Apparently healthy adults with high serum gamma-glutamyl transferase levels are at increased risk of asthma development in the near future: a Korean nationwide cohort study.

OBJECTIVE: Serum gamma-glutamyl transferase (GGT), an indicator of oxidative stress and/or a chronic inflammatory process, is associated with the levels of leukotrienes and other inflammatory mediators that play a critical role in the pathogenesis of asthma. This study aimed at investigating whether apparently healthy subjects with higher serum GGT levels at a national health check-up are at an increased risk of developing asthma in the near future. PATIENTS AND METHODS: We analyzed 564,213 Korean adults, aged 20-80 years who underwent a national general health examination, including measurement of baseline serum GGT between 2003 and 2015, using data from a large-scale representative cohort of the Korean population. Data were analyzed using a Cox proportional hazards regression analysis. RESULTS: In total, 516,956 participants were included in the final analysis. During the mean follow-up period of 8 years (standard deviation, 4.0), 7,439 incident asthma events occurred. We then classified the male and female participants according to quartiles of blood GGT levels (males: ≤ 20, 21-30, 31-51, and ≥ 52 IU/L; females: ≤ 12, 13-16, 17-22, and ≥ 23 IU/L, respectively). The adjusted hazard ratio (aHR) for incident asthma was significantly greater for subjects in the highest GGT quartile than for those in the lowest GGT quartile (aHR, 1.47; 95% confidence intervals, 1.36-1.59). Further, there was a significant linear trend across quartiles with regard to asthma (ptrend<0.001). We estimated the optimal cut-off values (using the minimum p-value approach) as 35 IU/L for the total population, 35 IU/L for males, and 36 IU/L for females, respectively. CONCLUSIONS: Clinicians should be aware of the risk of incident asthma in healthy subjects with elevated GGT levels. Our findings advance our understanding of asthma pathogenesis.

Quality characteristics of yogurts fermented with short-chain fatty acid-producing probiotics and their effects on mucin production and probiotic adhesion onto human colon epithelial cells.

Probiotics can ferment nondigestible carbohydrates and produce short-chain fatty acids (SCFA; acetate, propionate, and butyrate) in the human colon. In this study, the levels of SCFA were determined in the following yogurts fermented with different combinations of probiotics: (1) cocultures of Streptococcus thermophilus and Lactobacillus bulgaricus (control, C); (2) S. thermophilus, L. bulgaricus, and Bifidobacterium bifidum (C-Bb); (3) S. thermophilus, L. bulgaricus, and Lactobacillus acidophilus (C-La); and (4) S. thermophilus, L. bulgaricus, and Lactobacillus gasseri (C-Lg). Results showed that the acetate levels were significantly higher in C-Bb, C-La, and C-Lg yogurts than in C yogurt. Fermentation and physicochemical characteristics of all yogurts were identical. Treatment of mucus-secreting colon epithelial cells (HT29-MTX) with C-Bb, C-La, and C-Lg yogurt supernatants resulted in an increase in the expression of MUC2 and CDX2 and the production of mucin proteins. The adhesion of probiotics onto HT29-MTX cells increased following treatment with C-Bb, C-La, and C-Lg yogurt supernatants. Our data suggest that a yogurt diet rich in acetate improves the protective function of the intestinal epithelium.

Measurement of circulating tumor cells in squamous cell carcinoma of the head and neck and patient outcomes.

OBJECTIVES: We report the outcomes of patients with squamous cell carcinoma of the head and neck (HNSCC) whose circulating tumor cells (CTCs) were quantified using surface-enhanced Raman scattering (SERS) nanotechnology. METHODS: SERS tagged with EGF was used to directly measure targeted CTCs. Patient charts were retrospectively reviewed. An optimal cut point for CTCs in 7.5 ml of peripheral blood predictive of for distant metastasis-free survival (DMFS) was identified by maximizing the log-rank statistic. An ROC analysis was also performed. RESULTS: Of 82 patients, 13 experienced metastatic progression. The optimal cut point for DMFS was 675 CTCs (p = 0.047). For those with distant recurrence (n = 13) versus those without distant recurrence (n = 69), the CTC cut point which results in the largest combined sensitivity and specificity values is also 675 (sensitivity = 69%, specificity = 68%). CONCLUSION: Liquid biopsy techniques in HNSCC show promise as a means of identifying patients at greater risk of disease progression.

