Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species ...Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)—its presumptive ancestor—and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-O-acetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1A. We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1A, and infectivity assays with BCoV-S–pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1A. The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1A and that of HKU1 in domain S1B.
Metabolic reprogramming is one of the main characteristics of malignant tumors. The metabolic reprogramming of tumors is not only related to the characteristics of cancer cells, but also closely ...related to the tumor microenvironment (TME). 'Aerobic glycolysis' is considered to be the classic metabolic mode of tumor cells. However, recent experiments have shown that the TME plays a key role in carcinogenesis and epithelial-mesenchymal transition. Cancer-associated fibroblasts (CAFs) dominate in the microenvironment and affect the homeostasis of the TME. The interaction between cancer cells and the surrounding CAFs markedly affects the growth, metabolism, metastasis, and progression of cancer. Based on this, a 'dual-chamber' model, also known as the 'Reverse Warburg effect', is proposed. Specifically, cancer cells secrete hydrogen peroxide into the TME to induce oxidative stress in neighboring stromal cells. CAFs undergo aerobic glycolysis and produce high levels of energy-rich 'fuels' (such as pyruvate, ketone bodies, fatty acids, and lactic acid). In turn, these energy-rich 'fuels' then 'feed' cancer cells. The mitochondrial oxidative phosphorylation system produces a large quantity of ATP, such that tumor cells have a higher proliferation ability. The proposed 'Reverse Warburg effect' redefines the tumor cell microenvironment and tumor metabolic reprogramming. Therefore, understanding the 'Reverse Warburg effect' of CAFs and its related mechanisms will help us to understand the association between the microenvironment, the matrix, and cancer cells, and may lead to new treatment strategies and targets. Key words: cancer-associated fibroblasts, Reverse Warburg effect, signal transduction pathway, reactive oxygen species, transforming growth factor-beta, interleukin-6
Building upon Zimmerman's socio-cognitive view of self-regulation, we explored EFL (English as a Foreign Language) students' revision and the likely contribution to revision from three salient ...self-regulating sources: peer feedback, instructor feedback, and revision goals. Data was obtained from 70 Chinese EFL students in a writing class through a 300-word online writing assignment involving online instructor and peer feedback, free-response revision goals, and a required revision. We closely coded students' revision and then used the same coding scheme to analyze the relative levels of association of revision changes with peer comments, instructor comments and revision goals. We found that: (a) the majority of revision changes have been triggered by three mediating sources, with revision goals as the most significant contributing source. Additionally, most revision changes come from a combination of two or three sources, with the overlap of peer feedback and revision goals accounting for the biggest overlapping contribution for both high and low-level revisions; (b) as for the relationship among the three sources, no significant difference was found between revision goals' overlap rate with peer feedback and their overlap rate with instructor feedback. Instructor feedback and peer feedback did not overlap very much. Findings suggest that students could revise beyond instructor and peer feedback in their revision efforts guided by their own reflective goals, and peer feedback could function as a more productive and multiple-reader source of revision in comparison with instructor feedback. This study also provided evidence for students' self-regulated learning of writing through the use of self-regulating resources and charted a route for how writing could be improved.
Phonon transport properties of two-dimensional materials can play a crucial role in the thermal management of low-dimensional electronic devices and thermoelectric applications. In this study, both ...the empirical Stillinger–Weber (SW) and machine learning interatomic potentials are employed to investigate the lattice thermal conductivity of monolayer GeS and SnS through solving the phonon Boltzmann transport equation. The accuracy of the two types of interatomic potentials and their performance for the evaluation of thermal conductivity are verified by analyzing phonon harmonic and anharmonic properties. Our results indicate that the thermal conductivity can be predicted more accurately with a machine learning approach, while the SW potential gives rise to an overestimated value for both monolayers. In addition, the in-plane anisotropy of thermal transport properties existing in these monolayers can be confirmed by both potential models. Moreover, the origins of the deviation existing in calculated thermal conductivities, including both the effects of interatomic potential models and monolayer compositions, are elucidated through uncovering the underlying phonon transport mechanisms. This study highlights that in contrast to the machine learning approach, more careful verification is required for the simulation of thermal transport properties when empirical interatomic potential models are employed.
CD38: An important regulator of T cell function Li, Wentao; Liang, Lin; Liao, Qianjin ...
Biomedicine & pharmacotherapy,
September 2022, 2022-09-00, 20220901, 2022-09-01, Letnik:
153
Journal Article
Recenzirano
Odprti dostop
Cluster of differentiation 38 (CD38) is a multifunctional extracellular enzyme on the cell surface with NADase and cyclase activities. CD38 is not only expressed in human immune cells, such as ...lymphocytes and plasma cells, but also is abnormally expressed in a variety of tumor cells, which is closely related to the occurrence and development of tumors. T cells are one of the important immune cells in the body. As NAD consuming enzymes, CD38, ART2, SIRT1 and PARP1 are closely related to the number and function of T cells. CD38 may also influence the activity of ART2, SIRT1 and PARP1 through the CD38-NAD+ axis to indirectly affect the number and function of T cells. Thus, CD38-NAD+ axis has a profound effect on T cell activity. In this paper, we reviewed the role and mechanism of CD38+ CD4+ T cells / CD38+ CD8+ T cells in cellular immunity and the effects of the CD38-NAD+ axis on T cell activity. We also summarized the relationship between the CD38 expression level on T cell surface and disease prediction and prognosis, the effects of anti-CD38 monoclonal antibodies on T cell activity and function, and the role of anti-CD38 chimeric antigen receptor (CAR) T cell therapy in tumor immunity. This will provide an important theoretical basis for a comprehensive understanding of the relationship between CD38 and T cells.
