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This paper presents the structural performance of jacketed concrete columns subjected to cyclic lateral loading using ultrahigh-performance fiber-reinforced concrete (UHPFRC) with various advantages as construction materials of high strength and durability with self-compacting. The UHPFRC jacketing with/without textile reinforcement for concrete columns for the seismic retrofitting demonstrates its strengthening efficiency and reduction of jacket thickness through the experimental program in this study. Especially, textile-reinforced UHPFRC (TR-UHPFRC) jacketing has enhanced ductility compared with that of UHPFRC jacketing by changing critical failure crack patterns in jackets. The satisfactory interface shear strength between UHPFRC jackets and substrate concrete of columns was confirmed by a series of slant shear test programs provided that required roughness on substrate with moisture were prepared according to current design guidelines. This study also investigates the effects of discontinuity of tension forces in jackets at the floor level of columns on shear load paths, which are intended to alleviate jacketing construction for columns in existing buildings as a member intervention technique. Shears and axial forces induced in jacketed columns under lateral loading are mainly resisted by compression forces in diagonal struts through the jacket with substrate concrete columns and are explained by arch actions for enhancement of shear strength after jacketing. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is a feature of aging (termed sarcopenia) and various diseases, such as cancer and kidney failure. Effective drug treatment options for muscle atrophy are lacking. The tapeworm medication, niclosamide is being assessed for repurposing to treat numerous diseases, including end-stage cancer metastasis and hepatic steatosis. In this study, we investigated the potential of niclosamide as a repurposing drug for muscle atrophy. In a myotube atrophy model using the glucocorticoid, dexamethasone, niclosamide did not prevent the reduction in myotube diameter or the decreased expression of phosphorylated FOXO3a, which upregulates the ubiquitin-proteasome pathway of muscle catabolism. Treatment of normal myotubes with niclosamide did not activate mTOR, a major regulator of muscle protein synthesis, and increased the expression of atrogin-1, which is induced in catabolic states. Niclosamide treatment also inhibited myogenesis in muscle precursor cells, enhanced the expression of myoblast markers Pax7 and Myf5, and downregulated the expression of differentiation markers MyoD, MyoG and Myh2. In an animal model of muscle atrophy, niclosamide did not improve muscle mass, grip strength or muscle fiber cross-sectional area. Muscle atrophy is also feature of cancer cachexia. IC50 analyses indicated that niclosamide was more cytotoxic for myoblasts than cancer cells. In addition, niclosamide did not suppress the induction of iNOS, a key mediator of atrophy, in an in vitro model of cancer cachexia and did not rescue myotube diameter. Overall, these results suggest that niclosamide may not be a suitable repurposing drug for glucocorticoid-induced skeletal muscle atrophy or cancer cachexia. Nevertheless, niclosamide may be employed as a compound to study mechanisms regulating myogenesis and catabolic pathways in skeletal muscle. [ABSTRACT FROM AUTHOR]

Introduction: Visual field testing via standard automated perimetry (SAP) is a commonly used glaucoma diagnosis method. Applying machine learning techniques to the visual field test results, a valid clinical diagnosis of glaucoma solely based on the SAP data is provided. In order to reflect structural-functional patterns of glaucoma on the automated diagnostic models, we propose composite variables derived from anatomically grouped visual field clusters to improve the prediction performance. A set of machine learning-based diagnostic models are designed that implement different input data manipulation, dimensionality reduction, and classification methods.Methods: Visual field testing data of 375 healthy and 257 glaucomatous eyes were used to build the diagnostic models. Three kinds of composite variables derived from the Garway-Heath map and the glaucoma hemifield test (GHT) sector map were included in the input variables in addition to the 52 SAP visual filed locations. Dimensionality reduction was conducted to select important variables so as to alleviate high-dimensionality problems. To validate the proposed methods, we applied four classifiers-linear discriminant analysis, naïve Bayes classifier, support vector machines, and artificial neural networks-and four dimensionality reduction methods-Pearson correlation coefficient-based variable selection, Markov blanket variable selection, the minimum redundancy maximum relevance algorithm, and principal component analysis- and compared their classification performances.Results: For all tested combinations, the classification performance improved when the proposed composite variables and dimensionality reduction techniques were implemented. The combination of total deviation values, the GHT sector map, support vector machines, and Markov blanket variable selection obtains the best performance: an area under the receiver operating characteristic curve (AUC) of 0.912.Conclusion: A glaucoma diagnosis model giving an AUC of 0.912 was constructed by applying machine learning techniques to SAP data. The results show that dimensionality reduction not only reduces dimensions of the input space but also enhances the classification performance. The variable selection results show that the proposed composite variables from visual field clustering play a key role in the diagnosis model. [ABSTRACT FROM AUTHOR]