Cardiovascular risk in fire academy instructors during live-fire simulation activity.

Firefighting is an extreme occupation with a risk of cardiovascular disease and sudden cardiac death due to strenuous physical exertion and psychological stress during fire suppression activity. This study aimed to investigate the vital signs (hemodynamic status) and biomarkers related to cardiac disease during live firefighting activity. In this pilot case-controlled study, seven firefighting training instructors performed a live-fire simulation for 40 min in a multi-storey training tower at the Gyenoggi-do Fire Service Academy Institute. Seven participants in the control group undertook similar exercises while wearing personal protective equipment. Cardiovascular evaluation, including vital signs and related biomarkers, was done before and after simulation until 24 h later. Nonparametric statistics were used to compare between the two groups and within the simulation group. After live-fire simulation, pulse pressure, heart rate (HR) and body temperature (BT) in the simulation group were higher than in the control group (pulse pressure 74.6 mmHg vs. 53.3 mmHg, HR 110 beats per minute (bpm) vs. 77 bpm, and BT 37.6 °C vs. 36.0 °C, P < 0.05 for all). Inflammatory cytokines (IL- 6), coagulation protein (fibrinogen), and stress hormones (cortisol, adrenocorticotrophic hormone) were elevated immediately after live-fire simulation, and IL-6 and fibrinogen remained elevated until 24 h after the simulation (all P < 0.05). Our exploratory analysis found increased altered hemodynamic status and stress-related biomarkers in live-fire firefighting simulations compared to controls. These markers have the potential to be used to decrease cardiovascular risk for firefighters, and warrant further investigation.

L'attaque de feu est une activité épuisante physiquement et psychologiquement stressante augmentant le risque cardio-vasculaire dont la mort subite. Cette étude pilote cas-témoin avait pour but d'étudier l'état hémodynamique et les biomarqueurs de pathologie cardiaque pendant l'attaque de feu. Elle a été menée sur 7 instructeurs de l'institut de formation du service d'incendie de la province de Gyenoggi-do, pendant un exercice de 40 mn en conditions réelles dans la tour d'entraînement. Le groupe contrôle effectuait un effort similaire, avec la même tenue, hors incendie. Les évaluations clinique et biologique étaient réalisées préalablement puis pendant 24 h. Des tests non paramétriques ont été utilisés pour les comparaisons entre groupes et au sein des groupes. En conditions réelles, la température corporelle (37,6/36°C), la PAM (74,6/53,3) et la fréquence cardiaque (110/77) étaient statistiquement plus élevées (p<0,05) que dans le groupe contrôle. De la même manière, IL6, fibrinogène, cortisol et ACTH étaient plus élevées en conditions réelles, IL6 et fibrinogène restant élevés à h24. L'élévation de ces marqueurs cliniques et biologiques de risque cardio-vasculaire et de stress nécessitent une étude plus poussée avant leur utilisation éventuelle pour évaluer la prévention.

Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis.

Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis. We demonstrate that LDHA is phosphorylated at tyrosine 10 by upstream kinases, HER2 and Src. Targeting HER2 or Src attenuated LDH activity as well as invasive potential in head and neck cancer and breast cancer cells. Inhibition of LDH activity by small hairpin ribonucleic acid or expression of phospho-deficient LDHA Y10F sensitized the cancer cells to anoikis induction and resulted in attenuated cell invasion and elevated reactive oxygen species, whereas such phenotypes were reversed by its product lactate or antioxidant N-acetylcysteine, suggesting that Y10 phosphorylation-mediated LDHA activity promotes cancer cell invasion and anoikis resistance through redox homeostasis. In addition, LDHA knockdown or LDHA Y10F rescue expression in human cancer cells resulted in decreased tumour metastasis in xenograft mice. Furthermore, LDHA phosphorylation at Y10 positively correlated with progression of metastatic breast cancer in clinical patient tumour samples. Our findings demonstrate that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers.

