV clearance in vivo. Our findings suggest that HBV-triggered PTEN/β-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion. NEW & NOTEWORTHY This study demonstrates that during HBV infection, HBV can increase PD-L1 expression via PTEN/β-catenin/c-Myc signaling pathway, which in turn inhibits T cell response and ultimately promotes HBV immune evasion. Targeting this signaling pathway is a potential strategy for immunotherapy of chronic hepatitis B.
Currently, various attention-based neural networks have achieved successes in sentiment classification tasks, as attention mechanism is capable of focusing on those words contributing more to the sentiment polarity prediction than others. However, the major drawback of these approaches is that they only pay attention to the words, the sentimental information contained in the part-of-speech(POS) is ignored. To address this problem, in this paper, we propose Part-of-Speech based Transformer Attention Network(pos-TAN). This model not only uses the Self-Attention mechanism to learn the feature expression of the text but also incorporates the POS-Attention, which uses to capture sentimental information contained in part-of-speech. In addition, our innovative introduction of the Focal Loss effectively alleviates the impact of sample imbalance on model performance. We conduct substantial experiments on various datasets, and the encouraging results indicate the efficacy of our proposed approach.
Recently, MXenes (a class of two-dimensional transition metal carbides) have attracted great attention in various applications such as humidity sensors, owing to their unique electrical and thermal properties. However, previous...
The detection of ash fusion temperatures is important in the research of coal characteristics. The prevalent method is to build up ash cone with some dimension and detect the characteristic temperatures according to the morphological change. However Conditional detection work is not accurate and brings high intensity of labor as a result of both visualization and real-time observation. According to the insufficiency of conventional method, a new method to determine ash fusion temperatures with image processing techniques is introduced in this paper. Seven techniques (image cutting, image sharpening, edge picking, open operation, dilate operation, close operation, geometrical property extraction) are used in image processing program. The processing results show that image sharpening can intensify the outline of ash cone; Prewitt operator may extract the edge well among many operators; mathematical morphology of image can filter noise effectively while filling up the crack brought by filtration, which is useful for further disposal; characteristic temperatures of ash fusion temperatures can be measured by depth-to-width ratio. Ash fusion temperatures derived from this method match normal values well, which proves that this method is feasible in detection of ash fusion temperatures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.