This paper studies an explosive autoregression with conditionally heteroskedastic innovations. The asymptotic distributions of LS, GLS, t -statistics, heteroskedasticity-consistent t -statistics and GLS t -statistics are derived for nonstationary local-to-unity and mildly explosive roots, in which ρ n satisfies n 1 − ρ n → − ∞ , 0 . Combined with the existing results, we can cover the range of ρ n such that n 1 − ρ n → − ∞ , ∞ . Some results on pure explosive cases are also discussed. [ABSTRACT FROM AUTHOR]

Conjugated binary copolymers containing an electron donor (D) and acceptor (A) in the repeating unit have been extensively studied due to their excellent charge transport properties. Moreover, conjugated terpolymers containing a third monomer in addition to the two D and A monomers have been recognized to exhibit finely tuned properties relative to the binary D-A copolymer. Diketopyrrolopyrrole (DPP)–based conjugated regular terpolymers (CRTs) containing two different electron donor monomers were synthesized herein to exploit the advantages of the terpolymer. Two terpolymers were synthesized by using bithiophene and pyrene as third monomers. Compared to the reference copolymer, poly[3-(5-(benzo[1,2-b:4,5-b']dithiophen-2-yl)thiophen-2-yl)-2,5-bis(2-decyltetradecyl)-6-(thiophen-2-yl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione] (PDPPBDT), the new terpolymers exhibited distinct physical properties, absorption properties, and electronic energy levels. The terpolymers were employed in thin film transistors (TFTs) and polymer solar cells (PSCs) and the device performance was studied. The highest mobility achieved for the TFT devices was close to 1.0 cm 2  V −1  s −1 and was obtained with the PDPPBTBDT terpolymer film as the active layer, whereas the mobilities of the TFTs employing the PDPPPYBDT and PDPPBDT polymers were relatively low. In contrast with the TFT device results, the PSC fabricated with PDPPPYBDT:PC 71 BM showed the highest power conversion efficiency (PCE) of 4.46% due to the relatively high V oc and J sc . The results of this study confirmed that the use of a regular terpolymer structure permits fine adjustment of the light absorption range, the molecular energy levels, and the film morphology of the polymer, in turn influencing the device performance of TFTs or PSCs. [ABSTRACT FROM AUTHOR]

ABSTRACT We demonstrate a fully conjugated donor-acceptor-donor (D-A-D) triblock copolymer, PBDTT-PNDIBT-PBDTT, which contains PBDTT as the donor block and PNDIBT as the acceptor block. The polymer was synthesized by end-capping each block with a reactive unit, followed by condensation copolymerization between the two blocks. The physical, optical, and electrochemical properties of the polymer were investigated by comparing those of donor- and acceptor-homopolymers (i.e., PBDTT and PNDIBT), which are the oligomeric monomers, and their blends. On using the newly synthesized block copolymer, ambipolar charge transport behavior was observed in the corresponding thin-film transistor, and the behavior was compared to that of blend film of donor- and acceptor-homopolymers. Owing to the presence of donor and acceptor blocks in a single polymer chain, it was found that the triblock copolymer can store two-level information; the ability to store this information is one of the most intriguing challenges in memory applications. In this study, we confirmed the potential of the triblock copolymer in achieving distinct two-stage data storage by utilizing the ambipolar charge trapping phenomenon, which is expected in donor and acceptor containing random and block copolymers in a thin-film transistor. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3223-3235 [ABSTRACT FROM AUTHOR]

