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Abstract: Dielectric relaxation measurements for Y2O3-stabilized ZrO2 single crystals with different directions have shown anisotropic dielectric properties and approved the anisotropic diffusion paths of oxygen ions in fluorite structures suggested by neutron diffraction measurements. The activation energy including the migration energy of mobile oxygen ions obtained from the dielectric measurements suggested that oxygen ions easily diffuse along the 〈100〉 direction. The amount of mobile oxygen ions is also highest in the direction. The anisotropic dielectric properties are discussed along with the diffusion path of oxygen ions in fluorite structures. [Copyright &y& Elsevier]

Abstract: In order to clarify co-doping effects of trivalent rare earth ions to the ionic conduction and the crystal structure in ZrO2, dc- and ac-measurements along with XRD observations have been carried out to ((Y0.75La0.25)1−x Gd x )0.18Zr0.82O2−δ by changing x from 0 to 1, where the average ionic radius of (Y0.75La0.25)1−x Gd x is constant, i.e., 1.053 Å, being independent of x. These specimens contain dual phases, i.e., cubic and monoclinic phases. Dc conductivity in the heating process differs from that in the cooling process. This hysteresis has been discussed in terms of the monoclinic–cubic phase transition on the basis of XRD results at high temperatures. The x-dependencies of the energy values required for the bulk and grain boundary conductions are strongly related to the ionic radii of the trivalent rare earth ions because the states of oxygen vacancies, which are substantially responsible for ionic conductions, depend upon the rare earth ions that capture the vacancies at lower temperatures. Many combinations of oxygen vacancies and rare earth ions lead to the long-ranged hysteresis. [Copyright &y& Elsevier]

Background: Muscle-liver crosstalk plays an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). The measurement of muscle echo-intensity during ultrasonography is a real-time, non-invasive method of assessing muscle quality. In this retrospective study, we investigated the significance of poor muscle quality (namely, a greater mass of non-contractile tissue, including intramuscular fat) as a risk factor for advanced liver fibrosis and considered whether it may represent a useful tool for the diagnosis of advanced liver fibrosis., Methods: We analyzed data from 307 patients with NAFLD (143 men and 164 women) who visited the University of Tsukuba Hospital between 2017 and 2022. The patients were stratified into the following tertiles of muscle quality according to their muscle echo-intensity on ultrasonography: modest (84.1 arbitrary units [A.U.]), intermediate (97.4 A.U.), and poor (113.6 A.U.). We then investigated the relationships between muscle quality and risk factors for advanced liver fibrosis and calculated appropriate cutoff values., Results: Patients with poor muscle quality showed a significant, 7.6-fold greater risk of liver fibrosis compared to those with modest muscle quality. Receiver operating characteristic curve analysis showed that muscle quality assessment was as accurate as the fibrosis-4 index and NAFLD fibrosis score in screening for liver fibrosis and superior to the assessment of muscle quantity and strength, respectively. Importantly, a muscle echo-intensity of ≥92.4 A.U. may represent a useful marker of advanced liver fibrosis., Conclusion: Muscle quality may represent a useful means of identifying advanced liver fibrosis, and its assessment may become a useful screening tool in daily practice.

Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (P.g.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P.g. We generated macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-mRes mice were fed a high-fat diet for 18 weeks, and LPS from P.g. was administered intraperitoneally for the last 6 weeks. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The mRNA expressions of Toll-like receptor (Tlr)-2, which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin (αSma), which promotes hepatic fibrosis, were reduced in Nrf2-mRes mice compared with Nrf2-KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2-KO mice compared with WT mice; however, the levels were reduced in Nrf2-mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recently, the use of ergogenic aids in sports by both athletes and fans has increased. Moreover, the overall demand for new ergogenic aids has increased. Hesperidin is a polyphenol that is useful for improving exercise performance by activating energy generation through β-oxidation and oxidative phosphorylation in skeletal muscles. However, it is difficult to use this compound as an ergogenic aid because of its poor water solubility and low bioavailability. Glucosyl hesperidin is formed when one molecule of glucose is transferred to hesperidin via glycosyl-transferase. It is 10,000× more soluble and has 3.7× higher bioavailability than hesperidin. In this study, we assessed whether continuous (14 days) intake of glucosyl hesperidin improves the aerobic exercise capacity of rats during long-term acute exercise. Although glucosyl hesperidin intake did not improve the performance of high-intensity running (30 m/min), we did observe improvement in low-intensity running (15 m/min) (p < 0.05). We demonstrate that in sedentary rats, glucosyl hesperidin intake increased β-oxidation and oxidative phosphorylation in the skeletal muscle (p < 0.05 and p < 0.01, respectively). Glucosyl hesperidin intake may have created a metabolic state useful for long-term exercise. In conclusion, the continuous intake of glucosyl hesperidin improved the aerobic exercise capacity of rats during long-term acute exercise., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Non-alcoholic fatty liver disease is a growing health problem, and rapid diet assessment is required for personal nutrition education. This pilot study aimed to clarify associations between current food intake patterns identified from the short food frequency questionnaire (FFQ) and metabolic parameters, including liver function. We conducted a cross-sectional study on Japanese non-alcoholic residents of Tokyo and surrounding districts, 20 to 49 years of age. Anthropometric measurements, fasting blood samples, three-day dietary records, and FFQ with 21 items were collected. In all 198 participants, the proportions with obesity were 21% in men and 6% in women. Hypertriglyceridemia was significant only in men, affecting 26%. The traditional Japanese (TJ) pattern (greater intakes of green and yellow vegetables, other vegetables, seaweed/mushrooms/konjac, dairy, fruits, fish, salty, and soybeans/soy products) and the Westernized pattern (greater intakes of saturated-fat-rich foods, oily, egg/fish-eggs/liver, and sweets) were identified. The TJ pattern score showed an inverse relationship with body mass index, triglyceride, alkaline-phosphatase, leucine-aminopeptidase, and fatty liver index. The TJ pattern identified from the short FFQ was suggested to be associated with body fat storage. Further large-scale studies are needed to clarify the associations between this dietary pattern and metabolic parameters, including liver function.

Background: Ligament reconstruction and tendon interposition (LRTI) is currently the most performed procedure for osteoarthritis (OA) of the thumb carpometacarpal (CMC) joint. In general, satisfactory outcomes are expected, although some patients complain of residual pain after LRTI. The objective of this study is to determine the factors associated with residual pain., Method: All patients with OA of the thumb CMC joint who underwent LRTI at our hospital between October 2013 and October 2018 and were regularly observed for at least 1 year were included. The following variables were extracted and included in the univariate analysis: sex, age, dominant hand, pain visual analog scale (VAS) score, Eaton classification, grip strength, pulp pinch strength, and metacarpophalangeal joint hyperextension angle were recorded as variables. Mann-Whitney U test or Fisher exact test was used for univariate analysis of the above factors, and then multivariate logistic regression analysis was performed to find out the factors associated with residual pain., Results: The study included 60 thumbs of 53 patients. Eleven thumbs had postoperative residual pain. The surgery on the dominant hand was significantly associated with the presence of postoperative residual pain, especially in males., Conclusions: Dominant hand was associated with residual pain after LRTI for OA of the thumb CMC joint, although residual pain was minimal. Our findings will help in preoperative and postoperative counseling of patients. In the future, our results may also help select surgical procedures according to the patient's characteristics.

Taurine enhances physical performance; however, the underlying mechanism remains unclear. This study examined the effect of taurine on the overtime dynamics of blood glucose concentration (BGC) during endurance exercise in rats. Male F344 rats were subjected to transient treadmill exercise until exhaustion following 3 weeks of taurine supplementation or non-supplementation (TAU and CON groups). Every 10 min during exercise, BGC was measured in blood collected through cannulation of the jugular vein. Gluconeogenesis-, lipolysis-, and fatty acid oxidation-related factors in the plasma, liver, and skeletal muscles were also analyzed after 120-min run. Exercise time to exhaustion was significantly longer with taurine supplementation. BGC in the two groups significantly increased by 40 min and gradually and significantly decreased toward the respective exhaustion point. The decline in BGC from the peak at 40 min was significantly slower in the TAU group. The time when the once-increased BGC regressed to the 0-time level was significantly and positively correlated with exercise time until exhaustion. At the 120-min point, where the difference in BGC between the two groups was most significant, plasma free fatty acid concentration and acetyl-carnitine and N-acetyltaurine concentrations in skeletal muscle were significantly higher in the TAU group, whereas glycogen and glucogenic amino acid concentrations and G6Pase activity in the liver were not different between the two groups. Taurine supplementation enhances endurance capacity by delaying the decrease in BGC toward exhaustion through increases of lipolysis in adipose tissues and fatty acid oxidation in skeletal muscles during endurance exercise., (© 2022. The Author(s).)

