Hydrogen Peroxide Induces Ethanol-inducible CYP2E1 via the NFkB-classical Pathway: CYP2E1 mRNA Levels are not High in Alcoholic Hepatitis.

AIMS: The aim of the present study is to elucidate the mechanism of CYP2E1 induction as a causative factor of alcoholic hepatitis (AH) and its relationship with inflammation. BACKGROUND: Chronic alcohol consumption induces CYP2E1, which is involved in the development of alcoholic hepatitis (AH). However, the mechanisms underlying the induction of CYP2E1 by alcohol remain unclear. Therefore, we herein investigated the induction of drug-metabolizing enzymes, particularly CYP2E1, by hydrogen peroxide (H2O2), the concentration of which is elevated under inflammatory conditions. OBJECTIVE: The mechanisms underlying the induction of CYP2E1 by H2O2 were examined with a focus on Keap1, a target factor of H2O2. METHODS: We assessed changes in the expression of drug-metabolizing enzymes in the human hepatoma cell line, Hep3B, following treatment with H2O2, and evaluated changes in the expression of the NFkB-related factor RelA(p65) after the knockdown of Keap1, a regulator of Nrf2 expression by reactive oxygen species. We also performed a promoter analysis using the upstream region of the CYP2E1 gene. We herein used the GSE89632 series for non-alcoholic hepatitis (NASH) and the GSE28619 series for AH. RESULTS: The induction of CYP2E1 by H2O2 was significantly stronger than that of other drugmetabolizing enzymes. On the other hand, the knockdown of Keap1, a target of H2O2, markedly increased RelA(p65), an NFkB factor. Furthermore, the overexpression of RelA(p65) strongly induced the expression of CYP2E1. Four candidate p65-binding sequences were identified upstream of the CYP2E1 gene, and promoter activity assays showed that the third sequence was responsive to the overexpression of RelA(p65). We used the GSE89632 series for NASH and the GSE28619 series for AH in the present study. The expression of CYP2E1 mRNA in the liver was significantly lower in AH patients than in HC patients, but was similar in HC patients and NASH patients. CONCLUSION: We herein demonstrated that the expression of CYP2E1 was induced by H2O2. The overexpression of RelA(p65) also induced CYP2E1 mRNA expression, whereas H2O2 did not after the knockdown of RelA. These results suggest that H2O2 acts on Keap1 to upregulate RelA (p65) in the NFkB system. One of the mechanisms underlying the induction of CYP2E1 was dependent on the H2O2-Keap1-RelA axis. The results of the database analysis revealed that the expression of CYP2E1 in the liver was significantly lower in AHH patients than in NASH patients, suggesting that CYP2E1 is not the main cause of AH; however, CYP2E1 may exacerbate the pathogenesis of AH.

Estimating Blood Pressure during Exercise with a Cuffless Sphygmomanometer.

Accurately measuring blood pressure (BP) is essential for maintaining physiological health, which is commonly achieved using cuff-based sphygmomanometers. Several attempts have been made to develop cuffless sphygmomanometers. To increase their accuracy and long-term variability, machine learning methods can be applied for analyzing photoplethysmogram (PPG) signals. Here, we propose a method to estimate the BP during exercise using a cuffless device. The BP estimation process involved preprocessing signals, feature extraction, and machine learning techniques. To ensure the reliability of the signals extracted from the PPG, we employed the skewness signal quality index and the RReliefF algorithm for signal selection. Thereafter, the BP was estimated using the long short-term memory (LSTM)-based neural network. Seventeen young adult males participated in the experiments, undergoing a structured protocol composed of rest, exercise, and recovery for 20 min. Compared to the BP measured using a non-invasive voltage clamp-type continuous sphygmomanometer, that estimated by the proposed method exhibited a mean error of 0.32 ± 7.76 mmHg, which is equivalent to the accuracy of a cuff-based sphygmomanometer per regulatory standards. By enhancing patient comfort and improving healthcare outcomes, the proposed approach can revolutionize BP monitoring in various settings, including clinical, home, and sports environments.

An Advanced Internet of Things System for Heatstroke Prevention with a Noninvasive Dual-Heat-Flux Thermometer.

Heatstroke is a concern during sudden heat waves. We designed and prototyped an Internet of Things system for heatstroke prevention, which integrates physiological information, including deep body temperature (DBT), based on the dual-heat-flux method. A dual-heat-flux thermometer developed to monitor DBT in real-time was also evaluated. Real-time readings from the thermometer are stored on a cloud platform and processed by a decision rule, which can alert the user to heatstroke. Although the validation of the system is ongoing, its feasibility is demonstrated in a preliminary experiment.

Synthesis and herbicidal activity of 3-{[(hetero)aryl]methanesulfonyl}-4,5-dihydro-1,2-oxazole derivative; Discovery of the novel pre-emergence herbicide pyroxasulfone.

