Atorvastatin suppressed proliferation and facilitated apoptosis of A549 cells through mediating recruitment of Fas and CD59 in lipid raft

Purpose: Lipid raft facilitated progression of NSCLC and atorvastatin could break cholesterol. The purpose of this study was to determine the potential mechanism of atorvastatin through lipid raft mediation in NSCLC.Methods: A549 cells were first grouped as NC, methyl-β-cyclodextrin (MβCD, lipid raft inhibitor, 5mM and 10mM), atorvastatin (0, 5mM, 10mM and 15mM) and MβCD (10mM) with atorvastatin (15mM). Later 10mM MβCD treated A549 cells were divided into three groups: NC, 3BDO (mTOR agonist) (60μM) and 3BDO (60μM) with atorvastatin (15mM) group. Thereafter, FLOT-2, SLP-2 expressions were assessed with RT-qPCR，mTOR proteins were measured by western blot and cell viability by CCK-8 method. Meanwhile, apoptosis was analyzed by flow cytometry. Moreover, lipid raft isolation was performed for acquiring Fas and CD59 and concentrations were detected by ELISA.Results: MβCD treatment significantly inhibited FLOT-2 and SLP-2 RNA expressions and cell viability of A549 cells but up-regulated apoptosis. Besides that, Fas protein level was promoted and CD59 was suppressed. Atorvastatin also repressed FLOT-2 and SLP-2 RNA levels. Meanwhile, atorvastatin downregulated cell viability and accelerated apoptosis. Moreover, Fas was increased and CD59 was inhibited by atorvastatin and MβCD enhanced functions of atorvastatin. MβCD inhibited mTOR RNA expression in A549 cells was increased by 3BDO but atorvastatin restored 3BDO caused up-regulation of mTOR. Furthermore, up regulated cell viability of A549 by 3BDO was declined with atorvastatin and decreased apoptosis by 3BDO was reversed through atorvastatin. Fas suppressed by 3BDO and promotion of CD59 were also resumed by atorvastatin.Conclusion: Atorvastatin suppressed FLOT-2 and SLP-2 and mediated recruitments of Fas and CD59 with suppressing cell viability and facilitating apoptosis of A549 cells via mTOR signaling pathway

The Performance of Performance-Based Contracting in Human Services

Performance-based contracting (PBC) is becoming increasingly attractive to public human service agencies. By attaching contract compensation to contractors' performance achievement, PBC is expected to encourage quality services, better outcomes, and less administrative monitoring. However, the burgeoning popularity of PBC lacks sufficient evidence to confirm these promised benefits. In particular, the efforts of introducing PBC into human service systems needs first to address the effectiveness problem, i.e., whether PBC really produces better results. This problem constitutes the research question of the research project. After building the theoretical framework which incorporates the literature on formal and relational contracting, this project explores the effectiveness question using Indiana vocational rehabilitation program as a case. In particular, the study evaluates PBC effectiveness from two perspectives: service outcome and participating organizations. From a service-outcome perspective, the research employs a quasi-experimental design to compare the impacts of two contract arrangements, PBC and fee-for-service (FFS), on individual employment outcomes. From a participating-organization perspective, the project runs semi-structured interviews with service counselors and contractors. Triangulating these findings, this project proposes that PBC seems more promising than FFS in human services. It also implies PBC effectiveness might not be well-rounded and should not be exaggerated. Further, the study addresses the managerial implications of the findings. The research and the practice of PBC tend to ignore the relational face of contracting. PBC as a formal arrangement is always disturbed by the highly uncertain nature of human services and thus might result in incomplete performance improvement and contractor opportunism. If so, relational contracting, using informal and normative mechanisms, may enable desirable collaborative outcomes. The combination of formal PBC efforts with relational contracting would encourage high-quality results. In sum, this project represents an attempt to systematically examine PBC effectiveness in human services. It shows the difficulties and dynamics of introducing performance management to human service contracting. It also warns the launch of PBC systems should be very deliberate and careful. More broadly, the project underscores two key components of contracting management: control and trust

