Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in ...cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in these metabolic processes could provide novel approaches to improve cancer treatment. This review summarizes current findings on the role of glutaminolytic enzymes in human cancers and provides an update on the development of small molecule inhibitors to target glutaminolysis for cancer therapy.
Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause ...immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes. However, only a proportion of patients respond to the treatments. Further understanding of the regulation of PD-L1 expression could be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors and epigenetic factors. In this review, we summarise the recent progress of the regulation of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation. Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible factor-1α and signal transducer and activation of transcription-3 act on the promoter of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513, miR-197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD-L1 expression and cell proliferation.
•The oblique fin maintains boundary layer to be re-developed periodically.•The injection of secondary flow accelerates the heat propagation into fluid core.•The temperatures on the oblique fin are ...lower than those on the straight channel.•The T uniformity on oblique fin is much uniform than that on straight channel.•The oblique LCP achieves higher heat transfer coefficient.
The development of electric vehicles (EVs) demands for complementary technologies in battery thermal management. To achieve fast charging/discharging capacity, liquid cooling is an effective means of maintaining temperature of a battery in operation within a narrow optimal range. In conventional straight channels, convective heat transfer deteriorates along the axial direction with the development of the hydrodynamic boundary layer, resulting in elevated maximum temperature and significant temperature gradient in the fully developed region. This is a serious problem as temperature uniformity is of utmost importance to the performance and lifespan of a Li–ion battery. In this research, a simple configuration of oblique cuts across the straight fins of a conventional straight channel design was developed, to enhance the performance of the conventional channel with minimal pressure penalty. These oblique cuts across the straight fins form an oblique fin array. The designed liquid cold plate (LCP) contains these simple oblique fins with optimized angle and width. This segmentation of the continuous fin into oblique sections leads to the re-initialization of boundary layers, providing a solution to the elevated temperatures caused by a thick boundary layer in the fully developed region. Experimental results show that heat transfer coefficients of oblique minichannel are higher than those of conventional straight minichannel. The oblique LCP is able to maintain the battery surface average temperature below 50°C for a heat load of 1240W at a flow rate lower than 0.9l/min. This implies that a proper designed minichannel cold plate could be a promising solution for EV battery thermal management.
Abstract
In order to detect the pulse of LSI with high accuracy and efficiency, a new detection method of low frequency pulse signal of LSI based on deep self coding algorithm is proposed in this ...paper. Firstly, Radon transform is used to reduce the dimension of the time-frequency diagram of the pulse signal of the integrated circuit, and the short-time Fourier transform of the pulse signal is completed according to the Hamming window. Secondly, the principle of the depth self encoder is analyzed, and the pulse signal after the short time Fourier transform processing is input into the depth self encoder. Finally, according to the distance function, the gradient descent algorithm is used to update the parameters. Through iterative calculation, the detection of low frequency pulse signal of LSI is completed. The experimental results show that, compared with the traditional low-frequency pulse signal detection method, the detection accuracy of this method is greatly improved, up to 99.79%, and can shorten the overall detection time.
Objectives
This study presents the global burden of major oral diseases with an exegetical commentary on their current profiles, the critical issues in oral healthcare and future perspectives.
...Methods
A narrative overview of current literature was undertaken to synthesise the contexts with critical elaboration and commentary.
Results
Oral disease is one of the most common public health issues worldwide with significant socio‐economic impacts, and yet it is frequently neglected in public health policy. The oral data extracted from the Global Burden of Disease Study in 2010 (Murray et al, 2012) show that caries, periodontal disease, edentulism, oral cancer and cleft lip/palate collectively accounted for 18 814 000 disability‐adjusted life‐years; and the global burden of periodontal disease, oral cancer and caries increased markedly by an average of 45.6% from 1990 to 2010 in parallel with the major non‐communicable diseases like diabetes by 69.0%. Oral diseases and non‐communicable diseases are closely interlinked through sharing common risk factors (e.g. excess sugar consumption and tobacco use) and underlying infection/inflammatory pathways.
Conclusions
Oral disease remains a major public health burden worldwide. It is of great importance to integrate oral health into global health agenda via the common risk factor approach. The long‐term sustainable strategy for global oral health should focus on health promotion and disease prevention through effective multidisciplinary teamwork.
Psoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at ...the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7–9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7–9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7–9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7–9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs.
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