Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis

Objectives: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. Design: Tumours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription-quantitative real-time PCR (RT-PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplodeficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. Results: TonEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter. Conclusions: TonEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker

Selective Area Band Engineering of Graphene using Cobalt-Mediated Oxidation

This study reports a scalable and economical method to open a band gap in single layer graphene by deposition of cobalt metal on its surface using physical vapor deposition in high vacuum. At low cobalt thickness, clusters form at impurity sites on the graphene without etching or damaging the graphene. When exposed to oxygen at room temperature, oxygen functional groups form in proportion to the cobalt thickness that modify the graphene band structure. Cobalt/Graphene resulting from this treatment can support a band gap of 0.30 eV, while remaining largely undamaged to preserve its structural and electrical properties. A mechanism of cobalt-mediated band opening is proposed as a two-step process starting with charge transfer from metal to graphene, followed by formation of oxides where cobalt has been deposited. Contributions from the formation of both CoO and oxygen functional groups on graphene affect the electronic structure to open a band gap. This study demonstrates that cobalt-mediated oxidation is a viable method to introduce a band gap into graphene at room temperature that could be applicable in electronics applications

Self-Ordering Properties of Functionalized Acenes for Annealing-Free Organic Thin Film Transistors

Presented here is a study of the molecular self-ordering properties of four bis­(phenylethynyl) anthracene based organic semiconductors related to their electronic structure employing X-ray spectroscopy techniques and density functional theory (DFT) calculations. The local molecular order through polarization dependence of C 1<i>s</i> → π* transitions revealed ordered π-stacking nearly perpendicular to the substrate due to van der Waals interactions between alkyl groups. DFT calculations were used to deconvolute the measured electronic structure and examine effects of small changes in molecular geometry in relation to measured charge carrier mobility in top contact field effect transistors. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are found to be conjugated from the anthracene core across the bridging ethynyl groups to the thiophene and phenyl end groups. The inclusion of ethynyl bridges connecting the thiophenes has a twofold effect of both reducing the rotational freedom of this functional group and increasing HOMO/LUMO conjugation across the molecules. These features help create a more rigid upright structure for HB-ant-THT with better molecular orbital conjugation and subsequent higher mobility. With this understanding of how different functional groups interact with an acene core, future synthesis of new materials may be directed toward annealing-free organic semiconducting materials

A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles

Here, we present a novel model to predict the toxicity and bioavailability of polychlorinated biphenyls (PCBs) as model compounds based on a first principles approach targeting basic electronic characteristics. The predictive model is based on an initio density functional theory. The model suggests HOMO-LUMO energy gap as the overarching indicator of PCBs toxicity, which was shown to be the primary factor predicting toxicity, but not the only factor. The model clearly explains why chlorination of both para positions is required for maximum toxic potency. To rank toxic potency, the dipole moment in relation to the most chemically active Cl-sites was critical. This finding was consistent with the accepted toxic equivalency factor (TEF) model for these molecules, and was also able to improve on ranking toxic potency of PCBs with similar TEFs. Predictions of HOMO-LUMO gap made with the model were consistent with measured values determined by synchrotron based X-ray spectroscopy for a subset of PCBs. HOMO-LUMO gap can also be used to predict bioaccumulation of PCBs. Overall, the new model provides an in silico method to screen a wide range of chemicals to predict their toxicity and bioavailability to act as an AhR agonist

Species- and tissue-specific bioaccumulation of arsenicals in various aquatic organisms from a highly industrialized area in the Pohang City, Korea

Contamination of water and sediment with arsenic (As) in a highly industrialized area of Pohang City, Korea was investigated, with emphasis on in situ bioaccumulation of arsenicals by various aquatic organisms. Species- and tissue-specific concentrations of arsenicals were determined by use of HPLC-ICP/MS and ??-X-ray absorption near-edge structure (??-XANES). Concentrations of arsenic in aquatic organisms were strongly associated with corresponding water concentrations, which indicates point sources associated with land use and activities. Arsenobetaine was the most dominant form of arsenic found in fishes, bivalves, crabs, and shrimps, while AsIII was predominant in freshwater snails. The ??-XANES analysis provided additional information about the unidentified arsenicals such as As-thiol. Arsenicals were mainly localized in intestine of mullet and marsh clam. Distribution and bioaccumulation of arsenic were strongly correlated with salinity, which indicates that natural processes controlling biogeochemistry of arsenic would be important in estuarine lotic system.close0

