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.     

Mixing speed-controlled gold nanoparticle synthesis with pulsed mixing microfluidic system

Gold nanoparticles with diameters of a few tens of nanometer and a narrow size distribution were synthesized using a pulsed mixing method with a microfluidic system which consists of a Y-shaped mixing microchannel and two piezoelectric valveless micropumps. This mixing method enables control of the mixing speed of gold salts and reducing agent by changing the switching frequency of the micropumps, which was our focus to improve the particle size distribution, which is an essential parameter in gold nanoparticle synthesis. In the proposed method, the mixing time was inversely proportional to the switching frequency and the minimum mixing time was 95 ms at a switching frequency of 200 Hz. During synthesis experiments, the mean diameter of the synthesized gold nanoparticles was found to increase, and the coefficient of variation of particle size was found to decrease with decreasing mixing time. We successfully improved the coefficient of variation to less than 10% for a mean diameter of around 40 nm.     

Effect of wet-jet milling on the c-axis orientation of hydroxyapatite ceramics fabricated using a strong magnetic field

Controlling the crystal orientation of hydroxyapatite, an inorganic material that is a major component of human hard tissues is important to fabricate better artificial bones and artificial tooth roots. To obtain highly oriented hydroxyapatite ceramics under a strong magnetic field, a good dispersion of the raw materials in the slurry must be obtained. This study investigates the effect of wet-jet milling of a slurry on the orientation of hydroxyapatite ceramics fabricated using a strong magnetic field. Although the prolonged ball milling with ZrO₂ balls of the raw powder fractures the primary particles of hydroxyapatite, wet-jet milling is used to successfully pulverize agglomerated hydroxyapatite raw powder without changing the morphology of the primary particles. Evidently, ceramics with a highly oriented c-axis of hydroxyapatite are obtained by molding the wet-jet milled slurry in a strong rotating magnetic field. They exhibit anisotropy in fracture toughness, and the fracture toughness calculated from the crack length perpendicular to the rotating axis is higher than that calculated from the crack length parallel to it. Furthermore, these values are higher than those of randomly oriented hydroxyapatite ceramics, which may be owing to the crystal orientation dependence of the fracture toughness of the hydroxyapatite grains and grain boundaries.     

Effect of microstructures on dielectric breakdown strength of sintered reaction-bonded silicon nitride ceramics

Silicon nitride (Si₃N₄) was prepared from silicon by a sintered reaction-bonded silicon nitride method using yttria and magnesia as sintering additives. Post-sintering (PS) of nitrided compacts was carried out at 1850°C under a nitrogen pressure of 1 MPa. Effect of PS time on microstructure and dielectric breakdown strength (DBS) of the prepared Si₃N₄ ceramics was evaluated. The DBS was measured using specimens with four different thicknesses (0.30, 0.20, 0.10, and 0.05 mm) in order to examine the thickness dependence. The porosity of the sintered Si₃N₄ decreased by prolonging the PS time, and the full density could be achieved at the PS time of over 6 h. After full densification, rod-like β-Si₃N₄ grains grew up, and their maximum grain size increased from 45.1 to 154.7 μm by prolonging the PS time from 6 to 48 h. The DBS of the thick Si₃N₄ substrates (0.30 mm) showed little variation from 35.4 to 47.0 kV/mm, regardless of the PS time. On the other hand, that of the thin ones (0.05 mm) dramatically decreased from 99.5 to 9.8 kV/mm with increased the PS time from 6 to 48 h. Because the DBS sharply decreased at the thin substrate sintered for longer time in which some large-elongated grains might span the substrate thickness-wise throughout, it was inferred that the interface between β-Si₃N₄ grains and grain boundary phase/intergranular glassy films might be a path of the dielectric breakdown.     

Enhanced Immunostimulatory Activity of Covalent DNA Dendrons

The present study focused on the design and synthesis of covalent DNA dendrons bearing multivalent cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) that can stimulate the immune system through the activation of TLR9. These dendrons were synthesized using branching trebler phosphoramidite containing three identical protecting groups that enabled the simultaneous synthesis of multiple strands on a single molecule. Compared with linear ODNs, covalent DNA dendrons were found to be more resistant to nuclease degradation and were more efficiently taken up by macrophage-like RAW264.7 cells. Cellular uptake was suggested to be mediated by macrophage scavenger receptors. The covalent DNA dendrons composed of multivalent immunostimulatory branches enhanced the secretion of proinflammatory cytokines TNF-α and IL-6 from RAW264.7 cells, and 9-branched DNA dendrons showed the highest enhancement. Given their enhanced efficacy, we expect covalent DNA dendrons to be useful structures of oligonucleotide medicines.     

The content of tocopherols and oxidative quality of oils prepared from sunflower (Helianthus annuus L.) seeds roasted in a microwave oven

Sunflower seeds ((Helianthus annuus were roasted for 6, 12, 20 or 30 min at a frequency of 2450 MHz using a domestic microwave oven. After the kernels were separated from the sunflower seeds, the quality characteristics and the compositions of the oils were investigated in relation to their tocopherol distributions, and they were further evaluated as compared with an unroasted oil sample. Only minor increases (p < 0.05) in chemical and physical changes of the oils, such as the carbonyl value, the p‐anisidine value and the color development, occurred at a prolonged roasting period. Significant decrease (p < 0.05) was observed in the amounts of phospholipids in the oils after microwave roasting. Nevertheless, compared to the original level, more than 92 wt‐% tocopherols still remained after 30 min of roasting. With a few exceptions, these results indicate that the exposure of sunflower seeds to microwaves for 12 min caused no significant (p < 0.05) loss or change in the content of tocopherols and polyunsaturated fatty acids in the kernels.     

deNOx Performance and Reaction Mechanism of the Di-Air System

The detailed reaction mechanism of Di-Air, which showed the unprecedented high deNO_x performance at high temperature conditions, was studied in this work. Since the Di-Air phenomenon occurs with continuous short pulse injections of hydrocarbons over NSR (NO_x storage and reduction) catalyst, this study focused on the specific function of HC as an effective reductant for NO_x reduction reaction. As a first step, the deNO_x performance was compared with three different reductant gases including CO, H₂ and C₃H₆ in a modified synthetic gas bench equipped with a gas injector which enables continuous small amount of injections. At inlet gas temperature of 450 °C C₃H₆ showed the best deNO_x performance whereas H₂ was the best at 150 °C. Moreover the result of temperature programmed desorption showed that intermediate species represented by –NCO (isocyanates) produced from C₃H₆ was thermally more stable than that produced from CO. These results confirmed that the injected HC reacts with adsorbed NO_x on NSR catalyst generating thermally stable intermediates, which could contribute the high deNO_x performance at high temperature conditions.     

粒子网格混合方法模拟液滴夹带起始点

环状流动的特性对反应堆事故工况分析具有重要意义,本研究基于粒子网格混合方法对这一现象中的液滴夹带起始点问题进行了数值分析,利用网格求解流场,利用粒子模拟液膜及液滴的运动,探讨了气水流动大密度比情况下,不同流动方向,不同流体粘度,不同液膜厚度下的液滴夹带所需的临界气相流速,结果同经典关系式进行了对比,吻合良好．这一方法对于反应堆事故中的两相流动研究具有参考意义．