Precise observation of C. elegans dynamic behaviours under controlled thermal stimulus using a mobile phone-based microscope.

We investigated the temperature-dependent locomotion of Caenorhabditis elegans by using the mobile phone-based microscope. We developed the customized imaging system with mini incubator and smartphone to effectively control the thermal stimulation for precisely observing the temperature-dependent locomotory behaviours of C. elegans. Using the mobile phone-based microscope, we successfully followed the long-term progress of specimens of C. elegans in real time as they hatched and explored their temperature-dependent locomotory behaviour. We are convinced that the mobile phone-based microscope is a useful device for real time and long-term observations of biological samples during incubation, and can make it possible to carry out live observations via wireless communications regardless of location. In addition, this microscope has the potential for widespread use owing to its low cost and compact design.

Enhanced Th2 cell differentiation and function in the absence of Nox2.

BACKGROUND: Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models. METHODS: Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2-deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells. RESULTS: Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production. CONCLUSION: Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner.

The Synthesis and Properties of Solution Processable a Red Phosphorescent Iridium(III) Complex with Alkyl Group.

The (TMP-HT)2Ir(acac) was synthesized with 2-bromo-4-(trifluoromethyl)pyridine and 5-hexyl-2-thiopheneboronic acid pinacol ester for organic light-emitting diodes (OLEDs). This material was designed on the basis of Gaussian modeling program results. The ligands have both the electron donor and acceptor in a molecule. There are pyridyl group which decrease electron density and thiophene group which increase electron density. Therefore, it showed intramolecular charge transfer (ICT) property. For solution process, the ligand have a alkyl group which has hydrophobic property. The (TMP-HT)21r(acac) was synthesized by Suzuki coupling reaction and Nonoyama reaction. The (TMP-HT)21r(acac) emitted at approximately 600 nm. The device structures were ITO/PEDOT (500 Å)/TFB (170 Å)/PVK:PBD (40%): (TMPHT)21r(acac) (300 Å:10%)/BH:BD5% (150 Å)/L201(50 Å)/Liq(200 Å)/Al. Electroluminescent properties were observed with devices doped with various doping concentrations.

RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis.

Metastasis is responsible for >90% of cancer-related deaths. Complex signaling in cancer cells orchestrates the progression from a primary to a metastatic cancer. However, the mechanisms of these cellular changes remain elusive. We previously demonstrated that p90 ribosomal S6 kinase 2 (RSK2) promotes tumor metastasis. Here we investigated the role of RSK2 in the regulation of microtubule dynamics and its potential implication in cancer cell invasion and tumor metastasis. Stable knockdown of RSK2 disrupted microtubule stability and decreased phosphorylation of stathmin, a microtubule-destabilizing protein, at serine 16 in metastatic human cancer cells. We found that RSK2 directly binds and phosphorylates stathmin at the leading edge of cancer cells. Phosphorylation of stathmin by RSK2 reduced stathmin-mediated microtubule depolymerization. Moreover, overexpression of phospho-mimetic mutant stathmin S16D significantly rescued the decreased invasive and metastatic potential mediated by RSK2 knockdown in vitro and in vivo. Furthermore, stathmin phosphorylation positively correlated with RSK2 expression and metastatic cancer progression in primary patient tumor samples. Our finding demonstrates that RSK2 directly phosphorylates stathmin and regulates microtubule polymerization to provide a pro-invasive and pro-metastatic advantage to cancer cells. Therefore, the RSK2-stathmin pathway represents a promising therapeutic target and a prognostic marker for metastatic human cancers.

Hypotonic stress induces RANKL via transient receptor potential melastatin 3 (TRPM3) and vaniloid 4 (TRPV4) in human PDL cells.

