Lung adenocarcinoma (LUAD) is a non-small cell carcinoma. Ribonuclease/angiogenin inhibitor 1 (RNH1) exerts multiple roles in virous cancers. E2F1 is a critical transcription factor involved in the ...LUAD development. Here, we analyze the expression of RNH1 in LUAD patients, investigate the biological function of RNH1 in LUAD, and demonstrate its potential mechanisms through E2F1 in LUAD.
In the present study, we presented the expression of RNH1 in LUAD based on the database and confirmed it by western blot detection of RNH1 in human LUAD tissues. Lentiviral infection was constructed to silence or overexpress RNH1 in NCI-H1395 and NCI-H1437 cells. We assess the role of RNH1 on proliferation in LUAD cells by MTT assay, colony formation assays, and cell cycle detection. Hoechst staining and flow cytometry were used to evaluate the effects of RNH1 on apoptosis of LUAD cells. The function of RNH1 in invasion and migration was investigated by Transwell assay. Dual luciferase assay, ChIP detection, and pull-down assay were conducted to explore the association of E2F1 in the maintenance of RNH1 expression and function. The regulation of E2F1 on the functions of RNH1 in LUAD cells was explored. Mouse experiments were performed to confirm the in-vivo role of RNH1 in LUAD. mRNA sequencing indicated that RNH1 overexpression altered the expression profile of LUAD cells.
RNH1 expression in LUAD tissues of patients was presented in this work. Importantly, RNH1 knockdown improved the proliferation, migration and invasion abilities of cells and RNH1 overexpression produced the opposite effects. Dual luciferase assay proved that E2F1 bound to the RNH1 promoter (-1064 ∼ -1054, -1514 ∼ -1504) to reduce the transcriptional activity of RNH1. ChIP assay indicated that E2F1 DNA was enriched at the RNH1 promoter (-1148 ∼ -943, -1628 ∼ -1423). Pull-down assays also showed the association between E2F1 and RNH1 promoter (-1148 ∼ -943). E2F1 overexpression contributed to the malignant behavior of LUAD cells, while RNH1 overexpression reversed it. High-throughput sequencing showed that RNH1 overexpression induced multiple genes expression changes, thereby modulating LUAD-related processes.
Our study demonstrates that binding of E2F1 to the RNH1 promoter may lead to inhibition of RNH1 expression and thus promoting the development of LUAD.
This study aimed to investigate miR-3682 as a biomarker in hepatocellular carcinoma (HCC).
MiRNA and RNA profiles of 375 HCC tissues and 50 normal liver samples were downloaded from The Cancer Genome ...Atlas (TCGA) database. Multivariate Cox regression and Kaplan-Meier analyses were applied to examine the prognostic value of factors. Target genes of miR-3682 were analyzed by TargetScan and dual-luciferase reporter assay. Online Database for Annotation, Visualization, and Integrated Discovery (DAVID) to perform KEGG pathway enrichment. Cell counting kit-8, colony formation and migration and invasion assays were performed to analyze biological behaviors of HCC cells.
MiR-3682 was identified to be highly expressed in HCC tissues and cell lines. And miR-3682 was negatively and independently associated with the outcome of HCC patients. Inhibition of miR-3682 suppressed HCC cell viability and mobility. ADRA1A, predicted and confirmed as the novel target of miR-3682, was an independent and positive prognostic predictor for HCC. In addition, the knockdown of ADRA1A partially offset the inhibitory effect of miR-3682 inhibitor on the growth and mobility of HCC cells. DAVID enrichment and western blot of key signaling-related proteins analyses revealed that miR-3682 inactivated 5′-AMP-activated protein kinase (AMPK) signaling by negatively regulating ADRA1A. Mechanically, it was partially through suppressing AMPK signaling via targeting ADRA1A that miR-3682 supported the HCC cell malignant phenotype.
This study implicates that miR-3682 plays an oncogenetic role in HCC and can be considered a novel therapeutic target and prognostic indicator of HCC.
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•An interpretable Transformer-based deep learning model with physical constraints for predicting creep rupture life of Ni-based SX superalloys is developed.•The representation of ...superalloys with both effectiveness and interpretability is obtained from the Transformer-based neural network framework.•The material insights into the elemental interaction are extracted from the interpretable information contained in the SaTNC model.•The new type of SX superalloys with potential high creep resistance and low density at ultra-high temperatures is designed.
