Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of ...mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear.
The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network.
In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT.
In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.
An unprecedented Ir(III)-catalyzed C-H activation/amination/annulation of 2-phenyloxazoles with anthranils for the highly selective preparation of acridone derivatives in one-pot under controlled ...conditions is reported. This protocol is characterized by atom economy and high regioselectivity. A wide range of anthranils with 2-phenyloxazoles were well tolerated and afforded the desired products in moderate to good yields, in which the anthranil serves as a convenient amination reagent.
The YORP effect is the thermal torque generated by radiation from the surface of an asteroid. The effect is sensitive to surface topology, including small-scale roughness, boulders, and craters. The ...aim of this paper is to develop a computationally efficient semi-analytical model for the crater-induced YORP (CYORP) effect that can be used to investigate the functional dependence of this effect. This study linearizes the thermal radiation term as a function of the temperature in the boundary condition of the heat conductivity, and obtains the temperature field in a crater over a rotational period in the form of a Fourier series, accounting for the effects of self-sheltering, self-radiation, and self-scattering. By comparison with a numerical model, we find that this semi-analytical model for the CYORP effect works well for $K>0.1 W/m/K$. This semi-analytical model is computationally three-orders-of-magnitude more efficient than the numerical approach. We obtain the temperature field of a crater, accounting for the thermal inertia, crater shape, and crater location. We then find that the CYORP effect is negligible when the depth-to-diameter ratio is smaller than 0.05. In this case, it is reasonable to assume a convex shape for YORP calculations. Varying the thermal conductivity yields a consistent value of approximately 0.01 for the spin component of the CYORP coefficient, while the obliquity component is inversely related to thermal inertia, declining from 0.004 in basalt to 0.001 in metal. The CYORP spin component peaks at an obliquity of $0^ or $180^ while the obliquity component peaks at an obliquity of around $45^ or $135^ For a z-axis symmetric shape, the CYORP spin component vanishes, while the obliquity component persists. Our model confirms that the total YORP torque is damped by a few tens of percent by uniformly distributed small-scale surface roughness. Furthermore, for the first time, we calculate the change in the YORP torque at each impact on the surface of an asteroid explicitly and compute the resulting stochastic spin evolution more precisely. This study shows that the CYORP effect due to small-scale surface roughness and impact craters is significant during the history of asteroids. The semi-analytical method that we developed, which benefits from fast computation, offers new perspectives for future investigations of the YORP modeling of real asteroids and for the complete rotational and orbital evolution of asteroids accounting for collisions. Future research employing our CYORP model may explore the implications of space-varying roughness distribution, roughness in binary systems, and the development of a comprehensive rotational evolution model for asteroid groups.
The efficacy of nano-mediated drug delivery has been impeded by multiple biological barriers such as the mononuclear phagocyte system (MPS), as well as vascular and interstitial barriers. To overcome ...the abovementioned obstacles, we report a nano-pathogenoid (NPN) system that can in situ hitchhike circulating neutrophils and supplement photothermal therapy (PTT). Cloaked with bacteria-secreted outer membrane vesicles inheriting pathogen-associated molecular patterns of native bacteria, NPNs are effectively recognized and internalized by neutrophils. The neutrophils migrate towards inflamed tumors, extravasate across the blood vessels, and penetrate through the tumors. Then NPNs are rapidly released from neutrophils in response to inflammatory stimuli and subsequently taken up by tumor cells to exert anticancer effects. Strikingly, due to the excellent targeting efficacy, cisplatin-loaded NPNs combined with PTT completely eradicate tumors in all treated mice. Such a nano-platform represents an efficient and generalizable strategy towards in situ cell hitchhiking as well as enhanced tumor targeted delivery.
Uniform graphitic carbon nitride nanorods (CNR) were facilely obtained by a morphology-preserving strategy by templating a chiral mesostructured silica nanorod. The hexagonal mesostructured pore ...structures of one-dimensional silica nanorods can provide nanoconfinement space for carbon nitride condensation to perfect layered structures. CNR demonstrated excellent photocatalytic capability in generating hydrogen from water even with a small specific surface area, compared with its mesoporous counterpart. For further application demonstration, the CNR was used for photocatalytic regeneration of NAD+ to NADH, the biological form of hydrogen. The in situ NADH regeneration system was further coupled with l-glutamate dehydrogenase for sustainable generation of l-glutamate from α-ketoglutarate. The high yield and high efficiency obtained here point a high-throughput and sustainable way for practical enzymatic applications.