Bone remodeling occurs in response to various types of mechanical stress. The periodontal ligament (PDL) plays an important role in mechanical stress-mediated alveolar bone remodeling. However, the underlying mechanism at the cellular level has not been extensively studied. In this study, we investigated the effect of shear stress on the expression of bone remodeling factors, including receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and osteoprotegerin (OPG), as well as its upstream signaling pathway in primary human PDL cells. We applied hypotonic stress to reproduce shear stress to PDL cells. Hypotonic stress induced the messenger RNA (mRNA) and protein expression of RANKL but not OPG. It also increased intracellular Ca(2+) concentration ([Ca(2+)]i). Extracellular Ca(2+) depletion and nonspecific plasma membrane Ca(2+) channel blockers completely inhibited the increase in both [Ca(2+)]i and RANKL mRNA expression. We identified the expression and activation of transient receptor potential melastatin 3 (TRPM3) and vaniloid 4 (TRPV4) channels in PDL cells. Pregnenolone sulfate (PS) and 4α-phorbol 12, 13-didecanoate (4α-PDD), which are agonists of TRPM3 and TRPV4, augmented Ca(2+) influx and RANKL mRNA expression. Both pharmacological (2-aminoethoxydiphenyl borate [2-APB], ruthenium red [RR], ononetin [Ono], and HC 067047 [HC]) and genetic (small interfering RNA [siRNA]) inhibitors of TRPM3 and TRPV4 reduced the hypotonic stress-mediated increase in [Ca(2+)]i and RANKL mRNA expression. Our study shows that hypotonic stress induced RANKL mRNA expression via TRPM3- and TRPV4-mediated extracellular Ca(2+) influx and RANKL expression. This signaling pathway in PDL cells may play a critical role in mechanical stress-mediated alveolar bone remodeling.

Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis.

Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate.

The concept that adult tissue, including bone marrow (BM), contains early-development cells with broader differentiation potential has again been recently challenged. In response, we would like to review the accumulated evidence from several independent laboratories that adult tissues, including BM, harbor a population of very rare stem cells that may cross germ layers in their differentiation potential. Thus, the BM stem cell compartment hierarchy needs to be revisited. These dormant, early-development cells that our group described as very small embryonic-like stem cells (VSELs) most likely overlap with similar populations of stem cells that have been identified in adult tissues by other investigators as the result of various experimental strategies and have been given various names. As reported, murine VSELs have some pluripotent stem cell characteristics. Moreover, they display several epiblast/germline markers that suggest their embryonic origin and developmental deposition in adult BM. Moreover, at the molecular level, changes in expression of parentally imprinted genes (for example, Igf2-H19) and resistance to insulin/insulin-like growth factor signaling (IIS) regulates their quiescent state in adult tissues. In several emergency situations related to organ damage, VSELs can be activated and mobilized into peripheral blood, and in appropriate animal models they contribute to tissue organ/regeneration. Interestingly, their number correlates with lifespan in mice, and they may also be involved in some malignancies. VSELs have been successfully isolated in several laboratories; however, some investigators experience problems with their isolation.

Effect of reactive monomer on PS-b-P2VP film.

Poly(styrene-b-2-vinyl pyridine) (PS-b-P2VP) lamellar film which is hydrophobic block-hydrophilic polyelectrolyte block polymer of 52 kg/mol-b-57 kg/mol and PS-b-P2VP film with reactive monomer (RM257) were prepared for photonic gel films. The lamellar stacks, which is alternating layer of hydrophilic and hydrophobic moiety of PS-b-P2VP, were obtained by exposing the spin coated film under chloroform vapor. The lamellar films were quaternized with 5 wt% of iodomethane diluted by n-hexane. We reported about the influence of reactive monomer on those photonic gel films. Added reactive monomer photonic gel film had higher absorbance than pure photonic gel films. As a result the photonic gel film with RM had more clear color. The lamellar films were swollen by DI water, ethanol (aq) and calcium carbonate solution. The band gaps of the lamellar films were drastically shifted to longer wavelength swollen by calcium carbonate solution. And the lamellar films were shifted to shorter wave length swollen by ethanol. So each lamellar film showed different color.