Universal Temperature Crossover Behavior of Electrical Conductance in a Single Oligothiophene Molecular Wire

We have observed and analyzed a universal temperature crossover behavior of electrical conductance in a single oligothiophene molecular wire. The crossover between the Arrhenius-type temperature dependence at high temperature and the temperature-invariant behavior at low temperature is found at a critical molecular wire length of 5.6 nm, where we found a change from the exponential length dependence to the length-invariant behavior. We have derived a scaling function analysis for the origin of the crossover behavior. After assuring that the analysis fits the explanation of the Keldysh Green’s function calculation for the temperature dependence, we have applied it to our experimental results and found successfully that our scaling function gives a universal description of the temperature dependence for all over the temperature range

Impact of sputtered ZnO interfacial layer on the S-curve in conjugated polymer/fullerene based-inverted organic solar cells

The impact of crystalline structure changes of sputtered ZnO interfacial layer on performances of inverted organic solar cells (OSCs) has been investigated. We find that the structural modification of the ZnO cathode interfacial layer, obtained by thermal annealing, plays a crucial role in the origin and solving of the S-curve in conjugated polymer/fullerene photovoltaics. Our results show that the crystallization (i.e. crystallites size) of poly(3hexylthiophene) (P3HT) evolves as a function of that of ZnO according to the annealing temperature. This evolution can directly impact the interfacial orientation and organization of the chains of P3HT at the ZnO buried interface. Such an ordered profile favors the vertical phase segregation and raises the carrier mobility, which explains the disappearance of the S-shape observed in current density-voltage device characteristics for annealing temperatures above 200 degrees C. These results adequately address recent research and provide an important insight into the interfacial layers of inverted OSCs. (C) 2014 Elsevier B.V. All rights reserved

Control of Reversible Self-Bending Behavior in Responsive Janus Microstrips

Here, we demonstrate a simple method to systematically control the responsive self-bending behavior of Janus hydrogel microstrips consisting of a polymeric bilayer with a high modulus contrast. The Janus hydrogel microstrips could be easily fabricated by a simple micromolding technique combined with an initiated chemical vapor deposition (iCVD) coating, providing high flexibility in controlling the physical and chemical properties of the microstrips. The fabricated Janus hydrogel microstrip is composed of a soft, pH-responsive polymer hydrogel layer laminated with a highly cross-linked, rigid thin film, generating a geometric anisotropy at a micron scale. The large difference in the elastic moduli between the two layers of the Janus microstrips leads to a self-bending behavior in response to the pH change. More specifically, the impact of the physical and chemical properties of the microstrip on the self-bending phenomena was systematically investigated by changing the thickness and composition of two layers of the microstrip, which renders high controllability in bending of the microstrips. The curvature of the Janus microstrips, formed by self-bending, highly depends on the applied acidity. A reversible, responsive self-bending/unbending exhibits a perfect resilience pattern with repeated changes in pH for 5 cycles. We envision that the Janus microstrips can be engineered to form complex 3D microstructures applicable to various fields such as soft robotics, scaffolds, and drug delivery. The reliable responsive behaviors obtained from the systematic investigation will provide critical information in bridging the gap between the theoretical mechanical analysis and the chemical properties to achieve micron-scale soft robotics

Best available technique for the recovery of marine benthic communities in a gravel shore after the oil spill: A mesocosm-based sediment triad assessment

Ecotoxicological effects of spilled oils are well documented, but study of recovery of marine benthic communities is limited. Long-term recovery of hard bottom communities during physical and biological remediations after a spill was monitored. A 60-day experiment was conducted using a mesocosm with monitoring of eight endpoints by use of the sediment quality triad (SQT). First, physical treatment of hot water + high pressure flushing maximally removed residual oils (max=93%), showing the greatest recovery among SQT variables (mean=72%). Physical cleanup generally involved adverse effects such as depression of the microphytobenthic communityN