Thiocarbamate sulfoxides, which are the active forms of thiocarbamate herbicides, are quickly conjugated with glutathione and decomposed in soil. To achieve more potent and stable herbicidal activity, we previously developed a 5-{[(2,6-difluorophenyl)methoxy]methyl}-5-methyl derivative, which has a 4,5-dihydro-1,2-oxazole ring in place of the thiocarbamate to prevent conjugation and decomposition. Although the derivative showed pre-emergence herbicidal activity under flooded conditions, it displayed no herbicidal activity under upland conditions. In contrast, a 5-(methoxymethyl)-5-methyl derivative showed pre-emergence herbicidal activity against grass weeds under upland conditions. The aim of this study was to obtain a more potent compound with improved physicochemical properties for use as a pre-emergence upland herbicide via the structural optimization of a 3-{[(hetero)aryl]methanesulfonyl}-4,5-dihydro-1,2-oxazole as the core structure. In this way, we have developed the pre-emergence herbicide 3-{[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methanesulfonyl}-5,5-dimethyl-4,5-dihydro-1,2-oxazole, which has been named "pyroxasulfone." This novel compound displayed excellent herbicidal activity against grass and broadleaf weeds under upland conditions with no phytotoxicity against crops.

Wearable deep body thermometers and their uses in continuous monitoring for daily healthcare.

This paper introduces noninvasive deep body thermometers suitable for continuous deep body temperature (DBT) measurement. On the basis of their features, they were used in DBT monitoring for daily healthcare. A thermometer based on the dual-heat-flux method (T_DHFM), and an aural canal thermistor (ACT), were used in two studies of daily healthcare. The medical device CoreTemp by Terumo, based on the zero-heat-flux method, was also used for a DBT reference. The first study focused on preventing heat stroke in a high-temperature and high-humidity environment, while the other focused on the temperature monitoring of patients with spinal cord injuries. In the first study, CoreTemp and T_DHFM were used, whereas T_DHFM and ACT were used in the second study. Using the results from these two studies, we discuss the availability and performance of each thermometer and indicate the necessity of an appropriate method of measuring DBT.

Carbon-supported growth of cross-linked platinum nanowires by surfactant templating and their elecrochemical characterization.

Platinum/carbon (Pt/C) composite materials were prepared by the hydrazine reduction of H2PtCl6 confined to a mixed surfactant lytropic liquid crystal (LC)/C mixture with varying amounts of water. The reaction at relatively low water contents successfully yielded cross-linked Pt nanowires with wire-widths of 2-5 nm. The novel Pt nanostructure is believed to be from poorly hydrated hexagonal domains formed together with layered domains by the phase separation of the precursory LC mixture in the presence of carbon. Electrochemical measurements using cyclic volutammetry and membrane electrode assemblies revealed that the cross-linked nanowired Pt/C composite exhibits fairly high electrocatalytic activity for oxygen reduction reaction, as well as a high performance as the cathode material for polymer electrolyte fuel cells.

A wearable airbag to prevent fall injuries.

We have developed a wearable airbag that incorporates a fall-detection system that uses both acceleration and angular velocity signals to trigger inflation of the airbag. The fall-detection algorithm was devised using a thresholding technique with an accelerometer and gyro sensor. Sixteen subjects mimicked falls, and their acceleration waveforms were monitored. Then, we developed a fall-detection algorithm that could detect signals 300 ms before the fall. This signal was used as a trigger to inflate the airbag to a capacity of 2.4 L. Although the proposed system can help to prevent fall-related injuries, further development is needed to miniaturize the inflation system.

A preliminary study to demonstrate the use of an air bag device to prevent fall-related injuries.

We sought to develop a fall-related injury prevention system using a telemetry acceleration monitor and an air bag. In a preliminary study, we developed a fall detection system using an acceleration signal and triggering the inflation of an air bag. Sixteen subjects mimicked falls and their acceleration waveforms were monitored. Then, we developed a fall detection algorithm that could detect signals 300 ms before the fall. This signal was used as a trigger to inflate the air bag to a capacity of 2.4 L. While the proposed system can aid in preventing fall-related injuries, further development is needed to miniaturize the inflation system.

Self-organization of surfactant-metal-ion complex nanofibers on graphite surfaces and their application to fibrously concentrated platinum nanoparticle formation.

We report the fabrication of self-organized surfactant nanofibers containing platinum ions on a highly oriented pyrolytic graphite (HOPG) surface from mixed solutions of hexadecyltrimethylammonium hydroxide (C16TAOH) and hydrogen hexachloroplatinate (IV) (H2PtCl6). The fibrous surfactant self-assembly was stable in air, even after being soaked in water, in contrast to surfactant hemicylindrical micelles, which are stable only at graphite/solution interfaces. The results show that the graphite surface served as an essential template for the specific formation of fibrous surfactant self-assemblies. In addition, when surfactant nanofibers containing metal ions were treated with hydrazine, platinum nanoparticles concentrated in the nanofibers formed on the HOPG surface. We also prepared surfactant nanofibers containing gold ions on HOPG surfaces and formed gold nanoparticles in the nanofibers.