A phase 1 Bayesian dose selection study of bortezomib and sunitinib in patients with refractory solid tumor malignancies.

BACKGROUND: This phase 1 trial utilising a Bayesian continual reassessment method evaluated bortezomib and sunitinib to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended doses of the combination. METHODS: Patients with advanced solid organ malignancies were enrolled and received bortezomib weekly with sunitinib daily for 4 weeks, every 6 weeks. Initial doses were sunitinib 25 mg and bortezomib 1 mg m(-2). Cohort size and dose level estimation was performed utilising the Escalation with Overdose Control (EWOC) adaptive method. Seven dose levels were evaluated; initially, sunitinib was increased to a goal dose of 50 mg with fixed bortezomib, then bortezomib was increased. Efficacy assessment occurred after each cycle using RECIST criteria. RESULTS: Thirty patients were evaluable. During sunitinib escalation, DLTs of grade 4 thrombocytopenia (14%) and neutropenia (6%) at sunitinib 50 mg and bortezomib 1.3 mg m(-2) were seen. Subsequent experience showed tolerability and activity for sunitinib 37.5 mg and bortezomib 1.9 mg m(-2). Common grade 3/4 toxicities were neutropenia, thrombocytopenia, hypertension, and diarrhoea. The recommended doses for further study are bortezomib 1.9 mg m(-2) and sunitinib 37.5 mg. Four partial responses were seen. Stable disease >6 months was noted in an additional six patients. CONCLUSION: Bortezomib and sunitinib are well tolerated and have anticancer activity, particularly in thyroid cancer. A phase 2 study of this combination in thyroid cancer patients is planned.

Parental imprinting regulates insulin-like growth factor signaling: a Rosetta Stone for understanding the biology of pluripotent stem cells, aging and cancerogenesis.

In recent years, solid evidence has accumulated that insulin-like growth factor-1 (IGF-1) and 2 (IGF-2) regulate many biological processes in normal and malignant cells. Recently, more light has been shed on the epigenetic mechanisms regulating expression of genes involved in IGF signaling (IFS) and it has become evident that these mechanisms are crucial for initiation of embryogenesis, maintaining the quiescence of pluripotent stem cells deposited in adult tissues (for example, very-small embryonic-like stem cells), the aging process, and the malignant transformation of cells. The expression of several genes involved in IFS is regulated at the epigenetic level by imprinting/methylation within differentially methylated regions (DMRs), which regulate their expression from paternal or maternal chromosomes. The most important role in the regulation of IFS gene expression is played by the Igf-2-H19 locus, which encodes the autocrine/paracrine mitogen IGF-2 and the H19 gene, which gives rise to a non-coding RNA precursor of several microRNAs that negatively affect cell proliferation. Among these, miR-675 has recently been demonstrated to downregulate expression of the IGF-1 receptor. The proper imprinting of DMRs at the Igf-2-H19 locus, with methylation of the paternal chromosome and a lack of methylation on the maternal chromosome, regulates expression of these genes so that Igf-2 is transcribed only from the paternal chromosome and H19 (including miR-675) only from the maternal chromosome. In this review, we will discuss the relevance of (i) proper somatic imprinting, (ii) erasure of imprinting and (iii) loss of imprinting within the DMRs at the Igf-2-H19 locus to the expression of genes involved in IFS, and the consequences of these alternative patterns of imprinting for stem cell biology.

N-(phosphonacetyl)-L-aspartate induces TAp73-dependent apoptosis by modulating multiple Bcl-2 proteins: potential for cancer therapy.

