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Strain-induced modulation of electronic, magnetic, and photonic properties provides additional functionalities to oxide thin film-based electronics as compared to those of conventional rigid electr...

Conveyor fused deposition modelling (CFDM) 3D printing of graphene (GR)/polylactic acid (PLA) composite filament offers a unique capability to manufacture tailorable honeycomb structures which can be designed and optimized for specific applications. Among the various filaments that can be used for 3D printing, PLA, carbon black (CB)/PLA, and GR/PLA filaments were collected and then examined by differential scanning calorimetry (DSC), thermal gravity analysis (TGA), and Raman spectra. A stereolithography (STL) file with a 3D honeycomb structure model was prepared and transformed into a G-code file using a G-code generator. The extrusion conditions for CFDM 3D printing were controlled by infill and print speed. PLA, CB/PLA, and GR/PLA composite honeycomb samples were manufactured by 3D printing based on FDM using PLA, CB/PLA, and GR/PLA filaments. CFDM 3D printed honeycomb samples prepared by PLA, CB/PLA and GR/PLA filament were analyzed for morphology, surface resistance, electrical heating properties. For the 3D printed honeycomb structure sample using CB/PLA and GR/PLA, the optimum condition was set up 230 °C and 220 °C respectively of the printer temperature, 50 °C of bed temperature, and 30 mm/s of printer speed. Surface resistivity of honeycomb structure sample using CB/PLA and GR/PLA is about 299.0 Ω/sq and 118.0 Ω/sq. The maximum surface temperature of honeycomb structure sample using CB/PLA and GR/PLA is ca. 78.7 °C and 143.0 °C applied to 25 V.

Recent outbreaks of zoonotic coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have caused tremendous casualties and great economic shock. Although some repurposed drugs have shown potential therapeutic efficacy in clinical trials, specific therapeutic agents targeting coronaviruses have not yet been developed. During coronavirus replication, a replicase gene cluster, including RNA-dependent RNA polymerase (RdRp), is alternatively translated via a process called -1 programmed ribosomal frameshift (−1 PRF) by an RNA pseudoknot structure encoded in viral RNAs. The coronavirus frameshifting has been identified previously as a target for antiviral therapy. In this study, the frameshifting efficiencies of MERS-CoV, SARS-CoV and SARS-CoV-2 were determined using an in vitro −1 PRF assay system. Our group has searched approximately 9689 small molecules to identify potential −1 PRF inhibitors. Herein, we found that a novel compound, 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline (KCB261770), inhibits the frameshifting of MERS-CoV and effectively suppresses viral propagation in MERS-CoV-infected cells. The inhibitory effects of 87 derivatives of furo[2,3-b]quinolines were also examined showing less prominent inhibitory effect when compared to compound KCB261770. We demonstrated that KCB261770 inhibits the frameshifting without suppressing cap-dependent translation. Furthermore, this compound was able to inhibit the frameshifting, to some extent, of SARS-CoV and SARS-CoV-2. Therefore, the novel compound 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline may serve as a promising drug candidate to interfere with pan-coronavirus frameshifting.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive lysosomal storage disease caused by mutation of the iduronate-2-sulfatase gene. The mutation results in iduronate-2-sulfatase deficiency, which causes the progressive accumulation of heparan sulfate and dermatan sulfate in cellular lysosomes. The phenotype, age of onset, and symptoms of MPS II vary; accordingly, the disease can be classified into either the early-onset type or the late-onset type, depending on the age of onset and the severity of the symptoms. In patients with severe MPS II, symptoms typically first appear between 2 and 5 years of age. Patients with severe MPS II usually die in the second decade of life although some patients with less severe disease have survived into their fifth or sixth decade. Here, we report the establishment of a preimplantation genetic diagnosis (PGD) strategy using multiplex nested polymerase chain reaction, direct sequencing, and linkage analysis. Unaffected embryos were selected via the diagnosis of a single blastomere, and a healthy boy was delivered by a female carrier of MPS II. This is the first successful application of PGD in a patient with MPS II in Korea.

Hydrangea serrata (THUNB.) SER. (Hydrangeaceae) leaves have been used as herbal teas in Korea and Japan. The objective of this study was to identify anti-photoaging compounds in aqueous EtOH extract prepared from leaves of H. serrata and their effects on UVB-irradiated Hs68 human foreskin fibroblasts. Phytochemical study on H. serrata leaves led to the isolation and characterization of ten compounds: hydrangenol, thunberginol A, thunberginol C, hydrangenoside A, hydrangenoside C, cudrabibenzyl A, 2,3,4'-trihydroxystilbene, thunberginol F, quercetin 3-O-β-D-xylopyranosyl (1-2)-β-D-galactopyranoside, quercetin 3-O-β-D-xylopyranosyl (1-2)-β-D-glucopyranoside. Cudrabibenzyl A, 2,3,4'-trihydroxystilbene, quercetin 3-O-β-D-xylopyranosyl (1-2)-β-D-galactopyranoside, quercetin 3-O-β-D-xylopyranosyl (1-2)-β-D-glucopyranoside were firstly isolated from H. serrata. We estimated the effects of 10 compounds on cell viability and production of pro-collagen Type I, matrix metalloproteinase (MMP)-1, and hyaluronic acid (HA) after UVB irradiation. Of these compounds, hydrangenol showed potent preventive activities against reduced cell viability and degradation of pro-collagen Type I in UVB-irradiated Hs68 fibroblasts. Hydrangenol had outstanding inductive activities on HA production. It suppressed mRNA expression levels of MMP-1, MMP-3, hyaluronidase (HYAL)-1, HYAL-2, cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-8, and IL-1β in UVB-irradiated Hs68 fibroblasts. When Hs68 fibroblasts were exposed to hydrangenol after UVB irradiation, UVB-induced reactive oxygen species (ROS) production was suppressed. Hydrangenol also inhibited the activation of activator protein-1 (AP-1) and signal transduction and activation of transcription 1 (STAT-1) by downregulating phosphorylation of p38 and extracellular signal-regulated kinase (ERK). Our data indicate that hydrangenol isolated from H. serrata leaves has potential protective effects on UVB-induced skin photoaging.

Mg has received much attention as a next-generation implantable material owing to its biocompatibility, bone-like mechanical properties, and biodegradability in physiological environments. The application of various polymer coatings has been conducted in the past to reduce the rapid formation of hydrogen gas and the local change in pH during the initial phase of the chemical reaction with the body fluids. Here, we propose femtosecond (fs) laser-mediated Mg surface patterning for significant enhancement of the binding strength of the coating material, which eventually reduces the corrosion rate. Analyses of the structural, physical, crystallographic, and chemical properties of the Mg surface have been conducted in order to understand the mechanism by which the surface adhesion increases between Mg and the polymer coating layer. Depending on the fs laser conditions, the surface structure becomes rough owing to the presence of several microscaled pits and grooves of nanoporous MgO, resulting in a tightly bonded poly(lactic-co-glycolic acid) (PLGA) layer. The corrosion rate of the PLGA-coated, fs laser-treated Mg is considerably slow compared with the non-treated Mg; the treated Mg is also more biocompatible compared with the non-treated Mg. The fs laser-based surface modification technique offers a simple and quick method for introducing a rough coating on Mg; further, it does not require any chemical treatment, thereby overcoming a potential obstacle for its clinical use.