Creep rupture life is a key target for designing Ni-based single crystal (SX) superalloys. Machine learning (ML) has the potential to accelerate alloy design by accurately predicting the creep rupture life of potential superalloys. In this work, a physical-constrained neural network named Superalloy Transformer-based Network for Creep (SaTNC) is established, and the representation of superalloy is automatically learned based on deep representation learning. As core physical bias in the SaTNC model, the information associated with interaction among alloying elements achieved by Transformer-based neural network is introduced to constrain the representation of the superalloy. The SaTNC model exhibits competitive generalization performance and the results have verified the high capability of the SaTNC model to capture the sensitivities of creep rupture life on alloy composition and service conditions. Moreover, Transformer-based deep representation for superalloy with both effectiveness and interpretability is obtained. The material insights including the interactions among alloying elements and their combined effects on the creep rupture life of superalloy are extracted from this deep representation. Finally, with the aid of the SaTNC model, a potential alloy composition space with low density and excellent creep resistance at high temperatures is identified, which will be experimentally verified in the future.
CBX3 is an isoform of the heterochromatin protein 1 family, which is involved in carcinogenesis and promotes the progression of certain types of cancer. The expression level and clinicopathological ...significances of CBX3 in colorectal cancer (CRC) are still not well reported. In this study, we examined CBX3 protein expression in formalin‐fixed and paraffin‐embedded normal mucosae, hyperplastic polyps, low‐and high‐grade adenomas, and CRC tissue samples using immunohistochemistry. The associations of CBX3 expression levels with clinicopathological parameters, mismatch repair (MMR) protein expression, and kirsten rat sarcoma viral oncogene homolog (KRAS) and B‐raf proto‐oncogene (BRAF) mutations were analyzed. Our results showed that CBX3 protein was negatively expressed in normal mucosae and hyperplastic polyps, as well as in most low‐grade adenomas. Interestingly, CBX3 protein was positively expressed in most high‐grade adenomas and CRC tissues. CBX3 expression level was associated with tumor differentiation (p = 0.012), lymph node metastasis (p = 0.024), TNM stage (p = 0.008) and survival (p = 0.029). CBX3 expression was associated with MMR protein expression (p = 0.011) and KRAS mutation (p = 0.013), but not with BRAF mutation (p = 0.097). Our data suggest that CBX3 may be used as a molecular marker in CRC to evaluate tumor differentiation, lymph node metastasis, and pathological stage.
The generalized stacking fault energies of face centered cubic Ni-Mo solid solutions are calculated using the exact muffin-tin orbital method in combination with coherent potential approximation. The ...alloying of Mo in Ni is found to decrease the intrinsic stacking fault energy of the solid solution from 150mJ/m2 (pure Ni) to 50mJ/m2 (17.5at.% Mo) almost linearly. At the same time, the unstable stacking fault energy (the unstable twin fault energy) of the Ni-based solid solution increases (decreases) in a small extent with increasing Mo concentration. Three different twinnability measures are adopted and all indicate a substantially enhanced twinning mechanism in Ni-Mo solid solutions with increasing concentration of Mo. The weaker Ni-Ni bonding at high Mo concentrations is considered to be the main mechanism behind the disclosed phenomena. Segregation of Mo to the fault plane is proved to have strong effect on the generalized stacking fault energy of Ni-based solid solution.
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•The alloying of Mo in Ni decreases the intrinsic stacking fault energy of solid solution.•The twinning mechanism is enhanced in Ni-Mo solid solutions with increasing concentration of Mo.•The weaker Ni-Ni bonding at high Mo concentration is the main mechanism.•Segregation of Mo to fault plane has strong effect on the generalized stacking fault energy of Ni-Mo.
Craniopharyngioma is a benign tumor, and the predominant treatment methods are surgical resection and radiotherapy. However, both treatments may lead to complex complications, seriously affecting ...patients' survival rate and quality of life. Adamantinomatous craniopharyngioma (ACP), as one of the histological subtypes of craniopharyngioma, is associated with a high incidence and poor prognosis, and there is a gap in the targeted therapy of immune-related genes for ACP. In this study, two gene expression profiles of ACP, namely GSE68015 and GSE94349, were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the Limma package, and 271 differentially expressed immune-related genes (DEIRGs) were obtained from the Immport database. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for annotation, visualization, and integrated discovery. Five hub genes, including CXCL6, CXCL10, CXCL11, CXCL13, and SAA1, were screened out through protein-protein interaction (PPI) network interaction construction. Two diagnostic markers, namely S100A2 and SDC1 (both of which have the Area Under Curve value of 1), were screened by the machine learning algorithm. CIBERSORT analysis showed that M2 macrophages, activated NK cells, and gamma delta T cells had higher abundance in ACP infiltration, while CD8+ T cells, regulatory T cells, and Neutrophils had less abundance in ACP infiltration. The expression of gamma delta T cells was positively correlated with CXCL6, S100A2, SDC1, and SAA1, while CD8+ T cells expression was negatively correlated with CXCL6, S100A2, SDC1, and CXCL10. ACP with high CXCL6 showed remarkable drug sensitivity to Pentostatin and Wortmannin via CellMiner database analysis. Our results deepened the understanding of the molecular immune mechanism in ACP and provided potential biomarkers for the precisely targeted therapy for ACP.