p53 is essential for the cellular responses to DNA damage that help to maintain genomic stability. However, the great majority of human cancers undergo disruption of the p53-network. Identification and characterization of molecular components important in both p53-dependent and -independent apoptosis might be useful in developing novel therapies for cancers. In the complete absence of p53, cells treated with N-(phosphonacetyl)-L-aspartate (PALA) continue to synthesize DNA slowly and eventually progress through S-phase, suffering severe DNA damage that in turn triggers apoptosis, whereas cells with functional p53 undergo growth arrest. In this study, we investigated apoptotic signaling in response to PALA and the role of p53 expression in this pathway. We found that treatment of cells lacking p53 with PALA induced TAp73, Noxa and Bim and inactivation of these proteins with dominant-negative plasmids or small interfering RNAs significantly inhibited apoptosis, suggesting that PALA-induced apoptosis was mediated via TAp73-dependent expression of Noxa and Bim. However, PALA treatment inhibited the expression of ΔNp73 only in cells lacking p53 but not in cells expressing p53. In addition, PALA treatment inhibited Bcl-2, and overexpression of Bcl-2 significantly inhibited PALA-induced apoptosis. Moreover, expression of p53 in these cells protected them from PALA-induced apoptosis by activating p21, sustaining the expression of ΔNp73 and inhibiting the induction of Noxa and Bim. Taken together, our study identifies novel but opposing roles for the p53 and TAp73 in the induction of Noxa and Bim and regulation of apoptosis. Our data will help to develop strategies to eliminate cancer cells lacking p53 while protecting normal cells with wild-type p53.

A study on white organic light-emitting diodes co-doped with red fluorescent and blue phosphorescent dopants.

White organic light-emitting diodes (WOLEDs) have drawn increasing attention due to their potential use in various applications such as solid-state lighting and backlight of liquid crystal displays and full-color OLEDs of red, green, and blue pixel. N,N'-dicabazolyl-3,5-benzene (mCP), the host material, was co-doped with Iridium (III) bis[(4,6-difluorophenyl)-pyridinato-N,C2']-picolinate (FIrpic), which functions not only as phosphorescent sensitizer but also blue emitter, and (2Z,2'Z)-3,3'-[4,4"-bis (dimethylamino)-1,1':4',1"-terphenyl-2',5'-diyl]bis (2-phenylacrylonitrile) (ABCV-P), which is a red fluorescent material. The fabricated device structures were as follows: (device A) Indium tin oxide (ITO)/N,N'-bis-(1-naphyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine (NPB)/(mCP)/mCP:ABCV-P (1%)/4,7-diphenyl-1,10-phenanthroline (Bphen)/lithium quinolate (Liq)/aluminum (Al), (device B) ITO/NPB/mCP/mCP:FIrpic (8%)/Bphen/Liq/Al and (device C) ITO/NPB/mCP/mCP:FIrpic:ABCV-P (8%, 1%)/Bphen/Liq/Al, respectively. Phosphorescent FIrpic harvesting both singlet and triplet excitions not only emitted blue light but also transferred energy to fluorescent ABCV-P. The maximum luminance efficiency, external quantum efficiency, and luminance of white light device were measured to be 5.95 cd/A, 2.45% and 2500 cd/m2, respectively. The white device gave practically white light with the Commision Internationale de l'Eclairage (CIE(xy)) coordinate of (0.44, 0.49) which was close to warm white color (CIE(xy) = 0.45, 0.45).

EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis.

Epithelial-mesenchymal transition (EMT) is a crucial mechanism for the acquisition of migratory and invasive capabilities by epithelial cancer cells. By conducting quantitative proteomics in experimental models of human prostate cancer (PCa) metastasis, we observed strikingly decreased expression of EPLIN (epithelial protein lost in neoplasm; or LIM domain and actin binding 1, LIMA-1) upon EMT. Biochemical and functional analyses demonstrated that EPLIN is a negative regulator of EMT and invasiveness in PCa cells. EPLIN depletion resulted in the disassembly of adherens junctions, structurally distinct actin remodeling and activation of ß-catenin signaling. Microarray expression analysis identified a subset of putative EPLIN target genes associated with EMT, invasion and metastasis. By immunohistochemistry, EPLIN downregulation was also demonstrated in lymph node metastases of human solid tumors including PCa, breast cancer, colorectal cancer and squamous cell carcinoma of the head and neck. This study reveals a novel molecular mechanism for converting cancer cells into a highly invasive and malignant form, and has important implications in prognosis and treating metastasis at early stages.