Reactive Oxygen Species (ROS)-Assisted Nano-Therapeutics Surface-Decorated with Epidermal Growth Factor Fragments for Enhanced Wound Healing.

In this study, stimuli-responsive liberation of an epidermal growth factor fragment (EGFfr) is accomplished using nanofibrous meshes to improve wound healing effects. Electrospun nanofibers are fragmented by mechanical milling, followed by aminolysis to fabricate powdered nanofibrils (NFs). EGFfrs are covalently immobilized on NFs via thioketal linkers (EGFfr@TK@NF) for reactive oxygen species (ROS)-dependent liberation. EGFfr@TK@NF exhibits ROS-responsive liberation of EGFfr from the matrix at hydrogen peroxide (H2 O2 ) concentrations of 0-250 mm. Released EGFfr is confirmed to enhance the migration of HaCaT cell monolayers, and keratinocytic gene expression levels are significantly enhanced when H2 O2 is added to obtain the released fraction of NFs. An in vivo study on the dorsal wounds of mice reveals that EGFfr-immobilized NFs improve the expression levels of keratin1, 5, and 14 for 2 weeks when H2 O2 is added to the wound sites, suggesting that the wounded skin is re-epithelized with the original epidermis. Thus, EGFfrs-immobilized NFs are anticipated to be potential nanotherapeutics for wound treatment in combination with the conventional disinfection process with H2 O2 .

Prediction Model for Future Success of Early Orthopedic Treatment of Class III Malocclusion.

This study aimed to identify predictors for successful post-treatment outcomes in early orthopedic class III malocclusion treatment with a facemask and hyrax expander appliance. The study was performed on lateral cephalograms from 37 patients at the start of treatment (T0), post-treatment (T1), and a minimum of three years after treatment (T2). The patients were grouped as stable or unstable according to the existence of a 2-mm overjet at T2. For statistical analysis, independent t-tests were used to compare the baseline characteristics and measurements of the two groups, considering a significance level of < 0.05. Thirty variables of pretreatment cephalograms were considered during logistic regression analysis to identify predictors. A discriminant equation was established using a stepwise method. The success rate and area under the curve were calculated, with AB to the mandibular plane, ANB, ODI, APDI, and A-B plane angles as predictors. The A-B plane angle was the most significantly different between the stable and unstable groups. In terms of the A-B plane angle, the success rate of early class III treatment with a facemask and hyrax expander appliance was 70.3%, and the area under the curve indicated a fair grade.

Manganese Ferrite Nanoparticles Enhance the Sensitivity of Hepa1-6 Hepatocellular Carcinoma to Radiation by Remodeling Tumor Microenvironments.

We evaluated the effect of manganese ferrite nanoparticles (MFN) on radiosensitization and immunologic responses using the murine hepatoma cell line Hepa1-6 and the syngeneic mouse model. The clonogenic survival of Hepa1-6 cells was increased by hypoxia, while being restricted by ionizing radiation (IR) and/or MFN. Although MFN suppressed HIF-1α under hypoxia, the combination of IR and MFN enhanced apoptosis and DNA damage in Hepa1-6 cells. In the Hepa1-6 syngeneic mouse model, the combination of IR and MFN notably limited the tumor growth compared to the single treatment with IR or MFN, and also triggered more frequent apoptosis in tumor tissues than that observed under other conditions. Increased expression of PD-L1 after IR was not observed with MFN alone or the combination of IR and MFN in vitro and in vivo, and the percentage of tumor-infiltrating T cells and cytotoxic T cells increased with MFN, regardless of IR, in the Hepa1-6 syngeneic mouse model, while IR alone led to T cell depletion. MFN might have the potential to overcome radioresistance by alleviating hypoxia and strengthening antitumor immunity in the tumor microenvironment.

A band-gap database for semiconducting inorganic materials calculated with hybrid functional.

Semiconducting inorganic materials with band gaps ranging between 0 and 5 eV constitute major components in electronic, optoelectronic and photovoltaic devices. Since the band gap is a primary material property that affects the device performance, large band-gap databases are useful in selecting optimal materials in each application. While there exist several band-gap databases that are theoretically compiled by density-functional-theory calculations, they suffer from computational limitations such as band-gap underestimation and metastable magnetism. In this data descriptor, we present a computational database of band gaps for 10,481 materials compiled by applying a hybrid functional and considering the stable magnetic ordering. For benchmark materials, the root-mean-square error in reference to experimental data is 0.36 eV, significantly smaller than 0.75-1.05 eV in the existing databases. Furthermore, we identify many small-gap materials that are misclassified as metals in other databases. By providing accurate band gaps, the present database will be useful in screening materials in diverse applications.

