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The dispersibility of nanoparticles in solvents remains difficult to predict and control. In this paper, the dispersibility of organically-modified nanoparticles in various solvents ...with different solvent properties and molecular sizes are investigated. The study indicates that solvent molecular size, in addition to the affinity between organic modifier and solvent molecules, affects the dispersibility of the nanoparticles. The experimental results imply that solvents with molecular size small enough can disperse nanoparticles more efficiently. In addition, based on the concept that solvent accommodation induces the enhancement of dispersibility, two approaches to improve nanoparticle dispersibility in desired solvents are proposed. One is the addition of a small amount of solvent with the right size and properties to both penetrate the modifier shell and to act as intermediate between the desired solvent and the organic modifier molecules. The other is dual-molecule modification to create additional space at modifier-shell surface for the penetration of the desired solvent molecules. The results of these approaches based on the concept of the solvent accommodation can enhance the dispersibility trends.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Holonomic D-modules associated with certain kind of non-isolated hypersurface singularities, introduced by T. de Jong, are considered. Structures of these holonomic D-modules such as characteristic ...variety, monodromy are explicitly determined. The key of our approach is the use of the notion of algebraic local cohomology. An application to Betti numbers of local Milnor fibers is also discussed.
The inhibition of mevalonate kinase (MVK) by downstream metabolites is an important mechanism in the regulation of isoprenoid production in a broad range of organisms. The first feedback-resistant ...MVK was previously discovered in the methanogenic archaeon Methanosarcinamazei. Here, we report the cloning, expression, purification, kinetic characterization and inhibition analysis of MVKs from two other methanogens, Methanosaetaconcilii and Methanocellapaludicola. Similar to the M. mazei MVK, these enzymes were not inhibited by diphosphomevalonate (DPM), dimethylallyl diphosphate (DMAPP), isopentenyldiphosphate (IPP), geranylpyrophosphate (GPP) or farnesylpyrophosphate (FPP). However, they exhibited significantly higher affinity to mevalonate and higher catalytic efficiency than the previously characterized enzyme.
The reduced b-functions and the relevant holonomic D-modules associated to a family of hypersurfaces with non-isolated singularities are considered in the context of symbolic computation. Based on ...the theory of comprehensive Gröbner systems, algorithms of computing reduced b-functions and holonomic D-modules for parametric cases are introduced. A strategy for analyzing holonomic D-modules is described. Main ingredients of our approach are comprehensive Gröbner systems on Poincaré–Birkhoff–Witt algebra and local cohomology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Linalool, an acyclic monoterpene alcohol, is extensively used in the flavor and fragrance industries and exists as two enantiomers, (S)- and (R)-linalool, which have different odors and biological ...properties. Linalool extraction from natural plant tissues suffers from low product yield. Although linalool can also be chemically synthesized, its enantioselective production is difficult. Microbial production of terpenes has recently emerged as a novel, environmental-friendly alternative. Stereoselective production can also be achieved using this approach via enzymatic reactions. We previously succeeded in producing enantiopure (S)-linalool using a metabolically engineered Pantoea ananatis, a member of the Enterobacteriaceae family of bacteria, via the heterologous mevalonate pathway with the highest linalool titer ever reported from engineered microbes.
Here, we genetically modified a previously developed P. ananatis strain expressing the (S)-linalool synthase (AaLINS) from Actinidia arguta to further improve (S)-linalool production. AaLINS was mostly expressed as an insoluble form in P. ananatis; its soluble expression level was increased by N-terminal fusion of a halophilic β-lactamase from Chromohalobacter sp. 560 with hexahistidine. Furthermore, in combination with elevation of the precursor supply via the mevalonate pathway, the (S)-linalool titer was increased approximately 1.4-fold (4.7 ± 0.3 g/L) in comparison with the original strain (3.4 ± 0.2 g/L) in test-tube cultivation with an aqueous-organic biphasic fermentation system using isopropyl myristate as the organic solvent for in situ extraction of cytotoxic and semi-volatile (S)-linalool. The most productive strain, IP04S/pBLAAaLINS-ispA*, produced 10.9 g/L of (S)-linalool in "dual-phase" fed-batch fermentation, which was divided into a growth-phase and a subsequent production-phase. Thus far, this is the highest reported titer in the production of not only linalool but also all monoterpenes using microbes.
