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Initiation of epithelial-to-mesenchymal transition (EMT) is common in papillary thyroid carcinoma (PTC) and may contribute to its metastasis. Aims of the present study are to investigate whether and how the C-X-C motif chemokine ligand (CXCL)-5/C-X-C motif receptor 2 (CXCR2) axis affects PTC metastasis, with a focus on the EMT process. Herein, two PTC cell lines, KTC-1 and B-CPAP cells, identified as CXCR2-positive cells were used as the cell model. We found that a 24-h stimulation of 1 or 10 nM recombinant human CXCL5 (rhCXCL5) enhanced the migration and invasion of both KTC-1 and B-CPAP cells without affecting their proliferation. The migration- and invasion-promoting effects of rhCXCL5 were attenuated if CXCR2 was silenced by its specific short hairpin RNAs (shRNAs). EMT initiation is defined as downregulation of epithelial-cadherin (E-cadherin) and upregulation of N-cadherin, Vimentin and Snail. Our data showed that rhCXCL5-induced EMT in PTC cells was suppressed by CXCR2 shRNA. Furthermore, the active CXCL5-CXCR2 axis enhanced the phosphorylation of Akt at Ser 473 residue and that of glycogen synthase kinase-3 (GSK-3β) at Ser 9 residue, and accelerated the nuclear accumulation of β-catenin in PTC cells. Re-expression of the active form of β-catenin in PTC cells rescued their impaired invasiveness caused by the blockade of CXCL5-CXCR2 axis. In addition, CXCL5 and CXCR2 were overexpressed in the metastatic lymph nodes obtained from 18 patients with PTC. In summary, our study demonstrates that the activated CXCL5-CXCR2 axis contributes to the metastatic phenotype of PTC cells by modulating Akt/GSK-3β/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Abstract: Correlations of disease phenotypes with glycosylation changes have been analyzed intensively in tumor biology field. In this study we describe glycomic alterations of multidrug resistance in human leukemia cell lines. Using multiple glycan profiling tools: real-time PCR for quantification of glycogenes, FITC–lectin binding for glycan profiling, and mass spectrometry for glycan composition, we compared the glycomics of drug-resistant K562/ADR cells with parental K562 line. The results showed that the expression of glycogenes, glycan profiling and N-glycan composition were different in K562/ADR cells, as compared with those in K562 cells, whereas O-glycans of the two cell lines showed no different mass spectra. Further analysis of the N-glycan regulation by way of tunicamycin application or PNGase F treatment in K562/ADR cells showed partial inhibition of biosynthesis and increased sensitivity to chemotherapeutic drugs in vitro. We targeted glycogene B3GNT8 and ST8SIA4, which were over-expressed in K562/ADR cells, and silenced the expression levels of two glycogenes after using RNA interference approach. The results showed that the silencing of B3GNT8 or ST8SIA4 in K562/ADR cells resulted in increased chemosensitivity to anti-tumor drugs. In conclusion, glycomic alterations are responsible for the overcoming multidrug resistance in human leukemia therapy and the N-linked oligosaccharides are associated with the drug resistance of cancer cells. [Copyright &y& Elsevier]