This study manufactured a horseshoe pattern (HP)-type electrical heating element based on a graphene/polylactic acid (GR/PLA) filament using CFDM (conveyor-fused deposition modeling) 3D printing technology, which is a new manufacturing process technology. CFDM 3D printing HP was fabricated in the different printing directions of 0&deg, 45&deg, and 90&deg, To confirm the effects of different 3D printing directions, the morphology, surface resistivity, and electrical heating properties of the different HPs were analyzed. In addition, the CFDM 3D-printed HPs made using different printing directions were printed on cotton fabric to confirm their applicability as fabric heating elements, and their electrical heating properties were measured. Regarding the morphology of the GR/PLA-HP, each sample was stacked according to the printing direction. It was also confirmed through FE-SEM images that the graphene was arranged according to the printing direction in which the nozzle moved. In the XRD pattern analysis, the GR/PLA-HP samples showed two diffraction peaks of PLA and graphene. The sizes of those peaks were increased in the order of 90&deg, &lt, &le, 0&deg, according to the printing direction, which also affected the electrical and electric heating properties. The surface resistivities of the GR/PLA-HP samples were shown to be increased in the order of 0&deg, 90&deg, indicating that the electrical properties of GR/PLA HP printed at 0&deg, were improved compared to those of the other samples. When 30 V was applied to three GR/PLA-HP samples according to the printing direction, the surface temperatures were decreased in the order of 0&deg, and the samples were indicated as 83.6, 80.6, and 52.5 &deg, C, respectively, the same result was shown when the samples were printed on cotton fabric. Therefore, it was confirmed that the GR/PLA CFDM 3D-printed HP sample printed at 0&deg, direction showed low surface resistivity and high surface temperature, so that improving the electrical heating properties.

Campanula takesimana Nakai (Campanulaceae, Korean bellflower) is one of the endemic herbs of Korea. The plant has been used as traditional medicines for treating asthma, tonsillitis, and sore throat in Korea. A hot water extract of the leaves of C. takesimana exhibited a significant inhibitory effect on lipopolysaccharide (LPS)-stimulated prostaglandin E2 (PGE2) production. Repetitive chromatographic separation of the hot water extract led to the isolation of three new neolignan glucosides, campanulalignans A&ndash, C (1&ndash, 3), with 15 known compounds (4&ndash, 18). The structures of new compounds 1&ndash, 3 were elucidated by analyzing nuclear magnetic resonance (NMR) spectroscopic data, along with high resolution quadrupole time of flight mass (HR-Q-TOF-MS) spectrometric data. Among the isolates, simplidin (7), 5-hydroxyconiferaldehyde (11), icariside F2 (12), benzyl-&alpha, l-arabinopyranosyl-(1&Prime, &rarr, 6&prime, )-&beta, d-glucopyranoside (13), and kaempferol 3-O-&beta, d-apiosyl (1&rarr, 2)-&beta, d-glucopyranoside (15) were isolated from the Campanulaceae family for the first time. The isolates (1, 2, and 4&ndash, 18) were assessed for their anti-inflammatory effects on LPS-stimulated PGE2 production on RAW 264.7 cells. 7R,8S-Dihydrodehydrodiconiferyl alcohol (5), 3&prime, 4-O-dimethylcedrusin 9-O-&beta, glucopyranoside (6), pinoresinol di-O-&beta, d-glucoside (8), ferulic acid (10), 5-hydroxyconiferaldehyde (11), and quercetin (18) showed significant inhibitory effects on LPS-stimulated PGE2 production.

This study aims to fabricate an electro-conductive textile dip-coated with graphene/waterborne polyurethane (WPU) composite, and an evaluation of the laundering durability of this composite was conducted in order to confirm the application of the protective clothing. Samples were coated five times on the para-aramid knit with the graphene/WPU composite by the dip-coating method, and then hot-pressed processes were applied with various temperatures. The samples were washed 5, 10, 15, and 20 times, and then, morphology, surface resistance, and surface temperature were measured. After five laundering cycles, control and hot-pressed samples maintained surface resistivity from 10 kΩ/sq to 100 kΩ/sq. The surface resistivity of the control sample, however, was gradually increased up to 20 laundering cycles. The sample that was hot-pressed at 120 °C showed the lowest value of about 15 kΩ/sq with almost no variation from zero laundering cycles to 20, thus, it is the most stable sample up to 20 laundering cycles. When applied voltage at 50V, the surface temperature of the nonlaundering samples was presented as over 40.0 °C. In the case of the control sample, there was almost no electrical heating performance remaining after the fifth laundering test, but the hot-pressed samples maintained 40.0 °C or more at 50 V after the 10th laundering test. The sample that was hot-pressed at 120 °C in particular could maintain electrical heating performance at about an 80 % level up to the 10th laundering cycle. Therefore, the sample that was hot-pressed at 120 °C was the most stable in terms of electrical properties after 20 laundering cycles, and its electrical heating performance could be maintained even after 10 laundering cycles. It is expected that this process can be applied and used to make functional clothes for apparel and other applications.

Lactic acid is a platform chemical for the sustainable production of various materials. To develop a robust yeast platform for low-pH production of d-lactic acid (LA), an acid-tolerant yeast strain was isolated from grape skins and named Pichia kudriavzevii NG7 by ribosomal RNA sequencing. This strain could grow at pH 2.0 and 50°C. For the commercial application of P. kudriavzevii NG7 as a lactic acid producer, the ethanol fermentation pathway was redirected to lactic acid by replacing the pyruvate decarboxylase 1 gene (PDC1) with the d-lactate dehydrogenase gene (d-LDH) derived from Lactobacillus plantarum. To enhance lactic acid tolerance, this engineered strain was adapted to high lactic acid concentrations, and a new transcriptional regulator, PAR1, responsible for acid tolerance, was identified by whole-genome resequencing. The final engineered strain produced 135 g/L and 154 g/L of d-LA with productivity over 3.66 g/L/hr at pH 3.6 and 4.16 g/L/hr at pH 4.7, respectively.

Nickel oxide (NiO) is a well-known electrochromic (EC) material with anodic coloration. However, NiO degrades significantly upon cycling with Li+/H+-conducting electrolytes. Doping with various additives is the most effective method to enhance the cycling stability of NiO films. In this study, films of tantalum-doped nickel oxide, denoted as Ni1-xTax oxide, were deposited onto indium tin oxide (ITO)-coated glass substrates by reactive DC magnetron co-sputtering from Ni and Ta metal targets for use as counter electrodes in monolithic inorganic EC devices (ECDs). The influence of the Ta content on the composition, structure, optical properties and EC properties of NiO was investigated. It was found that the microstructure of the Ni1-xTax oxide films was closely related to the EC performance and cycling stability. With moderate optical modulation, the cycling stability and optical transmittance of the Ni1-xTax oxide film with x = 0.274 were increased. All-solid-state inorganic ECDs were fabricated with the configuration ITO/WO3/Ta2O5/Ni1-xTax oxide/ITO/glass. The full ECDs showed different EC behaviors compared to those of the Ni1-xTax oxide single layers, which was attributed to the different counter electrode/ion conductor interfaces of the solid–solid and solid–liquid interfaces, respectively. The ECD fabricated with the Ni1-xTax oxide film with x = 0.065 showed stable transmittance modulation up to 1000 cycles. We propose a degradation mechanism for monolithic all-solid-state inorganic ECDs based on the observed degradation in the EC performance, which can pave the way for highly durable ECDs for various optoelectronic devices.