Flexural Properties of Textile-Reinforced Concrete with Nonorthogonal Grids

Textile-reinforced concrete (TRC) is a cement-based composite material that uses textile as a reinforcement material. The weft-direction fiber bundles in the traditional orthogonally arranged warp–weft textile hardly bear force, and its bonding strength with the weft fiber bundle is not ideal. Under the action of force, a small included angle between the stressed fiber bundle and the stressed direction can effectively increase the anchoring effect of their fibers in the matrix, resulting in higher bonding and reinforcement efficiency. To improve the utilization rate of fibers and the bonding strength between the textile and the concrete matrix, an arrangement along the diagonal of the grids was proposed in this paper. The flexural properties of basalt TRC plates with orthogonal grids (OG-BTRC) and plates with nonorthogonal grids (NOG-BTRC) with different grid angles and grid sizes with different laying methods, namely, a side layout (SL) and diagonal layout (DL), were studied through four-point bending tests. A comparative analysis was carried out with an ABAQUS simulation and the test results. The results showed that with a decrease in the grid angle, the BTRC specimens gradually showed a failure mode of multiple cracks, and most of the cracks appeared in the pure bending area; as the grid angle decreased, the BTRC specimens exhibited excellent flexural bearing capacity, good ductility, and high toughness. The total number of cracks on the specimen increased when it failed, while the spacing of the cracks decreased, and the fracture morphology appeared as fine and uniform features. The toughness of the specimen with a small grid angle using the DL laying method was greater than that using the SL laying method. The software simulation value matched the test data well, which proved that the test result was reliable

Preparation of Pd-Diimine@SBA-15 and Its Catalytic Performance for the Suzuki Coupling Reaction

A highly efficient and stable Pd-diimine@SBA-15 catalyst was successfully prepared by immobilizing Pd onto diimine-functionalized mesoporous silica SBA-15. With the help of diimine functional groups grafted onto the SBA-15, Pd could be anchored on a support with high dispersion. Pd-diimine@SBA-15 catalyst exhibited excellent catalytic performance for the Suzuki coupling reaction of electronically diverse aryl halides and phenylboronic acid under mild conditions with an ultralow amount of Pd (0.05 mol % Pd). When the catalyst amount was increased, it could catalyze the coupling reaction of chlorinated aromatics with phenylboronic acid. Compared with the catalytic performances of Pd/SBA-15 and Pd-diimine@SiO2 catalysts, the Pd-diimine@SBA-15 catalyst exhibited higher hydrothermal stability and could be repeatedly used four times without a significant decrease of its catalytic activity

Study on the Expansion and Compression Resistance of 3D-Textile-Reinforced Self-Stressing Concrete

Textile-reinforced concrete (TRC), as a kind of high-crack-resistance and high-corrosion-resistance material, has been widely studied. The current research has begun the exploration of the change of textile form, such as 3D-textile-reinforced concrete (3D TRC), and its superior bending performance has been verified. In order to pursue better mechanical properties, combined with the characteristics of self-stressing concrete and 3D textiles, three-dimensional-textile-reinforced self-stressing concrete (3D-TRSSC) specimens were designed in this research. The expansive and compressive properties of specimens with two types of textiles were tested by self-stress and compressibility tests, and the results showed the compressive property and failure mode of 3D-TRSSC were improved compared with 2D-TRSSC and SSC: the increase in compressive strength was 16.3% and 35.1%, respectively. In order to explain the improvement of the compressive strength of the 3D-TRSSC specimens, the triaxial self-stress state analysis of the compressive specimen was carried out, and then a set of calculation methods based on deformation analysis was designed to explain the upward displacement of the necking position of the TRSSC compressive specimen. The theoretical results and experimental data were 27.2 mm and 28–30 mm, respectively. In addition, the improvement of the compressive strength of the 3D-TRSSC specimens relative to that of the 2D-TRSSC specimen was predicted. The calculation results were highly consistent with the predicted values

Generation Paths of Major Road Accidents Based on Fuzzy-Set Qualitative Comparative Analysis

In the process of continuously promoting safety management, major road accidents have become a key obstacle to improving overall road safety. The analysis of the overall road accidents hides the characteristics and laws of major road accidents. To clarify the causes of major road accidents, an analysis framework of “individual-vehicle-environment-management” is presented based on a literature review. Considering the interaction of the above variables, the fuzz-set qualitative comparative analysis (fsQCA) was used to explore the generating paths of major road accidents based on 42 road accidents. The work shows that: (1) Major road accidents are caused due to the interactive coupling of “individual-vehicle-environment-management” elements. Major road accidents can occur with normal driving behaviors or sufficient response and rescue capabilities. (2) General road accidents and relatively major road accidents are more likely to occur in the presence of driving behavior errors, favorable road facilities, and sufficient response and rescue capabilities. Moreover, major road accidents are more likely to occur due to large vehicles with adverse vehicle performances. (3) There are three path modes and five condition configurations in major road accidents, namely individual-vehicle-management induced, individual-vehicle-environment induced, and vehicle induced mode. This work enriches the accident causation mode from a new configuration perspective and explains which variable combinations lead to the occurrence of major road accidents. Clarification of the differences between general accidents and major accidents will help to accurately predict and restrain the development of major road accidents

