Takasago (Japan)

This study aimed to evaluate the feasibility and safety of pulsed-current iontophoresis (IP) for the transdermal delivery of teriparatide, a therapeutic peptide for osteoporosis. Female rats were subjected to in vivo iontophoretic administration under constant or pulsed-current conditions. Serum teriparatide concentrations, skin irritation scores, and transepidermal water loss (TEWL) were assessed. After 2 h of IP, serum teriparatide concentrations reached 53.3 ± 4.0 pg/mL with pulsed current and 48.8 ± 12.6 pg/mL with constant current, confirming successful transdermal absorption of teriparatide (≈4 kDa) into systemic circulation. Skin irritation was significantly reduced under pulsed-current conditions, as indicated by lower erythema, edema, and TEWL values, despite identical total current exposure. These results suggest that intermittent current application during pulsed-current IP alleviates local electrical stress through partial depolarization and may provide a delivery efficiency comparable to that of constant direct current IP while improving tolerability. Overall, pulsed-current IP enables noninvasive and effective systemic delivery of peptide drugs with minimized skin irritation, representing a promising alternative to injection-based administration for macromolecular therapeutics.

目的：嚥下造影検査（VF）は嚥下障害の診断や治療法の決定において重要な情報源となる．現行の評価法は主観的要素が強く，客観的評価の臨床活用が望まれる．本研究では嚥下障害の対照群と疾患群との比較研究から，疾患群の嚥下障害の病態を定量的に示すことを目指した．

Cyclic lipopeptides (CLPs) produced by the genus Bacillus are amphiphiles composed of hydrophilic amino acid and hydrophobic fatty acid moieties and are biosynthesised by non-ribosomal peptide synthetases (NRPSs). CLPs are produced as a mixture of homologues with different fatty acid moieties, whose length affects CLP activity. Iturin family lipopeptides are a family of CLPs comprising cyclic heptapeptides and β-amino fatty acids and have antimicrobial activity. There is little research on how the length of the fatty acid moiety of iturin family lipopeptides is determined. Here, we demonstrated that the acyl ligase (AL) domain determines the length of the fatty acid moiety in vivo. In addition, enzyme assays revealed how mutations in the substrate-binding pocket of the AL domain affected substrate specificity in vitro. Our findings have implications for the design of fatty acyl moieties for CLP synthesis using NRPS.

Sonocrystallization is a promising technology for improving the reproducibility and productivity of the crystallization process because of the unique cavitation effect of ultrasound as well as for controlling crystal polymorphs and particle size. Despite these advantages, the use of ultrasound for crystallization has typically been limited to laboratory studies and has not been widely adopted on an industrial scale by the pharmaceutical industry. In this study, ultrasound was combined with continuous crystallization using a mixed-suspension, mixed-product removal (MSMPR) crystallizer, and this technology was applied to the crystallization of perampanel, demonstrating the effects of ultrasound and its practicality. Finally, the continuous sonocrystallization process was successfully scaled up using a 10 L ultrasonic crystallizer capable of direct ultrasound irradiation, providing a methodology for the scale-up of the continuous sonocrystallization process.

Garlic consumption is a well-known cause of unpleasant breath and body odour, with volatile organosulfur compounds, such as diallyl disulfide (DADS) and allyl methyl sulfide (AMS) responsible for the characteristic odour. Certain foods that are rich in polyphenols (PPs) and polyphenol oxidase (PPO) are known to deodorise garlic breath. However, no study into garlic body odour has been reported owing to the very low amounts of emitted volatile organosulfur compounds. Herein, we aimed to demonstrate the effects of ingesting natural food additives rich in both PPs and PPO on the emissions of skin-derived DADS and AMS using a passive flux sampler in conjunction with gas chromatography–mass spectrometry. Three healthy male subjects were subjected to garlic-consumption testing, with all subjects commonly observed to exhibit remarkably higher dermal DADS- and AMS-emission fluxes after consuming 45 g of cooked garlic, which then gradually decreased toward their initial baseline levels. In comparison, remarkably lower emission fluxes of both organosulfur compounds were observed after consuming a natural food additive following garlic consumption in a dose-dependent manner. The optimal amount of ingested natural food additive required to reduce garlic body odour was found to be 1–2 g. Considering the metabolic pathway associated with garlic-derived sulfur compounds and elimination reactions involving PPs and PPO, allyl mercaptan is likely to be a key substance involved in reducing garlic body odour through the ingestion of natural food additives.

