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Akihiro Honda Shotaro Kamata Makoto Akahane Yui Machida Kie Uchii Yui Shiiyama Yuki Habu Saeka Miyawaki Chihiro Kaneko Takuji Oyama Isao Ishii 《International journal of molecular sciences》2022,23(9)
Among the agonists against three peroxisome proliferator-activated receptor (PPAR) subtypes, those against PPARα (fibrates) and PPARγ (glitazones) are currently used to treat dyslipidemia and type 2 diabetes, respectively, whereas PPARδ agonists are expected to be the next-generation metabolic disease drug. In addition, some dual/pan PPAR agonists are currently being investigated via clinical trials as one of the first curative drugs against nonalcoholic fatty liver disease (NAFLD). Because PPARα/δ/γ share considerable amino acid identity and three-dimensional structures, especially in ligand-binding domains (LBDs), clinically approved fibrates, such as bezafibrate, fenofibric acid, and pemafibrate, could also act on PPARδ/γ when used as anti-NAFLD drugs. Therefore, this study examined their PPARα/δ/γ selectivity using three independent assays—a dual luciferase-based GAL4 transactivation assay for COS-7 cells, time-resolved fluorescence resonance energy transfer-based coactivator recruitment assay, and circular dichroism spectroscopy-based thermostability assay. Although the efficacy and efficiency highly varied between agonists, assay types, and PPAR subtypes, the three fibrates, except fenofibric acid that did not affect PPARδ-mediated transactivation and coactivator recruitment, activated all PPAR subtypes in those assays. Furthermore, we aimed to obtain cocrystal structures of PPARδ/γ-LBD and the three fibrates via X-ray diffraction and versatile crystallization methods, which we recently used to obtain 34 structures of PPARα-LBD cocrystallized with 17 ligands, including the fibrates. We herein reveal five novel high-resolution structures of PPARδ/γ–bezafibrate, PPARγ–fenofibric acid, and PPARδ/γ–pemafibrate, thereby providing the molecular basis for their application beyond dyslipidemia treatment. 相似文献
23.
Isamu Ogura Mari Kotake Hiromu Sakurai Kazumasa Honda 《Aerosol science and technology》2016,50(8):846-856
The flat surface of Nuclepore filters is suitable for observing collected particles with a scanning electron microscope (SEM). However, experimental data on surface-collection efficiency are limited because surface-collection efficiencies cannot be measured directly using aerosol measuring instruments. In this study, the surface-collection efficiencies of Nuclepore filters were determined by establishing the ratio of the number of particles deposited on the surface of the filter visually counted with an SEM to the number of inflow particles counted by a condensation particle counter, using monodispersed polystyrene latex particles (30–800 nm) and silver particles (15–30 nm). Because Nuclepore filters with smaller pore sizes would be expected to produce higher minimum surface-collection efficiency and a higher pressure-drop, 0.08 and 0.2 µm Nuclepore filters were chosen as the test filters in view of both collection efficiency and pressure drop. The results showed that the minimum surface-collection efficiencies of the 0.08 µm pores at face velocities of 1.9 and 8.4 cm·s?1 were approximately 0.6 and 0.7, respectively, and those of the 0.2 µm pores at face velocities of 1.5 and 8.6 cm·s?1 were approximately 0.8 and 0.6, respectively. Because the pressure drop of the 0.2 µm pore filter was lower than that of the 0.08 µm pore filter under the same flow-rate conditions, the 0.2 µm pore filter would be more suitable considering the pressure drop and collection efficiency. The obtained surface collection efficiencies were quantitatively inconsistent with theoretical surface-collection efficiencies calculated using conventional theoretical models developed to determine the collection efficiency of filters with larger pores.© 2016 American Association for Aerosol Research 相似文献
24.
