The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as ...well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells.
Endoplasmic reticulum (ER) stress has been implicated in Parkinson disease. We previously reported that thioredoxin 1 (Trx-1) suppressed the ER stress caused by ...1-methy-4-phenyl-1,2,3,6-tetrahydropyridine; however, its molecular mechanism remains largely unknown. In the present study, we showed that 1-methyl-4-phenylpyridinium ion (MPP+) induced ER stress by activating glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinase (JNK), caspase-12, and C/EBP homologous protein (CHOP) in PC12 cells. The downregulation of Trx-1 aggravated the ER stress and further increased the expression of the above molecules induced by MPP+. In contrast, overexpression of Trx-1 attenuated the ER stress and repressed the expression of the above molecules induced by MPP+. More importantly, the overexpression of Trx-1 in transgenic mice suppressed ER stress by inhibiting the activation of these molecules. We present, for the first time, the molecular mechanism of Trx-1 suppression of endoplasmic reticulum stress in Parkinson disease in vitro and in vivo. Based on our findings, we conclude that Trx-1 plays a neuroprotective role in Parkinson disease by suppressing ER stress by regulating the activation of GRP78, IRE1α, TRAF2, JNK, caspase-12, and CHOP.
•MPP+/MPTP induces ER stress by activating GRP78, IRE1α, TRAF2, JNK, caspase-12, and CHOP.•Trx-1 knockdown aggravates the MPP+-induced ER stress.•Trx-1 overexpression attenuates the MPP+/MPTP-induced ER stress.•Trx-1 play a neuroprotective role in Parkinson disease.
Conventionally, Chopped Strand Mat (CSM) and Woven Roving Mat (WRM) fabrics are combined to manufacture Glass Fiber Reinforced Polymer (GFRP) laminate structures for small vessels, such as fishing ...boats and yachts, according to established practical experience and traditional methods rather than the application of elaborate design rules. Combinations of the aforementioned fabrics positively contribute to improve the strength of hull structures. In this study, effects of fabric combination types on the quality of GFRP structures such as hull plates are quantitatively verified through experiments and statistical analysis. The results confirm the following: (1) hull plates fabricated by combining CSM and WRM exhibit enhanced strength in the normal glass fiber weight fraction (Gc) regions with an E-glass fiber content of 30–50%, and (2) the effect of reducing the amount of decrease in the strength is observed in high-Gc regions with an E-glass fiber content of 50% or higher. Furthermore, a combination of these fabrics demonstrated a significant effect in improving the quality of the composite laminates owing to a reduction in void defects in the hull plates.
Metallic nano-structures in micro-cavity organic light emitting diode (OLED) can significantly enhance light out-coupling efficiency. Nevertheless, they are not widely accepted in conventional ...devices due to its complicated process and increased manufacturing cost. In this study, we demonstrate a production-ready alternative for increasing the efficiency of OLEDs by implementing thermal-assisted self-aggregated metallic nanoparticles (NPs). Silver NPs are fabricated by thermal annealing of vacuum deposited thin silver layer without any complicated process, which is easily scalable in large area with low cost. Theoretical calculation and dark field microscopy image indicate that these stochastic Ag NPs provide light scattering in broad range. By incorporating Ag NPs to OLED with micro-cavity structure, 11% improvement in the external quantum efficiency was obtained without deteriorating viewing angle.
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•Stochastic thermal assisted self-aggregated silver nano particles in OLEDs.•Scattering effect of TSA-Ag NPs in broad range of visible light.•OLEDs employing TSA-Ag NPs exhibit enhanced out-coupling efficiency.•Suppression of angular dependence of micro-cavity OLEDs by employing randomly distributed silver NPs.
The reduction of the interlayer in hybrid white organic light-emitting diodes (WOLEDs) provides a potential for improving the device efficiency. Reported herein are non-interlayer hybrid WOLEDs ...prepared using a mixed host for the blue-fluorescent-emitting layer. The proposed device exhibits high efficiency with the maximum external quantum efficiency up to 17.1%, and stable colors. Moreover, the effect of the interlayer on the device lifetime was demonstrated.
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•Composite film of MoO3 and PEDOT:PSS as an efficient HIL in PLED.•MoO3 mixed PEDOT:PSS enhances hole injection with reduced resistance.•PLEDs using MoO3 mixed PEDOT:PSS as a HIL ...exhibit improved performances and lifetime.
