Gas Kinetic Scheme Coupled with High-Speed Modifications for Hypersonic Transition Flow Simulations.

The issue of hypersonic boundary layer transition prediction is a critical aerodynamic concern that must be addressed during the aerodynamic design process of high-speed vehicles. In this context, we propose an advanced mesoscopic method that couples the gas kinetic scheme (GKS) with the Langtry-Menter transition model, including its three high-speed modification methods, tailored for accurate predictions of high-speed transition flows. The new method incorporates the turbulent kinetic energy term into the Maxwellian velocity distribution function, and it couples the effects of high-speed modifications on turbulent kinetic energy within the computational framework of the GKS solver. This integration elevates both the transition model and its high-speed enhancements to the mesoscopic level, enhancing the method's predictive capability. The GKS-coupled mesoscopic method is validated through a series of test cases, including supersonic flat plate simulation, multiple hypersonic cone cases, the Hypersonic International Flight Research Experimentation (HIFiRE)-1 flight test, and the HIFiRE-5 case. The computational results obtained from these cases exhibit favorable agreement with experimental data. In comparison with the conventional Godunov method, the new approach encompasses a broader range of physical mechanisms, yielding computational results that closely align with the true physical phenomena and marking a notable elevation in computational fidelity and accuracy. This innovative method potentially satisfies the compelling demand for developing a precise and rapid method for predicting hypersonic boundary layer transition, which can be readily used in engineering applications.

P-Induced Permeation of Nickel into WO3 Octahedra to Form a Synergistic Catalyst for Urea Oxidation.

Small-molecule induction can lead to the oriented migration of metal elements, which affords functional materials with synergistic components. In this study, phosphating nickel foam (NF)-supported octahedral WO3 with phosphine affords P-WO3 /NF electrocatalyst. Ni is found to form Ni-P bonds that migrate from NF to WO3 under the induction of P, resulting in the complex oxides W1.3 Ni0.24 O4 and Ni2 P2 O7 in the particle interior and nickel phosphide on the octahedral grain surface. The catalytic activity of P-WO3 /NF in the urea oxidation reaction (UOR) is improved by synergistic action of the components in the synthesized hybrid particles. A current density of 10 mA cm-2 can be reached at a potential of 1.305 V, the double layer capacitance of the catalyst is significantly increased, and the electron transfer impedance in catalytic UOR is reduced. This work demonstrates that small-molecule induction is suitable for constructing co-catalysts with complex components in a simple protocol, which provides a new route for the design of highly efficient urea oxidation electrocatalysts.

Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer associated with an unstable prognosis. Thus, there is an urgent demand for the identification of novel diagnostic and prognostic biomarkers as well as targeted drugs for LUAD. The present study aimed to identify potential new biomarkers associated with the pathogenesis and prognosis of LUAD. Three microarray datasets (GSE10072, GSE31210, and GSE40791) from the Gene Expression Omnibus database were integrated to identify the differentially expressed genes (DEGs) in normal and LUAD samples using the limma package. Bioinformatics tools were used to perform functional and signaling pathway enrichment analyses for the DEGs. The expression and prognostic values of the hub genes were further evaluated by Gene Expression Profiling Interactive Analysis and real-time quantitative polymerase chain reaction. Furthermore, we mined the "Connectivity Map" (CMap) to explore candidate small molecules that can reverse the tumoral of LUAD based on the DEGs. A total of 505 DEGs were identified, which included 337 downregulated and 168 upregulated genes. The PPI network was established with 1,860 interactions and 373 nodes. The most significant pathway and functional enrichment associated with the genes were cell adhesion and extracellular matrix-receptor interaction, respectively. Seven DEGs with high connectivity degrees (ZWINT, RRM2, NDC80, KIF4A, CEP55, CENPU, and CENPF) that were significantly associated with worse survival were chosen as hub genes. Lastly, top 20 most important small molecules which reverses the LUAD gene expressions were identified. The findings contribute to revealing the molecular mechanisms of the initiation and progression of LUAD and provide new insights for integrating multiple biomarkers in clinical practice.

CPI-1189 protects neuronal cells from oxygen glucose deprivation/re-oxygenation-induced oxidative injury and cell death.

Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces profound oxidative injury and neuronal cell death. It mimics ischemia-reperfusion neuronal injury. CPI-1189 is a novel tumor necrosis factor alpha-inhibiting compound with potential neuroprotective function. Here in SH-SY5Y neuronal cells and primary murine cortical neurons, CPI-1189 pretreatment potently inhibited OGDR-induced viability reduction and cell death. In OGDR-stimulated neuronal cells, p38 phosphorylation was blocked by CPI-1189. In addition, CPI-1189 alleviated OGDR-induced reactive oxygen species production, lipid peroxidation, and glutathione consumption. OGDR-induced neuronal cell apoptosis was also inhibited by CPI-1189 pretreatment. Furthermore, in SH-SY5Y cells and cortical neurons, CPI-1189 alleviated OGDR-induced programmed necrosis by inhibiting mitochondrial p53-cyclophilin D-adenine nucleotide translocase 1 association, mitochondrial depolarization, and lactate dehydrogenase release to the medium. In summary, CPI-1189 potently inhibited OGDR-induced oxidative injury and neuronal cell death.