This study demonstrates the potential of our metabolically engineered P. ananatis strain as a platform for economically feasible (S)-linalool production and provides insights into the stereoselective production of terpenes with high efficiency. This system is an environmentally friendly and economically valuable (S)-linalool production alternative. Mass production of enantiopure (S)-linalool can also lead to accurate assessment of its biological properties by providing an enantiopure substrate for study.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this study, we investigated the characteristics of water-in-oil (W/O) emulsions formed by hydrophilic nanoparticles in three-phase emulsification and discussed their stability by performing an ...energy analysis. W/O emulsions prepared using the three-phase emulsification method are stable in several systems, even in those with a high internal-phase ratio of water up to 85 wt%. Hydrophilic nanoparticles can exist in the internal water phase independently, and the emulsifying action does not depend on the concentration of nanoparticles or the state of the internal water phase. The energy analysis of the model, in which nanoparticles partially penetrate from the aqueous phase to the oil phase, suggests that hydrophilic nanoparticles can form W/O emulsions. It was also found that the entropy change based on the hydrophobic hydration around the nanoparticles was the main driving force for the nanoparticles to partially penetrate the oil phase.
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•Formation of water-in-oil emulsion using hydrophilic nanoparticles.•Highly water-containing water-in-oil emulsion formed by three-phase emulsification.•Thermodynamic analysis in the formation of water-in-oil three-phase emulsions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Evidence on the effects of a community-wide intervention (CWI) on population-level physical activity (PA), especially in the long term, is limited. Therefore, we evaluated the five-year effect of CWI ...on promoting PA through information dissemination, education, and community support primarily targeting older adults, by incorporating Japanese guidelines, in Fujisawa City, from 2013. To assess the effect of the whole-city intervention, we distributed questionnaires in 2013, 2015, and 2018 to three independent random samples of 3,000 community-dwelling adults (aged ≥ 20 years) using a quasi-experimental study design. Three separate samples responded to the survey (41% at baseline, 46% at the two-year mark, and 48% at the five-year follow-up). The primary outcome was change in PA participation. At the five-year follow-up, PA (median: 120 minutes/day) was significantly higher than at baseline (86 minutes/day) and the two-year follow-up (90 minutes/day). The results of the multivariate analysis indicated that PA among older adults—the primary target population of the CWI—increased significantly at the five-year follow-up, compared to those aged 20–64 (mean difference of change between groups: 14.7 minutes/day, P= 0.029). Among older adults, PA was significantly lower in those with poorer perceived economic status than in their more well-off counterparts at the two-year follow-up (P= 0.003); however, there was no significant difference at the five-year follow-up (P= 1.000). There was a positive interaction between group and period (mean difference of change between groups: 40.9 minutes/day, P= 0.001). In conclusion, the five-year CWI targeting older adults, incorporating national guidelines, improved population-level PA.
•A 5-year community-wide intervention improved city-level physical activity (PA).•PA time of older adults improved by about 15 min/day compared with younger adults.•Among older adults, those with poorer perceived economic status showed improved PA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target ...concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples (
= 210) and liver tissue samples (
= 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC
values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus, respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance (CL
) was identified as a significant covariate influencing total clearance when CL
was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC
for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.
Several inflammatory response biomarkers, including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to predict ...survival in various cancers. The aim of this study is to evaluate the clinical value of these biomarkers in patients undergoing curative resection for esophageal cancer.
The LMR, NLR and PLR were calculated in 147 consecutive patients who underwent esophagectomy between January 2006 and February 2015. We examined the prognostic significance of the LMR, NLR, and PLR in both elderly and non-elderly patients. We evaluated the cancer-specific survival (CSS), with the cause of death determined from the case notes or computerized records.
Univariate analyses demonstrated that TNM pStage (p < 0.0001), tumor size (p = 0.0014), operation time (p = 0.0209), low LMR (p = 0.0008), and high PLR (p = 0.0232) were significant risk factors for poor prognosis. Meanwhile, TNM pStage (p < 0.0001) and low LMR (p = 0.0129) were found to be independently associated with poor prognosis via multivariate analysis. In non-elderly patients, univariate analyses demonstrated that TNM pStage (p < 0.0001), tumor size (p = 0.0001), operation time (p = 0.0374), LMR (p < 0.0001), and PLR (p = 0.0189) were significantly associated with a poorer prognosis. Multivariate analysis demonstrated that TNM pStage (p = 0.001) and LMR (p = 0.0007) were independent risk factors for a poorer prognosis. In elderly patients, univariate analysis demonstrated that that TNM pStage (p = 0.0023) was the only significant risk factor for a poor prognosis.
LMR was associated with cancer-specific survival (CSS) of esophageal cancer patients after curative esophagectomy. In particular, a low LMR was a significant and independent predictor of poor survival in non-elderly patients. The LMR was convenient, cost effective, and readily available, and could thus act as markers of survival in esophageal cancer.
Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and ...long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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