The treatment of rheumatoid arthritis (RA) is now entering a new era, the era of Janus kinase (JAK) inhibitors. JAK inhibitors target multiple cytokines including IL-6 and exhibit a beneficial ...treatment effect in patients with RA and inadequate response to conventional synthetic or biologic disease-modifying anti-rheumatic drugs. Since the treatment effect of JAK inhibitors is promising even for patients refractory to anti-IL-6 therapy, it needs to be considered how multiple cytokines play roles in the pathogenesis of RA. It is also worth noting that an increased risk of herpes zoster is specifically related to the use of JAK inhibitors. Among cytokines targeted by JAK inhibitors, the current review focuses on IFN-γ, particularly on its role in synovial biology, autoimmunity, bone metabolism, pain, and varicella zoster virus infection. Recent studies provided new insights into IFN-γ in the pathogenesis of RA, which may account for the efficacy of JAK inhibitors.
Abstract
We have developed three-dimensional molecular dynamics method, in which anisotropy of a superconductor and vortex core energy are included. We have applied it to a superconductor with ...splayed columnar defects. We have found that under a driving force due to an external current, vortices show wandering structures, which comes from the pinning force from splayed columnar defects. Especially, for weak core energy, vortices become soft or flexible. In an isotropic superconductor, these wandering structures disappear.
Drug efficacy is improved by selective delivery of the drug to the target by encapsulation within liposomes. Although many new and generic liposomal drugs are under development, only a limited number ...have been approved. One of the reasons for the small number of successes is the difficulty in analyzing liposomal drugs. In the case of liposomal drugs, the evaluation of various parameters, such as composition, drug amount, size, and surface state, is required for quality control and safety considerations. The fact that these parameters change constantly depending on time and the surrounding environment makes these analyses difficult. This mini review focuses on analytical methods for liposomal drugs that use high-performance liquid chromatography, which is the most popular analytic technique for drug development and quality assurance.
Because proteins control cellular function, intracellular protein analysis is needed to gain a better understanding of life and disease. However, in situ protein analysis still faces many ...difficulties because proteins are heterogeneously located within the cell and the types and amount of proteins within the cell are ever changing. Recently, nanotechnology has received increasing attention and multiple protein-containing nanoparticles have been developed. Nanoparticles offer a promising tool for intracellular protein analysis because (1) they can permeate the cellular membrane after modification or changing composition, (2) the stability of various proteins is improved by encapsulation within nanoparticles, and (3) protein release and activity can be controlled. In this review, we discuss the development of analytical methods for intracellular functional protein analysis using signal-responsive silica and organic nanoparticles.
In oxide films on CoCrCuFeNi medium-entropy alloys with Cu contents of 0–5 at%, Cu existed as CuO, and the concentration increased with increasing Cu content in the alloys. Active dissolution in HCl ...was suppressed by the addition of Cu. The pitting potential in NaCl increased with the addition of 1 at% Cu, but it decreased with the addition of 3 at% Cu or more. The role of Cu was clarified by relating the active dissolution rate and pitting potential. In addition, the effects of Mo and W are discussed.
•Copper was present as CuO in the oxide film, with a concentration twice the alloy content.•Dissolution of CuO from the films was responsible for suppressing active dissolution and decreasing pitting potential.•The addition of Mo or W improved the pitting corrosion resistance of the CoCrCuFeNi medium-entropy alloys.
The excellent antibacterial activity of manuka honey has been well-documented and is often evaluated according to the unique manuka factor (UMF) index. UMF is determined by an assay based on a ...bacterial culture, which is time-consuming and does not allow for quantitative analysis. This study developed a simple and rapid method for UMF evaluation using fluorescence fingerprints, principal component analysis (PCA), and partial least squares (PLS) regression. Manuka honey samples were diluted four times with water and fluorescence was observed at three wavelength combinations, namely 260–300 (excitation; ex) to 370 (emission; em) nm, 340 (ex) to 480 nm (em), and 440 (ex) to 520 nm (em), that are mainly attributed to lepteridine, leptosperin, 2-methoxybenzoic acid, and N-methyl phenazinium. Analyzing fluorescence fingerprints using PCA and PLS regression provided a reliable evaluation of the UMF in manuka honey and could be used to differentiate between manufacturers.