Efficacy and Safety of Intensity-Modulated Radiotherapy Following Transarterial Chemoembolization in Patients With Unresectable Hepatocellular Carcinoma.

Three-dimensional conformal radiotherapy in combination with transarterial chemoembolization (TACE) has been beneficial in patients with unresectable hepatocellular carcinoma (HCC). There have been few clinical reports on the use of intensity-modulated radiotherapy (IMRT) in combination with TACE for these patients. The purpose of this study was to assess the efficacy and toxicity of IMRT following TACE in unresectable HCC.The medical records of consecutive patients with unresectable HCC, who underwent IMRT following TACE from January 2009 to June 2014, were retrospectively reviewed in order to assess the overall survival (OS), progression-free survival (PFS), tumor response, and treatment-associated toxicity.A total of 64 lesions in 54 patients were included in the analysis. IMRT was delivered at a median dose of 50 Gy (range 44-70 Gy) at 1.8 to 2.0 Gy per fraction. The overall response rate was achieved in 64.8% of patients with complete response in 20.4% of patients at 3 months after completion of IMRT. The median OS was 20.2 months (95% CI = 8.6-31.9), and the actuarial 1-, 2-, and 3-year OS rates were 84.6%, 49.7%, and 36.7%, respectively. The median PFS was 10.5 months (95% CI = 7.3-13.7) and the 1-, 2-, and 3-year PFS rates were 44.2%, 23.4%, and 14.6%, respectively. The responders had a significantly higher OS rate than the nonresponders (3-year OS 48.0% vs 14.4%, P = 0.001). During and the first month following IMRT, 10 (18.5%) patients developed grade 3 hematological toxicity, and 3 (5.6%) developed grade 3 hepatic toxicity. No patient experienced grade 4 or 5 toxicity. Radiation-induced liver disease was not observed.Our findings suggest that IMRT following TACE could be a favorable treatment option for both its safety profile and clinical benefit in patients with unresectable HCC.

Islet antigen-specific Th17 cells can induce TNF-α-dependent autoimmune diabetes.

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic ß-cells. Although Th1 cells are key orchestrators of T1D, the function(s) of the more recently identified Th17 subset are unclear due to inherent plasticity. In this study, we analyzed Th17 cells for stability and diabetogenicity in NOD mice. We found that like Th1 cells, Th17 are a distinct population throughout the prediabetic phase. At diabetes onset, there were marked increases in IL-17-producing Th17 cells and IFN-γ-producing Th1 cells in the pancreas as well as in the serum levels of these cytokines, indicating that these proinflammatory mediators serve as biomarkers of advanced autoimmunity. Although naturally occurring Th17 cells in diabetic mice did not contribute to diabetes development in transfer models, islet-specific Th17 cells were diabetogenic independently of IL-17 and displayed inflammation-induced Th17-to-Th1 reprogramming that could be elicited by Th1 cells. However, an inability to generate Th1 cells because of Stat4, Ifngr, and Ifng deficiencies did not prevent diabetes. Instead, TNF-α could mediate diabetes in response to either Th17 cells or Th1 cells. The results identify a previously unknown mechanism by which Th17 cells can contribute to T1D. Our studies also suggest that when developing interventions for T1D, it will be potentially advantageous to focus on mechanisms common to effector T cells rather than on the signature cytokines of various subsets.

Itk is not essential for CD28 signaling in naive T cells.

Itk, a member of the Tec family of tyrosine kinases, is critical for TCR signaling, leading to the activation of phospholipase C gamma1. Early biochemical studies performed in tumor cell lines also implicated Itk in CD28 signaling. These data were complemented by functional studies on primary Itk-/- T cells that suggested a negative role for Itk in CD28 signaling. In this report, we describe a thorough analysis of CD28-mediated responses in T cells lacking Itk. Using purified naive CD4+ T cells from Itk-/- mice, we examine a range of responses dependent on CD28 costimulation. We also analyze Akt and glycogen synthase kinase-3beta phosphorylation in response to stimulation of CD28 alone. Overall, these experiments demonstrate that CD28 signaling, as well as CD28-mediated costimulation of TCR signaling, function efficiently in the absence of Itk. These findings indicate that Itk is not essential for CD28 signaling in primary naive CD4+ T cells.