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•As a NAD consuming enzyme, CD38 is closely related to the number and function of T cells.•The expression of CD38 in CD4+ T cells and CD8+ T cell affects the function of CD4+T cell.•The expression level of CD38 on T cell surface is associated with disease prediction and prognosis.
The molecular weight (MW) of PBnDT‐FTAZ can be precisely controlled by adjusting the stoichiometric ratio of the two monomers, following the Carothers equation. The study of a set of PBnDT‐FTAZ ...polymers with different MWs reveals that the MW significantly influences the morphology and structural order of PBnDTFTAZ in its bulk heterojunction solar cells, with the highest efficiency (over 7%) achieved with the use of a MW of 40 000 g mol−1.
Significance Self-incompatibility (SI) in plants prevents inbreeding by rejection of pollen from closely related individuals of the same species. Unilateral interspecific incompatibility (UI) blocks ...cross-hybridization between related species, typically when the pollen donor is self-compatible and the pistil parent is self-incompatible. In this study, we show that ui1.1 , a pollen UI factor in tomato, encodes an S-locus F-box protein that is homologous to an SI gene that in Petunia determines pollen specificity. We previously showed that another pollen factor, ui6.1 , encodes a Cullin1 protein that functions in both UI and SI. Cullin1 and F-box proteins are components of SCF-type (Skp1, Cullin1, F-box) ubiquitin ligase complexes. The results provide further evidence that pollen rejection in UI involves biochemical mechanisms related to SI.
Unilateral interspecific incompatibility (UI) is a postpollination, prezygotic reproductive barrier that prevents hybridization between related species when the female parent is self-incompatible (SI) and the male parent is self-compatible (SC). In tomato and related Solanum species, two genes, ui1.1 and ui6.1 , are required for pollen compatibility on pistils of SI species or hybrids. We previously showed that ui6.1 encodes a Cullin1 (CUL1) protein. Here we report that ui1.1 encodes an S-locus F-box (SLF) protein. The ui1.1 gene was mapped to a 0.43-cM, 43.2-Mbp interval at the S-locus on chromosome 1, but positional cloning was hampered by low recombination frequency. We hypothesized that ui1.1 encodes an SLF protein(s) that interacts with CUL1 and Skp1 proteins to form an SCF-type (Skp1, Cullin1, F-box) ubiquitin E3 ligase complex. We identified 23 SLF genes in the S. pennellii genome, of which 19 were also represented in cultivated tomato ( S. lycopersicum ). Data from recombination events, expression analysis, and sequence annotation highlighted 11 S. pennellii genes as candidates. Genetic transformations demonstrated that one of these, SpSLF-23 , is sufficient for ui1.1 function. A survey of cultivated and wild tomato species identified SLF-23 orthologs in each of the SI species, but not in the SC species S. lycopersicum, S. cheesmaniae , and S. galapagense , pollen of which lacks ui1.1 function. These results demonstrate that pollen compatibility in UI is mediated by protein degradation through the ubiquitin–proteasome pathway, a mechanism related to that which controls pollen recognition in SI.
Developing novel materials and device architectures to further enhance the efficiency of polymer solar cells requires a fundamental understanding of the impact of chemical structures on photovoltaic ...properties. Given that device characteristics depend on many parameters, deriving structure–property relationships has been very challenging. Here we report that a single parameter, hole mobility, determines the fill factor of several hundred nanometer thick bulk heterojunction photovoltaic devices based on a series of copolymers with varying amount of fluorine substitution. We attribute the steady increase of hole mobility with fluorine content to changes in polymer molecular ordering. Importantly, all other parameters, including the efficiency of free charge generation and the coefficient of nongeminate recombination, are nearly identical. Our work emphasizes the need to achieve high mobility in combination with strongly suppressed charge recombination for the thick devices required by mass production technologies.
Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV ...belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacoronavirus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.
Ultrasonic arrays have been investigated for inspecting the quality of special materials. Unfortunately, non-destructive testing and evaluation (NDT&E) of internal defects in additive manufacturing ...(AM) materials are difficult due to the anisotropy and the coarse grain. To solve the problem, this paper brings forward research on the inspection of TC18 AM titanium alloy products using an ultrasonic array. Firstly, a three-dimensional acoustic field distribution of different ultrasonic array transducers is established to design an optimal detection solution for an AM titanium alloy. Then, a total focusing method (TFM) for the ultrasonic annular array transducer is proposed and its imaging method is analyzed. Besides, the relation between ultrasonic group velocities in a TC18 AM specimen with different propagating angles is measured using the full matrix capture (FMC) method. Based on the measurements, the anisotropy of the AM titanium alloy is discussed and the TFM algorithm of annular array is optimized as well. Finally, C-scan experiments are conducted on the specimen with a height of 55 mm using the linear ultrasonic array transducer of the conventional focusing method and the TFM of annular array transducer, respectively. The results show that the TFM of annular array has higher accuracy in quantifying the defects of flat bottom holes and transverse holes with a diameter of 0.8 mm. In addition, the detection results of different forming directions are analyzed and the 3D imaging of defects in the specimen is realized based on FMC data. The TFM of annular array is an innovative ultrasonic testing technology with high resolution for AM titanium alloy products.
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