Effect of Polymer Dispersant Structure on Electrosteric Interaction and Dense Alumina Suspension Behavior

The present paper reports on research on the effect of molecular structure of polymer dispersants on the relationship between the electrosteric interaction of dispersants on solid surfaces and the viscosity of suspensions. Ammonium polyacrylate with different hydrophilic to hydrophobic ratios ( m:n ) was prepared and added to dense Al₂O₃ suspensions (40 vol%). The steric interactions and adsorbed structures of dispersants on Al₂O₃ powders were examined under an atomic force microscope (AFM). An optimum hydrophilic to hydrophobic group ratio, which was obtained from the maximum repulsive force and the minimum viscosity of suspension, was determined at m :n = 3:7. The changing mechanism of the adsorbed structure and the steric interaction of dispersants and the suspension viscosity by the hydrophilic to hydrophobic molecular ratio were discussed by comparing the experimental force curve and DLVO theory.     

High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system and in vivo evaluation

Purpose: To design a high drug loading formulation of self-microemulsifying/micelle system. Methods: A poorly-soluble model drug (CH5137291), 8 hydrophilic surfactants (HS), 10 lipophilic surfactants (LS), 5 oils, and PEG400 were used. A high loading formulation was designed by a following stepwise approach using a high-throughput formulation screening (HTFS) system: (1) an oil/solvent was selected by solubility of the drug; (2) a suitable HS for highly loading was selected by the screenings of emulsion/micelle size and phase stability in binary systems (HS, oil/solvent) with increasing loading levels; (3) a LS that formed a broad SMEDDS/micelle area on a phase diagram containing the HS and oil/solvent was selected by the same screenings; (4) an optimized formulation was selected by evaluating the loading capacity of the crystalline drug. Aqueous solubility behavior and oral absorption (Beagle dog) of the optimized formulation were compared with conventional formulations (jet-milled, PEG400). Results: As an optimized formulation, d-α-tocopheryl polyoxyethylene 1000 succinic ester: PEG400?=?8:2 was selected, and achieved the target loading level (200?mg/mL). The formulation formed fine emulsion/micelle (49.1?nm), and generated and maintained a supersaturated state at a higher level compared with the conventional formulations. In the oral absorption test, the area under the plasma concentration-time curve of the optimized formulation was 16.5-fold higher than that of the jet-milled formulation. Conclusions: The high loading formulation designed by the stepwise approach using the HTFS system improved the oral absorption of the poorly-soluble model drug.     

Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure

We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.     

Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β‐carotene and Ascorbic Acid in Human HepG2 Cells

Lead (Pb) is an environmental pollutant that can get entry into human body through contaminated foods, drinks, and inhaled air leading to severe biological consequences, and has been responsible for many deaths worldwide. The objectives of this study were 1st to investigate the modulatory effects of environmentally relevant concentrations of Pb on AhR gene battery, which is controlling xenobiotics metabolism. 2nd, trials to reduce Pb‐induced adverse effects were done using some phytochemicals like β‐carotene or ascorbic acid. Human hepatoma (HepG2) cell lines were exposed to a wide range of Pb concentrations varying from physiological to toxic levels (0 to 10 mg/L) for 24 h. High Pb concentrations (1 to 10 mg/L) significantly reduced phase I (CYP1A1 and 1A2) and phase II (UGT1A6 and NQO1) xenobiotic metabolizing enzyme mRNA expression in a mechanistic manner through the AhR regulation pathway. Additionally, these Pb concentrations induced oxidative stress in HepG2 cells in terms of production of reactive oxygen species (ROS) and induced heme oxygenase‐1 mRNA expression in a concentration‐dependent phenomenon. Coexposure of HepG2 cells to physiological concentrations of some micronutrients, like β‐carotene (10 μM) or ascorbic acid (0.1 mM), along with Pb (1 mg/L) for 24 h significantly reduced the levels of ROS production and recovered AhR mRNA expression into the normal levels. Thus, consumption of foods rich in these micronutrients may help to reduce the adverse effects of lead in areas with high levels of pollution.     

Visible Light Emission From Dye Molecular Grains via Infrared Excitation Based on the Nonadiabatic Transition Induced by the Optical Near Field

We observed light emission in the visible wavelength range (lambda = 600-690 nm) from aggregated 4-dicyanomethylene-2-methyl-6-p-dimethylaminostyryl-4H-pyran (DCM) dye molecule grains excited by infrared light (lambda_ex = 805 nm). The domains of visible light emission were localized at the surface and edges of the dye grains, where the optical near field was strengthened. The emitted visible light intensity decayed exponentially according to the time constants tau₁ = 0.45 ns and tau² = 1.37 ns, which were equivalent to those of conventional fluorescence excited by visible light at lambda_ex = 402 nm. The emitted light intensity increased with the infrared excitation intensity, in agreement with the theoretical results of the exciton-phonon polariton model. This confirmed that the visible light emission originated from the nonadiabatic transition process due to optical near-field features. The frequency upconversion efficiency for excitation from infrared (lambda_ex = 805 nm) to visible (lambda = 600-690 nm) in the film of the DCM molecular grains was experimentally estimated to be higher than that of the second harmonic generation (SHG) from a potassium dihydrogen phosphate (KDP) crystal. In particular, it was higher when the fundamental light power density was lower than 100 W/cm². Visible light emission from the grains of the rhodamine 6G (N-{2-[2-(2-aminoethoxy)ethoxy]ethyl} rhodamine 6G-amide bis[trifluoroacetate]) dye molecule was also observed in the infrared light (lambda_ex = 805 nm). Our results demonstrated the universality of the nonadiabatic transition process.     