Graphene is classified as a carbon-based material. Structurally, graphene is made up of carbon-based two-dimensional atomic crystals and a one atom thick planar sheet of sp2-bonded carbon atoms. This sort of arrangement in graphene makes it a unique material with exceptional mechanical, physicochemical, thermal, electrical, optical, and biomedical properties. Methods for graphene-based fabric production mainly use graphene-based materials such as graphene (G), graphene oxide (GO), and reduced graphene oxide (rGO) coated on fabric or yarn. Waterborne polyurethane (WPU) is one of the most rapidly developing and active branches of polyurethane chemistry. More and more attention is being paid to graphene-coated fabrics owing to their low temperature flexibility, the presence of zero or very few VOCs (volatile organic compounds), water resistance, pH stability, superior solvent resistance, excellent weathering resistance, and desirable chemical and mechanical properties. It is used as a coating agent or adhesive for fibers, textiles, and leather. Also, graphene-containing materials have been used to enhance the properties of WPU. In this study, graphene/WPU composite solution and film was prepared to conduct basic research for developing electrical heating textiles which is not harmful to the human body, flexible and excellent in electrical properties. Graphene/WPU composite solutions were prepared with a graphene content of 0, 2, 4, 8, and 16 wt%, and graphene/WPU film was prepared with solution casting method. The graphene contents were analyzed for their surface morphology, electrical properties, and electrical heating properties.

In this study, two Listeria bacteriophages, LMP1 and LMP7, were isolated from chicken feces as a means of biocontrol of L. monocytogenes. Both bacteriophages had a lytic effect on L. monocytogenes ATCC 7644, 15313, 19114, and 19115. Phages LMP1 and LMP7 were able to inhibit the growth of L. monocytogenes ATCC 7644 and 19114 in tryptic soy broth at 10°C and 30°C. Nevertheless, LMP1 was more effective than LMP7 at inhibiting L. monocytogenes ATCC 19114. On the contrary, LMP7 was more effective than LMP1 at inhibiting L. monocytogenes ATCC 7644. The morphology of LMP1 and LMP7 resembled that of members of the Siphoviridae family. The growth of L. monocytogenes ATCC 7644 was inhibited by both LMP1 and LMP7 in milk; however, the growth of L. monocytogenes ATCC 19114 was only inhibited by LMP1 at 30°C. The lytic activity of bacteriophages was also evaluated at 4°C in milk in order to investigate the potential use of these phages in refrigerated products. In conclusion, these two bacteriophages exhibit different host specificities and characteristics, suggesting that they can be used as a component of a phage cocktail to control L. monocytogenes in the food industry.

The pathogenicity of enterohemorrhagic Escherichia coli O157:H7 were extensively studied by genomic and proteomic approaches. However, the possible virulence mechanism of E. coli O157:H7 in its hosts has never been studied using a metabolomic approach. In this study, the intracellular metabolites of C. elegans fed with pathogenic E. coli O157:H7 and non-pathogenic E. coli were profiled by gas chromatography/time-of-flight mass spectrometry. In C. elegans fed with O157:H7, the levels of metabolites related to the mammalian target of rapamycin (mTOR) signaling pathway, such as amino acids and glucose, highly increased. In addition, the levels of metabolites related to lipid oxidation and nucleotide salvage pathways increased. The metabolic intermediates of organic acidurias and atypical hemolytic uremic syndrome also increased when fed with O157:H7. However, the level of trehalose, an mTOR-independent autophagy enhancer, decreased in C. elegans fed with O157:H7. These results showed that infection with O157:H7 alters intracellular metabolite abundance in C. elegans. This study suggest that the metabolomics may be applied to elucidating the virulence mechanisms of pathogenic bacteria.

Purpose: Clear cell ovarian carcinoma (CCOC) is an aggressive disease that often demonstrates resistance to standard chemotherapies. Approximately 25% of patients with CCOC show a strong APOBEC mutation signature. Here, we determine which APOBEC3 enzymes are expressed in CCOC, establish clinical correlates, and identify a new biomarker for detection and intervention. Experimental Designs: APOBEC3 expression was analyzed by IHC and qRT-PCR in a pilot set of CCOC specimens (n = 9 tumors). The IHC analysis of APOBEC3B was extended to a larger cohort to identify clinical correlates (n = 48). Dose-response experiments with platinum-based drugs in CCOC cell lines and carboplatin treatment of patient-derived xenografts (PDXs) were done to address mechanistic linkages. Results: One DNA deaminase, APOBEC3B, is overexpressed in a formidable subset of CCOC tumors and is low or absent in normal ovarian and fallopian tube epithelial tissues. High APOBEC3B expression associates with improved progression-free survival (P = 0.026) and moderately with overall survival (P = 0.057). Cell-based studies link APOBEC3B activity and subsequent uracil processing to sensitivity to cisplatin and carboplatin. PDX studies extend this mechanistic relationship to CCOC tissues. Conclusions: These studies demonstrate that APOBEC3B is overexpressed in a subset of CCOC and, contrary to initial expectations, associated with improved (not worse) clinical outcomes. A likely molecular explanation is that APOBEC3B-induced DNA damage sensitizes cells to additional genotoxic stress by cisplatin. Thus, APOBEC3B is a molecular determinant and a candidate predictive biomarker of the therapeutic response to platinum-based chemotherapy. These findings may have broader translational relevance, as APOBEC3B is overexpressed in many different cancer types.

A flexible smart window with electrochromic (EC) and thermochromic (TC) properties is fabricated on a highly durable transparent indium-tin oxide (ITO)/graphene/polyethylene terephthalate (PET) electrode. An amorphous WO3 film and crystalline VO2 film are used as the EC and TC material, respectively, in the device. The ITO film deposited via atomic layer deposition acts as a protective layer and suppresses the plasma-induced damage of graphene, which typically occurs during the sputtering process. In this device, the amorphous WO3 film undergoes cathodic electrochromic reactions with high coloration efficiency, while the crystalline VO2 film shows characteristic thermochromic behavior. Thus, the flexible EC–TC hybrid smart window shows the controlled transmission of optical and solar energies according to the surrounding temperature and the applied voltage, allowing selective modulation of the visible and near-infrared light. The flexible EC–TC hybrid device is also very stable under mechanical bending, owing to the robust adhesion of the ITO film on the graphene support and the reduced plasma-induced damage of graphene. The fabricated high-performance, durable ITO/graphene/PET transparent electrode can pave the way for next-generation flexible optoelectronic devices as well as multifunctional flexible smart windows.