Objective: Excessive exercise increases the production of reactive oxygen species in skeletal muscles. Sulforaphane activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces a protective effect against oxidative stress. In a recent report, sulforaphane intake suppressed exercise-induced oxidative stress and muscle damage in mice. However, the effect of sulforaphane intake on delayed onset muscle soreness after eccentric exercise in humans is unknown. We evaluated the effect of sulforaphane supplement intake in humans regarding the delayed onset muscle soreness (DOMS) after eccentric exercise., Research Methods & Procedures: To determine the duration of sulforaphane supplementation, continuous blood sampling was performed and NQO1 mRNA expression levels were analyzed. Sixteen young men were randomly divided into sulforaphane and control groups. The sulforaphane group received sulforaphane supplements. Each group performed six set of five eccentric exercise with the nondominant arm in elbow flexion with 70% maximum voluntary contraction. We assessed muscle soreness in the biceps using the visual analog scale, range of motion (ROM), muscle damage markers, and oxidative stress marker (malondialdehyde; MDA)., Results: Sulforaphane supplement intake for 2 weeks increased NQO1 mRNA expression in peripheral blood mononuclear cells (PBMCs). Muscle soreness on palpation and ROM were significantly lower 2 days after exercise in the sulforaphane group compared with the control group. Serum MDA showed significantly lower levels 2 days after exercise in the sulforaphane group compared with the control group., Conclusion: Our findings suggest that sulforaphane intake from 2 weeks before to 4 days after the exercise increased NQO1, a target gene of Nrf2, and suppressed DOMS after 2 days of eccentric exercise., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

During endurance exercises, a large amount of mitochondrial acetyl-CoA is produced in skeletal muscles from lipids, and the excess acetyl-CoA suppresses the metabolic flux from glycolysis to the TCA cycle. This study evaluated the hypothesis that taurine and carnitine act as a buffer of the acetyl moiety of mitochondrial acetyl-CoA derived from the short- and long-chain fatty acids of skeletal muscles during endurance exercises. In human subjects, the serum concentrations of acetylated forms of taurine (NAT) and carnitine (ACT), which are the metabolites of acetyl-CoA buffering, significantly increased after a full marathon. In the culture medium of primary human skeletal muscle cells, NAT and ACT concentrations significantly increased when they were cultured with taurine and acetate or with carnitine and palmitic acid, respectively. The increase in the mitochondrial acetyl-CoA/free CoA ratio induced by acetate and palmitic acid was suppressed by taurine and carnitine, respectively. Elevations of NAT and ACT in the blood of humans during endurance exercises might serve the buffering of the acetyl-moiety in mitochondria by taurine and carnitine, respectively. The results suggest that blood levels of NAT and ACT indicate energy production status from fatty acids in the skeletal muscles of humans undergoing endurance exercise.

Although the adverse effects of excessively generated reactive oxygen species (ROS) on the body during aerobic exercise have been debated, there are few reports on the remarkable effects of the application of conventional antioxidants on exercise performance. The conventional antioxidants could not enhance exercise performance due to their rapid excretion from the body and serious adverse effects on the cellular respiratory system. In this study, impact of the original antioxidant self-assembling nanoparticle, redox-active nanoparticle (RNP), is investigated on the exercise performance of rats during running experiments. With an increase in the dose of the administered RNP, the all-out time of the rat running extends in a dose-dependent manner. In contrast, with an increase in the dose of the low-molecular-weight (LMW) antioxidant, the all-out running time of the rats decreases. The control group and LMW antioxidant treated group decrease in the number of red blood cells (RBCs) and increase oxidative stress after running. However, the RNP group maintains a similar RBC level and oxidative stress as that of the sedentary group. The results suggest that RNP, which shows long-blood circulation without disturbance of mitohormesis, effectively removes ROS from the bloodstream to suppresses RBC oxidative stress and damage, thus improving exercise performance., (© 2021 Wiley-VCH GmbH.)

