Global existence of solutions for compressible Navier–Stokes equations with vacuum

AbstractIn this paper, we will investigate the global existence of solutions for the one-dimensional compressible Navier–Stokes equations when the density is in contact with vacuum continuously. More precisely, the viscosity coefficient is assumed to be a power function of density, i.e., μ(ρ)=Aρθ, where A and θ are positive constants. New global existence result is established for 0<θ<1 when the initial density appears vacuum in the interior of the gas, which is the novelty of the presentation

Survivin-based recombinant overlapping peptides induce t lymphocyte cytotoxicity and prolong the survival in in vivo melanoma model

Anti-cancer vaccination emerged as a promising and cost-effective immunotherapy, but the lack of immunogenicity has hindered the success of therapeutic vaccine development. To address this issue and improve therapeutic efficacy, this study presents the examination of recombinant overlapping peptides (ROP) based on the tumor-associated antigen, survivin, on in vivo immunogenicity and anti-tumor efficacy using a melanoma C57/BL mouse model. Results show that ROPs induce a remarkable 46.5% cytotoxic activity mediated by activated cytotoxic T lymphocytes, compared to only 3% in wild-type (WT) survivin protein. Additionally, ROPs significantly reduce tumor size by over 500 mm3 and prolong survival rates in mice with zero deaths in the first 17 days and 30% survival at the end of day 23, while no mice immunized with WT survivin protein survive beyond day 20. ROPs combined with anti-4-1BB agonists lead to additional tumor size reduction by 500 mm3 and 70% survival on day 23. These findings underscore the importance of survivin as a trigger for tumor-restricting immunity and provide therapeutic evidence of ROPs' anti-tumor potential, especially when combined with other immunostimulants, such as anti-4-1BB agonists. ROPs and adjuvant immunostimulants represent a potent vaccine strategy for therapeutic purposes, increasing vaccine immunogenicity and improving survival against cancer

Effect of Matrix-Wellbore Flow and Porosity on Pressure Transient Response in Shale Formation Modeling by Dual Porosity and Dual Permeability System

A mathematical dual porosity and dual permeability numerical model based on perpendicular bisection (PEBI) grid is developed to describe gas flow behaviors in shale-gas reservoirs by incorporating slippage corrected permeability and adsorbed gas effect. Parametric studies are conducted for a horizontal well with multiple infinite conductivity hydraulic fractures in shale-gas reservoir to investigate effect of matrix-wellbore flow, natural fracture porosity, and matrix porosity. We find that the ratio of fracture permeability to matrix permeability approximately decides the bottom hole pressure (BHP) error caused by omitting the flow between matrix and wellbore and that the effect of matrix porosity on BHP is related to adsorption gas content. When adsorbed gas accounts for large proportion of the total gas storage in shale formation, matrix porosity only has a very small effect on BHP. Otherwise, it has obvious influence. This paper can help us understand the complex pressure transient response due to existence of the adsorbed gas and help petroleum engineers to interpret the field data better

MicroRNA-223 Increases the Sensitivity of Triple-Negative Breast Cancer Stem Cells to TRAIL-Induced Apoptosis by Targeting HAX-1

<div><p>Drug resistance remains a significant challenge in the treatment of triple-negative breast cancer (TNBC). Recent studies have demonstrated that this drug resistance is associated with a group of cells known as cancer stem cells (CSCs), which are believed to determine the sensitivity of tumor cells to cancer treatment. MicroRNAs (miRNAs) are small, non-coding RNAs that play significant roles in normal and cancer cells. MiR-223 reportedly acts as a tumor suppressor in a range of cancers. However, the role of miR-223 in TNBC, especially in triple-negative breast cancer stem cells (TNBCSCs), remains unknown. Here, we found that miR-223 expression was down-regulated in CD44⁺CD24^-/low TNBCSCs compared with non-CSCs. Furthermore, we found that miR-223 overexpression resensitized TNBCSCs to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. The HAX-1 gene, which is located in the mitochondria and functions as an anti-apoptotic protein, was found to be directly regulated by miR-223 in MDA-MB-231 cells. We demonstrated that miR-223 overexpression promoted TRAIL-induced apoptosis through the mitochondria/ROS pathway. In conclusion, our results suggest that miR-223 increases the sensitivity of TNBCSCs to TRAIL-induced apoptosis by targeting HAX-1. Our findings have improved our understanding of the role of miR-223 in TNBC and may contribute to TNBC treatment.</p></div

Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-&kappa;B Signaling

The abnormal immune response is an early change in the pathogenesis of Alzheimer&rsquo;s disease (AD). Microglial activation is a crucial regulator of the immune response, which contributes to progressive neuronal injury by releasing neurotoxic products. Therefore, finding effective drugs to regulate microglial homeostasis and neuroinflammation has become a new AD treatment strategy. Artemisinin has potent anti-inflammatory and immune activities. However, it is unclear whether Artemisinin contributes to the regulation of microglial activation, thereby improving AD pathology. This study found that Artemisinin significantly reduced amyloid beta-peptide 1&ndash;42 (A&beta;1&ndash;42)-induced increases in nitric oxide and reactive oxygen species and inflammatory factors in BV2 cells. In addition, Artemisinin inhibited the migration of microglia and prevented the expansion of the inflammatory cascade. The mechanical studies showed Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-&kappa;B) signaling pathway. Similar results were obtained in AD model mice, in which Artemisinin administration attenuated A&beta;1&ndash;42-induced neuroinflammation and neuronal injury, reversing spatial learning and memory deficits. The anti-inflammatory effect of Artemisinin is also accompanied by the activation of the TLR4/NF-&kappa;B signaling pathway in the animal model. Our results indicate that Artemisinin attenuated A&beta;1&ndash;42-induced neuroinflammation and neuronal injury by stimulating the TLR4/NF-&kappa;B signaling pathway. These findings suggest that Artemisinin is a potential therapeutic agent for AD

TNBCSC and non-CSC sensitivity to TRAIL treatment.

<p>(A) Sensitivity of MCF-10A and breast cancer stem cells and non-stem cells to TRAIL was determined via MTT assays. *<i>P</i><0.05, t test. (B) The IC50 of TRAIL was determined according to the cell viability curves calculated based on the MTT assay results. *<i>P</i><0.05, t test.</p

MiR-223 promoted TRAIL-induced apoptosis through the mitochondria/ROS pathway.

<p>(A) The mitochondrial membrane potential (ΔΨ_m) of MDA-MB-231 CSCs and MDA-MB-435 CSCs cells treated with miR-223 and TRAIL was detected using JC-1 staining and flow cytometry. (B) ROS generation was detected using DHE staining and flow cytometry. (C) MDA-MB-231 CSCs and MDA-MB-435 CSCs cells were treated with miR-223 and TRAIL (10 ng/ml) in the presence or absence of 5 mM NAC. Cell viability was then detected by MTT assay. *<i>P</i><0.05 <i>vs</i>. the TRAIL+miR-NC group, ^&<i>P</i><0.05 <i>vs</i>. the TRAIL group, ^#<i>P</i><0.05 <i>vs</i>. the TRAIL+miR-223 group, t test.</p