An extract of Ulmus macrocarpa Hance, commonly known as the large-fruited elm, has been prescribed as a traditional medicine. In this study, we aimed to investigate the cellular immune effects of U. macrocarpa stem cortex extracts on cyclophosphamide (CY)-treated splenocytes and mice. A methanol extract showed an improved survival rate of splenocytes after 72 h. The extract was successively partitioned with dichloromethane, ethyl acetate, n-butanol, and water; and the fractions so obtained were also examined for their proliferative activity. Among them, the water fraction of U. macrocarpa showed the highest proliferation of splenocytes and was used throughout the present study. We tested the survival rate of splenocytes through dose-dependent treatment of CY and the suppression of the survival effect by CY was recovered by treatment with the water extract of U. macrocarpa. To determine the mechanism involved, we examined the expression of B-cell lymphoma-extra large (Bcl-xL) anti-apoptotic protein...

The main objective of this study was to develop improved functional textiles for marine leisure clothing. Neoprene fabrics we re coated with carbon nanofibers (CNFs)/ Poly(vinylidenefluoride-co-hexafluoropropylene) (PVDF-HFP) composite solution compris- ing 0�16 wt% CNF in 1�5 wt% PVDF-HFP via electrospinning. Electrospinning was carried out from 15 to 24 kV. Neoprene textiles coated with the CNF/PVDF-HFP composite with various applied voltages were characterized as follows: Morphology was examined using an image analyzer microscope system and a field emission scanning electron microscope (FE-SEM). The thermal storage property of these materials was also analyzed using a ther- mal imaging camera with a forward looking infrared (FLIR) system. The resultant samples that were laminated with a knitted fabric composed of 80% nylon and 20% polyurethane were subjected to a thermal insulation property test. The test and control specimens were irradiated for 60 min. The test specimen and the control specimen were analyzed by con- sidering the differences in temperature between both specimens on heating. Water pene- tration resistance of the laminated knitted fabric with the CNF/PVDF-HFP composite nanoweb-coated neoprene fabric was measured. The water repellent property test was conducted using a drop shape analyzer (DE/DSA 100, Kruse). The results indicated that an increase in the density of nanoweb-coated neoprene fabric surface correlated with improved thermal storage, thermal insulation, water penetration resistance, and water repellent properties. In addition, increasing amounts of CNFs in the CNFs/PVDF-HFP com- posite solution resulted in increased thermal storage, thermal insulation, and water repel- lent properties.

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

This study aimed to screen lactic acid bacteria (LAB) for their anti-inflammatory activity by using RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis. In all, 192 LAB strains were isolated from healthy human feces, of which 8 strains showed excellent nitric oxide (NO) inhibitory activity. Peptidoglycan extracts of these 8 LAB strains were subjected to NO assay, Western blot, and ELISA. Among the 8 tested strains, extracts of 4 strains significantly inhibited the production of NO, related enzyme activities such as inducible nitric oxide synthase and cyclooxygenase 2, and key cytokines such as tumor necrosis factor-α and IL-6 in RAW264.7 cells. The 4 strains belonged to Lactobacillus (CAU1054, CAU1055, CAU1064, and CAU1301). Oral administration of the 4 strains inhibited DSS-induced body weight loss, colon shortening, and colon damage in ICR mice. The colon tissue of the mice treated with Lactobacillus plantarum strain CAU1055 had significantly reduced levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor-α, and IL-6. We found that strain CAU1055 could be used as a candidate probiotic strain for the prevention and treatment of inflammatory bowel disease. Further studies are warranted to confirm the mechanisms of interaction between peptidoglycan of L. plantarum strain CAU1055 and upstream cellular signaling mediators.

The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d‑ or l‑forms of 2‑hydroxyglutarate (2HG) from α‑ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA) cycle. However, it is unclear whether the oncometabolite d‑2HG increases angiogenesis in endothelial cells. Therefore, in this study, we analyzed the levels of various metabolites, including d‑2HG, under hypoxic conditions and in IDH2R172K mutant breast cancer cells by mass spectrometry. We then further evaluated the effects of this metabolite on angiogenesis in breast cancer cells. The results revealed that treatment with d‑2HG increased the levels of secreted vascular endothelial growth factor (VEGF) in cancer cells and enhanced endothelial cell proliferation in a concentration‑dependent manner. Wound healing and cell migration (examined by Transwell assay) were significantly increased by d‑2HG to a level similar to that induced by VEGF. Tube formation was significantly stimulated by d‑2HG, and chick chorioallantoic membrane angiogenesis was also enhanced by d‑2HG. d‑2HG activated VEGF receptor (VEGFR)2 and VEGFR2 downstream signaling, extracellular signal‑regulated kinase 1/2, focal adhesion kinase, AKT and matrix metalloproteinase (MMP)2. Taken together, the findings of this study suggested that d‑2HG induced angiogenic activity via VEGFR2 signaling and increased MMP2 activity.

Mature microRNAs (miRNAs) are 21 to 23 nucleotide noncoding RNA molecules that can downregulate multiple gene expression by mRNA degradation or translational repression. miRNAs are considered to play important roles in cell proliferation, apoptosis, and differentiation during mammalian development. The Runt-related transcription factor 3 (RUNX3) expression and activity are frequently downregulated by various mechanisms in gastric cancer. We have reported that RUNX3 inactivation is crucial for early tumorigenesis. In this study, we investigated the role of miRNAs targeting RUNX3 in early tumorigenesis. miR-130a and miR-495 upregulated under hypoxic conditions that bind to the RUNX3 3'-untranslated region (3'-UTR) were identified in gastric cancer cells by using microarray analysis and bioinformatics programs. Combination of miR-130a and miR-495 inhibited RUNX3 expression at the protein level, but not at the mRNA level. miR-130a and miR-495 significantly inhibited the RUNX3-3'UTR-luciferase activity. Combination of miR-130a and miR-495 significantly decreased apoptosis determined by Annexin V-FITC/propidium iodide staining and flow cytometric analysis, and the expression of Bim in SNU484 gastric cancer cells. In addition, p21 and Bim, RUNX3 target genes, were completely downregulated by the combination of miR-130a and miR-495. Using matrigel plug assay, we found that antagomiRs specific for miR-130a and miR-495 significantly reduced angiogenesis in vivo. In conclusion, targeting miR-130a and miR-495 could be a potential therapeutics to recover RUNX3 expression under hypoxic conditions and in early tumorigenic progression.

The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities.

