•Role of latent genes encoded by EBV.•Role of lytic genes encoded by EBV.•Immunotherapy for EBV-associated malignancies.•Expression of PD-L1 in EBV-associated malignancies.•Regulatory mechanism of ...PD-L1 expression in EBV-associated malignancies.
Epstein-Barr virus infection is closely related to the occurrence and development of a variety of malignant tumors. Tumor immunotherapy has been combined with modern biological high-tech technology, and has become the fourth cancer treatment mode after surgery, chemotherapy and radiotherapy. In 2013, immunotherapy was named the first of ten scientific breakthroughs by science. It aims to control and destroy tumor cells by stimulating and enhancing autoimmune function. In recent years, immune checkpoint inhibitors (ICIs) targeting PD-L1 have become a research hotspot in the field of cancer. Recent studies have shown that EBV infection can upregulate PD-L1 through complex mechanisms. Further understanding of these mechanisms and prevention of hyperprogressive disease (HPD) can make PD-L1 immune checkpoint inhibitors an effective way of immunotherapy for EBV related malignant tumors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The key to solving fine-grained image categorization is finding discriminate and local regions that correspond to subtle visual traits. Great strides have been made, with complex networks designed ...specifically to learn part-level discriminate feature representations. In this paper, we show that it is possible to cultivate subtle details without the need for overly complicated network designs or training mechanisms - a single loss is all it takes. The main trick lies with how we delve into individual feature channels early on, as opposed to the convention of starting from a consolidated feature map. The proposed loss function, termed as mutual-channel loss (MC-Loss), consists of two channel-specific components: a discriminality component and a diversity component. The discriminality component forces all feature channels belonging to the same class to be discriminative, through a novel channel-wise attention mechanism. The diversity component additionally constraints channels so that they become mutually exclusive across the spatial dimension. The end result is therefore a set of feature channels, each of which reflects different locally discriminative regions for a specific class. The MC-Loss can be trained end-to-end, without the need for any bounding-box/part annotations, and yields highly discriminative regions during inference. Experimental results show our MC-Loss when implemented on top of common base networks can achieve state-of-the-art performance on all four fine-grained categorization datasets (CUB-Birds, FGVC-Aircraft, Flowers-102, and Stanford Cars). Ablative studies further demonstrate the superiority of the MC-Loss when compared with other recently proposed general-purpose losses for visual classification, on two different base networks. Codes are available at: https://github.com/dongliangchang/Mutual-Channel-Loss.
Crystallization and transformation of iron (oxyhydr)oxides occur widely in redox-dynamic environments, which are closely linked to iron cycling, (im)mobilization of co-associated elements, and ...microbial iron metabolisms. Although numerous studies have been conducted to investigate the occurrence and fate of iron (oxyhydr)oxides under various redox conditions, the mechanism controlling these processes is still incompletely understood. Here, we present a theoretical model, based on Classical Nucleation Theory (CNT), that can be used to predict and rationalize phase-selection and crystallization pathways of iron (oxyhydr)oxides under different redox conditions. By calculating the energy landscapes of dissolved or solid-phase iron species in a Fe-H2O system as a function of Eh, pH, and particle size, we show how the stability regions of iron (oxyhydr)oxides change with geochemical environments (pH and redox potential) and initial properties of precursors (particle size and crystallinity). Through the calculation of thermodynamic driving forces and energy barriers for the nucleation of different metastable phases, the crystallization pathways of iron (oxyhydr)oxides via hydrolysis of Fe3+(aq), oxidation of Fe2+(aq), and Fe(II)-catalyzed ferrihydrite transformation can be predicted. The computational results show good agreement with previously reported experimental data. This study provides a unified model to predict and understand relative stability, transformation, and persistence of iron (oxyhydr)oxides under varying pH and redox conditions in natural environments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Apoptosis is an important process for an organism's innate immune system to respond to pathogens, while also allowing for cell differentiation and other essential life functions. Caspases are one of ...the key protease enzymes involved in the apoptotic process, however there is currently a very limited understanding of bivalve caspase diversity and function.
In this work, we investigated the presence of caspase homologues using a combination of bioinformatics and phylogenetic analyses. We blasted the Crassostrea gigas genome for caspase homologues and identified 35 potential homologues in the addition to the already cloned 23 bivalve caspases. As such, we present information about the phylogenetic relationship of all identified bivalve caspases in relation to their homology to well-established vertebrate and invertebrate caspases. Our results reveal unexpected novelty and complexity in the bivalve caspase family. Notably, we were unable to identify direct homologues to the initiator caspase-9, a key-caspase in the vertebrate apoptotic pathway, inflammatory caspases (caspase-1, - 4 or - 5) or executioner caspases-3, - 6, - 7. We also explored the fact that bivalves appear to possess several unique homologues to the initiator caspase groups - 2 and - 8. Large expansions of caspase-3 like homologues (caspase-3A-C), caspase-3/7 group and caspase-3/7-like homologues were also identified, suggesting unusual roles of caspases with direct implications for our understanding of immune response in relation to common bivalve diseases. Furthermore, we assessed the gene expression of two initiator (Cg2A, Cg8B) and four executioner caspases (Cg3A, Cg3B, Cg3C, Cg3/7) in C. gigas late-larval development and during metamorphosis, indicating that caspase expression varies across the different developmental stages.
