A Risk Model Developed Based on Homologous Recombination Deficiency Predicts Overall Survival in Patients With Lower Grade Glioma

The role of homologous recombination deficiency (HRD) in lower grade glioma (LGG) has not been elucidated, and accurate prognostic prediction is also important for the treatment and management of LGG. The aim of this study was to construct an HRD-based risk model and to explore the immunological and molecular characteristics of this risk model. The HRD score threshold = 10 was determined from 506 LGG samples in The Cancer Genome Atlas cohort using the best cut-off value, and patients with highHRDscores had worse overall survival. A total of 251 HRD-related genes were identified by analyzing differentially expressed genes, 182 of which were associated with survival. A risk score model based on HRD-related genes was constructed using univariate Cox regression, least absolute shrinkage and selection operator regression, and stepwise regression, and patients were divided into high- and low-risk groups using the median risk score. High-risk patients had significantly worse overall survival than lowrisk patients. The risk model had excellent predictive performance for overall survival in LGG and was found to be an independent risk factor. The prognostic value of the riskmodel was validated using an independent cohort. In addition, the risk score was associated with tumor mutation burden and immune cell infiltration in LGG. High-risk patients had higher HRD scores and “hot” tumor immune microenvironment, which could benefit from poly-ADP-ribose polymerase inhibitors and immune checkpoint inhibitors. Overall, this big data study determined the threshold of HRD score in LGG, identified HRD-related genes, developed a risk model based on HRD-related genes, and determined the molecular and immunological characteristics of the risk model. This provides potential new targets for future targeted therapies and facilitates the development of individualized immunotherapy to improve prognosis

On the Inertial Single Phase Flow in 2D Model Porous Media: Role of Microscopic Structural Disorder

In this work, single-phase incompressible laminar flow in 2D model porous media is studied and the influence of microscopic structural disorder on the flow is thoroughly investigated. Emphasis is laid upon the onset of the deviation from Darcy’s law and the identification of different inertia regimes observed before the flow becomes unsteady. For this purpose, six globally disordered pore structures were generated and the values of the critical Reynolds number at which the flow becomes unsteady corresponding to the first Hopf bifurcation were determined. Numerical simulations of steady laminar single-phase flow were then carried out to investigate the effects of the microstructures on the inertial correction to Darcy’s law. Different flow regimes, namely weak inertia, strong inertia and the regime beyond strong inertia, are identified. Comparisons are made with results presented in the literature which were restricted to ordered and locally disordered structures. The critical Reynolds number decreases and inertia intensity increases as more disorder is introduced into the pore structure. Results on flow inertia widely extend some previous studies on the subject and show that it is mainly influenced by the shape of the obstacles (either circular or square), slightly affected by the inclination of the square cylinders and hardly disturbed by the size distribution of the obstacles

MDM2 promotes the proliferation and inhibits the apoptosis of pituitary adenoma cells by directly interacting with p53

Introduction: Pituitary adenomas constitute one of the most common intracranial tumours. The mouse double minute 2 homologue (MDM2) is considered as an important oncogene in many tumours, but it has been little studied in pituitary adenomas and the mechanism is not well understood. The purpose of this study was to investigate the function of MDM2 and its primary mechanism of action in pituitary adenoma cells. Material and methods: The expression of MDM2 in pituitary adenoma cell lines and normal cells was determined by real-time polymerase chain reaction (RT-PCR). The proliferation and apoptosis of pituitary adenoma cells after inhibition of MDM2 expression were detected by MTS and flow cytometry, respectively. The protein expressions of MDM2 and p53 were detected by western blot. Co-IP was used to detect the direct binding between MDM2 and p53. Results: The results of RT-PCR showed that MDM2 was significantly up-regulated in pituitary adenoma cell lines. Inhibition of MDM2 suppressed the proliferation and promoted apoptosis of pituitary adenoma cells. However, inhibiting the expression of MDM2 can promotethe protein expression of p53. The results of co-IP showed that MDM2 interacted with p53 by direct combination. Then, we inhibited the expressions of p53 and MDM2 simultaneously in the pituitary adenoma cells by co-transfecting siRNAs, and the results showed that, compared with the group that inhibited MDM2 alone, cell proliferation of the co-transfected group increased and apoptosis of the cotransfected group decreased, which was similar to the NC group. Conclusions: Taken together, these results suggest that MDM2 promoted the proliferation and inhibited the apoptosis of pituitary adenoma cells by directly interacting with p53 in pituitary adenoma cells. Therefore, MDM2-p53 may serve as a novel marker and therapeutic target for pituitary adenomas

High-performance chiral all-optical logic gate based on topological edge states of valley photonic crystal

For all-optical communication and information processing, it is necessary to develop all-optical logic gates based on photonic structures that can directly perform logic operations. All-optical logic gates have been demonstrated based on conventional waveguides and interferometry, as well as photonic crystal structures. Nonetheless, any defects in those structures will introduce high scattering loss, which compromises the fidelity and contrast ratio of the information process. Based on the spin-valley locking effect that can achieve defect-immune unidirectional transmission of topological edge states in valley photonic crystals (VPCs), we propose a high-performance all-optical logic OR gate based on a VPC structure. By tuning the working bandwidth of the two input channels, we prevent interference between the two channels to achieve a stable and high-fidelity output. The transmittance of both channels is higher than 0.8, and a high contrast ratio of 28.8 dB is achieved. Moreover, the chirality of the logic gate originated from the spin-valley locking effect allows using different circularly polarized light as inputs, representing "1" or "0", which is highly desired in quantum computing. The device's footprint is small, allowing high-density on-chip integration. In addition, this design can be experimentally fabricated using current nanofabrication techniques and will have potential applications in optical communication, information processing, and quantum computing.Comment: 10 pages, 6 figure

Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma

Background/Aims: To investigate the biological roles and underlying molecular mechanisms of long non-coding RNA (lncRNA) PVT1 in Hepatocellular carcinoma (HCC). Methods: qRT-PCR was performed to measure the expression of miRNA and mRNA. Western blot was performed to measure the protein expression. CCK-8 assay was performed to determine cell proliferation. Flow cytometry was performed to detect cell apoptosis. Wounding-healing assay and Transwell assay was performed to detect cell migration and invasion. Dual luciferase reporter assay was performed to verify the target relationship. Quantichrom iron assay was performed to check uptake level of cellular iron. Results: PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. In addition, the expression of miR-150 was down-regulated, while the expression of HIG2 was up-regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could partly reverse the biological effects of PVT1 knockdown on proliferation, motility, apoptosis and iron metabolism in vitro, which might be associated with dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed tumorigenesis and iron metabolism disorder by regulating the expression of miR-150 and HIG2. Conclusion: Taken together, the present study demonstrates that PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and provide potential therapeutic targets for HCC