Glyceollins, a group of phytoalexins isolated from soybean, are known to exhibit anticancer, antiestrogenic, and antiangiogenic activities. However, whether glyceollins regulate tumor growth through regulation of hypoxia-inducible factor (HIF)-1α has not been investigated. We determined whether and how glyceollins regulate the synthesis and stability of HIF-1α. Quantitative real-time PCR revealed that glyceollins inhibited the expression of HIF-1-induced genes such as vascular endothelial growth factor (VEGF) in cancer cells. Enzyme-linked immunosorbent assay and reporter luciferase assay showed that glyceollins decreased VEGF secretion and its promoter activity, respectively. Treatment of various cancer cells with 0.5–100 µM glyceollins under hypoxic conditions reduced the expression of HIF-1α. Glyceollins blocked translation of HIF-1α by inhibiting the PI3K/AKT/mTOR pathway under hypoxic conditions. Glyceollins decreased the stability of HIF-1α after treatment with cycloheximide, a protein synthesis inhibitor, and increased the ubiquitination of HIF-1α after treatment with MG132, a proteasome inhibitor. Glyceollins blocked the interaction of Hsp90 with HIF-1α, as shown by immunoprecipitation assay. Chemical binding of Hsp90 with glyceollins, as confirmed by computational docking analysis, was stronger than that with geldanamycin at the HSP90 ATP-binding pocket. We found that glyceollins decreased microvessel density, as well as expression of phosphorylated AKT/mTOR and the Hsp90 client protein CDK4, in solid tumor tissues. Glyceollins potently inhibited HIF-1α synthesis and decreased its stability by blocking the PI3K/AKT/mTOR pathway and HSP90 binding activity, respectively. These results may provide new perspectives into potential therapeutic application of glyceollins for the prevention and treatment of hypervascularized diseases and into the mechanism of their anticancer activity. J. Cell. Physiol. 230: 853–862, 2015. © 2014 Wiley Periodicals, Inc.

Patients with diabetes have many different kinds of complications involving multiple organs, but those involving the musculoskeletal system are relatively uncommon. Diabetic muscle infarction (DMI) is a rare, painful, and potentially serious condition in patients with poorly controlled diabetes mellitus. A 35-year-old man diagnosed with type 2 diabetes eight years ago, visited with severe muscle pain in the right anteromedial thigh without any event of trauma. He had been treated with metformin, but his glycemic control was very poor with a glycated hemoglobin of 14.5%. Evaluation of his painful thigh lesion did not reveal any evidence of infection or vasculitis, but the magnetic resonance imaging and bone scan showed findings of DMI at vastus medialis muscle and an insufficiency fracture at the right medial tibial condyle. He was diagnosed with retinopathy, neuropathy and microalbuminuria but not macrovascular complications. We also diagnosed his diabetes as latent autoimmune diabetes in adults (LADA) based on his low C-peptide level, positive anti-glutamic acid decarboxylase (GAD) antibody and early onset diabetes. Instead of antibiotics, bed rest, analgesics and strict blood glucose control with multiple daily insulin injections led to symptom improvement. This is an unusual case of a young man with LADA experiencing severe musculoskeletal complication of DMI and insufficiency fracture. If a poorly controlled diabetic patient appears to have unaccounted soft tissue pain, musculoskeletal complications such as DMI associated with hyperglycemia should be considered.

Mutation of isocitrate dehydrogenase (IDH) 1 (R132H) and IDH2 (R172K) and induction of hypoxia in various solid tumors results in changes to metabolic profiles, including production of the d- or l-forms of 2-hydroxyglutarate (2HG) from α-ketoglutarate in aerobic metabolism in the TCA cycle. However, it is unclear whether the oncometabolite d-2HG increases angiogenesis in endothelial cells. Therefore, in this study, we analyzed the levels of various metabolites, including d-2HG, under hypoxic conditions and in IDH2R172K mutant breast cancer cells by mass spectrometry. We then further evaluated the effects of this metabolite on angiogenesis in breast cancer cells. Our results showed that treatment with d-2HG increased the levels of secreted vascular endothelial growth factor (VEGF) in cancer cells and enhanced endothelial cell proliferation in a concentration-dependent manner. Wound healing and transwell migration were significantly increased by d-2HG to a level similar to that induced by VEGF. Tube formation was significantly stimulated by d-2HG, and chick chorioallantoic membrane angiogenesis was also enhanced by d-2HG. d-2HG activated VEGF receptor (VEGFR) 2 and VEGFR2 downstream signaling, extracellular signal-regulated kinase 1/2, focal adhesion kinase, AKT, and matrix metalloproteinase (MMP) 2. Taken together, our results suggested that d-2HG induced angiogenic activity via VEGFR2 signaling and increased MMP2 activity. Citation Format: You Mie Lee, Jiyoon Seok, Soo-Hyun Yoon, Sun-Hee Lee, Jong Hwa Jung. The oncometabolite d-2-hydroxyglutarate induces angiogenic activity through the vascular endothelial growth factor receptor 2 signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 188.

The neuroprotective effects of a butanol fraction of white rose petal extract (WRPE-BF) were investigated in a middle cerebral artery occlusion (MCAO) model. Seven week-old male rats were orally administered WRPE-BF for 2 weeks and subjected to MCAO for 2 h, followed by reperfusion. Twenty-four h later, MCAO-induced behavioral dysfunctions were markedly improved in a dose-dependent manner by pretreatment with WRPE-BF. Moreover, higher dose of WRPE-BF not only decreased infarction area but also effectively reduced astrogliosis. The expression of inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein in MCAO model were markedly inhibited by WRPE-BF treatment. Notably, WRPE-BF decreased nitric oxide and malondialdehyde levels in the striatum and subventricular zone of stroke-challenged brains. These data suggested that WRPE-BF may exert its neuroprotective effects via anti-oxidative and anti-inflammatory activities against ischemia-reperfusion brain injury and could be a good candidate as a therapeutic target for ischemic stroke.

During the past two decades, Runt domain transcription factors (RUNX1, 2, and 3) have been investigated in regard to their function, structural elements, genetic variants, and roles in normal development and pathological conditions. The Runt family proteins are evolutionarily conserved from Drosophila to mammals, emphasizing their physiological importance. A hypoxic microenvironment caused by insufficient blood supply is frequently observed in developing organs, growing tumors, and tissues that become ischemic due to impairment or blockage of blood vessels. During embryonic development and tumor growth, hypoxia triggers a stress response that overcomes low-oxygen conditions by increasing erythropoiesis and angiogenesis and triggering metabolic changes. This review briefly introduces hypoxic conditions and cellular responses, as well as angiogenesis and its related signaling pathways, and then describes our current knowledge on the functions and molecular mechanisms of Runx family proteins in hypoxic responses, especially in angiogenesis.