Isamu Ogura Naomi Hashimoto Mari Kotake Hiromu Sakurai Atsuo Kishimoto Kazumasa Honda 《Aerosol science and technology》2014,48(7):758-767
A simple sampling method to collect aerosol particles for transmission electron microscope (TEM) analysis was developed by R’mili and others in 2013. The method involves passing air through a holey carbon film-coated copper mesh TEM grid (holey carbon grid) and sampling particles by filtration. In this study, we proposed a modified calculation method to represent the collection efficiencies of holey carbon grids, taking into consideration the porosity of the copper mesh. We then evaluated the particle collection efficiencies of holey carbon grids both theoretically and experimentally. We tested the collection efficiency of two types of holey carbon grids, with nominal pore sizes of 1.2 and 0.6 μm, using particles of monodispersed polystyrene latex (PSL) and potassium chloride. The overall collection efficiency of each grid (Egrid) was determined by the downstream/upstream concentration ratio measured by condensation particle counters (CPCs). In addition, for PSL particles, the collection efficiency of the holey carbon film (Efilm) was determined by the ratio of the number of particles on the film (counted on a scanning electron microscope) to the number of inflow particles (counted by a CPC). We compared model calculations against the experimental results obtained in this study and those reported by R’mili and others in 2013. These data showed that the calculated Egrid values were in reasonably good agreement with the experimental Egrid values. However, although the model calculation indicated that Efilm ≈ Egrid, there was an inconsistency between the experimental Efilm and Egrid, which requires further investigation in order to determine its cause.
Copyright 2014 American Association for Aerosol Research 相似文献
25.
Masaki Honda Hakuto Kageyama Takashi Hibino Rungaroon Waditee‐Sirisattha Tetsuya Fukaya Yoshiaki Hayashi Motonobu Goto 《European Journal of Lipid Science and Technology》2020,122(3)
Z‐isomers of lycopene exhibit higher bioavailability and antioxidant capacity than those of the all‐E‐isomer. Therefore, it is important to develop an efficient and environmentally friendly procedure for Z‐isomerization. The current methods for Z‐isomerization of (all‐E)‐lycopene use toxic chemicals such as organic solvents and catalysts. This study is aimed to develop a chemical‐free method for Z‐isomerization of (all‐E)‐lycopene in tomato powder by hot air and superheated steam heating. The Z‐isomerization reaction is promoted by heating above the melting point of lycopene. When heated with superheated steam, the thermal decomposition of lycopene is suppressed compared to that when heated with hot air. When tomato powder is heated at 240 °C for 5 min by superheated steam, the total Z‐isomer content and remaining lycopene are 69.0% and 90.7%, respectively, while with hot air heating, the total Z‐isomer content and remaining lycopene are 69.9% and 68.0%, respectively. These results indicate that the thermal Z‐isomerization of lycopene occurs in the molten state and heating in a low oxygen atmosphere suppresses the thermal decomposition of lycopene. Practical Applications: Tomato powder rich in lycopene Z‐isomers is an important ingredient for the food and animal feed industries. Since Z‐isomers of lycopene are more soluble in solvents including ethanol which is a low‐toxicity and environmentally friendly solvent, the efficiency of lycopene extraction with ethanol can be improved by using the Z‐isomer‐rich tomato powder as a raw material. The obtained Z‐isomer‐rich extract has a high added value because the Z‐isomers have higher bioavailability and antioxidant capacity than those of the all‐E‐isomer. In addition, since lycopene Z‐isomers exhibit higher accumulation efficiency and better color improvement in hen egg yolks than those of the all‐E‐isomer, Z‐isomer‐rich tomato powder is an effective animal feed. 相似文献
26.