We propose a novel tricyanovinyldihydrofuran (TCF)-based molecule called DBOB-DTCF that is designed and synthesized for application in n-type field-effect transistors (FETs). It can be operated in a stable manner under ambient conditions. DBOB-DTCF is successfully fabricated as crystalline microplates (CMs) because of its capability of self-assembly. A high electron mobility of ∼1.9 cm2 V−1 s−1 is observed for a CM-based FET, measured under ambient conditions. This suggests that TCF is an excellent acceptor unit that organizes air stable n-type organic semiconductors. [ABSTRACT FROM AUTHOR]

There is a continual need to develop novel and effective melanogenesis inhibitors for the prevention of hyperpigmentation disorders. The plant Artemisia capillaris Thunberg (Oriental Wormwood) was screened for antipigmentation activity using murine cultured cells (B16-F10 malignant melanocytes). Activity-based fractionation using HPLC and NMR analyses identified the compound 4,5-O-dicaffeoylquinic acid as an active component in this plant. 4,5-O-Dicaffeoylquinic acid significantly reduced melanin synthesis and tyrosinase activity in a dose-dependent manner in the melanocytes. In addition, 4,5-O-dicaffeoylquinic acid treatment reduced the expression of tyrosinase-related protein-1. Significantly, we could validate the antipigmentation activity of this compound in vivo, using a zebrafish model. Moreover, 4,5-O-dicaffeoylquinic acid did not show toxicity in this animal model. Our discovery of 4,5-O-dicaffeoylquinic acid as an inhibitor of pigmentation that is active in vivo shows that this compound can be developed as an active component for formulations to treat pigmentation disorders. [ABSTRACT FROM AUTHOR]

We demonstrated the effective structural control of the conjugation length and various donor moieties using thiophene and selenophene derivatives in a regular terpolymer system and compared the properties with two copolymers of PDPP-SS and PDPP-TT. The three different terpolymers are composed of diketopyrrolopyrrole (DPP)-based polymers such as PDPP-TTS, PDPP-TSS, and PDPP-TTSS. The optical and electronic properties of these regular terpolymers can be precisely controlled by varying the conjugation length of the repeating unit and the composition ratio of the thiophene and selenophene moieties. It was found from the grazing incidence X-ray diffraction that PDPP-TTS and PDPP-TSS with different lengths of donor moieties exhibited mixed chain orientations in face-on and edge-on manners on the substrate. However, PDPP-TTSS showed edge-on chain orientation which is similar to the copolymers of PDPP-TT and PDPP-SS, and much improved charge-carrier mobility. Moreover, the enhanced power conversion efficiencies (PCEs) of polymer solar cells made of PDPP-TSS and PDPP-TTSS were observed to be 4.18 and 4.76%, respectively, owing to the higher composition of thiophene, which could be compensated by the properties of thiophene. As a result, the PCEs of regular terpolymers were markedly enhanced by inserting the thiophene moiety into the donor part of the DPP-based terpolymer, PDPP-SS. [ABSTRACT FROM AUTHOR]

Abstract: Thrust variation, flow structures and geometric factors of pintle-perturbed conical nozzle are studied experimentally and numerically under the condition of constant mass flow rate. Regulators and choking orifice are installed for constant mass flow rate and static pressure distributions along the nozzle wall, chamber pressure and thrust are measured. In order to prevent transfer of non-linear load to the load cell by the flexible tubes, the load cell for thrust measurement is calibrated. Roeʼs flux-difference splitting scheme is applied to resolve the flow discontinuities such as the lip shock, trailing shock and oblique shock typical in the pintle-perturbed nozzle flows. Three different turbulent models of , SST and Spalart–Allmaras are examined to assess their validity for resolving the turbulence. The predicted thrust by empirical method, which includes influence of deliverable thrust coefficient by flow separation, showed good agreement with measured thrust at the minimum and maximum throat area. Spalart–Allmaras model and SST model showed good agreement with experiment on predicting the thrust especially in the case that the flow separation occurs in the nozzle diverging section, and the Spalart–Allmaras model predicted wall separation point more accurately than the other models. Shock impinging point and the flow separation point induced by shock wave separation occur and move in the nozzle flow as the pintle inserted into the nozzle throat. Because, the dominant factor which determines thrust is chamber pressure, the pintle shape must be considered essentially in view of minimizing the force acting on the pintle. [Copyright &y& Elsevier]

