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We propose an extension of the symmetric teleparallel gravity, in which the gravitational action L is given by an arbitrary function f of the non-metricity Q and of the trace of the matter-energy-momentum tensor T, so that \\[L=f(Q,T)\\]. The field equations of the theory are obtained by varying the gravitational action with respect to both metric and connection. The covariant divergence of the field equations is obtained, with the geometry–matter coupling leading to the nonconservation of the energy-momentum tensor. We investigate the cosmological implications of the theory, and we obtain the cosmological evolution equations for a flat, homogeneous and isotropic geometry, which generalize the Friedmann equations of general relativity. We consider several cosmological models by imposing some simple functional forms of the function f(Q, T), corresponding to additive expressions of f(Q, T) of the form \\[f(Q,T)=\\alpha Q+\\beta T\\], \\[f(Q,T)=\\alpha Q^{n+1}+\\beta T\\], and \\[f(Q,T)=-\\alpha Q-\\beta T^2\\]. The Hubble function, the deceleration parameter, and the matter-energy density are obtained as a function of the redshift by using analytical and numerical techniques. For all considered cases the Universe experiences an accelerating expansion, ending with a de Sitter type evolution. The theoretical predictions are also compared with the results of the standard \\[\\Lambda \\]CDM model.

We consider an f ( Q ,  T ) type gravity model in which the scalar non-metricity Q α μ ν of the space-time is expressed in its standard Weyl form, and it is fully determined by a vector field w μ . The field equations of the theory are obtained under the assumption of the vanishing of the total scalar curvature, a condition which is added into the gravitational action via a Lagrange multiplier. The gravitational field equations are obtained from a variational principle, and they explicitly depend on the scalar nonmetricity and on the Lagrange multiplier. The covariant divergence of the matter energy-momentum tensor is also determined, and it follows that the nonmetricity-matter coupling leads to the nonconservation of the energy and momentum. The energy and momentum balance equations are explicitly calculated, and the expressions of the energy source term and of the extra force are found. We investigate the cosmological implications of the theory, and we obtain the cosmological evolution equations for a flat, homogeneous and isotropic geometry, which generalize the Friedmann equations of standard general relativity. We consider several cosmological models by imposing some simple functional forms of the function f ( Q ,  T ), and we compare the predictions of the theory with the standard Λ CDM model.

Background. Adenosine, derived from the degradation of ATP via ectonucleotidases CD39 and CD73, is a critical immunosuppressive metabolite in the hypoxic microenvironment of tumor tissue. Adenosine signaling via A2aR can inhibit the antitumor immune response of CD8+ T cells. CD39 and CD73 high-expressing Tregs play a critical role in tumor immune evasion of gastric cancer (GC). The present study investigated the underlying mechanism by which Tregs suppress antitumor immune responses in GC. Materials and Methods. Fifty-two GC samples were collected, and the frequency of FoxP3+ Tregs and CD8+ T cells and density ratios of A2aR+/CD8+ T cells, CD39+/FoxP3+ Tregs, and CD73+/FoxP3+ Tregs in GC were assessed with multiplex immunofluorescence. The expression of FoxP3 and A2aR in GC tissues was also detected by the immunoblotting assay. We next investigated the relationship between density of FoxP3+ Tregs, ratio of A2aR+/CD8+ T cells, and clinicopathological parameters. At the same time, Tregs and CD8+ T cells were isolated from peripheral blood of five GC patients, and the antagonists of CD39 and CD73 were used to assess the ability of Tregs to decompose ATP into adenosine. In addition, we cocultured CD8+ T cells and Tregs with antagonists of A2aR and A2bR in order to examine the alterations in immune function of CD8+ T cells. Results. The density of both FoxP3+ Tregs and A2aR+/CD8+ T cells was higher in GC tissue compared to peritumoral normal tissue and significantly correlated with the TNM stage, lymph node metastasis, and distant metastasis of GC. The process of Treg hydrolysis of ATP into adenosine was blocked by the antagonists of CD39 and CD73. In addition, Tregs could induce apoptosis and inhibit proliferation of CD8+ T cells, while this effect could be obviously reduced by applying the antagonist of A2aR or A2aR+A2bR. Moreover, IFN-γ, TNF-α, and perforin generated by CD8+ T cells could also be inhibited through the adenosine A2aR pathway. Conclusions. The FoxP3+ Tregs and A2aR+/CD8+ T cells were excessively infiltrated in GC tissue. Tregs from GC can decompose ATP to adenosine and in turn induce apoptosis and inhibit the proliferation of CD8+ T cells through the A2aR pathway, further leading to immune escape of GC.

Three-dimensional graphene network is a promising structure for improving both the mechanical properties and functional capabilities of reinforced polymer and ceramic matrix composites. However, direct application in a metal matrix remains difficult due to the reason that wetting is usually unfavorable in the carbon/metal system. Here we report a powder-metallurgy based strategy to construct a three-dimensional continuous graphene network architecture in a copper matrix through thermal-stress-induced welding between graphene-like nanosheets grown on the surface of copper powders. The interpenetrating structural feature of the as-obtained composites not only promotes the interfacial shear stress to a high level and thus results in significantly enhanced load transfer strengthening and crack-bridging toughening simultaneously, but also constructs additional three-dimensional hyperchannels for electrical and thermal conductivity. Our approach offers a general way for manufacturing metal matrix composites with high overall performance. Graphene networks have been used to reinforce polymer and ceramic composites, but connecting graphene into a three dimensional network in a metal matrix is challenging. Here the authors use a powder-metallurgy-based strategy to construct a three-dimensional graphene network reinforced copper matrix composite.