Our analysis provides the first overview of caspases across different bivalve species with essential new insights into caspase diversity, knowledge that can be used for further investigations into immune response to pathogens or regulation of developmental processes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The absorption, distribution and excretion of drugs are largely determined by their transporters (DTs), the variability of which has thus attracted considerable attention. There are three ...aspects of variability: epigenetic regulation and genetic polymorphism, species/tissue/disease-specific DT abundances, and exogenous factors modulating DT activity. The variability data of each aspect are essential for clinical study, and a collective consideration among multiple aspects becomes crucial in precision medicine. However, no database is constructed to provide the comprehensive data of all aspects of DT variability. Herein, the Variability of Drug Transporter Database (VARIDT) was introduced to provide such data. First, 177 and 146 DTs were confirmed, for the first time, by the transporting drugs approved and in clinical/preclinical, respectively. Second, for the confirmed DTs, VARIDT comprehensively collected all aspects of their variability (23 947 DNA methylations, 7317 noncoding RNA/histone regulations, 1278 genetic polymorphisms, differential abundance profiles of 257 DTs in 21 781 patients/healthy individuals, expression of 245 DTs in 67 tissues of human/model organism, 1225 exogenous factors altering the activity of 148 DTs), which allowed mutual connection between any aspects. Due to huge amount of accumulated data, VARIDT made it possible to generalize characteristics to reveal disease etiology and optimize clinical treatment, and is freely accessible at: https://db.idrblab.org/varidt/ and http://varidt.idrblab.net/.
Ferrihydrite (Fh) is a major Fe(III)-(oxyhydr)oxide nanomineral distinguished by its poor crystallinity and thermodynamic metastability. While it is well known that in suboxic conditions aqueous ...Fe(II) rapidly catalyzes Fh transformation to more stable crystalline Fe(III) phases such as lepidocrocite (Lp) and goethite (Gt), because of the low solubility of Fe(III) the mass transfer pathways enabling these rapid transformations have remained unclear for decades. Here, using a selective extractant, we isolated and quantified a critical labile Fe(III) species, one that is more reactive than Fe(III) in Fh, formed by the oxidation of aqueous Fe(II) on the Fh surface. Experiments that compared time-dependent concentrations of solid-associated Fe(II) and this labile Fe(III) against the kinetics of phase transformation showed that its accumulation is directly related to Lp/Gt formation in a manner consistent with the classical nucleation theory. 57Fe isotope tracer experiments confirm the oxidized Fe(II) origin of labile Fe(III). The transformation pathway as well as the accelerating effect of Fe(II) can now all be explained on a unified basis of the kinetics of Fe(III) olation and oxolation reactions necessary to nucleate and sustain growth of Lp/Gt products, rates of which are greatly accelerated by labile Fe(III).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A synthetic biomimetic SERS sensor for highly specific and sensitive detection of ACP is realized.•Boronate affinity-based surface imprinting approach is applied for specific extraction of trace ...targets.•The approach shows great versatility by imprinting different glycoproteins.
In this paper, we introduce a synthetic biomimetic receptors-based surface enhanced Raman scattering (SERS) sensor for highly specific recognition and detection of acid phosphatase in complex biological samples. It depends on the establishment of molecular imprinted polymers (MIPs) which capture the target glycoprotein via biomimetic recognition, and SERS probes which bind to glycoproteins by boronate affinity. The MIPs layer was synthesized through self-polymerization of dopamine on the surface of glycoprotein-immobilized polymeric skeletons, which was prepared by choosing 4-vinylphenylboronic acid (VPBA) as functional monomers, pentaerythritol triacrylate (PETA) as crosslinker, ethyleneglycol (EG) and cyclohexanol as porogens. The accessible and stable recognition sites allowed the rebinding of the template and offered good reproducibility. The proposed biomimetic recognition-based SERS sensor showed superb performances for acid phosphatase detection with high sensitivity (LOD of 0.1 ng mL−1) and excellent selectivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The dysregulation of glycolysis has been suggested to lead to alteration of cell drug resistance signals, proliferation and metastasis. Emerging evidence indicates that lncRNAs play a key role in the ...cellular processes of tumor cells, including glycolysis, growth, and movement. However, the role and potential mechanism of lncRNAs in glycolysis-mediated metastasis has not been explored. In this study, we identified a novel lncRNA lnc-p23154 which is associated with OSCC patient metastasis and the promotion of OSCC cell migration and invasion in vitro and in vivo. Furthermore, we found that lnc-p23154 also participates in OSCC glycolysis by facilitating Glut1 expression. Rescue of lnc-p23154 reversed the suppression of OSCC cell migration and invasion induced by Glut1 knockdown. In addition, lnc-p23154 is mainly located in the nucleus and binds to the promoter region of miR-378a-3p, which represses Glut1 expression by targeting to its 3ʹUTR directly. Therefore, we concluded that lnc-p23154 may play an important role in Glut1-mediated glycolysis by inhibiting miR-378a-3p transcription and accelerate OSCC metastasis.
•A novel lncRNA, lnc-p23154, is upregulated in OSCC and associated with metastasis.•Lnc-p23154 affects glycolysis by facilitating Glut1 expression.•Lnc-p23154 regulates Glut1 by inhibiting miR-378a-3p transcription.•Glut1 is involved in OSCC metastasis.•The lnc-p23154-miR-378a-3p/Glut1 pathway is a potential biomarker for OSCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A universal post-compensation scheme for fiber impairments in wavelength-division multiplexing (WDM) systems is proposed based on coherent detection and digital signal processing (DSP). Transmission ...of 10 x 10 Gbit/s binary-phase-shift-keying (BPSK) signals at a channel spacing of 20 GHz over 800 km dispersion shifted fiber (DSF) has been demonstrated numerically.
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