Random mutagenesis improves the low-temperature activity of the tetrameric 3-isopropylmalate dehydrogenase from the hyperthermophile Sulfolobus tokodaii

In general, the enzymes of thermophilic organisms are more resistant to thermal denaturation than are those of mesophilic or psychrophilic organisms. Further, as is true for their mesophilic and psychrophilic counterparts, the activities of thermophilic enzymes are smaller at temperatures that are less than the optimal temperature. In an effort to characterize the properties that would improve its activity at temperatures less than the optimal, we subjected the thermostable Sulfolobus tokodaii (S. tokodaii) 3-isopropylmalate dehydrogenase to two rounds of random mutagenesis and selected for improved low-temperature activity using an in vivo recombinant Escherichia coli system. Five dehydrogenase mutants were purified and their catalytic properties and thermostabilities characterized. The mutations favorably affect the K(m) values for NAD (nicotinamide adenine dinucleotide) and/or the k(cat) values. The results of thermal stability measurements show that, although the mutations somewhat decrease the stability of the enzyme, the mutants are still very resistant to heat. The locations and properties of the mutations found for the S. tokodaii enzyme are compared with those found for the previously isolated low-temperature adapted mutants of the homologous Thermus thermophilus enzyme. However, there are few, if any, common properties that enhance the low-temperature activities of both enzymes; therefore, there may be many ways to improve the low-temperature catalytic activity of a thermostable enzyme.     

Synthesis of well-defined star-branched polymers by stepwise iterative methodology using living anionic polymerization

This article reviews the synthesis of regular and asymmetric star-branched polymers with well-defined structures by methodologies using living anionic polymerization, especially focusing on the synthetic approaches accessible for precisely controlled architectures of star-branched polymers concerning molecular weight, molecular weight distribution, arm number, and composition. The reason for selecting living anionic polymerization from many living/controlled polymerization systems so far developed is that this living polymerization system is still the best to meet the strict requirements for the precise structures of star-branched polymers. Furthermore, we herein mainly introduce a novel and quite versatile stepwise iterative methodology recently developed by our group for the successive synthesis of many-armed and multi-compositional asymmetric star-branched polymers. The methodology basically involves only two sets of the reaction conditions for the entire iterative synthetic sequence. The reaction sequence can be, in principle, limitlessly iterated to introduce a definite number of the same or different polymer segments at each stage of the iteration. As a result, a wide variety of many-armed and multi-compositional asymmetric star-branched polymers can be synthesized.     

Suppression of floatability of pyrite in coal processing by carrier microencapsulation

Carrier microencapsulation, CME, is a technique to form a thin layer of metal oxide or hydroxide on pyrite surface using a water soluble organic carrier combined with metal ions. The present study investigated the effect of CME using a tris-catecholato complex of Si⁴⁺, Si(cat)₃²⁻ on pyrite-coal separation by dynamic bubble pick-up experiments and Hallimond tube flotation experiments using coal, pyrite, and a coal-pyrite mixture. The mineral samples were treated in 0-5 mol m^− 3 Si(cat)₃²⁻ solutions at pH 4-9 at treatment times of 1-24 h. Dynamic bubble pick-up experiments showed that CME treatment converted the pyrite surface from hydrophobic to hydrophilic but did not affect coal's hydrophobic surface. The results of the Hallimond tube flotation experiments of a coal-pyrite mixture at pH 7-9 in the presence of kerosene as a collector showed that pyrite floatability was selectively suppressed after 1 h CME treatment with 0.5 mol^− 3 Si(cat)₃²⁻ while both coal and pyrite were floated without the treatment. This indicates that CME treatment is effective in suppressing pyrite floatability in coal-pyrite flotation.     

Angiotensin I-converting enzyme inhibitory activities of Chinese fermented soypaste and estimation of the inhibitory substances

Angiotensin I-converting enzyme (ACE) inhibitory activities of aqueous extracts of Chinese commercial soypaste were investigated in this work. Six samples from northern China showed potent ACE inhibitory activities with IC₅₀ values less than 40.0 μg/mL. ACE inhibitors in the sample with the strongest activity were purified by ultrafiltration, solid-phase extraction and gradient RP-HPLC. According to spectroscopic methods, a compound (M328.1) was separated as C₁₅H₂₁NO₇. It was supposed to be a conjugate of phenylalanine and glucose generated by Maillard reaction during soypaste production, providing support on the contribution of Maillard reaction products to the ACE inhibitory activity of the sample. Results further indicated that the total ACE inhibition by the sample occurred from the combined function of various bioactive substances, suggesting that Chinese soypaste could be a good source of ACE inhibitors for exploring functional foods or ingredients with antihypertensive effect.