Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil elastase inhibitor, sivelestat, could alleviate pulmonary fibrosis; however, the antifibrotic ...mechanisms have not yet been clarified. We examined the antifibrotic mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, in this study. To elucidate the antifibrotic mechanisms of sivelestat, we examined a murine model of bleomycin-induced early-stage pulmonary fibrosis. After intratracheal instillation of bleomycin, sivelestat was administered intraperitoneally once a day for 7 or 14 days. Bronchoalveolar lavage fluid and lung samples were examined on day 7 or day 14 after bleomycin instillation. In the bleomycin-induced early-stage pulmonary fibrosis model, the neutrophil elastase level was increased in the lungs. Sivelestat significantly inhibited the increase in lung collagen content, fibrotic changes, the numbers of total cells (including macrophages, neutrophils and lymphocytes), the levels of the active form of TGF-β1 and phospho-Smad2 in bleomycin-induced early-stage pulmonary fibrosis. The total TGF-β1 levels and relative changes of TGF-β1 mRNA expression, however, were not decreased significantly by sivelestat. These results suggest that sivelestat alleviated bleomycin-induced pulmonary fibrosis via inhibition of both TGF-β activation and inflammatory cell recruitment in the lung.
A polarizable ion model was applied to the solid and molten alkaline-earth halide MX2, the parameters of which were determined by using first-principles calculations based on density functional ...theory, where M = Ca, Sr, Ba, and X = F, Cl, Br. The obtained parameters were used to evaluate the ionic conductivity, shear viscosity, and thermal conductivity in the molten and solid states by molecular dynamics simulations using the Green-Kubo relations. The calculated results were in good agreement with the experimental ionic conductivities and shear viscosities. The behaviors of all the calculated properties were well accounted for by ionic mass, number density, and packing fraction. Especially, the calculated thermal conductivities were well expressed by the empirical formula obtained for molten alkali halides. In addition, it was revealed that the reversal of cationic dependence in ionic conductivity of fluorides between solids and melts is due to the mass effects of carrier ions.
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•The tracer diffusion coefficients were calculated by MD simulation for both Ar in n-alkane and n-alkane in Ar.•The effects of the molecular differences between solute and solvent on ...the tracer diffusion were evaluated.•Among the differences in the mass, size, shape, and interaction energy, the size and interaction energy are important.•The differences clearly account for the breakdown of the Stokes–Einstein relation for Ar in n-alkanes.
Molecular size and shape effects are evaluated on the Stokes–Einstein (SE) relation from the viewpoint of molecular differences between the solute and solvent. To this end, dilute solutions of both an n-alkane in Ar and Ar in an n-alkane were simulated using the molecular dynamics method. The molecular-based SE relation derived for the Lennard-Jones liquid mixtures was found to be applicable to both systems, which shows that the effects of the differences in the size and interaction energy are predominant but that those in the shape are negligible in these systems.
A polarizable ion model was applied to the solid and molten alkaline-earth halide MX2, the parameters of which were determined by using first-principles calculations based on density functional ...theory, where M = Ca, Sr, Ba, and X = F, Cl, Br. The obtained parameters were used to evaluate the ionic conductivity, shear viscosity, and thermal conductivity in the molten and solid states by molecular dynamics simulations using the Green-Kubo relations. The calculated results were in good agreement with the experimental ionic conductivities and shear viscosities. The behaviors of all the calculated properties were well accounted for by ionic mass, number density, and packing fraction. Especially, the calculated thermal conductivities were well expressed by the empirical formula obtained for molten alkali halides. In addition, it was revealed that the reversal of cationic dependence in ionic conductivity of fluorides between solids and melts is due to the mass effects of carrier ions.
Self-assembled ionic liquid crystals can transport water and ions via the periodic nanochannels, and these materials are promising candidates as water treatment membranes. Molecular insights on the ...water transport process are, however, less investigated because of computational difficulties of ionic soft matters and the self-assembly. Here we report specific behavior of water molecules in the nanochannels by using the self-consistent modeling combining density functional theory and molecular dynamics and the large-scale molecular dynamics calculation. The simulations clearly provide the one-dimensional (1D) and 3D-interconnected nanochannels of self-assembled columnar and bicontinuous structures, respectively, with the precise mesoscale order observed by x-ray diffraction measurement. Water molecules are then confined inside the nanochannels with the formation of hydrogen bonding network. The quantitative analyses of free energetics and anisotropic diffusivity reveal that, the mesoscale geometry of 1D nanodomain profits the nature of water transport via advantages of dissolution and diffusion mechanisms inside the ionic nanochannels.
Formulation of rotational diffusion coefficient and the Stokes-Einstein-Debye (SED) relation is presented for diatomic molecular liquids by molecular dynamics simulation with two-center Lennard-Jones ...(2CLJ) potentials. Shear viscosity ηsv and rotational diffusion coefficient Dr are expressed as a function of molecular mass and number density N/V, or moment of inertia, packing fraction, temperature T, interaction energy, and molecular elongation l∗ ≡ l/σ, where N is the number of molecules included in the system volume V, l the bond length in the diatomic molecules, and σ the size parameter used in the LJ potentials. The packing fraction and elongation are the variables expressing molecular size and shape, respectively. These results produce directly a molecular-basis SED relation as Drηsv/T ∝ vm∗1/3l∗−3(N/V), where vm∗ is the dimensionless molecular volume expressed as an analytical function only of elongation l∗. That is, this SED equation depends not on the size but on the shape. This is highly contrasted with the original SED relation based on the size, which suggests overall reconsideration of the relation on a molecular scale. The shape term accounts for a paradox that more spherical molecules such as N2 deviate more strongly from the original SED equation based on a spherical particle. In addition, the SED relation without the size is consistent with the Stokes-Einstein relation for both the Lennard-Jones and 2CLJ liquids expressed as Dηsv/T ∝ (N/V)1/3, where D is the translational self-diffusion coefficient.
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•Pure molecular shape effect is formulated on the rotational diffusion coefficient of diatomic molecular liquids.•The Stokes-Einstein-Debye (SED) relation which depends not on molecular size but on shape is presented for the pure liquids.•The packing fraction terms remove the size terms from both the original SED and Stokes-Einstein relations for pure liquids.
Aquatic functional liquid crystals, which are ordered molecular assemblies that work in water environment, are described in this review. Aquatic functional liquid crystals are liquid‐crystalline (LC) ...materials interacting water molecules or aquatic environment. They include aquatic lyotropic liquid crystals and LC based materials that have aquatic interfaces, for example, nanoporous water treatment membranes that are solids preserving LC order. They can remove ions and viruses with nano‐ and subnano‐porous structures. Columnar, smectic, bicontinuous LC structures are used for fabrication of these 1D, 2D, 3D materials. Design and functionalization of aquatic LC sensors based on aqueous/LC interfaces are also described. The ordering transitions of liquid crystals induced by molecular recognition at the aqueous interfaces provide distinct optical responses. Molecular orientation and dynamic behavior of these aquatic functional LC materials are studied by molecular dynamics simulations. The molecular interactions of LC materials and water are key of these investigations. New insights into aquatic functional LC materials contribute to the fields of environment, healthcare, and biotechnology.
Aquatic functional liquid crystals, which are ordered molecular assemblies that work in water environment, have great potential for contribution to the fields of environment, resources, healthcare, and bio‐applications. In this perspective, recent progress in water treatment liquid‐crystalline (LC) polymer membranes and aquatic LC sensors is described, from design, assembly, and functionalization to molecular simulation of these aquatic functional liquid crystals.
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