17 research outputs found

    Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma

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    Background/Aims: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1–cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms. Methods: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays were performed to determine the link between PAK1 and CREB. NSCLC xenograft models were used to study oncogenic function of PAK1 in vivo. Results: We observed that PAK1 and CREB expression levels were significantly elevated in human squamous NSCLC-tissue specimens, compared with those in adjacent normal bronchial or bronchiolar epithelial-tissue specimens, as well as their phosphorylated forms, based on western blotting. We showed in vitro that PAK1 knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133, based on western blotting. In addition, PAK1 interacted with CREB in co-immunoprecipitation assays. Additionally, our in vitro findings detected by flow cytometry revealed that PAK1 silencing attenuated cell cycle progression, inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses by modulating CREB expression and activation in xenograft models. Conclusion: These results suggest a novel mechanism whereby the PAK1–CREB axis drives carcinogenesis of squamous-cell carcinomas, and have important implications in the development of targeted therapeutics for squamous-cell lung cancer

    Assessing the Residual Stand Damage after Thinning with Different Levels of Mechanization

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    Thinning is a silvicultural process in which trees are both harvested selectively and systematically removed from a stand to enhance forest management and ecosystem dynamics. However, this practice is challenged by the mechanical damage to residual trees, and the nature of this damage, particularly on stand damage during mechanized row-thinning and manual selective thinning, in South Korea is unknown. Therefore, objectives of this study were to compare stand damage levels and wound characteristics between three different thinning operations: manual selective, manual row-, and mechanized row-thinning. After thinning, 12%, 15%, and 10% of the residual damaged trees were observed in manual selective, manual row-, and mechanized row-thinning, respectively. Both types of row-thinning predominantly demonstrated damages at the stem and butt region, whereas in manual selective thinning, the most of the damages occurred on the roots. Manual selective thinning exhibited a slightly larger average wound size (207 cm2) compared to mechanized row- (181 cm2) and manual row-thinning (165 cm2). The wound sizes on the stem in mechanized row-thinning were significantly higher than manual selective (p < 0.05). These results may be helpful in understanding exposure to damage among different thinning types and in managing its occurrence in future practices

    Transformation of ZnO Nanobelts into Single-Crystalline Mn<sub>3</sub>O<sub>4</sub> Nanowires

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    Single-crystalline Mn<sub>3</sub>O<sub>4</sub> nanowires were prepared using the vapor-phase transformation of ZnO nanobelts. Mn<sub>3</sub>O<sub>4</sub>-decorated ZnO nanobelts and ZnO–ZnMn<sub>2</sub>O<sub>4</sub> core–shell nanocables (NCs) were also obtained as reaction intermediates. Heteroepitaxial growth of tetragonal spinel Mn<sub>3</sub>O<sub>4</sub> (or ZnMn<sub>2</sub>O<sub>4</sub>) on wurtzite ZnO is a possible reason for the growth of single-crystalline Mn<sub>3</sub>O<sub>4</sub> nanowires. Growth interfaces are possibly formed between the wurtzite (101̅0)/(21̅1̅0) and spinel (1̅01)/(4̅11) planes. Various one-dimensional homonanostructures and heteronanostructures consisting of <i>n</i>-ZnO, <i>p</i>-Mn<sub>3</sub>O<sub>4</sub>, and <i>p</i>-ZnMn<sub>2</sub>O<sub>4</sub> can be used to design high-performance gas sensors

    Co-Doped Branched ZnO Nanowires for Ultraselective and Sensitive Detection of Xylene

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    Co-doped branched ZnO nanowires were prepared by multistep vapor-phase reactions for the ultraselective and sensitive detection of <i>p</i>-xylene. Highly crystalline ZnO NWs were transformed into CoO NWs by thermal evaporation of CoCl<sub>2</sub> powder at 700 °C. The Co-doped ZnO branches were grown subsequently by thermal evaporation of Zn metal powder at 500 °C using CoO NWs as catalyst. The response (resistance ratio) of the Co-doped branched ZnO NW network sensor to 5 ppm <i>p</i>-xylene at 400 °C was 19.55, which was significantly higher than those to 5 ppm toluene, C<sub>2</sub>H<sub>5</sub>OH, and other interference gases. The sensitive and selective detection of <i>p</i>-xylene, particularly distinguishing among benzene, toluene, and xylene with lower cross-responses to C<sub>2</sub>H<sub>5</sub>OH, can be attributed to the tuned catalytic activity of Co components, which induces preferential dissociation of <i>p</i>-xylene into more active species, as well as the increase of chemiresistive variation due to the abundant formation of Schottky barriers between the branches

    PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer

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    P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung cancer (NSCLC). We evaluated PAK1 mRNA and protein expression in NSCLC cells and resected tumor specimens, as well as in healthy human bronchial epithelial cells and adjacent healthy lung tissues, respectively, for effective comparison. Immunohistochemical tissue microarray analysis of 201 NSCLC specimens showed the correlation of PAK1 expression with clinicopathological characteristics. The mRNA and protein expression of PAK1 were 2.9- and 4.3-fold higher in six of seven NSCLC cell types and human tumors (both, p &lt; 0.001) than in healthy human bronchial epithelial BEAS-2B cells and adjacent healthy lung tissues, respectively. Decreased survival was significantly associated with PAK1 overexpression in the entire cohort (&chi;2 = 8.48, p = 0.0036), men (&chi;2 = 17.1, p &lt; 0.0001), and current and former smokers (&chi;2 = 19.2, p &lt; 0.0001). Notably, epidermal growth factor receptor (EGFR) mutation-positive lung cancer patients with high PAK1 expression showed higher mortality rates than those with low PAK1 expression (91.3% vs. 62.5%, p = 0.02). Therefore, PAK1 overexpression could serve as a molecular target for the treatment of EGFR mutation-positive lung cancer, especially among male patients and current/former smokers

    Enhanced Ethanol Sensing Characteristics of In<sub>2</sub>O<sub>3</sub>‑Decorated NiO Hollow Nanostructures via Modulation of Hole Accumulation Layers

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    In this work, we report a dramatic enhancement in ethanol sensing characteristics of NiO hollow nanostructures via decoration with In<sub>2</sub>O<sub>3</sub> nanoclusters. The pure NiO and 1.64–4.41 atom % In-doped NiO and In<sub>2</sub>O<sub>3</sub>-decorated NiO hollow spheres were prepared by ultrasonic spray pyrolysis, and their gas sensing characteristics were investigated. The response (the ratio between the resistance in gas and air) of the In<sub>2</sub>O<sub>3</sub>-decorated NiO hollow spheres to 5 ppm ethanol (C<sub>2</sub>H<sub>5</sub>OH) was 9.76 at 350 °C, which represents a significant improvement over the In-doped NiO and pure NiO hollow spheres (3.37 and 2.18, respectively). Furthermore, the 90% recovery time was drastically reduced from 1880 to 23 s, and a selective detection of ethanol with negligible cross-response to other gases was achieved. The enhanced gas response and fast recovery kinetics were explained in relation to the thinning of the near-surface hole accumulation layer of p-type NiO underneath n-type In<sub>2</sub>O<sub>3</sub>, the change of charge carrier concentration, and the variation of oxygen adsorption
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