Exercise ameliorates nonalcoholic fatty liver disease (NAFLD) by inducing phenotypic changes in Kupffer cells (KCs). p62/Sqstm1-knockout (p62-KO) mice develop NAFLD alongside hyperphagia-induced obesity. We evaluated (1) the effects of long-term exercise on the foreign-body phagocytic capacity of KCs, their surface marker expression, and the production of steroid hormones in p62-KO mice; and (2) whether long-term exercise prevented the development of non-alcoholic steatohepatitis (NASH) in p62-KO mice fed a high-fat diet (HFD). In experiment 1, 30-week-old male p62-KO mice were allocated to resting (p62-KO-Rest) or exercise (p62-KO-Ex) groups, and the latter performed long-term exercise over 4 weeks. Then, the phenotype of their KCs was compared to that of p62-KO-Rest and wild-type (WT) mice. In experiment 2, 5-week-old male p62-KO mice that were fed a HFD performed long-term exercise over 12 weeks. In experiment 1, the phagocytic capacity of KCs and the proportion of CD68-positive cells were lower in the p62-KO-Rest group than in the WT group, but they increased with long-term exercise. The percentage of CD11b-positive KCs was higher in the p62-KO-Rest group than in the WT group, but lower in the p62-KO-Ex group. The circulating dehydroepiandrosterone (DHEA) concentration was higher in p62-KO-Ex mice than in p62-KO-Rest mice. In experiment 2, the body mass and composition of the p62-KO-Rest and p62-KO-Ex groups were similar, but the hepatomegaly, hepatic inflammation, and fibrosis were less marked in p62-KO-Ex mice. The DHEA concentration was higher in p62-KO-Ex mice than in WT or p62-KO-Rest mice. Thus, long-term exercise restores the impaired phagocytic capacity of KCs in NAFLD obese mice, potentially through greater DHEA production, and prevents the development of NASH by ameliorating hepatic inflammation and fibrogenesis. These results suggest a molecular mechanism for the beneficial effect of exercise in the management of patients with NAFLD., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Self-assembly processes of three octahedron-shaped [Pd6L12]12+ cages were investigated by an NMR-based quantitative approach. As to the on-pathway of the Pd6L12 cage assembly, the final intramolecular ligand exchange in an incomplete cage, [Pd6L12Py*]12+ (Py*: 3-chloropyridine, which was used as a leaving ligand), is the rate-determining step in the self-assembly of all the three [Pd6L12]12+ cages. Contrary to the previous finding that the self-assembly of [PdmL2m]2m+ structures (m = 2, 3) and [Pd6L8]12+ capsules from rigid multitopic ligands efficiently takes place without the formation of kinetically trapped species under mild conditions, in the self-assembly of the [Pd6L12]12+ cages, even relatively rigid ditopic ligands co-produced 100 nm-sized kinetic traps through off-pathways, which would be because the energy landscape becomes more complicated by increasing the number of components in the final assembly. It was found that when Py* was used as a leaving ligand in CD3CN, the [Pd6L12]12+ cages were produced in high yield, preventing the formation of the kinetically trapped species, which indicates that the use of Py* as a leaving ligand in CD3CN is effective to obtain the thermodynamically most stable species.

The self-assembly processes of two kinds of octahedron-shaped M 6 L 4 cages consisting of cis-protected Pd(II) complexes and organic tritopic ligands were investigated. Whether kinetically trapped species larger than the cages are produced or the M 6 L 4 cage is assembled without the formation of such kinetic traps is determined by a balance between the rates of oligomerization and intramolecular cyclization, which is affected by slight changes in the chemical structure of the tritopic ligand. A numerical analysis of the experimental data based on a reaction network model where 249 reactions between the possible 56 species were considered revealed the self-assembly pathways of one of the two M 6 L 4 cages.