Iron ore (pellet, sinter and lump ore) is gradually reduced to iron in blast furnace. The reductions are a serial of heterogeneous gas solid reactions that take place from the top of the furnace and throughout the shaft region of the furnace. Two major categories of iron ore reaction model had been developed and applied for modeling the iron ore reduction: Un-Reacted shrinking Core (URC) model and grain model. The URC model had been widely adopted in blast furnace numerical model due to its simplicity for numerical implementation. However, the URC model assumes the reaction taking place in a sharp interface inside the iron ore. The sharp interface assumption may not be valid in the entire reaction stage due to the porous natural of the iron ore. The grain model was proposed to overcome such limitation. But the complexity of the grain model restricts its application to single ore granule reaction process and it has not been applied full blast furnace modeling. In this paper, a novel methodology is proposed to implement the grain model to predict iron ore reduction in blast furnace. The model considers the gas diffusion in porous iron ore, the dynamic composition changes of iron ore along the radius of the iron ore, the iron ore transport in blast furnace. The gas flow and interphase heat transfer are also considered. The result reveals the detailed heat and mass transfer process for the iron ore reduction in blast furnace shaft. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant cell-surface glycosylation patterns are present on tumors and have been linked to tumor progression. This study aimed to identify the alterations of glycogene and N-glycan involved in tumor invasion, tumorigenicity and drug resistance in MHCC97-H and MHCC97-L human hepatocarcinoma cell lines, which have high, low metastatic potential, respectively. Using real-time PCR for quantification of glycogene and FITC-lectin binding for glycan profiling, we found that the expression of glycogenes and glycan profiling were different in MHCC97-H cells, as compared to those in MHCC97-L cells. We silenced the expression levels of glycogenes MGAT3 and MGAT5, which were over-expressed in MHCC97-L and MHCC97-H cells. Knockdown of MGAT3 expression promoted MHCC97-L cells invasion and increased resistance to 5-fluorouracil in vitro. The silencing of MGAT5 in MHCC97-H cells inhibited invasion and increased sensitivity to 5-fluorouracil in vitro. Further analysis of the N-glycan regulation by tunicamycin application or PNGase F treatment in MHCC97-H and MHCC97-L cells showed partial inhibition of N-glycan glycosylation, decreased invasion, tumorigenicity and increased sensitivity to 5-fluorouracil both in vitro and in vivo. These findings suggest that alterations of glycogene and N-glycan in human hepatocarcinoma cells correlate with tumor invasion, tumorigenicity and sensitivity to chemotherapeutic drug, and have significant implications for the development of treatment strategies. [Copyright &y& Elsevier]

The effect of 60 Co gamma ray irradiation on the physicochemical and crystalline properties of native corn starch were investigated. Fourier transform infrared spectroscopy and X-ray diffraction showed that irradiation had a slight effect on the molecular structure of corn starch with crystallinity decreasing with increasing irradiation dose. Particle size analysis showed that 59.1% of native corn starch granules had sizes of ≥8 μm, which decreased to only 24.1% after treatment with an irradiation dose of 40 kGy. Irradiated-corn-starch films were prepared by casting gelatinized irradiated-corn-starch solutions. An increased irradiation dose was found to increase the tensile strength of the resultant films, but caused a significant decrease in water vapor permeability. The irradiated-corn-starch films showed potential for the development of biodegradable starch films with improved properties. [ABSTRACT FROM AUTHOR]

Gamma-irradiation induced degradation of dexamethasone (DEX) in aqueous solution was investigated under different conditions. The results indicate that low-concentration DEX could be effectively decomposed during gamma irradiation. H 2 O 2 and Fenton reagent were favorable for DEX radiolytic removal. However, DEX radiolysis was restrained in the presence of NO 3 - , CO 3 2 - , 2-propanol and tert -butanol. DEX radiolytic degradation was in accordance with the pseudo first-order reaction kinetics. The rate constant ratios of OH, e aq - and H towards DEX degradation could be calculated as k OH : k e aq - : k H = 10:1.5:1. Besides, it is observed that radiolytic degradation of DEX restrained algae growth. Finally, LC-MS analysis was employed to identify the intermediates and Gaussian 03 software was used to optimize DEX geometry structure. On the basis of LC-MS analysis and Gaussian calculations, we attributed DEX radiolytic removal to OH oxidation, OH radical substitution and direct cleavage of DEX molecules. [ABSTRACT FROM AUTHOR]

Fucosylation is the final step in the glycosylation machinery, which produces glycans involved in tumor multidrug resistance development. MicroRNAs (miRNAs) are endogenous negative regulators of gene expression and have been implicated in most cellular processes of tumors, including drug resistance. This study was undertaken to determine the roles of fucosylation and miR-224-3p in multidrug resistance of human breast cancer cell lines. Comparative analysis revealed differential modification patterns of fucosylation of the fucosylated N-glycans in drug-resistant T47D/ADR cells and sensitive line T47D cells. The expressional profiles of fucosyltransferase genes in two pairs of parental and chemoresistant human breast cancer cell lines showed that FUT4 was up-regulated highly in MDR cell lines. Altered level of FUT4 affected the drug-resistant phenotype of T47D and T47D/ADR cells both in vitro and in vivo. By bioinformatics analysis, we identified FUT4 as one of the miR-224-3p-targeted genes. Further studies showed an inverse relationship between of FUT4 and miR-224-3p in parental and ADR-resistant breast cancer cells, wherein miR-224-3p was downregulated in resistant cells. 3′-UTR dual-luciferase reporter assay confirmed that miR-224-3p directly targeted 3′-untranslation region (3′-UTR) of FUT4 mRNA. In addition, miR-224-3p overexpression sensitized T47D/ADR cells to chemotherapeutics and reduced the growth rate of breast cancer xenografts in vivo. Our results indicate that FUT4 and miR-224-3p are crucial regulators of cancer response to chemotherapy, and may serve as therapeutic targets to reverse chemotherapy resistance in breast cancer. [ABSTRACT FROM AUTHOR]

Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials. However, the underlying mechanism remains to be elucidated. Here we show that LGX818 potently decreased ERK phosphorylation and inhibited proliferation in BRAFV600E melanoma cell lines. Moreover, LGX818 downregulated CyclinD1 in a glycogen synthase kinase 3β-independent manner and induced cell cycle arrest in the G1 phase, Surprisingly, LGX818 triggered cellular senescence in BRAFV600E melanoma cells, as evidenced by increased β-galactosidase staining, while no appreciable induction of apoptosis was detected, as determined by Annexin V and propidium iodide staining and immunoblot analysis of caspase-3 processing and poly (ADP-ribose) polymerase cleavage. Increased p27KIP1 expression and retinoblastoma protein activation were detected during LGX818-induced senescence. Additionally, inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 1B by AZ191 reversed LGX818-induced CyclinD1 turnover and senescence. Interestingly, autophagy is triggered through inhibition of the mTOR/70S6K pathway during LGX818-induced senescence. Moreover, autophagy inhibition by pharmacological and genetic regulation attenuates LGX818-induced senescence. Notably, combining LGX818 with autophagy modulators has anti-proliferative effect in LGX818-resistant BRAF mutant melanoma cells. Altogether, we uncovered a mechanism by which LGX818 exerts its anti-tumor activity in BRAFV600E melanoma cells. [ABSTRACT FROM AUTHOR]

Abstract: Small-molecule cell-permeable Bcl-2/Bcl-xL antagonist ABT-737 has recently emerged as a novel cancer therapeutic agent because it potently induces apoptosis in certain cancer cells. However, since ABT-737 binds to Mcl-1 with low affinity, ABT-737-mediated apoptosis signaling is inhibited in hepatocellular carcinoma (HCC) cells and other solid cancer cells due to the elevated expression of Mcl-1. Accordingly, strategies that target Mcl-1 are explored for overcoming ABT-737-resistance. In this study, we reported that Norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), induced transcriptional repression of Mcl-1 and considerably enhanced ABT-737-triggered cell viability inhibition and apoptosis in multiple HCC cell lines. Moreover, we observed that the enhancement of ABT-737-mediated apoptosis by NCTD was associated with activation of mitochondrial apoptosis signaling pathway, which involved cytosolic release of cytochrome c, cleavage of caspase-9 and caspase-3. Additionally, knockdown of Bax/Bak, the key effectors permeabilizing mitochondrial outer membrane significantly attenuated the enhancement, indicating mitochondrial apoptosis pathway played an essential role in the execution of the apoptosis. Finally, knockdown of Mcl-1 substantially potentiated ABT-737-mediated apoptotic cell death, confirming the potency of Mcl-1 repression by NCTD in enhancing ABT-737-induced apoptosis. These results therefore suggest that combination treatment with NCTD can overcome ABT-737 resistance and enhance ABT-737 therapeutic efficacy in treating human HCC. [Copyright &y& Elsevier]

Aiming at corrosion issues of structural materials in supercritical carbon dioxide Brayton systems, the corrosion behaviors of T91 and 316 were studied under S-CO 2 at 500 ℃, 600℃and 20 MPa. The corrosion kinetics conform to the parabolic law. The corrosion products of T91 are mainly composed of outer columnar Fe 3 O 4 and inner Fe-Cr spinel, which had porous structure and no protective effect for further corrosion. Thin and dense Cr 2 O 3 formed on the 316 surface after 500℃corrosion.While large numbers of Fe-oxide nodules formed on surface of Cr-rich scale at 600 ℃. The corrosion mechanism was discussed. • The corrosion behavior and mechanism of T91 and 316 exposed to supercritical carbon dioxide at 500 ℃, 600 ℃ and 20 MPa up to 1000 h was studied. • The morphology, structure and composition of oxide layers and carburization behavior of T91 and 316 were compared and analyzed. • The corrosion mechanism of T91 and 316 were discussed. [ABSTRACT FROM AUTHOR]