Abstract: KRN7000 is an important ligand identified for CD1d protein of APC, and KRN7000/CD1d complex can stimulate NKT cells to release a broad range of bioactive cytokines. In an effort to understand the structure–activity relationships, we have carried out syntheses of 26 new KRN7000 analogues incorporating aromatic residues in either or both side chains. Structural variations of the phytosphingosine moiety also include varying stereochemistry at C3 and C4, and 4-deoxy and 3,4-dideoxy versions. Their biological activities are described. [Copyright &y& Elsevier]

Abstract: Sphingolipids such as ceramide and sphingosine-1-phosphate have recently attracted intense research interests because of their functional roles as signaling molecules in many important physiological processes, such as growth arrest, apoptosis, and inflammatory responses, and cell proliferation, vascular maturation and trafficking of lymphocytes. The well-defined modular structures of ceramides and related glycosylceramides are ideally amenable to library formation for medicinal chemistry investigation. We have developed divergent synthetic routes to all eight phytosphingosine stereoisomers and then proceeded to prepare phytosphingosine-based ceramide library composed of more than 500 compounds. [Copyright &y& Elsevier]

Abstract: Effects of essential performance parameters on the starting transient of a straight cylindrical supersonic exhaust diffuser (SED) are numerically investigated. Diffuser starting and evacuation transients are examined in terms of SED lengths and pre-evacuation configuration. Preconditioned Favre-averaged Navier–Stokes equations incorporated with a low Reynolds number turbulence model and Sakar’s method to treat turbulence compressibility is solved for strongly turbulent all-Mach diffuser flows. The numerical method is properly validated with the measurements with accuracy. Characteristic locus of diffuser-starting and diffuser-unstarting modes is constructed for the diffusers of three different lengths (L/D =2, 5, and 20). Flow evolutions visualized in diffuser mode-transition regimes manifest a threshold L/D over which the SED starting transient is unique. An occurrence of plume blowback into the vacuum chamber due to lower initial pressure (P C,INIT/P A =0.0027) expedites expansion of nozzle exhaust and diffuser choking, and causes faster chamber evacuation than the atmospheric starting. [Copyright &y& Elsevier]

Abstract: KRN7000 is an important ligand identified for CD1d protein of APC, and KRN7000/CD1d complex can stimulate NKT cells to release Th1 and Th2 cytokines. In an effort to understand the structure–activity relationships, we have carried out the synthesis of a complete set of the eight KRN7000 stereoisomers, and their biological activities have been examined. [Copyright &y& Elsevier]

Abstract: The nozzle parts of solid rocket motors must endure both the internal pressure generated by high temperature exhaust gas and the mechanical load generated by steering operation. Therefore, the nozzle parts of solid rocket motors are fabricated with thick carbon fiber phenolic resin composites. When the thick-walled phenolic composite cylinder is cooled down from the curing temperature of about 155°C to the room temperature, thermal residual stresses are created due to the anisotropic thermal deformation of the composite structure. In this paper, a smart cure method with cooling and reheating was developed to reduce residual stresses in thick-wound composite cylinders made of carbon phenolic woven composite. The optimal cure cycle was obtained to reduce the residual stresses without increasing processing time and applied to fabrication of the thick-walled composite cylinder. From the residual stresses measured by the radial-cut-cylinder-bending method, it was found that the residual stresses were reduced 30% by using the smart cure method. [Copyright &y& Elsevier]