// Kyunghye Park 1 , Hye Eun Lee 1 , Sun Hee Lee 1 , Doohyun Lee 2 , Taeho Lee 2 , You Mie Lee 1, 2 1 BK21 Plus KNU Multi-Omics based Creative Drug Research Team, National Basic Research Laboratory of Vascular Homeostasis Regulation, Kyungpook National University, Buk-gu, 702-701, Daegu, Republic of Korea 2 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Buk-gu, 702-701, Daegu, Republic of Korea Correspondence to: You Mie Lee, email: lym@knu.ac.kr Keywords: HIF-1α inhibitor, chemical library, benzopyranyl 1,2,3-triazole Received: September 27, 2016 Accepted: December 01, 2016 Published: December 15, 2016 ABSTRACT Hypoxia occurs in a variety of pathological events, including the formation of solid tumors. Hypoxia-inducible factor (HIF)-1α is stabilized under hypoxic conditions and is a key molecule in tumor growth and angiogenesis. Seeking to develop novel cancer therapeutics, we investigated small molecules from our in-house chemical libraries to target HIF-1α. We employed a dual-luciferase assay that uses a luciferase (Luc) reporter vector harboring five copies of hypoxia-responsive element (HRE) in the promoter. Under hypoxic conditions that increased Luc reporter activity by four-fold, we screened 144 different compounds, nine of which showed 30–50% inhibition of hypoxia-induced Luc reporter activity. Among these, “Compound 12, a benzopyranyl 1,2,3-triazole” was the most efficient at inhibiting the expression of HIF-1α under hypoxic conditions, reducing its expression by 80%. Under hypoxic conditions, the half maximal IC 50 of the compound was 24 nM in HEK-293 human embryonic kidney cells, and 2 nM in A549 human lung carcinoma cells. Under hypoxic conditions, Compound 12 increased hydroxylated HIF-1α levels and HIF-1α ubiquitination, and also dose-dependently decreased HIF-1α target gene expression as well as vascular endothelial growth factor (VEGF) secretion. Furthermore, this compound inhibited VEGF-induced in vitro angiogenesis in human umbilical vein endothelial cells (HUVECs), and in vivo , it inhibited chick chorioallantoic membrane angiogenesis. In allogaft assays, cotreatment with Compound 12 and gefitinib significantly inhibited tumor growth and angiogenesis. Compound 12 can be a novel inhibitor of HIF-1α by accelerating its degradation, and shows much potential as an anti-cancer agent through its ability to suppress tumor growth and angiogenesis.

BACKGROUND With the advent of sodium glucose co-transporter 2 inhibitors to control glucose and treat diabetes, laboratory data aided by either timed or spot glucose levels in the urine could be used as an alternative marker of drug response. The aim of this study was to assess the agreement between overnight urinary glucose excretion (UGE) and morning spot urinary glucose-to-creatinine ratio (UGCR). METHODS In this prospective cross-sectional study, we enrolled a total of 215 participants with either normal glucose tolerance (NGT), pre-diabetes, or type 2 diabetes mellitus (T2DM). To exclude external factors such as food intake and physical activity, urine samples collected overnight at an 8-hr interval and the first-voided morning spot urine were collected and compared. RESULTS The median values of overnight 8-hr UGE in participants with NGT (N=14), pre-diabetes (N=41), and T2DM (N=160) were 35.0 mg, 35.6 mg, and 653.4 mg, respectively. In participants with T2DM, the median values of overnight 8-hr UGCR and first-voided morning spot UGCR (M-UGCR) were 1.37 mg/mg and 0.16 mg/mg, respectively. Quantitative analyses using an intraclass correlation coefficient (ICC) demonstrated a good reliability of measurement of the overnight 8-hr UGCR and M-UGCR (ICC=0.943, P

We developed the solution processed Ag source/drain electrodes for stable organic thin-film transistor (OTFT) with 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene). Even though there is a large hole injection barrier between Ag and TIPS-pentacene, the TFT with solution-processed Ag shows good performance. It is due to the continuous formation of organic semiconductor between solution-processed Ag electrodes and TFT channel region with well-organized π–π stacking. The electrical stability of the TFT is much better than that of the TFT using sputtered Ag source/drain electrodes.

The effects of annealing on the fine structure and moisture regain of nylon 4 copolymer films were investigated in terms of the content of nylon 4. Nylon 6-ran-nylon 4 (50/50), (30/70), and (0/100) films were prepared using melt pressing and solution casting methods, respectively. The (N6-ran-N4) copolymer films were annealed in a silicon oil bath at 50, 75, 100, 125 and , and the properties of resultant film were examined by WAXD, DSC, DMTA and moisture regain. The crystal structure in (N6-ran-N4)(50/50) and (30/70) films with increasing annealing temperature was very similar to the gamma phase of nylon 6. The thermal property of (N6-ran-N4)(50/50) and (30/70) films annealed under high temperature exhibit an increase in melting temperature and enthlapy. The result of the tan behavior of (N6-ran-N4)(0/100) film was confirmed to the appearance of two transition peaks. The moisture regain of (N6-ran-N4) copolymer films, except in the case of (N6-ranN4)(30/70) films, decreased when the annealing temperature was increased.

We synthesized a series of tri-component biodegradable copolymers with elastic characteristics by ring-opening copolymerization of cyclic lactones, that is, glycolide, L-lactide, and ϵ-caprolactone, in the presence of stannous octoate as a catalyst. We evaluated the physical and chemical characteristics of poly(glycolide-co-L-lactide-co-ϵ-caprolactone) (PGLCL) copolymers. The synthesized PGLCL had a high molecular weight of about 100 kD and an amorphous structure. It was confirmed that the physical and chemical properties of these terpolymers could be modulated by adjusting copolymer composition. PGLCL films exhibited rubber-like elasticity and showed almost complete recovery when subjected to 50% of the tensile strain. To examine the biodegradability of the PGLCL copolymers, we performed in vitro degradation tests for 12 weeks and observed changes in molecular weight, gross weight, and composition. These results showed that the glycolide was degraded most quickly and that ϵ-caprolactone was the slowest to degrade. Additionally, cytotoxicity tests revealed that none of the polymers were toxic. In summary, the mechanical properties and biodegradability of PGLCL terpolymers could be controlled by changing the monomer content, which may be useful for a wide range of tissue engineering applications based on mechanical property requirements.

Phosphatidylserine (PS) exposure on the external leaflet of the plasma membrane is widely observed during apoptosis and forms the basis for the annexin V binding assay to detect apoptotic cell death. Current efforts to explain PS exposure focus on two potential mechanisms, activation of a phospholipid scramblase or calcium-mediated trafficking of lysosomes to the cell surface. Here, we provide evidence that apoptotic PS exposure instead reflects bidirectional trafficking of membrane between the cell surface and cytoplasm. Using a series of cell lines, some of which expose large amounts of PS during apoptosis and some of which do not, we demonstrate that accumulation of plasma membrane-derived cytoplasmic vesicles in a dynamin-, clathrin- and Cdc42-independent manner is a previously undescribed but widely occurring feature of apoptosis. The apoptotic exposure of PS occurs when these vesicles traffic back to cell surface in a calcium-dependent process that is deficient in a substantial fraction of human cancer cell lines. These observations provide a new model for PS externalization during apoptosis and simultaneously identify an altered step that accounts for the paucity of apoptotic PS exposure in many cell lines.

3,6-Anhydro-l-galactose (L-AHG) constitutes 50 % of agarose, which is the main component of red macroalgae. No information is currently available on the mass production, metabolic fate, or physiological effects of L-AHG. Here, agarose was converted to L-AHG in the following three steps: pre-hydrolysis of agarose into agaro-oligosaccharides by using acetic acid, hydrolysis of the agaro-oligosaccharides into neoagarobiose by an exo-agarase, and hydrolysis of neoagarobiose into L-AHG and galactose by a neoagarobiose hydrolase. After these three steps, L-AHG was purified by adsorption and gel permeation chromatographies. The final product obtained was 95.6 % pure L-AHG at a final yield of 4.0 % based on the initial agarose. In a cell proliferation assay, L-AHG at a concentration of 100 or 200 μg/ mL did not exhibit any significant cytotoxicity. In a skin whitening assay, 100 μg/ mL of L-AHG showed significantly lower melanin production compared to arbutin. L-AHG at 100 and 200 μg/ mL showed strong anti-inflammatory activity, indicating the significant suppression of nitrite production. This is the first report on the production of high-purity L-AHG and its physiological activities.