Acacetin exerts antitumor effects on gastric cancer by targeting EGFR

Background: Gastric cancer (GC) is a common malignant tumor with a poor prognosis. Combination treatments may prolong the survival of patients with GC. Acacetin, which is a flavonoid, exerts potent inhibitory effects on several types of cancer cells; however, the mechanisms of action remain poorly understood.Methods: Network pharmacology and RNA sequencing were used to predict the targets of acacetin, which were then verified by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking. The biological functions of acacetin in MKN45 and MGC803 cells were investigated using TUNEL assays, crystal staining and colony formation assays. The pathways affected by acacetin were verified through reverse experiments. The in vivo antitumor efficacy of acacetin was assessed in a subcutaneous xenotransplanted tumor model.Results: In this study, we identified EGFR from more than a dozen predicted targets as a protein that directly binds to acacetin. Moreover, acacetin affected the level of phosphorylated EGFR. In vitro, acacetin promoted the apoptosis of GC cells. Importantly, EGFR agonists reversed the inhibitory effects of acacetin on the STAT3 and ERK pathways. In vivo, acacetin decreased the protein levels of pEGFR in tumors, resulting in increased GC xenograft tumor regression without obvious toxicity.Conclusion: Our findings highlight EGFR as one of the direct targets of acacetin in GC cells. Acacetin inhibited the phosphatase activity of EGFR in vitro and in vivo, which played a role in the antitumor effects of acacetin. These studies provide new evidence for the use of acacetin as a potential reagent for the treatment of GC

Investigation of Unsteady Flow Interactions in a Transonic High Pressure Turbine Using Nonlinear Harmonic Method

The performance of a transonic high pressure turbine is mainly influenced by the unsteady interactions associated with the passing blades. In this paper, the unsteady flow interactions in a transonic turbine have been numerically investigated using the nonlinear harmonic (NLH) method in comparison with the steady and unsteady Reynolds-averaged Navier–Stokes (RANS). The comparison shows that the NLH method using three harmonics could capture the main unsteady flow interactions efficiently with about seven times smaller computational cost than the unsteady RANS, resulting in a more accurate time-averaged flow than for steady RANS. However, the continuity of the flow variables across the rotor-stator interface has shown some discrepancies compared with the unsteady RANS, which can be further satisfied by increasing the numbers of harmonics. The unsteady interactions are analyzed in detail; the results show that the wake and trailing edge shock from the upstream stator are the major sources of unsteadiness in the downstream rotor passage. The stator trailing edge shock impinges on the suction side of the passing rotor blades and generates pressure waves. These pressure waves are periodically reflected back to trigger the stator wake shedding. These waves are strong enough to travel through the rotor passage, and eventually affect the flow at the rotor’s trailing edge. The stator wakes are chopped by the downstream rotor, and travel through the rotor passage. This significantly enhances the unsteadiness of the flow near the rotor trailing edge. Lastly, the deterministic stresses and enthalpy distributions extracted from the NLH method have revealed that the effects of the unsteadiness are relatively weaker in the axial direction. Furthermore, the deterministic correlations analysis has shown that, some empirical deterministic correlations models based on the decay concept of compressors are not suitable for turbines

Application of Digital Twin in Smart Battery Management Systems

Abstract Lithium-ion batteries have always been a focus of research on new energy vehicles, however, their internal reactions are complex, and problems such as battery aging and safety have not been fully understood. In view of the research and preliminary application of the digital twin in complex systems such as aerospace, we will have the opportunity to use the digital twin to solve the bottleneck of current battery research. Firstly, this paper arranges the development history, basic concepts and key technologies of the digital twin, and summarizes current research methods and challenges in battery modeling, state estimation, remaining useful life prediction, battery safety and control. Furthermore, based on digital twin we describe the solutions for battery digital modeling, real-time state estimation, dynamic charging control, dynamic thermal management, and dynamic equalization control in the intelligent battery management system. We also give development opportunities for digital twin in the battery field. Finally we summarize the development trends and challenges of smart battery management