Groundwater is unique resource for agriculture, domestic use, industry and environment in the Heihe River Basin, northwestern China. Numerical models are effective approaches to simulate and analyze ...the groundwater dynamics under changeable conditions and have been widely used all over the world. In this paper, the groundwater dynamics of the middle reaches of the Heihe River Basin was simulated using one numerical model and three machine learning algorithms (multi-layer perceptron (MLP); radial basis function network (RBF); support vector machine (SVM)). Historical groundwater levels and streamflow rates were used to calibrate/train and verify the different methods. The root mean square error and R
were used to evaluate the accuracy of the simulation/training and verification results. The results showed that the accuracy of machine learning models was significantly better than that of numerical model in both stages. The SVM and RBF performed the best in training and verification stages, respectively. However, it should be noted that the generalization ability of numerical model is superior to the machine learning models because of the inclusion of physical mechanism. This study provides a feasible and accurate approach for simulating groundwater dynamics and a reference for model selection.
Abstract
Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression ...in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8
+
T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.
While most monogenic diseases are caused by loss or reduction of protein function, the need for technologies that can selectively increase levels of protein in native tissues remains. Here we ...demonstrate that antisense-mediated modulation of pre-mRNA splicing can increase endogenous expression of full-length protein by preventing naturally occurring non-productive alternative splicing and promoting generation of productive mRNA. Bioinformatics analysis of RNA sequencing data identifies non-productive splicing events in 7,757 protein-coding human genes, of which 1,246 are disease-associated. Antisense oligonucleotides targeting multiple types of non-productive splicing events lead to increases in productive mRNA and protein in a dose-dependent manner in vitro. Moreover, intracerebroventricular injection of two antisense oligonucleotides in wild-type mice leads to a dose-dependent increase in productive mRNA and protein in the brain. The targeting of natural non-productive alternative splicing to upregulate expression from wild-type or hypomorphic alleles provides a unique approach to treating genetic diseases.
Graphene-based mixed-dimensional materials hybridization is important for a myriad of applications. However, conventional manufacturing techniques face critical challenges in producing arbitrary ...geometries with programmable features, continuous interior networks, and multimaterials homogeneity. Here we propose a generalized three-dimensional (3D) printing methodology for graphene aerogels and graphene-based mixed-dimensional (2D + nD, where n is 0, 1, or 2) hybrid aerogels with complex architectures, by the development of hybrid inks and printing schemes to enable mix-dimensional hybrids printability, overcoming the limitations of multicomponents inhomogeneity and harsh post-treatments for additives removal. Importantly, nonplanar designed geometries are also demonstrated by shape-conformable printing on curved surfaces. We further demonstrate the 3D-printed hybrid aerogels as ultrathick electrodes in a symmetric compression tolerant microsupercapacitor, exhibiting quasi-proportionally enhanced areal capacitances at high levels of mass loading. The excellent performance is attributed to the sufficient ion- and electron-transport paths provided by the 3D-printed highly interconnected networks. The encouraging finding indicates tremendous potentials for practical energy storage applications. As a proof of concept, this general strategy provides avenues for various next-generation complex-shaped hybrid architectures from microscale to macroscale, for example, seawater desalination devices, electromagnetic shielding systems, and so forth.
Essential oils (EOs) have been proposed as an alternative to conventional pesticides to inhibit fungal pathogens. However, the application of EOs is considerably limited due to their highly volatile ...nature and unpredictable effects on other microbes. In our study, the composition of bacterial and fungal communities from the rhizosphere soil of P. notoginseng under four treatment levels of Alpinia officinarum Hance EO was characterized over several growth stages. Leaf weight varied dramatically among the four EO treatment levels after four months of growth, and the disease index at a low concentration (0.14 mg/g) of EO addition was the lowest among the P. notoginseng growth stages. The content of monomeric saponins was elevated when EO was added. Bacterial and fungal diversity in the absence of plants showed a decreasing trend with increasing levels of EO. Bacterial diversity recovery was more correlated with plant growth than was fungal diversity recovery. Compared with the control (no EO addition), a low concentration of EO significantly accumulated Actinomycota, including Acidothermus, Blastococcus, Catenulispora, Conexibacter, Rhodococcus, and Sinomonas, after one month of plant-microbial interaction. Overall, the results showed that both the plant growth stage and EOs drive changes in the microbial community composition in the rhizosphere of P. notoginseng. Plant development status had a stronger influence on bacterial diversity than on fungal diversity. EO had a more significant effect on fungal community composition, increasing the dominance of Ascomycota when EO concentration was increased. Under the interaction of P. notoginseng growth and EO, a large number of bacterial genera that have been described as plant growth-promoting rhizobacteria (PGPR) responded positively to low concentrations of EO application, suggesting that EO may recruit beneficial microbes in the root zone to cope with pathogens and reduce root rot disease. These results offer novel insights into the relationship between EO application, altered microbial communities in the plant roots, plant growth stage, and disease occurrence.
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