Inflammation-mediated skeletal muscle wasting occurs in patients with sepsis and cancer cachexia. Both conditions severely affect patient morbidity and mortality. Lithium chloride has previously been shown to enhance myogenesis and prevent certain forms of muscular dystrophy. However, to our knowledge, the effect of lithium chloride treatment on sepsis-induced muscle atrophy and cancer cachexia has not yet been investigated. In this study, we aimed to examine the effects of lithium chloride using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell-conditioned media, maintained the expression of the muscle fiber contractile protein, myosin heavy chain 2, and inhibited the upregulation of the E3 ubiquitin ligase, Atrogin-1. In addition, it inhibited the upregulation of inflammation-associated cytokines in macrophages treated with lipopolysaccharide. In the animal model of sepsis, lithium chloride treatment improved body weight, increased muscle mass, preserved the survival of larger fibers, and decreased the expression of muscle-wasting effector genes. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength, and increased fiber cross-sectional area, with no significant effect on tumor mass. These results indicate that lithium chloride exerts therapeutic effects on inflammation-mediated skeletal muscle wasting, such as sepsis-induced muscle atrophy and cancer cachexia. [ABSTRACT FROM AUTHOR]

Obesity is a medical condition that impacts on all levels of society and causes numerous comorbidities, such as diabetes, cardiovascular disease, and cancer. We assessed the suitability of targeting enolase, a glycolysis pathway enzyme with multiple, secondary functions in cells, to treat obesity. Treating adipocytes with ENOblock, a novel modulator of these secondary 'moonlighting' functions of enolase, suppressed the adipogenic program and induced mitochondrial uncoupling. Obese animals treated with ENOblock showed a reduction in body weight and increased core body temperature. Metabolic and inflammatory parameters were improved in the liver, adipose tissue and hippocampus. The mechanism of ENOblock was identified as transcriptional repression of master regulators of lipid homeostasis (Srebp-1a and Srebp-1c), gluconeogenesis (Pck-1) and inflammation (Tnf-α and Il-6). ENOblock treatment also reduced body weight gain, lowered cumulative food intake and increased fecal lipid content in mice fed a high fat diet. Our results support the further drug development of ENOblock as a therapeutic for obesity and suggest enolase as a new target for this disorder. [ABSTRACT FROM AUTHOR]

CCL2 mitigates cyclic AMP-suppressed Th2 immune response in human dendritic cells Keywords: allergic rhinitis; cAMP; CCL2; dendritic cells; Gnas CD11c mice EN allergic rhinitis cAMP CCL2 dendritic cells Gnas CD11c mice 1 4 4 07/29/20 20200801 NES 200801 Allergic rhinitis (AR) is a Th2-type chronic inflammatory disease of the nasal mucosa, characterized by symptoms including rhinorrhea, obstruction, and sneezing. However, CCL7 mRNA in AR MDDCs was not different from that in control MDDCs (Figure S4), suggesting that decreased cAMP levels in AR DCs induce the Th2 immune response through upregulation of CCL2. [Extracted from the article]

Trisubstituted piperidines [(II), (III), and (V)] are formed from homopropargylic alkoxyamines by Au(I)-catalysis. [ABSTRACT FROM AUTHOR]

Two regioisomeric π-conjugated terpolymers bearing carboxylated thiophene (CT) as electron accepting unit and thienothiophene (TT) and bithiophene (BT) as electron donating units were successfully synthesized for enhancing the performance of polymer solar cells (PSCs). Regio-regular and regio-random binary copolymers based on CT and BT were also prepared as control polymers. All polymers showed unique optical properties and crystalline behaviors. Among the PSC devices fabricated in this study, the PSC based on the regio-random terpolymer ( Ran-TT ) and 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis (4-hexylphenyl) dithieno [2,3-d:2′,3′- d ′]- s -indaceno [1,2-b:5,6b′]-dithiophene (ITIC) exhibited the highest power conversion efficiency of 5.65% with a high short circuit current density ( J sc ) of 12.63 mA cm −2 and an open circuit voltage ( V oc ) of 0.81 V. The promising PCE value is attributed to the low-lying highest occupied molecular orbital (HOMO) of Ran-TT , effective complementary absorption spectrum and favorable internal morphology of the blend film. The internal morphology of the Ran-TT was observed to be more fine phase separation than that of the regio-regular terpolymer, facilitating exciton diffusion and dissociation in the bulk heterojunction. [ABSTRACT FROM AUTHOR]