Material Design of New p-Type Tin Oxyselenide Semiconductor through Valence Band Engineering and Its Device Application.

This paper reports a new p-type tin oxyselenide (SnSeO), which was designed with the concept that the valence band edge from O 2p orbitals in the majority of metal oxides becomes delocalized by hybridizing Se 4p and Sn 5s orbitals. As the Se loading increased, the SnSeO film structures were transformed from tetragonal SnO to orthorhombic SnSe, which was accompanied by an increase in the amorphous phase portion and smooth morphologies. The SnSe0.56O0.44 film annealed at 300 °C exhibited the highest Hall mobility (µHall), 15.0 cm2 (V s)-1, and hole carrier density (nh), 1.2 × 1017 cm-3. The remarkable electrical performance was explained by the low hole effective mass, which was calculated by a first principle calculation. Indeed, the fabricated field-effect transistor (FET) with a p-channel SnSe0.56O0.44 film showed the high field-effect mobility of 5.9 cm2 (V s)-1 and an ION/OFF ratio of 3 × 102. This work demonstrates that anion alloy-based hybridization provides a facile route to the realization of a high-performance p-channel FET and complementary devices.

Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells.

PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

High-throughput ab initio calculations on dielectric constant and band gap of non-oxide dielectrics.

High-k dielectrics, materials having a large band gap (Eg) and high dielectric constant (k) simultaneously, constitute critical components in microelectronic devices. Because of the inverse relationship between Eg and k, materials with large values in both properties are rare. Therefore, massive databases on Eg and k will be useful in identifying optimal high-k materials. While experimental and theoretical data on Eg and k of oxides are accumulating, corresponding information is scarce for non-oxide dielectrics with anions such as C, N, F, P, S, and Cl. To identify promising high-k dielectrics among these material groups, we screen 869 compounds of binary carbides, nitrides, sulfides, phosphides, chlorides, and fluorides, through automated ab initio calculations. Among these compounds, fluorides exhibit an Eg-k relation that is comparable to that of oxides. By further screening over ternary fluorides, we identify fluorides such as BiF3, LaF3, and BaBeF4 that could serve as useful high-k dielectrics.

AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells.

Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect. The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer.In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3-dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738. Inhibition of ATM in SNU-484 cells enhanced AZD6738 sensitivity to a level comparable with that observed in SNU-601 cells, showing that activation of the ATM-Chk2 signaling pathway attenuates AZD6738 sensitivity. In addition, decreased HDAC1 expression was found to be associated with ATM inactivation in SNU-601 cells, demonstrating the interaction between HDAC1 and ATM can affect sensitivity to AZD6738. Furthermore, in an in vivo tumor xenograft mouse model, AZD6738 significantly suppressed tumor growth and increased apoptosis.These findings suggest synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. Mol Cancer Ther; 16(4); 566-77. ©2017 AACR.

Property database for single-element doping in ZnO obtained by automated first-principles calculations.

Throughout the past decades, doped-ZnO has been widely used in various optical, electrical, magnetic, and energy devices. While almost every element in the Periodic Table was doped in ZnO, the systematic computational study is still limited to a small number of dopants, which may hinder a firm understanding of experimental observations. In this report, we systematically calculate the single-element doping property of ZnO using first-principles calculations. We develop an automation code that enables efficient and reliable high-throughput calculations on thousands of possible dopant configurations. As a result, we obtain formation-energy diagrams for total 61 dopants, ranging from Li to Bi. Furthermore, we evaluate each dopant in terms of n-type/p-type behaviors by identifying the major dopant configurations and calculating carrier concentrations at a specific dopant density. The existence of localized magnetic moment is also examined for spintronic applications. The property database obtained here for doped ZnO will serve as a useful reference in engineering the material property of ZnO through doping.

Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells.

