Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions

Metformin is a metabolic disruptor, and its efficacy and effects on metabolic profiles under different oxygen and nutrient conditions remain unclear. Therefore, the present study examined the effects of metformin on cell growth, the metabolic activities and consumption of glucose, glutamine, and pyruvate, and the intracellular ratio of nicotinamide adenine dinucleotide (NAD⁺) and reduced nicotinamide adenine dinucleotide (NADH) under normoxic (21% O₂) and hypoxic (1% O₂) conditions. The efficacy of metformin with nutrient removal from culture media was also investigated. The results obtained show that the efficacy of metformin was closely associated with cell types and environmental factors. Acute exposure to metformin had no effect on lactate production from glucose, glutamine, or pyruvate, whereas long-term exposure to metformin increased the consumption of glucose and pyruvate and the production of lactate in the culture media of HeLa and HaCaT cells as well as the metabolic activity of glucose. The NAD⁺/NADH ratio decreased during growth with metformin regardless of its efficacy. Furthermore, the inhibitory effects of metformin were enhanced in all cell lines following the removal of glucose or pyruvate from culture media. Collectively, the present results reveal that metformin efficacy may be regulated by oxygen conditions and nutrient availability, and indicate the potential of the metabolic switch induced by metformin as combinational therapy.     

Bactericidal effect of cationic hydrogels prepared from hydrophilic polymers

This study investigated whether hydrogels comprising hydrophilic cationic polymers have similar bactericidal effects. Bacteria were seeded on hydrogels and agar and their viability was assessed with time. Cationic hydrogels displayed bactericidal effects upon long-term bacterial contact. Furthermore, we assessed the areal density of cationic monomer unit of the cationic hydrogels, water content, and the initial elastic modulus. We examined correlations between each factor and bacterial death ratios; consequently, the bacterial death ratios were strongly correlated with the areal density of cationic hydrogel monomers. Elastic energy (W_el) generated at the cytomembrane ion-binding region and the cationic hydrogel and the cytomembrane interfacial energy (W_f) were estimated; consequently, W_el exceeded W_f at higher contact areas. The cationic hydrogel may extract cytomembranes with a reasonable adsorption area. Therefore, cationic hydrogels may be used as probes for ultrasonic echo to sterilize medical equipment.     

Effect of morphology on shear viscosity for binary blends of polycarbonate and polystyrene

The structure and rheological properties of binary blends of polycarbonate (PC) and polystyrene (PS) were investigated using various PS samples with different molecular weights, namely PS1k (M_w = 1,000), PS53k (M_w = 53,000), and PS240k (M_w = 240,000). The blends with PS53k and PS240k show phase-separated structures, whereas the blend with PS1k is miscible. The shear viscosity decreases greatly on addition of PS53k and PS240k, especially at high shear rates, which would be a great advantage at processing operations. Because the nonlinear response occurs in the small strain region for multilayered films of PC and PS240k, the origin of the significant viscosity drop for the phase-separated system is interfacial slippage at the phase boundary.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

关于日本智能社区(Smart Community)发展动向的介绍

本文摘录介绍了近年来日本在节能环保领域内,从国家的政策引导到地方政府和民间企业的积极参与建设新型智能社区的情况.并具体说明了一些关键应用,如新能源利用,能源管理系统,智能电网,EV电动车和新型交通系统在智能社区里的应用实例及日本在此领域内的标准化推进方面的情况.     

Occurrence and sources of perfluorinated surfactants in rivers in Japan

We analyzed perfluorinated surfactants (PFSs) in 20 river samples and 5 wastewater secondary effluent samples in Japan to reveal their occurrence and sources. Nine PFS species were determined: perfluorooctanesulfonate (PFOS), perfluorooctane sulfonamide (FOSA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUA), perfluorododecanoate (PFDDA), and perfluorotridecanoate (PFTDA). PFSs were detected in all rivers, revealing nationwide contamination of rivers. In particular, 11 out of 20 river samples exceeded New Jersey guidance for PFOA in drinking water (40 ng/L). PFOS, PFHpA, PFOA, and PFNA were major species in Japan. Concentrations of PFOS, PFHpA, and PFNA in rivers were strongly correlated with population density, suggesting that the chemicals were derived from urban activities. PFOA showed a significant but weak correlation. We used crotamiton, a marker of sewage effluent, for further source analysis. Concentrations of PFOS, PFHpA, and PFNAwere strongly correlated with those of crotamiton, and plots of secondary effluents fell near the regression lines of rivers, indicating that the PFOS, PFHpA, and PFNA in rivers were derived from sewage effluent. On the other hand, PFOA was found at remarkably high levels (54-192 ng/L) in seven river samples containing low levels of crotamiton, suggesting that it was derived from nonsewage point sources, as well as sewage effluent. The total fluxes of sewage-derived PFOS, PFHpA, PFOA, and PFNA from Japan were estimated to be 3.6, 2.6, 5.6, and 2.6 t/year, respectively. This is the first report to identify PFOA in several rivers, derived from nonsewage point sources, by using a marker of sewage effluent.     

Normal Spectral Emissivity Measurement of Molten Cu–Co Alloy Using an Electromagnetic Levitator Superimposed with a Static Magnetic Field

The normal spectral emissivity of molten Cu–Co alloy with different compositions was measured in the wavelength range of 780 nm to 920 nm and in the temperature range of 1430 K to 1770 K including the undercooled condition by an electromagnetic levitator superimposed with a static magnetic field. The emissivity was determined as the ratio of the radiance from a levitated molten Cu–Co droplet measured by a spectrometer to the radiance from a blackbody calculated by Planck’s law at a given temperature, where a static magnetic field of 2.5 T to 4.5 T was applied to the levitated droplet to suppress the surface oscillation and translational motion of the sample. We found little temperature dependence of the normal spectral emissivity of molten Cu–Co alloy. Concerning the composition dependence, the emissivity decreased markedly above 80 at%Cu and reached that of pure Cu, although its dependence was low between 20 at%Cu and 80 at%Cu. In addition, this composition dependence of the emissivity of molten Cu–Co alloy can be explained well by the Drude free-electron model.     

Determination of dissolved natural thorium and uranium in Horonobe and Mizunami Underground Research Laboratory groundwater and its thermodynamic analysis

At two underground research laboratories situated at Horonobe and Mizunami, Japan, trace amounts of natural thorium and uranium dissolved in deep groundwater were investigated with the help of chemical pre-concentration method. The groundwater was sampled from underground boreholes under the geochemical condition of no atmospheric exposure, and the colloid contribution was checked by in situ two size-fractionated ultrafiltration systems. A rough decrease by half in the concentration after in situ filtration suggested the presence of natural colloids and suspended matter that were carriers of a portion of the elements. The Th and U concentrations in groundwater after 10 kDa filtration was evaluated as dissolved species, and was identified thermodynamically using existing hydrogeological and geochemical data, such as the mineral components in the groundwater at a given pH, ionic strength, concentration of co-existing ions, redox potential, and a hypothetical solubility-limiting solid phase. The crystalline solid phase of tetravalent thorium and uranium dioxides made the solubility very low compared with that of the amorphous phase.