Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. 相似文献
The electrical proprieties of poly (3-hexylthiophene): Silicon nanowires (P3HT: SiNWs) nanocomposite was investigated by impedance spectroscopy technique. The effect of bias voltage under and without illumination was discussed. Indeed, the imaginary part of the impedance shows a high relaxation frequency related to Maxwell–Wagner–Sillars (MWS) polarization. The relaxation time was found in the range of ms and it was shifted towards high frequency with increasing the bias voltage especially at 0.6 V At bias voltage equal to Vth and under illumination, the conductivity increases because the trapped charges acquire the necessary energy to escape from the interface and the hopping time found was reduced. This indicates a change of the conduction mechanism. The Cole–Cole diagram was excellently fitted through an equivalent circuit including a chemical capacitance Cµ, a contact electrical resistance Rs and recombination resistance Rp. 相似文献
Two green nanocomposites of Co3O4 decorated CTAB/bentonite (Co@CT/BE) and chitosan/bentonite (Co@CH/BE) were synthesized as enhanced and environmental photocatalysts and antibacterial agents. As photocatalysts, the products were applied in the effective oxidation of toxic methyl parathion pesticide (MP) in wastewater under a visible light source. The application of Co@CH/BE (0.02 g) resulted in the complete oxidation of MP (50 mg/L) after 40 min and complete mineralization after 60 min. while the complete oxidation and mineralization of MP (50 mg/L) by Co@CT/BE was recognized after 75 min and 100 min, respectively. The Co@CH/BE composite is of higher activity than Co@CT/BE and can cause complete oxidation for MP at high concentrations up to 100 mg/L after 75 min. The oxidation pathway was illustrated considering the existence of the hydroxyl radicals as the active oxidizing species and the identified secondary organic compounds during the oxidation tests. The detected intermediate converted into end products of CO2 and inorganic anions of SO4?2, NO3?, and PO4?3 at the final stages of the oxidation processes. As antibacterial agents, the two composites exhibit considerable inhabitation zones of about 20 mm against both the Gram-positive Staphylococcus aureus and Gram-negative bacterium Vibrio Sp. The synthetic Co@CH/BE showed the best antibacterial properties with 200 μg/mL as minimum inhibitory against Staphylococcus aureus.
Journal of Inorganic and Organometallic Polymers and Materials - Historically, the recording of information over paper has always been regarded as the most important factor for maintaining records... 相似文献
Abstract—This article presents an efficient multi-objective optimization approach based on the supervised big bang–big crunch method for optimal planning of dispatchable distributed generator. The proposed approach aims to enhance the system performance indices by optimal sizing and placement of distributed generators connected to balanced/unbalanced distribution networks. The distributed generation units in the proposed algorithms are modeled as a voltage-controlled node with the flexibility to be converted to a constant power node in the case of reactive power limit violation. The proposed algorithm is implemented in the MATLAB (The MathWorks, Natick, Massachusetts, USA) environment, and the simulation studies are performed on IEEE 69-bus and IEEE 123-node distribution test systems. Validation of the proposed method is done by comparing the results with published results obtained from other competing methods, and the consequent discussions prove the effectiveness of the proposed approach. 相似文献
Recently, academic and industrial research communities are paying more explicit attention to the 5G multiple radio access technology ultra‐dense networks (5G multi‐RAT UDNs) for boosting network capacity, especially in UD urban zones. To this aim, in this paper, we intend to tackle the user association problem in 5G multi‐RAT UDNs. By considering the decoupled uplink/downlink access (DUDA), we divide our user association problem into two distinct subproblems representing, respectively, the uplink and the downlink channels. Next, we formulated each one as a nonlinear optimization problem with binary variables. Then, to solve them, we were restricted by the hard complexity, as well as the hard feasibility of centralized user association schemes. Thus, to resolve our user association problem in a reasonable time and distributed manner, we formulated each subproblem as a many‐to‐one matching game based on matching theory. Next, we provide two fully distributed association algorithms to compute the uplink and downlink stable matching among user equipments (UEs) and base stations (BSs). Simulation results corroborate our theoretical model and show the effectiveness and improvement of our achieved results in terms of the overall network performance, quality of service (QoS), and energy efficiency (EE) of UEs. 相似文献
Computational Economics - This paper presents the Multi-Objective Local Environmental Simulator (MOLES), an urban Computable General Equilibrium model with selected microsimulation features that... 相似文献