Ataxia telangiectasia and Rad3-related (ATR) proteins are sensors of DNA damage, which induces homologous recombination (HR)-dependent repair. ATR is a master regulator of DNA damage repair (DDR), signaling to control DNA replication, DNA repair and apoptosis. Therefore, the ATR pathway might be an attractive target for developing new drugs. This study was designed to investigate the antitumor effects of the ATR inhibitor, AZD6738 and its underlying mechanism in human breast cancer cells. Growth inhibitory effects of AZD6738 against human breast cancer cell lines were studied using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (methyl thiazolyl tetrazolium, MTT) assay. Cell cycle analysis, Western blotting, immunofluorescence and comet assays were also performed to elucidate underlying mechanisms of AZD6738 action. Anti-proliferative and DDR inhibitory effects of AZD6738 were demonstrated in human breast cancer cell lines. Among 13 cell lines, the IC50 values of nine cell lines were less than 1 µmol/L using MTT assay. Two cell lines, SK-BR-3 and BT-474, were chosen for further evaluation focused on human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. Sensitive SK-BR-3 but not the less sensitive BT-474 breast cancer cells showed increased level of apoptosis and S phase arrest and reduced expression levels of phosphorylated check-point kinase 1 (CHK1) and other repair markers. Decreased functional CHK1 expression induced DNA damage accumulation due to HR inactivation. AZD6738 showed synergistic activity with cisplatin. Understanding the antitumor activity and mechanisms of AZD6738 in HER2-positive breast cancer cells creates the possibility for future clinical trials targeting DDR in HER2-positive breast cancer treatment.

Recognition of sign language with an inertial sensor-based data glove.

Communication between people with normal hearing and hearing impairment is difficult. Recently, a variety of studies on sign language recognition have presented benefits from the development of information technology. This study presents a sign language recognition system using a data glove composed of 3-axis accelerometers, magnetometers, and gyroscopes. Each data obtained by the data glove is transmitted to a host application (implemented in a Window program on a PC). Next, the data is converted into angle data, and the angle information is displayed on the host application and verified by outputting three-dimensional models to the display. An experiment was performed with five subjects, three females and two males, and a performance set comprising numbers from one to nine was repeated five times. The system achieves a 99.26% movement detection rate, and approximately 98% recognition rate for each finger's state. The proposed system is expected to be a more portable and useful system when this algorithm is applied to smartphone applications for use in some situations such as in emergencies.

Arduino-based automation of a DNA extraction system.

There have been many studies to detect infectious diseases with the molecular genetic method. This study presents an automation process for a DNA extraction system based on microfluidics and magnetic bead, which is part of a portable molecular genetic test system. This DNA extraction system consists of a cartridge with chambers, syringes, four linear stepper actuators, and a rotary stepper actuator. The actuators provide a sequence of steps in the DNA extraction process, such as transporting, mixing, and washing for the gene specimen, magnetic bead, and reagent solutions. The proposed automation system consists of a PC-based host application and an Arduino-based controller. The host application compiles a G code sequence file and interfaces with the controller to execute the compiled sequence. The controller executes stepper motor axis motion, time delay, and input-output manipulation. It drives the stepper motor with an open library, which provides a smooth linear acceleration profile. The controller also provides a homing sequence to establish the motor's reference position, and hard limit checking to prevent any over-travelling. The proposed system was implemented and its functionality was investigated, especially regarding positioning accuracy and velocity profile.

Psychometric Properties of a Short Korean Version of the Revised Obsessive Intrusion Inventory.

OBJECTIVE: The Revised Obsessive Intrusion Inventory (ROII) is a 52-item scale that evaluates obsessional intrusive thoughts. The aim of the present study was to validate a short, 20-item Korean version of the ROII (ROII-20). METHODS: Of the 1125 participants who completed the ROII-20, 895 participants completed the scale to examine the factor structure of the scale. A subgroup of these participants (n=53) completed the scale twice to determine test-retest reliability. To establish external validity, 230 participants completed the scale and other questionnaires. RESULTS: Exploratory factor analyses suggested a hierarchical model comprising two higher order factors of autogenous obsessions (resulting from aggressive thoughts and sexual thoughts) and reactive obsessions (resulting from thoughts about contamination, thoughts about accidents, and thoughts about dirt). Confirmatory factor analyses supported this model. The results indicated good internal consistency and test-retest reliability. External validity was supported by relationships with obsessive-compulsive symptoms and general distress. CONCLUSION: The ROII-20 presents good psychometric properties and may be considered as a promising instrument for measuring obsessional intrusions.