The previously proposed theoretical models of film condensation in horizontal microfin tubes have been modified to describe the characteristics of condensing two-phase flow more accurately. The stratified flow regime and the annular flow regime were considered. For the stratified flow regime, the previously proposed theoretical model was modified to take account of the curvature of stratified condensate due to the surface tension force. For the annular flow regime, a more accurate expression for the interfacial shear stress was incorporated. Generally, the modified theoretical models predicted a lower circumferential average heat transfer coefficient than the previously proposed ones. Comparison of the theoretical predictions with available experimental data for six tubes and five refrigerants revealed that a good agreement (r.m.s error of less than 21.1%) was obtained for all cases when the higher of the two theoretical predictions were adopted as the calculated value. 相似文献
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Experiments were carried out on the flow pattern, heat transfer, and pressure drop of flow boiling of pure CO2 and CO2‐oil mixtures in horizontal smooth and micro‐fin tubes. The smooth tube is a stainless steel tube with an inner diameter of 3.76 mm. The micro‐fin tube is a copper tube with a mean inner diameter of 3.75 mm. The experiments were carried out at mass velocities from 100 to 500 kg/(m2·s), saturation temperature of 10 °C, and the circulation ratio of lubricating oil (PAG) was from 0 to 1.0 mass%. Flow pattern observations mainly showed slug and wavy flow for the smooth tube, but annular flow for the micro‐fin tube. Compared with the flow patterns in the case of pure CO2, an increase in frequency of slug occurrence in the slug flow region, and a decrease in the quantity of liquid at the top of the tube in the annular flow region were observed in the case of CO2‐oil mixtures. With pure CO2, the flow boiling heat transfer was dominated by nucleate boiling in the low vapor quality region, and the heat transfer coefficients for the micro‐fin tube were higher than those of the smooth tube. With CO2‐oil mixtures, the flow boiling heat transfer was dominated by convective evaporation, especially in the high vapor quality region. In addition, the heat transfer coefficient decreased significantly when the oil circulation ratio was larger than 0.1 mass%. For the pressure drop characteristics, in the case of pure CO2, the homogeneous flow model agreed with the experimental results within ±30% for the smooth tube. The pressure drops of the micro‐fin tube were 0–70% higher than those predicted with the homogeneous flow model, and the pressure drops increased for the high oil circulation ratio and high vapor quality conditions. The increases in the pressure drops were considered to be due to the increase in the thickness of the oil film and the decrease in the effective flow cross‐sectional area. © 2010 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/htj.20287 相似文献
29.
Honda Y Kitaoka M Sakka K Ohmiya K Hayashi K 《Journal of Bioscience and Bioengineering》2002,93(3):313-317
The kinetic parameters of Cex, a family 10 xylanase from Cellulomonas fimi, were determined at various pH levels using soluble birchwood xylan (BWX) as a natural polymeric substrate along with three other synthetic aryl-beta-D-xylobioside substrates. Using BWX, a high level of substrate inhibition was observed which increased with decreasing pH. In contrast, typical Michaelis-Menten-type profiles were obtained using the three aryl-beta-D-xylobiosides as substrates. The k(cat) values determined using o-nitrophenyl-beta-D-xylobioside did not change as the pH increased, whereas the k(cat) values obtained with BWX, phenyl-beta-D-xylobioside and p-nitrophenyl-beta-D-xylobioside decreased, suggesting that the presence of an ortho nitro group affects the activity displayed by Cex. These differences were not observed with XynB from Clostridium stercorarium F9, a member of the same family of xylanases as Cex. These results indicate that a careful evaluation is required when employing substituted aryl-beta-D-xylobiosides in the characterization of xylanases. 相似文献
30.
Theory is little used in the prediction of physician cancer screening stage of change. Structural equation modeling was used to evaluate the theoretical predictors of stage of change to recommend colonoscopy among 235 urban physicians. Constructs from the theory of planned behavior, social-cognitive theory, and the transtheoretical model were systematically tested. As predicted, contextual factors, such as the physicians' ages, their race-ethnicities, patient race-ethnicity, and office-related barriers to preventive care were associated with stage of change through self-efficacy, normative beliefs, and negative behavioral beliefs. The findings demonstrate the relevance of these models to studying the behavior of physicians and support the development of interventions that are tailored to normative beliefs and specific physician cognitions for colonoscopy recommendation. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献