Oil recovery is an essential parameter for reservoir development performance evaluation, but there is no specific research on the theoretical oil recovery prediction model of polymer microspheres ...(PMs)' conformance control. This research aims to establish an oil recovery prediction model that depends on the definition of oil recovery based on stream tube theory. PMs' enhanced oil recovery mechanism is to plug the pore throat to expand the swept area. The assumption that the stream tube between injection and production wells is trapezoidal is proposed. Based on this premise, the area sweep efficiency equation suitable for the rhombus inverse nine-spot well pattern is established based on the stream tube theory. The vertical sweep efficiency equation is optimized by introducing the equivalent mobility ratio. Additionally, the model's adaptability and validity are studied. The analysis results show that oil recovery decreases with increasing injection rate, injection concentration, and PMs size but increases with the increasing injection period. The theoretical oil recovery is 1.37%, and the actual oil recovery of the field application is 1.22%, with an error of 0.15%. This model has good consistency with the actual physical process of the field application. The oil recovery prediction model can provide oil recovery and optimize PMs' conformance control injection scheme. This study fills the gap in the mathematical model for oil recovery prediction of PMs' conformance control.
Anomalous yield is a critical characteristic of temperature-resisted superalloys. However, it is undesirably anisotropic, being absent sometimes in the 111 crystallographic orientation. Here the ...orientation dependence of the yield behavior and the corresponding mechanism have been investigated. We show how the orientation affects the dislocations' motion in the γ-γ′ structure, where overcoming the critical resolved shear stress associated with anti-phase boundary plays a significant role. The influence of the orientation on anomalous yield is rationalized, and the criterion for the onset or absence of yield anomaly is proposed. An alloy design is then provided to effectively enhance yield strength anomaly.
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•Anomalous yield is onset in 001- and 011-orientated superalloys but sometimes absent via 111 orientation.•Inhibiting γ'-shearing process, evidenced by {001} fracture surface and dislocation-free γ'-phases, causes such absence.•Overcoming the critical resolved shear stress associated with anti-phase boundary facilitates yield anomaly.•An effective approach to enhance temperature resistance is proposed and a resulting alloy has remarkable yield anomaly.
How to make a sandcastle with good stability is an interesting modeling problem, the core of which is how to design the shape of its foundation and select appropriate material so that it can fully ...resist wave erosion. First, we design the Foundation Shape Optimization (FSO) Model to obtain the geometric shape that last longest. By pre-screening, we preliminarily select the circular truncated cone. Then we analyse the impact force of the sea waves, list the constraint conditions and calculate the optimal parameters for it. Second, the water-to-sand mixture is identified by microcosmic Normalized Extremum Model. Before getting results, the Ideal Sand Particles Plane (ISPP) Model helps us figure out the equivalent relationship among three functions. Finally, we get the objective function through normalization and work out the best proportion (13.14%) with the optimal sub-humid angle through Genetic Algorithm (GA).
The energy storage density of ferroelectric thin film capacitors is mainly limited by the breakdown strength. Here we demonstrate that the high breakdown strength and high energy storage density can ...be achieved by constructing BiFeO3/Al2O3 ferroelectricity-insulators heterojunction. The breakdown strength, leakage current density and energy storage performance are investigated systematically of the multilayer thin films. The relatively high breakdown strength is achieved in the Al2O3/BiFeO3/Al2O3/BiFeO3 thin film, which is benefited from the amorphous structure, built-in electric field and boundary conditions of electromagnetic field. At the same time, the excellent energy storage density of the thin film is obtained mainly due to the effect of high breakdown strength. The proposed structure of this work provides an useful method to improve the energy storage density of thin film capacitors.
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