The hydrogen production by reaction of aluminum foils and powders with KOH aqueous alkaline solutions was studied. Effect of different physical factors on the specific hydrogen production rate was analyzed. The efficiency of activation of aluminum by copper was examined. Three variants of contacting copper with aluminum were considered: 1) preliminary chemical coating of the aluminum surface, 2) embedding copper into the melt of aluminum or pressing the aluminum – copper powder mixture, 3) continuous supplying copper to the aluminum surface during the reaction. The results showed that presence of copper on the surface or in the bulk of aluminum essentially increased the effective hydrogen production rate. The filtration corrosion in pressed aluminum powder was found. Hydrogen production at reaction of aluminum with NaCl + CuSO 4 solutions was studied. [ABSTRACT FROM AUTHOR]

In the present article, the rheological behavior and thermal conductivity for dispersions of paraffin rods in silicone oil were investigated experimentally by examining the effects of surfactant concentration, particle volume concentration and temperature. The test suspensions at 15°C showed a strong shear-thinning viscosity as the particle concentration increased, whereas the test emulsions at 58°C showed typical Newtonian viscosity behavior. Relative viscosities of the present results agree with the theoretical results for rodlike particle suspensions. Thermal conductivities of the paraffin, silicon oil and mixture were measured with varying temperatures, respectively. Thermal conductivities of paraffin dispersions correlated satisfactorily with the Brailsford-Major equation. [Copyright &y& Elsevier]

Aging is associated with increased prevalence of skeletal and cardiac muscle disorders, such as sarcopenia and cardiac infarction. In this study, we constructed a compendium of purified ginsenoside compounds from Panax ginseng C.A. Meyer, which is a traditional Korean medicinal plant used to treat for muscle weakness. Skeletal muscle progenitor cell-based screening identified three compounds that enhance cell viability, of which 20(R)-ginsenoside Rh2 showed the most robust response. 20(R)-ginsenoside Rh2 increased viability in myoblasts and cardiomyocytes, but not fibroblasts or disease-related cells. The cellular mechanism was identified as downregulation of cyclin-dependent kinase inhibitor 1B (p27Kip1) via upregulation of Akt1/PKB phosphorylation at serine 473, with the orientation of the 20 carbon epimer being crucially important for biological activity. In zebrafish and mammalian models, 20(R)-ginsenoside Rh2 enhanced muscle cell proliferation and accelerated recovery from degeneration. Thus, we have identified 20(R)-ginsenoside Rh2 as a p27Kip1 inhibitor that may be developed as a natural therapeutic for muscle degeneration. [ABSTRACT FROM AUTHOR]

Background: A20 protein has ubiquitin-editing activities and acts as a key regulator of inflammation and immunity. Previously, our group showed that A20 promotes tumor metastasis through multi-monoubiquitylation of SNAIL1 in basal-like breast cancer. Here, we investigated survival outcomes in patients with breast cancer according to A20 expression. Patients and methods: We retrospectively collected tumor samples from patients with breast cancer. Immunohistochemistry (IHC) with an A20-specific antibody was performed, and survival outcomes were analyzed. Results: A20 expression was evaluated in 442 patients. High A20 expression was associated with advanced anatomical stage and young age. High A20 expression showed significantly inferior recurrence-free-survival and overall-survival (P<0.001 and P<0.001, respectively). Multivariate analysis showed that A20 was an independent prognostic marker for RFS (HRs: 2.324, 95% CIs: 1.446–3.736) and OS (HRs: 2.629, 95% CIs: 1.585–4.361). In human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) subtypes, high A20 levels were associated with poor OS. Conclusion: We found that A20 expression is a poor prognostic marker in breast cancer. The prognostic impact of A20 was pronounced in aggressive tumors, such as HER2-positive and TNBC subtypes. Our findings suggested that A20 may be a valuable target in patients with aggressive breast cancer. [ABSTRACT FROM AUTHOR]