In order to study the crystal structures of Nylon 4 copolymer films by elevating temperature and shooting Xray along the three principal directions (through, edge, and end directions), HT (high temperature) WAXD (wide angle X-ray diffraction) was used. Three conclusions were derived from this work. First, the diffraction intensity of samples was strongest in the edge direction. Also, the diffraction intensity became stronger as the draw ratio increased. Second, the Brill transition appeared at , which indicates that two peaks merged into one peak within the X-ray diffraction intensity graph. Finally, after cooling the specimen for 24 hours, the WAXD data returned to the same initial state.

Silk fabrics were coated with carbon nano fibers (CNFs)/poly(vinylidene fluoride-co-hexafluoropropylene)(PVDF-HFP) composite solution by the knife edge method. The various contents of CNFs/PVDF-HFP coated silk fab-rics were investigated through their morphological, mechanical, and electrical properties. In the results regarding surfacemorphology, it was shown that the CNFs were evenly distributed in coated silk fabrics through SEM images; the exist-ence of CNFs in coated silk fabrics was confirmed. For the results regarding the mechanical properties, the tensile lin-earity and compression linearity improved as CNFs contents increased. Also, the electrical properties of CNFs/PVDF-HFP coated silk fabrics increased with 4% CNFs contents. Therefore, the results confirm the ability of conductive tex-tiles by using CNFs/PVDF-HFP composite-coated silk fabrics.Keywords: carbon nanofibers, poly(vinylidene fluoride-hexafluoropropylene), conductive silk fabrics, mechanical property,electrical property

How HIV-1 resistant to small-molecule CCR5 antagonists uses the coreceptor for entry has been studied in a limited number of isolates. We characterized dependence on the N terminus (NT) and the second extracellular loop (ECL2) of CCR5 of three vicriviroc (VCV)-resistant clinical isolates broadly cross-resistant to other CCR5 antagonists. Pseudoviruses were constructed to assess CCR5 use by VCV-sensitive and -resistant envelopes of subtype B and C viruses. We determined the extent of entry inhibition by monoclonal antibodies (MAbs) directed against the NT and ECL2 in the presence and absence of VCV and the capacity of these pseudoviruses to use CCR5 mutants that contained scanning alanine substitutions in the CCR5 NT and ECL2 domains. Sensitive and resistant viruses were completely and competitively inhibited by the ECL2-specific MAb 2D7, whereas the NT-specific MAb CTC5 led to partial noncompetitive inhibition. VCV-resistant clones showed greater sensitivity to 2D7 than VCV-sensitive clones, but in the presence of saturating VCV concentrations, the 2D7 susceptibilities of two VCV-resistant viruses were similar to that of VCV-sensitive virus. The entry of VCV-sensitive and -resistant isolates was impaired to differing degrees by alanine mutations in CCR5; substitutions in NT had the greatest effect on viral entry. HIV-1 clinical isolates broadly resistant to CCR5 antagonists demonstrated significant heterogeneity in their use of CCR5. This heterogeneity makes it difficult to draw general conclusions about the relationship between patterns of CCR5 antagonist resistance and the use of specific CCR5 domains for entry.

Various factors affecting on the bioassay were investigated. Experiments with a low mixture ratio (cell to toxicant solution) of 0.5 : 9.5 (v/v) produced observable bioluminescence intensity for assay. Both sodium lactate and potassium nitrate stimulate bioluminescence activity; 2.6~4.0 times of control. Distilled water and MSM, which gave non significant effects on the bioluminescence activity, were determined as proper diluent or extract solutions. A wide range of toxic responses of metals and organics were observed. In general, organics were much less sensitive than metals. Samples collected from eleven sites showed the bioluminescence activity ranging from 29 to 111% of the control. Significant correlation between toxicity and total metal contents was not observed, but the toxicity of two groups, sorted based on the contaminated arsenic concentration in soils, was 44% and 20%, showing considerable differences.

HIV CCR5 antagonists select for env gene mutations that enable virus entry via drug-bound coreceptor. To investigate the mechanisms responsible for viral adaptation to drug-bound coreceptor-mediated entry, we studied viral isolates from three participants who developed CCR5 antagonist resistance during treatment with vicriviroc (VCV), an investigational small-molecule CCR5 antagonist. VCV-sensitive and -resistant viruses were isolated from one HIV subtype C- and two subtype B-infected participants; VCV-resistant isolates had mutations in the V3 loop of gp120 and were cross-resistant to TAK-779, an investigational antagonist, and maraviroc (MVC). All three resistant isolates contained a 306P mutation but had variable mutations elsewhere in the V3 stem. We used a virus-cell β-lactamase (BlaM) fusion assay to determine the entry kinetics of recombinant viruses that incorporated full-length VCV-sensitive and -resistant envelopes. VCV-resistant isolates exhibited delayed entry rates in the absence of drug, relative to pretherapy VCV-sensitive isolates. The addition of drug corrected these delays. These findings were generalizable across target cell types with a range of CD4 and CCR5 surface densities and were observed when either population-derived or clonal envelopes were used to construct recombinant viruses. V3 loop mutations alone were sufficient to restore virus entry in the presence of drug, and the accumulation of V3 mutations during VCV therapy led to progressively higher rates of viral entry. We propose that the restoration of pre-CCR5 antagonist therapy HIV entry kinetics drives the selection of V3 loop mutations and may represent a common mechanism that underlies the emergence of CCR5 antagonist resistance.

Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT), an enzyme responsible for acetylcholine (ACh) synthesis, is observed. In the present study we investigated if brain transplantation of human neural stem cells (NSCs) genetically modified to encode ChAT gene improves cognitive function of kainic acid (KA)-induced learning deficit rats. Intrahippocampal injection of KA to hippocampal CA3 region caused severe neuronal loss, resulting in profound learning and memory deficit. F3.ChAT human NSCs transplanted intracerebroventricularly improved fully the learning and memory function of KA-induced learning deficit animals, in parallel with the elevation of ACh levels in cerebrospinal fluid. F3.ChAT human NSCs migrated to the KA-induced injury site (CA3) and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs expressing ChAT have lesion-tropic property and improve cognitive function of learning deficit model rats with hippocampal injury by increasing ACh level.

Antitumor effects of a ginsenoside Rg3-fortified red ginseng preparation (Rg3-RGP) were investigated in human non-small cell lung carcinoma (H460) cells using in vitro cytotoxicity assay and in vivo nude mouse xenograft model. Immunomodulatory effects of the preparation were also assessed by measuring the facilitating activities on the nitric oxide (NO) release from peritoneal macrophages, in vitro and in vivo lymphocyte proliferation, and the carbon clearance from circulating blood. In a cell level, Rg3-RGP exerted H460 cytotoxicity and facilitated splenocyte proliferation at very high concentrations, without affecting NO production. However, oral administration of Rg3-RGP (100–300 mg/kg) enhanced carbon particle-phagocytic index of blood macrophages up to 360–397% of control value. In addition, Rg3-RGP significantly increased the splenocyte proliferation (23% at 100 mg/kg). In tumorbearing mice, 28-day oral treatment with Rg3-RGP (100 mg/kg) remarkably suppressed the tumor growth, leading to the decrease of the tumor volume and weight by 30–31%, which was comparable to the effect (27–29% reduction) of doxorubicin (2 mg/kg at 3-day intervals). While Rg3-RGP did not cause adverse effects, intravenous injection of doxorubicin markedly decreased body and testes weights, and exhibited severe depletion of spermatogenic cells in the atrophic seminiferous tubules. These results indicate that Rg3-RGP exerts antitumor activities via indirect immunomodulatory actions, without causing adverse effects as seen in doxorubicin.