Acyl-CoA synthetase long-chain family members (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their acyl-CoAs. ACSL4 is an ACSL isozyme with a strong preference for ...arachidonic acid (AA) and has been hypothesized to modulate the metabolic fates of AA. There are two ACSL4 splice variants: ACSL4V1, which is the more abundant transcript, and ACSL4V2, which is believed to be restricted to the brain. In the present study, we expressed recombinant human ACSL4V1 and V2 in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus expression system and then partially purified both variants by cobalt affinity column chromatography. We then established a novel ACSL assay system with LC-MS/MS, which is highly sensitive and applicable to various kinds of fatty acids, and used it to investigate the substrate specificity of recombinant human ACSL4V1 and V2. The results showed that both ACSL4 variants preferred various kinds of highly unsaturated fatty acids (HUFAs), including docosahexaenoic acid (DHA), adrenic acid (docosatetraenoic acid) and eicosapentaenoic acid (EPA), as well as AA as a substrate. Moreover, our kinetic studies revealed that the two variants had similar relative affinities for AA, EPA and DHA but different reaction rates for each HUFA. These results confirmed the importance of both of ACSL4 variants in the maintenance of membrane phospholipids bearing HUFAs. Structural analysis of these variants might reveal the molecular mechanism by which they maintain membrane phospholipids bearing HUFAs.
Photosynthesis is responsible for the sunlight-powered conversion of carbon dioxide and water into chemical energy in the form of carbohydrates and the release of O2 as a by-product. Although many ...proteins are involved in photosynthesis, the fascinating machinery of Photosystem II (PSII) is at the heart of this process. This tutorial review describes an emerging technique named protein film photoelectrochemistry (PF-PEC), which allows for the light-dependent activity of PSII adsorbed onto an electrode surface to be studied. The technique is straightforward to use, does not require highly specialised and/or expensive equipment, is highly selective for the active fractions of the adsorbed enzyme, and requires a small amount of enzyme sample. The use of PF-PEC to study PSII can yield insights into its activity, stability, quantum yields, redox behaviour, and interfacial electron transfer pathways. It can also be used in PSII inhibition studies and chemical screening, which may prove useful in the development of biosensors. PSII PF-PEC cells also serve as proof-of-principle solar water oxidation systems; here, a comparison is made against PSII-inspired synthetic photocatalysts and materials for artificial photosynthesis.
Nitrate anion is one of the main nitrogen-containing-pollutants in groundwater and can be removed using denitrification systems including electrocatalytic systems. Herein we report on ...electrocatalytic nitrate reduction catalyzed on tin-modified single crystalline electrodes of palladium, platinum and palladium-platinum alloy in acidic and neutral media. We have prepared electrodes with the (111) surface or the (100) surface and modified their surface with tin. Cyclic voltammetry of the electrodes has revealed that the tin-modified alloy (trimetallic) electrodes show higher electrocatalytic activity than the tin-modified platinum or palladium (bimetallic) electrodes, and the catalytic reaction is more efficiently catalyzed on the (100) surface rather than the (111) surface. The tin-modified PdPt(100) electrode shows the highest catalytic activity in acidic media as well as in neutral media. X-ray photoelectron spectroscopy suggests that metallic tin forms on the (100) surface, but divalent tin species on the (111) surface, indicating that a surface alloy of tin may form on the (100) surface, resulting in enhancement of the electrocatalytic activity. Our findings suggest that design and preparation of ternary metallic electrodes with the (100) surface will pave the way to the development of practical systems on electrocatalytic denitrification.
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•Tin-modified single crystalline Pd, Pt and PdPt alloy electrodes are prepared.•Electrocatalytic nitrate reduction occurs efficiently on the (100) surface.•A surface alloy may form for Sn/PdPt(100), revealed by using XPS.•Sn/PdPt(100) is highly active for electrocatalytic nitrate reduction.•Sn/PdPt(100) shows the catalytic activity in not only acidic but also neutral media.
Abstract
When a current applied to an intrinsic Josephson junction (IJJ) in a copper oxide high-temperature superconductor is increased, the IJJ enters a voltage state and then the voltage increases ...stepwise. After these voltage states, when the current is lowered, THz oscillation occurs. The voltage state is described as a running state of a particle in a washboard potential, using the RCSJ model of the Josephson junction (JJ). In this study, we investigate these running states in the IJJ, using a coupled layered JJ model with the finite element method. Especially, we focus on time evolution of phase differences in all JJs in the IJJ under weak external current.
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