We designed and synthesized two kinds of spirobifluorene (SP)-based acceptor–donor–acceptor (A–D–A)-type acceptor materials, denoted by SP-IC and SP-TCF, which have an A–D–A structure consisting of a 3D tetrathienospirobifluorene donor core and 2-(3-oxo-2,3-dihydro-1 H -inden-1-ylidene)malononitrile (IC) or 2-(3-cyano-4,5,5-trimethylfuran-2(5 H )-ylidene)malononitrile (TCF) acceptors as terminal units, respectively. Their LUMO levels (−3.91 eV for SP-IC and −3.97 eV for SP-TCF) are suitable as n-type molecules for PTB7-Th-based polymer solar cells. However, their morphologies in blend films with a conjugated donor polymer, Poly([2,6′-4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,3-b]dithiophene]{3-fluoro-2[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}) (PTB7-Th), exhibited considerable differences. The PTB7-Th:SP-IC blend film exhibited a better-defined nanophase-separated morphology than PTB7-Th:SP-TCF blend film. The corresponding bulk heterojunction polymer solar cell based on PTB7-Th:SP-IC showed four times higher power conversion efficiency (PCE = 4.50%) than that of PTB7-Th:SP-TCF. The higher PCE was well explained by investigating the morphology, which was affected by the surface energy of the acceptor molecules at the donor–acceptor interface. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) significantly impacts on human health and patient numbers are predicted to rise. Discovering novel drugs and targets for treating T2DM is a research priority. In this study, we investigated targeting of the glycolysis enzyme, enolase, using the small molecule ENOblock, which binds enolase and modulates its non-glycolytic 'moonlighting' functions. In insulin-responsive cells ENOblock induced enolase nuclear translocation, where this enzyme acts as a transcriptional repressor. In a mammalian model of T2DM, ENOblock treatment reduced hyperglycemia and hyperlipidemia. Liver and kidney tissue of ENOblock-treated mice showed down-regulation of known enolase target genes and reduced enolase enzyme activity. Indicators of secondary diabetic complications, such as tissue apoptosis, inflammatory markers and fibrosis were inhibited by ENOblock treatment. Compared to the well-characterized anti-diabetes drug, rosiglitazone, ENOblock produced greater beneficial effects on lipid homeostasis, fibrosis, inflammatory markers, nephrotoxicity and cardiac hypertrophy. ENOblock treatment was associated with the down-regulation of phosphoenolpyruvate carboxykinase and sterol regulatory element-binding protein-1, which are known to produce anti-diabetic effects. In summary, these findings indicate that ENOblock has potential for therapeutic development to treat T2DM. Previously considered as a 'boring' housekeeping gene, these results also implicate enolase as a novel drug target for T2DM. [ABSTRACT FROM AUTHOR]

Abnormalities in skin pigmentation can produce disorders such as albinism or melasma. There is a research need to discover novel compounds that safely and effectively regulate pigmentation. To identify novel modulators of pigmentation, we attempted to purify compounds from a bioactive fraction of the Korean medicinal plant Artemisia capillaris Thunberg. The novel compound isofraxidin 7-O-(6′-O-p-coumaroyl)-β-glucopyranoside (compound 1) was isolated and its pigmentation activity was characterized in mammalian melanocytes. Compound 1 stimulated melanin accumulation and increased tyrosinase activity, which regulates melanin synthesis. Moreover, compound 1 increased the expression of tyrosinase and the key melanogenesis regulator microphthalmia-associated transcription factor (MITF) in melanocytes. Compared to the parent compound, isofraxidin, compound 1 produced greater effects on these pigmentation parameters. To validate compound 1 as a novel hyperpigmentation agent in vivo, we utilized the zebrafish vertebrate model. Zebrafish treated with compound 1 showed higher melanogenesis and increased tyrosinase activity. Compound 1 treated embryos had no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity. In summary, our results describe the characterization of novel natural product compound 1 and its bioactivity as a pigmentation enhancer, demonstrating its potential as a therapeutic to treat hypopigmentation disorders. [ABSTRACT FROM AUTHOR]