We demonstrate improved performances in polymer light-emitting diodes (PLEDs) using a composite film of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and MoO3 powder as a hole injection layer. The PLED with the composite film exhibits the current efficiency of 13.5cd/A, driving voltage of 3.4V, and half lifetime of 108.1h, while those values of the PLED with a pristine PEDOT:PSS was 11.3cd/A, 3.8V, and 41.5h, respectively. We also analyze the morphological, optical and electrical properties of the composite films by atomic force microscopy (AFM), UV–Vis-IR absorption, and ultraviolet photoemission spectroscopy (UPS). This work suggests that mixing MoO3 into PEDOT:PSS is a simple and promising technique for use solution-based devices as an hole injection layer.
Interactions between proteins are fundamental for every biological process and especially important in cell signaling pathways. Biochemical techniques that evaluate these protein-protein interactions ...(PPIs), such as in vitro pull downs and coimmunoprecipitations, have become popular in most laboratories and are essential to identify and validate novel protein binding partners. Most PPIs occur through small domains or motifs, which are challenging and laborious to map by using standard biochemical approaches because they generally require the cloning of several truncation mutants. Moreover, these classical methodologies provide limited resolution of the interacting interface. Here, we describe the development of an alternative technique to overcome these limitations termed "Protein Domain mapping using Yeast 2 Hybrid-Next Generation Sequencing" (DoMY-Seq), which leverages both yeast two-hybrid and next-generation sequencing techniques. In brief, our approach involves creating a library of fragments derived from an open reading frame of interest and enriching for the interacting fragments using a yeast two-hybrid reporter system. Next-generation sequencing is then subsequently employed to read and map the sequence of the interacting fragment, yielding a high-resolution plot of the binding interface. We optimized DoMY-Seq by taking advantage of the well-described and high-affinity interaction between KRAS and CRAF, and we provide high-resolution domain mapping on this and other protein-interacting pairs, including CRAF-MEK1, RIT1-RGL3, and p53-MDM2. Thus, DoMY-Seq provides an unbiased alternative method to rapidly identify the domains involved in PPIs by advancing the use of yeast two-hybrid technology.
Interactions between proteins are fundamental for every biological process and especially important in cell signaling pathways. Biochemical techniques that evaluate these protein–protein interactions ...(PPIs), such as in vitro pull downs and coimmunoprecipitations, have become popular in most laboratories and are essential to identify and validate novel protein binding partners. Most PPIs occur through small domains or motifs, which are challenging and laborious to map by using standard biochemical approaches because they generally require the cloning of several truncation mutants. Moreover, these classical methodologies provide limited resolution of the interacting interface. Here, we describe the development of an alternative technique to overcome these limitations termed “Protein Domain mapping using Yeast 2 Hybrid-Next Generation Sequencing” (DoMY-Seq), which leverages both yeast two-hybrid and next-generation sequencing techniques. In brief, our approach involves creating a library of fragments derived from an open reading frame of interest and enriching for the interacting fragments using a yeast two-hybrid reporter system. Next-generation sequencing is then subsequently employed to read and map the sequence of the interacting fragment, yielding a high-resolution plot of the binding interface. We optimized DoMY-Seq by taking advantage of the well-described and high-affinity interaction between KRAS and CRAF, and we provide high-resolution domain mapping on this and other protein-interacting pairs, including CRAF-MEK1, RIT1-RGL3, and p53-MDM2. Thus, DoMY-Seq provides an unbiased alternative method to rapidly identify the domains involved in PPIs by advancing the use of yeast two-hybrid technology.
We demonstrate enhanced light out-coupling efficiency of organic light-emitting diodes by applying a multilayer stacked electrode structure consisting of fast and cost-effective sol-gel processed ...tantalum pentoxide (Ta2O5), thin layer of Au and molybdenum trioxide (MoO3). The application of the Ta2O5/Au/MoO3 electrode can modulate the optical characteristics of the device due to the optical microcavity effect. The refractive index of the sol-gel processed Ta2O5 thin film varied depending on the annealing temperature and reached a maximum at 400 °C (n = 2.2 at 512 nm). The influence of the refractive index of the Ta2O5 layer and the thickness of the multilayer electrode stack on the optical microcavity effect was systematically investigated. The device with the Ta2O5/Au/MoO3 electrode, fabricated at an optimum condition based on the simulation result by calculating the photon flux, exhibited 52% enhancement in light out-coupling efficiency at 1000 cd/m2 and improved color stability with the viewing angle, having near-Lambertian emission.
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