Effect of Reaction and Regeneration on the Production of Pyridine Bases through Glycerol and Ammonia Route

The HZSM-22-At-acid and HZSM-5-At-acid catalysts were synthesized by alkaline-acid sequential treatment and the ZnO/HZSM-5-At-acid catalyst was synthesized by wet-impregnated method. Influence factors, including the types of reactors, impurities in glycerol and regeneration, were systematically investigated. The catalysts were characterized by XRD, TG, N2-physorption and NH3-TPD techniques. The catalytic evaluation showed that the total yield of pyridine bases in the series-connected two-stage reactors was significantly higher than that of the single reactor while the catalytic pair (HZSM-22-At-acid + ZnO/HZSM-5-At-acid) was employed in these reactors, respectively. It was found that the presence of methanol and sodium chloride in glycerol played a great negative effect on the total yield of pyridine bases. The coke was a key factor leading to the deactivation of catalyst. The catalytic activity was basically restored after the regeneration. The total yield of pyridine bases was increased up to 72% after the 6 th reaction, which was obviously higher than that of the similar reports. The characterization results demonstrated that the larger pore size and the declined concentration of acid site (particularly strong acid site) were main reasons for improving the catalytic activity

A multiphase-field model for simulating the hydrogen-induced multi-spot corrosion on the surface of polycrystalline metals: Application to uranium metal

Hydrogen-induced multi-spot corrosion on the surface of polycrystalline rare metals is a complex process, which involves the interactions between phases (metal, hydride and oxide), grain orientations, grain boundaries, and corrosion spots. To accurately simulate this process and comprehend the underlying physics, a theoretical method is required that includes the following mechanisms: i) hydrogen diffusion, ii) phase transformation, iii) elastic interactions between phases, especially, the interactions between the oxide film and the hydride, iv) elastic interactions between grains, and v) interactions between hydrogen solutes and grain boundaries. In this study, we report a multiphase-field model that incorporates all these requirements, and conduct a comprehensive study of hydrogen-induced spot corrosion on the uranium metal surface, including the investigation of the oxide film, multi-spot corrosion, grain orientation, and grain boundary in the monocrystal, bicrystal, and polycrystal systems. The results indicate that the oxide film can inhibit the growth of hydrides and plays a crucial role in determining the correct morphology of the hydride at the triple junction of phases. The elastic interaction between multiple corrosion spots causes the merging of corrosion spots and promotes the growth of hydrides. The introduction of grain orientations and grain boundaries results in a variety of intriguing intracrystalline and intergranular hydride morphologies. The model presented here is generally applicable to the hydrogen-induced multi-spot corrosion on any rare metal surface.Comment: 22 pages (text), 16 figures (text), 2 table (text), 8 pages (SI), 12 figures (SI

SPEEK Membrane of Ultrahigh Stability Enhanced by Functionalized Carbon Nanotubes for Vanadium Redox Flow Battery

Proton exchange membrane is the key factor of vanadium redox flow battery (VRB) as their stability largely determine the lifetime of the VRB. In this study, a SPEEK/MWCNTs-OH composite membrane with ultrahigh stability is constructed by blending sulfonated poly(ether ether ketone) (SPEEK) with multi-walled carbon nanotubes toward VRB application. The carbon nanotubes disperse homogeneously in the SPEEK matrix with the assistance of hydroxyl group. The blended membrane exhibits 94.2 and 73.0% capacity retention after 100 and 500 cycles, respectively in a VRB single cell with coulombic efficiency of over 99.4% at 60 mA cm−2 indicating outstanding capability of reducing the permeability of vanadium ions and enhancing the transport of protons. The ultrahigh stability and low cost of the composite membrane make it a competent candidate for the next generation larger-scale vanadium redox flow battery

VS-4718 Antagonizes Multidrug Resistance in ABCB1- and ABCG2-Overexpressing Cancer Cells by Inhibiting the Efflux Function of ABC Transporters

Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for multi-drug resistance (MDR). VS-4718, a tyrosine kinase inhibitor targeting focal adhesion kinase (FAK) with a potential anticancer effect, is currently evaluated in clinical trials. In this study, we investigated whether VS-4718 could reverse MDR mediated by ABC transporters, including ABCB1, ABCG2, and ABCC1. The results showed that VS-4718 significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR mediated by ABCC1. Treatment of VS-4718 did not alter the protein level and subcellular localization of ABCB1 or ABCG2. Mechanism studies indicated that the reversal effects of VS-4718 were related to attenuation of the efflux activity of ABCB1 and ABCG2 transporters. ATPase analysis indicated that VS-4718 stimulated the ATPase activity of ABCB1 and ABCG2. Docking study showed that VS-4718 interacted with the substrate-binding sites of both ABCB1 and ABCG2, suggesting that VS-4718 may affect the activity of ABCB1 and ABCG2 competitively. This study provided a novel insight for MDR cancer treatment. It indicated that combination of VS-4718 with antineoplastic drugs could attenuate MDR mediated by ABCB1 or ABCG2 in ABCB1- or ABCG2-overexpressing cancer cells

S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.</p

Olmutinib (BI1482694/HM61713), a Novel Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Reverses ABCG2-Mediated Multidrug Resistance in Cancer Cells

The main characteristic of tumor cell resistance is multidrug resistance (MDR). MDR is the principle cause of the decline in clinical efficacy of chemotherapeutic drugs. There are several mechanisms that could cause MDR. Among these, one of the most important mechanisms underlying MDR is the overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) super-family of transporters, which effectively pump out cytotoxic agents and targeted anticancer drugs across the cell membrane. In recent years, studies found that ABC transporters and tyrosine kinase inhibitors (TKIs) interact with each other. TKIs may behave as substrates or inhibitors depending on the expression of specific pumps, drug concentration, their affinity for the transporters and types of co-administered agents. Therefore, we performed in vitro experiments to observe whether olmutinib could reverse MDR in cancer cells overexpressing ABCB1, ABCG2, or ABCC1 transporters. The results showed that olmutinib at 3 μM significantly reversed drug resistance mediated by ABCG2, but not by ABCB1 and ABCC1, by antagonizing the drug efflux function in ABCG2-overexpressing cells. In addition, olmutinib at reversal concentration affected neither the protein expression level nor the localization of ABCG2. The results observed from the accumulation/efflux study of olmutinib showed that olmutinib reversed ABCG2-mediated MDR with an increasing intracellular drug accumulation due to inhibited drug efflux. We also had consistent results with the ATPase assay that olmutinib stimulated ATPase activity of ABCG2 up to 3.5-fold. Additionally, the molecular interaction between olmutinib and ABCG2 was identified by docking simulation. Olmutinib not only interacts directly with ABCG2 but also works as a competitive inhibitor of the transport protein. In conclusion, olmutinib could reverse ABCG2-mediated MDR. The reversal effect of olmutinib on ABCG2-mediated MDR cells is not due to ABCG2 expression or intracellular localization, but rather related to its interaction with ABCG2 protein resulting in drug efflux inhibition and ATPase stimulation

Y6, an Epigallocatechin Gallate Derivative, Reverses ABCG2-Mediated Mitoxantrone Resistance

Multidrug resistance is reported to be related to the transmembrane transportation of chemotherapeutic drugs by adenosine triphosphate-binding cassette (ABC) transporters. ABC subfamily G member 2 (ABCG2) is a member of the ABC transporter superfamily proteins, which have been implicated as a key contributor to the development of multidrug resistance in cancers. A new epigallocatechin gallate derivative, Y6 was synthesized in our group. Our previous study revealed that Y6 increased the sensitivity of drug-resistant cells to doxorubicin, which was associated with down-regulation of P-glycoprotein expression. In this study, we further determine whether Y6 could reverse ABCG2-mediated multidrug resistance. Results showed that, at non-toxic concentrations, Y6 significantly sensitized drug-selected non-small cell lung cancer cell line NCI-H460/MX20 to substrate anticancer drugs mitoxantrone, SN-38, and topotecan, and also sensitized ABCG2-transfected cell line HEK293/ABCG2-482-R2 to mitoxantrone and SN-38. Further study demonstrated that Y6 significantly increased the accumulation of [3H]-mitoxantrone in NCI-H460/MX20 cells by inhibiting the transport activity of ABCG2, without altering the expression levels and the subcellular localization of ABCG2. Furthermore, Y6 stimulated the adenosine triphosphatase activity with a concentration-dependent pattern under 20 μM in membranes overexpressing ABCG2. In addition, Y6 exhibited a strong interaction with the human ABCG2 transporter protein. Our findings indicate that Y6 may potentially be a novel reversal agent in ABCG2-positive drug-resistant cancers