Soybeans are known to protect against osteoporosis, but other legumes frequently consumed in Asia have not been studied to learn if they have a similar protective effect. This study investigated the hypothesis that consumption of soybean, mung bean, cowpea, and adzuki bean has beneficial effects on bone biomarkers in ovariectomized rats. Female Sprague-Dawley rats were either sham operated (sham; n = 7) or surgically ovariectomized and then fed a regular AIN-93M diet (OVX; n = 7) or AIN-93M containing soybean (n = 7), mung bean (n = 7), cowpea (n = 7), or adzuki beans (n = 7) for 10 weeks. No bean consumption significantly altered the body, subcutaneous fat, or uterus weight; however, consumption significantly increased the serum calcium/phosphorous ratio and decreased urinary calcium excretion compared with those of the OVX group. Serum concentration of 17β-estradiol was significantly lower in the OVX group compared with that of the sham group and was lowest in the group fed OVX diet containing soybean. Serum osteocalcin concentration was significantly higher in all OVX rats given a diet with beans compared with the same diet without, but urinary deoxypyridinoline excretion was lowest in the group fed OVX diet containing cowpea. There were no significant differences in bone mineral density or bone mineral content of the right femur, tibia, or lumbar spine or in the trabecular bone volume of the tibia among the diet groups. In conclusion, the consumption of soybean, mung bean, cowpea, and adzuki bean in OVX rats improved osteocalcin, but only those fed cowpea showed decreased bone resorption biomarker, suggesting that cowpea may have the most protective effect on bone in OVX rats.

UV-curing technique was employed in this study to prepare polyester-acrylate nanocomposite films with silane-grafted silica nanoparticles. Methacryloxypropyl trimethoxysilane was grafted to the surfaces of silica nanoparticles to improve dispersion of silica nanoparticles as well as interfacial adhesion between the resin matrix and silica nanoparticles. The silane-grafting was confirmed by nuclear magnetic resonance and infrared spectroscopy. The effects of the silane-grafting on the mechanical and optical properties as well as UV-curing behavior of the nanocomposite films were investigated. The tensile strength, transmittance, UV-curing rate, and final chemical conversion of the nanocomposite films were increased by use of the grafted silica nanoparticles as compared to the use of neat silica nanoparticles. Copyright © 2011 John Wiley & Sons, Ltd.

Acrolein is a highly reactive α, β-unsaturated aldehyde that is an environmental pollutant, a product of endogenous lipid peroxidation and a major component of cigarette smoke, which has been linked to the development of atherosclerotic vascular disease. Activation of endothelial cells by stimuli such as cigarette smoke is an important risk factor in atherosclerosis. Several studies have reported that acrolein levels are increased in atherosclerosis. Presently, a whole human DNA chip containing 24,000 genes was utilized to examine atherogenesis-related gene expression profiles of acrolein-stimulated human umbilical vein endothelial cells (HUVECs). Genes whose expression changed more than 2-fold included 3,174 up-regulated genes and 551 down-regulated genes. The affected genes included human atherogenesis-related genes such as cytokines, chemokines and adhesion molecules. These results support the view that acrolein-stimulated changes in HUVEC gene expression contribute to the development of atherosclerosis.

We studied the fabrication of stable ink-jet printed organic thin-film transistors (OTFTs) with printed source/drain electrodes. On the top of printed Ag source/drain electrodes, 6, 13-bis(4-pentylphenylethynyl) pentacene was ink-jet printed as an active semiconductor. The printed OTFT exhibited the field-effect mobility of 0.042 cm2/V, an on/off current ratio of 106, a threshold voltage of 2.9 V and the gate voltage swing of 0.6 V/dec. The printed OTFT shows negligible hysteresis in air and stable performance under gate bias stress.

Pseudomonas fulva TY16 biosynthesized medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) containing unsaturated 3-hydroxydodecenoate unit (approximately 8–9%) when grown with volatile aromatic compounds including benzene, toluene, and ethylbenzene as sole carbon substrate. In particular, when cultivated using a continuous feeding system designed to supply toluene at a flow rate of 0.42 g L −1 h −1 into a 7-L jar fermentor, the growth of the organism reached up to approximately 3.87 g L −1 after the 48 h fed-batch fermentation, representing an accumulated cellular MCL-PHA of 58.9% by weight. The obtained MCL-PHA was a copolyester primarily consisting of 3-hydroxydecanoate (55.2%) and 3-hydroxyoctanoate (26.8%) with minor constituents being 3-hydroxyhexanoate (3.7%), 3-hydroxydodecenoate (8.2%), and 3-hydroxydodecanoate (6.1%). The present results suggest that P. fulva TY16 is a promising candidate for the biotechnological conversion of toxic petrochemical wastes to valuable biopolymers.

To confirm the anti-allergic effects of the ethanolic extract of Angelica gigas (EAG), the levels of ear erythema, ear weight, vascular leakage, heamatology, tumor-necrosis factor-α, interleukin-6 and immunoglobulin E from mice sensitized with 2,4-dinitroflurorobenzene were examined. The results showed that EAG reduced ear erythema and ear weight; we also found that Evan's blue leakage decreased. Furthermore, the levels of interleukin-6 and immunoglobulin E in the serum were significantly inhibited. In RAW264.7 cells, EAG drastically inhibited the mRNA levels of inducible nitric oxide synthease, tumor-necrosis factor-α and macrophage inflammatory protein-1β, suggesting that EAG may inhibit the release of pro-inflammatory cytokines and acute neutrophilic inflammation. Western blot analysis showed that EAG inhibited nuclear factor-κB- and extracelullar signal-regulated protein kinase-dependent inflammatory pathways. Interestingly, EAG effectively inhibited the release of β-hexosaminidase, a granule marker from mast cells. Taken together, our results demonstrate that EAG inhibits focal and systemic inflammatory and allergic reactions, and holds great promise for the treatment of several inflammatory diseases.

We have studied the selective coating on the TFT region by spin-casting of 6,13-bis(4-pentylphenylethynyl) pentacene (PPE pentacene). The island of PPE pentacene was formed inside of the banks for TFT, which was independent of self-assembled monolayer layer on source/drain electrodes. A bottom contact TFT with the PPE pentacene using selective coating on TFT region, exhibited the field-effect mobility of 0.02 cm 2 /V s, an on/off current ratio of 10 7 and gate voltage swing of 0.8 V/dec. An inverter made of PPE pentacene TFTs was demonstrated to have the signal gain of >1.5 ( V DD = −40 V) using selective coating.