A bstract We show that thermal effective field theory controls the long-distance expansion of the partition function of a d -dimensional QFT, with an insertion of any finite-order spatial isometry. Consequently, the thermal partition function on a sphere displays a fractal-like structure as a function of angular twist, reminiscent of the behavior of a modular form near the real line. As an example application, we find that for CFTs, the effective free energy of even-spin minus odd-spin operators at high temperature is smaller than the usual free energy by a factor of 1/2 d . Near certain rational angles, the partition function receives subleading contributions from “Kaluza-Klein vortex defects” in the thermal EFT, which we classify. We illustrate our results with examples in free and holographic theories, and also discuss nonperturbative corrections from worldline instantons.

Background Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored. Methods CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT–PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R. Results CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression. Conclusions Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.

Background Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. However, the biological functions of circRNAs in colorectal cancer (CRC) are largely unknown. Methods RT-qPCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circSPARC. Function-based experiments were performed using circSPARC knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and metastasis models. Mechanistically, luciferase reporter assay, western blots, RNA immunoprecipitation (RIP), Chromatin isolation by RNA purification (ChIRP) and immunohistochemical stainings were performed. Results CircSPARC was upregulated in both the tissues and plasma of CRC patients. High expression of circSPARC was associated with advanced TNM stage, lymph node metastases, and poor survival. Silencing circSPARC inhibited CRC cell migration and proliferation in vitro and vivo. Mechanistically, circSPARC sponged miR-485-3p to upregulate JAK2 expression and ultimately contribute to the accumulation of phosphorylated (p)-STAT3. Besides, circSPARC recruited FUS, which facilitated the nuclear translocation of p-STAT3. Conclusions These findings suggest that circSPARC might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for CRC treatment by regulating JAK2/STAT3 pathway.

Background Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. Methods The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. Results The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m 6 A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. Conclusions Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

Due to global warming, drought events have become more frequent, which resulted in aggravated crop failures, food shortage, larger and more energetic wildfires, and have seriously affected socio-economic development and agricultural production. In this study, a global long-term (1981–2021), high-resolution (4 km) improved vegetation health index (VHI) dataset integrating climate, vegetation and soil moisture was developed. Based on drought records from the Emergency Event Database, we compared the detection efficiency of the VHI before and after its improvement in the occurrence and scope of observed drought events. The global drought detection efficiency of the improved high-resolution VHI dataset reached values as high as 85%, which is 14% higher than the original VHI dataset. The improved VHI dataset was also more sensitive to mild droughts and more accurate regarding the extent of droughts. This improved dataset can play an important role in long-term drought monitoring but also has the potential to assess the impact of drought on the agricultural, forestry, ecological and environmental sectors.

Prospective randomized trials and observational studies have revealed that early detection, classification, and removal of neoplastic colorectal polyp (CP) significantly improve the prevention of colorectal cancer (CRC). The current effectiveness of the diagnostic performance of colonoscopy remains unsatisfactory with unstable accuracy. The convolutional neural networks (CNN) system based on artificial intelligence (AI) technology has demonstrated its potential to help endoscopists in increasing diagnostic accuracy. Nonetheless, several limitations of the CNN system and controversies exist on whether it provides a better diagnostic performance compared to human endoscopists. Therefore, this study sought to address this issue. Online databases (PubMed, Web of Science, Cochrane Library, and EMBASE) were used to search for studies conducted up to April 2020. Besides, the quality assessment of diagnostic accuracy scale-2 (QUADAS-2) was used to evaluate the quality of the enrolled studies. Moreover, publication bias was determined using the Deeks’ funnel plot. In total, 13 studies were enrolled for this meta-analysis (ranged between 2016 and 2020). Consequently, the CNN system had a satisfactory diagnostic performance in the field of CP detection (sensitivity: 0.848 [95% CI: 0.692–0.932]; specificity: 0.965 [95% CI: 0.946–0.977]; and AUC: 0.98 [95% CI: 0.96–0.99]) and CP classification (sensitivity: 0.943 [95% CI: 0.927–0.955]; specificity: 0.894 [95% CI: 0.631–0.977]; and AUC: 0.95 [95% CI: 0.93–0.97]). In comparison with human endoscopists, the CNN system was comparable to the expert but significantly better than the non-expert in the field of CP classification (CNN vs . expert: RDOR: 1.03, P = 0.9654; non-expert vs . expert: RDOR: 0.29, P = 0.0559; non-expert vs . CNN: 0.18, P = 0.0342). Therefore, the CNN system exhibited a satisfactory diagnostic performance for CP and could be used as a potential clinical diagnostic tool during colonoscopy.