Abstract: Diuron degradation efficiencies and the proposed mechanism by gamma-ray irradiation were investigated. Several factors that might affect the degradation values were further examined. The UV absorbances at 200–400nm and diuron concentration decreased with the increase of radiation dose. When diuron initial concentration was 18.5mgL−1 and 1.0kGy was selected as the radiation dose, diuron removal value and loss of total organic carbon were 100 and 34.1%, respectively. However, the concentration of Cl− ion increased with the increase of radiation dose. The process could be depicted by first order reaction kinetics and the reaction was mainly caused by the reaction of diuron with e:italic>e aq −. The degradation efficiency decreased with the increase of initial concentration at the same radiation dose. H2O2, HCO3 −, NO3 −, NO2 −, CH3OH and humic acid as additives reduced the degradation efficiency. Furthermore, the increase of NO3 −, NO2 −, CH3OH and humic acid would result in the decrease of the degradation values. The pH value could affect the removal efficiency and the degradation process was enhanced in acid condition. The pH value became lower with increasing radiation dose after gamma-ray irradiation. [Copyright &y& Elsevier]

The Eocene beach-bar sandstones are among the most important petroleum exploration targets of Dongying Depression, China. A little is known about the heterogeneous pore structure characteristics, contributing factors and their relations with highly variable macroscopic petrophysical properties. In this study, various testing techniques and methods have been conducted to investigate the depositional and diagenetic features, petrophysical properties and pore structure characters. Three major lithologies, namely fine sandstones, siltstones and argillaceous siltstones, are identified with distinct sandstones texture, diagenetic components and petrophysical properties. Relatively good sorting and large particle size are the dominant sedimentological factors that result in well-preserved primary porosity of fine sandstones. The exceptionally high permeability of argillaceous siltstones with low porosity is largely related with micro-fractures. Compaction is the main porosity-reducing factor of beach-bar sandstones, in addition to cementation of carbonate, quartz overgrowth and clay. Dissolution process crucially depends on the preservation of primary porosity, and it is often limited due to strong compaction. The reconstructed pore network and MICP experiments both suggest that the pore space connectivity is closed related with pore and throat size, and large pore throats are more likely to be connected by neighboring throats and form connected paths in the sandstones. The large pore systems determine the reservoir quality by contributing the vast majority of permeability, even if they may occupy small proportion of pore volume. The pore structures of fine sandstones mainly consist of large pore systems, which cause favorable high reservoir quality and strong correlations between porosity and permeability. The unfavorable reservoir quality, great fractal dimensions and poor correlations between porosity and permeability of argillaceous siltstones samples are largely attributed to the dominating micro pore throats. • Pore throat size distribution and fractal features of Eocene beach-bar sandstones with variable petrophysical properties are clarified. • Impact of sedimentological parameters and diagenetic alterations on pore structure and reservoir quality are discussed. • The correlations between microscopic pore structures and macroscopic petrophysical properties are investigated. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the leading causes of cancer mortality worldwide. Inspired by the biological structure and function of low-density lipoprotein (LDL), in this study, an ApopB-100 based targeted lipid nanoparticles was synthesized to improve the therapeutic efficacy in liver cancer treatment. The biological composition of ApopB is similar to LDL which can effectively increase the targeting efficiency of nanoparticles in LDL receptor (LDLR)-overexpressed liver tumors. We have demonstrated that the co-administration of sorafenib (SRF) and Dihydroartemisinin (DHA) could exhibit synergistic anticancer effect in HepG2 liver cancer cells. DHA produced excessive cellular reactive oxygen species (ROS) and induced greater apoptosis of cancer cells. LDL-based SRF/DHA-loaded lipid nanoparticles (LD-SDN) showed remarkable decrease in the cell viability compared to that of either of single drug treated cancer cells. Combination of SRF+DHA resulted in predominant SubG1 proportion of cells. LD-SDN exhibited the highest SubG1 (%) of cells compared to that of any of the individual drugs. Most importantly, robust antitumor response and delayed tumor growth was observed for LD-SDN treated xenograft tumor model. Ki67 proliferation index of LD-SDN (22.1 ± 5.6%) is significantly lesser compared to that of either control (86.2 ± 6.9%) or SRF (75.4 ± 4.89%) or DHA (69.4 ± 6.9%). These data provide strong evidence that LDL-mimetic lipid nanoformulations could be utilized as a biocompatible and tumor targeted platform for the delivery of multiple anticancer drugs in cancer treatment. [ABSTRACT FROM AUTHOR]