The replacement of coal with lignocellulosic biomass as feedstock for blast furnace coke is a crucial approach to decarbonizing the steel industry, which is a sector that is difficult to abate. Unlike the addition of a small amount of biomass or its charcoal to blended coal for conventional coke, the use of 100% biomass as a raw material is possible with formed coke, while its practical application requires an improvement in strength. Here, we report that the addition of a low-molecular-weight fraction obtained from degradative solvent extraction of biomass, called Soluble, is highly effective in enhancing the strength of the formed coke from softwood biomass. When used alone as a raw material, Soluble foams during carbonization, preventing coke formation. However, when mixed with woody biomass, it disperses within and between biomass particles during pelletization (hot press at 130 °C) or carbonization (cold press). Soluble has a minimal impact on the pyrolysis of biomass and dimensional changes of the biomass-derived carbonaceous substrate during carbonization, but it acts as a binder to sustain the strength of the resulting coke. As a result, the tensile strength of formed coke from biomass alone, which was 1.2 MPa with a cold press and 7.5 MPa with a hot press, improved with the increasing addition of Soluble, reaching around 25 MPa at 30 wt % addition. The effect of addition varied significantly depending on the preparation method and properties of Soluble, particularly highlighting the importance of the resolidification temperature during the carbonization process. This method was also effective for formed coke derived from lower-quality raw materials such as rice husk and lignite compared to softwood, but the optimal addition amount varied due to differences in the Soluble retention capacity.

Abstract This study presents data-driven modelling of the Reynolds stress tensor and turbulent heat flux vector for improving unsteady RANS (Reynolds-averaged Navier Stokes) predictions of natural convection problems. While RANS-based calculations are cost-effective, conventional models fail to deliver the requisite predictive precision for high-Rayleigh-number practical engineering flows. To rectify this limitation, a gene-expression programming (GEP)-based machine-learning technique was employed to train novel models using a high-fidelity dataset from a vertical cylinder case with Ra = O(1013), which was generated using LES and validated against experimental data from Mitsubishi Heavy Industries (MHI). The newly developed data-driven closures for Reynolds stress and turbulent heat flux were then used to extend the realisable k-epsilon (RKE) turbulence model. The efficacy of these models was rigorously tested through a full a posteriori approach, involving URANS calculations with the newly constructed closures for the training case and two different testing cases. The results show that for cases with high Ra number (≥ 1011), the Nusselt number, temperature profiles, and velocity profiles exhibit significant enhancements due to the application of the GEP-based closures, initially developed using the Ra = O(1013) training case. However, for cases featuring lower Ra numbers, where standard RANS models already perform relatively well, the utilisation of the current data-driven closures becomes unnecessary, potentially even leading to reduced simulation accuracy. This investigation carries implications for cost reduction in the design process of thermal engineering applications involving high-Rayleigh-number natural convection flows.

Abstract This paper presents a multi-component optimization approach for improving overall performance of the axial turbine blade and axial-radial diffuser of a marine turbocharger. Blade throat-to-pitch distribution and diffuser passage shape are concurrently optimized, exploiting coupling between blade exit flow and diffuser pressure recovery to boost overall efficiency. Algorithmic approaches are used for shape generation of both blade and diffuser. For the blade, a spanwise twisting and re-staggering approach fixing turbine mass-flow is adopted. For the diffuser, a NURBS-based process allowing for non-axisymmetric passages is developed by visual programming. Steady RANS CFD is used for aerodynamic evaluation and optimization is performed by a parallelized hill climbing method for both axisymmetric and non-axisymmetric passages. The best design from concurrent optimization with axisymmetric passage achieves overall efficiency improvement of +0.49% (abs) compared to the base case. This performance is 40% higher than the combination of best blade and diffuser optimized individually. The best concurrently optimized design consists of a blade with triple-peak, W-profile throat-to-pitch distribution with more uniform mid-span flow and accelerated tip-side flow and swirl combined with a diffuser with 14% higher passage area ratio and 9% higher pressure recovery without sacrificing separation margin. Over 70% of efficiency gain is due to the blade, far exceeding the effect of passage shape. This design also retains its performance improvement under overloaded operation, showing viability for actual use. Best design with non-axisymmetric passage achieves +0.04% (abs) further improvement but shows little difference in terms of flow mechanisms. This result shows the utility of this approach in exploiting coupled mechanisms between turbomachinery components. In future, this approach could support existing part-by-part design methods with greater understanding of the influence of interdependencies between components on overall performance.