One-dimensional assemblies of platinum nanoparticles on a graphite surface using nonionic/ionized mixed hemicylindrical micelle templates.

One-dimensional (1-D) self-assemblies of Pt nanoparticles on a graphite surface have been synthesized via a template-directed sintering process of individual nanoparticles, using nonionic/cationic mixed hemicylindrical micelle templates of dodecyldimethylamine oxide surfactant at graphite/solution interfaces. The dimension and morphology of Pt nanoparticles can be widely controlled by the concentration of Pt ions equivalent to the mixing ratio of nonionic and cationic species in the surfactant micelle. This approach could be extended to fabricate a wide range of self-assembling metallic nanostructures on surfaces using various nonionic/cationic mixed micelle-like self-assemblies carrying metal ions at interfaces, while providing a fundamental insight into a 1-D self-assembly from individual nanoparticles.

Single-crystalline platinum nanosheets from nonionic surfactant 2-D self-assemblies at solid/aqueous solution interfaces.

Single-crystalline platinum nanosheets have been prepared via a new methodology based on the chemical reduction of a platinum salt (H2PtCl6) with hydrazine at a graphite/solution interface, using polyoxyethylene (20) sorbitan monostearate (Tween 60) based self-assembly (hemicylindrical micelle) templates. The platinum nanosheets with a uniform thickness of as thin as 3.5 +/- 1 nm are surface-smooth and continuous over relatively large length scales of micrometer sizes. In striking contrast to the Tween 60 based system, no Pt nanosheets are obtained with nonaethylene glycol monododecyl ether (C12EO9) and polyoxyethylene (23) dodecyl ether (C12EO23). No Pt nanosheets are also obtainable with a laterally homogeneous layer of Tween 60 formed at the silica/solution interface. These results indicate that surfactant Tween 60 molecules with a triple polyoxyethylene structure, as well as their hemicylindrical micelle templates, play an essential role for the formation of the Pt nanosheets. It is also suggested that the interfacially directed growth of Pt metals within the aqueous shells of the Tween 60 hemicylindrical micelles induces the thin Pt crystals as thick as the aqueous shells. The present approach could be extended to prepare a wide range of novel nanostructures of noble metals, using various micelle-like self-assemblies at interfaces.

Synthesis of high surface area hydroxyapatite nanoparticles by mixed surfactant-mediated approach.

A new surfactant-mediated approach was developed to synthesize hydroxyapatite (HAp) nanoparticles with high surface areas by calcination of their precursors encapsulated with calcium stearate using mixed surfactant-containing reaction mixtures. Acidic aqueous solution of calcium phosphate was mixed with both or either nonaoxyethylene dodecyl ether (C12EO9) and polyoxyethylene(20) sorbitan monostearate (Tween 60) and then was treated with aqueous ammonium at 25 degrees C. The C12EO9-based single surfactant system yielded an aggregate of platy HAp nanoparticles 20-40 nm in size, whereas the Tween 60-based single and mixed systems led to lath-shaped HAp nanoparticles 2-8 nm wide and encapsulated with calcium stearate. On calcination at 500 degrees C, the stearate-encapsulated HAp nanoparticles in the latter two systems were deorganized into high surface area HAp nanoparticles. Particularly, the HAp nanoparticles in the mixed system exhibited a specific surface area as high as 364 m2 g(-1) that is roughly 3 times larger than 160 m2 g(-1) for those in the single system. The significantly high surface area for the former is attributed to much less adhesion of decapsulated HAp nanoparticles, which originated from the particle-separating effect of the C12EO9 molecules adsorbed on the outer surface of the stearate-encapsulated HAp nanoparticles to inhibit their agglomeration or interfacial coordination. The present results demonstrate that the mixed use of two different surfactants as a source of encapsulating and templating agent and a particle-separating agent is specifically effective for the synthesis of high surface area HAp nanoparticles.

Development and evaluation of a simple calorimeter for the measurement of resting metabolism.

1. A simple calorimeter based on the measurement of oxygen uptake has been developed. 2. A respiratory simulator was used to evaluate oxygen uptake at different flow rates. A known concentration of mixed gases flows into the calorimeter via the respiratory simulator. Oxygen concentration and flow rate were measured and stored to memory for further analysis. 3. Results indicate that large errors occur at low flow rates, but that the error is less than 5% under normal conditions. 4. This device can be used to measure oxygen uptake under resting conditions.

Development and evaluation of a simple calorimeter for the measurement of resting metabolism.

1. A simple calorimeter based on the measurement of oxygen uptake has been developed. 2. A respiratory simulator was used to evaluate oxygen uptake at different flow rates. A known concentration of mixed gases flows into the calorimeter via the respiratory simulator. Oxygen concentration and flow rate were measured and stored to memory for further analysis. 3. Results indicate that large errors occur at low flow rates, but that the error is less than 5% under normal conditions. 4. This device can be used to measure oxygen uptake under resting conditions.