NOD-like receptor family protein 3 (NLRP3)-mediated inflammasome activation promotes caspase-1-dependent production of interleukin-1β ( IL-1β) and requires the adaptor protein ASC. Compared with the priming and activation mechanisms of the inflammasome signaling pathway, post-translational ubiquitination/deubiquitination mechanisms controlling inflammasome activation have not been clearly addressed. We here demonstrate that the deubiquitinating enzyme USP50 binds to the ASC protein and subsequently regulates the inflammasome signaling pathway by deubiquitinating the lysine 63-linked polyubiquitination of ASC. USP50 knockdown in human THP-1 cells and mouse bone marrow-derived macrophages shows a significant decrease in procaspase-1 cleavage, resulting in a reduced secretion of IL-1β and interleukin-18 ( IL-18) upon treatment with NLRP3 stimuli and a reduction in ASC speck formation and oligomerization. Thus, we elucidate a novel regulatory mechanism of the inflammasome signaling pathway mediated by the USP50 deubiquitinating enzyme. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the incidence of divided-shaped kidney and the relationship between divided-shaped kidney and collecting system duplication.Subjects and Methods: Between May 1 and June 30, 2012, 857 patients (men:women, 493:364; mean age 39.6 years; age range 2-98 years) with 1699 kidneys underwent enhanced computed tomography of the abdomen and pelvis at our institution. Sixty kidneys were excluded (tumor, 3; percutaneous nephrostomy, 9; polycystic kidney disease, 4; renal injury, 1; infarct, 1; hydronephrosis, 18; parapelvic cyst, 17; artifact, 5; horseshoe kidney, 2). Finally, 845 patients and 1639 kidneys were included. The number of cases of prominent column of Bertin (divided by grade of prominence as either divided-shaped kidney or hypertrophy) and collecting system duplication (bifid, partial, and complete) were evaluated. Fisher exact test was used to determine the relationship between divided-shaped kidney and collecting system duplication, and between hypertrophy and collecting system duplication.Results: Of 1639 kidneys, 66 (4%) were divided-shaped kidneys, and 88 (5%) had collecting system duplication (bifid, 69; partial, 19; complete, 0); among the 66 divided-shaped kidneys, 28 (42%) had collecting system duplication. Among the 429 cases of hypertrophy and 1144 normal kidneys, 51 (11.9%) and 9 (0.8%) had collecting system duplication, respectively.Conclusions: The incidence of divided-shaped kidney was 4%, and there was a significant association between divided-shaped kidney and collecting system duplication. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated fibroblasts (CAFs) promote tumor progression and play an important role in evading immune surveillance. The previous study showed that BAG2 could be elevated in cancer associated fibroblasts (CAFs). Here, we evaluated BAG2 expression of CAF and tumor cells and assessed metastasis risk in patients with breast cancer. We found that patients with either BAG2-high or BAG2(+) CAF had significantly worse distant metastasis-free survival than those with BAG2-double negative. Evaluation of BAG2 expression on both CAFs and tumor cells could be helpful to estimate the risk of metastasis in breast cancer. Few studies have examined the role of BAG2 in malignancies. We investigated the prognostic value of BAG2-expression in cancer-associated fibroblasts (CAFs) and tumor cells in predicting metastasis-free survival in patients with breast cancer. Tissue-microarray was constructed using human breast cancer tissues obtained by surgical resection between 1992 and 2015. BAG2 expression was evaluated by immunohistochemistry in CAFs or the tumor cells. BAG2 expression in the CAFs and cytoplasm of tumor cells was classified as positive and negative, and low and high, respectively. BAG2-CAF was evaluated in 310 patients and was positive in 67 (21.6%) patients. Kaplan–Meier plots showed that distant metastasis-free survival (DMFS) was lesser in patients with BAG2(+) CAF than in patients with BAG2(−) CAF (p = 0.039). Additionally, we classified the 310 patients into two groups: 109 in either BAG2-high or BAG2(+) CAF and 201 in BAG2-low and BAG2(−) CAF. DMFS was significantly reduced in patients with either BAG2-high or BAG2(+) CAF than in the patients of the other group (p = 0.005). Multivariable analysis demonstrated that DMFS was prolonged in patients with BAG2(−) CAF or BAG2-low. Evaluation of BAG2 expression on both CAFs and tumor cells could help in determining the risk of metastasis in breast cancer. [ABSTRACT FROM AUTHOR]