Association of Plasma Lipopolysaccharide-Binding Protein Concentration with Dietary Factors, Gut Microbiota, and Health Status in the Japanese General Adult Population: A Cross-Sectional Study.

The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms' muscle mass [ß = -0.02, -0.03]), renal (plasma renin activity [ß = 0.27], urine albumin creatinine ratio [ß = 0.50]), adrenal cortical (cortisol [ß = 0.14]), and thyroid function (free thyroxine [ß = 0.05]), iron metabolism (serum iron [ß = -0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all ßs ≤ -0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (ß = 0.32), Megamonas (ß = 0.56), and Streptococcus (ß = 0.65); and negatively correlated with Roseburia (ß = -0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all ßs ≥ 0.07) or negatively (all ßs ≤ -0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria.

Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice.

Sulforaphane (SFN) is a potent activator of the transcriptional factor, Nuclear Factor Erythroid 2 (NF-E2)-Related factor 2 (NRF2). SFN and its precursor, glucoraphanin (sulforaphane glucosinolate, SGS), have been shown to ameliorate cognitive function in clinical trials and in vivo studies. However, the effects of SGS on age-related cognitive decline in Senescence-Accelerated Mouse Prone 8 (SAMP8) is unknown. In this study, we determined the preventive potential of SGS on age-related cognitive decline. One-month old SAMP8 mice or control SAM resistance 1 (SAMR1) mice were fed an ad libitum diet with or without SGS-containing broccoli sprout powder (0.3% w/w SGS in diet) until 13 months of age. SGS significantly improved long-term memory in SAMP8 at 12 months of age. Interestingly, SGS increased hippocampal mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A (TFAM), which are master regulators of mitochondrial biogenesis, both in SAMR1 and SAMP8 at 13 months of age. Furthermore, mRNAs for nuclear respiratory factor-1 (NRF-1) and mitochondrial DNA-encoded respiratory complex enzymes, but not mitochondrial DNA itself, were increased by SGS in SAMP8 mice. These results suggest that SGS prevents age-related cognitive decline by maintaining mitochondrial function in senescence-accelerated mice.

Electrical mapping of thermoelectric power factor in WO3 thin film.

With growing environmental awareness and considerable research investment in energy saving, the concept of energy harvesting has become a central topic in the field of materials science. The thermoelectric energy conversion, which is a classic physical phenomenon, has emerged as an indispensable thermal management technology. In addition to conventional experimental investigations of thermoelectric materials, seeking promising materials or structures using computer-based approaches such as machine learning has been considered to accelerate research in recent years. However, the tremendous experimental efforts required to evaluate materials may hinder us from reaping the benefits of the fast-developing computer technology. In this study, an electrical mapping of the thermoelectric power factor is performed in a wide temperature-carrier density regime. An ionic gating technique is applied to an oxide semiconductor WO3, systematically controlling the carrier density to induce a transition from an insulating to a metallic state. Upon electrically scanning the thermoelectric properties, it is demonstrated that the thermoelectric performance of WO3 is optimized at a highly degenerate metallic state. This approach is convenient and applicable to a variety of materials, thus prompting the development of novel functional materials with desirable thermoelectric properties.

Effects of broccoli sprout supplements enriched in glucoraphanin on liver functions in healthy middle-aged adults with high-normal serum hepatic biomarkers: A randomized controlled trial.

Sulforaphane (SFN), an isothiocyanate derived from glucoraphanin, has antioxidant, and anti-inflammatory effects that may be beneficial for improving liver function. However, few studies regarding the effects of glucoraphanin on the biological markers related to liver function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (γ-GTP) in healthy individuals have been reported. This randomized, double-blind, placebo-controlled parallel- group trial was conducted from April 22 to December 25, 2021 and compared the effects of broccoli sprout supplements enriched in glucoraphanin (glucoraphanin supplements) (n = 35) with those of placebo supplements (n = 35). This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR; ID number UMIN000044005) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view. cgi?recptno=R000050252. Glucoraphanin significantly improved serum ALT levels at 24 weeks compared to placebo supplements. However, no significant difference in serum glutathione levels, one of the major antioxidants synthesized in the liver, was observed between the two groups. In conclusion, daily intake of the glucoraphanin supplements is beneficial for maintaining liver health in healthy, middle-aged adults with high-normal serum hepatic biomarkers, although further studies focusing on other antioxidant markers are needed to understand how glucoraphanin improves liver function.

Association between Serum Concentration of Carotenoid and Visceral Fat.

Consumption of fruits and vegetables rich in carotenoids has been widely reported to prevent cardiovascular diseases. However, the relationship between serum carotenoid concentrations and visceral fat area (VFA), which is considered a better predictor of cardiovascular diseases than the body-mass index (BMI) and waist circumference, remains unclear. Therefore, we examined the relationship in healthy individuals in their 20s or older, stratified by sex and age, to compare the relationship between serum carotenoid concentrations and VFA and BMI. The study was conducted on 805 people, the residents in Hirosaki city, Aomori prefecture, who underwent a health checkup. An inverse relationship between serum carotenoid concentrations and VFA and BMI was observed only in women. In addition, the results were independent of the intake of dietary fiber, which is mainly supplied from vegetables as well as carotenoids. This suggests that consumption of a diet rich in carotenoids (especially lutein and beta-carotene) is associated with lower VFA, which is a good predictor of cardiovascular disease, especially in women. This study is the first to comprehensively evaluate the association between serum carotenoid levels and VFA in healthy individuals.

Oxidation-induced thermopower inversion in nanocrystalline SnSe thin film.

Given the growing demand for environmentally friendly energy sources, thermoelectric energy conversion has attracted increased interest as a promising CO2-free technology. SnSe single crystals have attracted attention as a next generation thermoelectric material due to outstanding thermoelectric properties arising from ultralow thermal conductivity. For practical applications, on the other hand, polycrystalline SnSe should be also focused because the production cost and the flexibility for applications are important factors, which requires the systematic investigation of the stability of thermoelectric performance under a pseudo operating environment. Here, we report that the physical properties of SnSe crystals with nano to submicron scale are drastically modified by atmospheric annealing. We measured the Seebeck effect while changing the annealing time and found that the large positive thermopower, + 757 µV K-1, was completely suppressed by annealing for only a few minutes and was eventually inverted to be the large negative value, - 427 µV K-1. This result would further accelerate intensive studies on SnSe nanostructures, especially focusing on the realistic device structures and sealing technologies for energy harvesting applications.

Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging.

PURPOSE: Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people. METHODS: Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements. RESULTS: We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age. CONCLUSIONS: This study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging.

Skin Carotenoid Level as an Alternative Marker of Serum Total Carotenoid Concentration and Vegetable Intake Correlates with Biomarkers of Circulatory Diseases and Metabolic Syndrome.

To confirm the usefulness of noninvasive measurements of skin carotenoids to indicate vegetable intake and to elucidate relationships between skin carotenoid levels and biomarkers of circulatory diseases and metabolic syndrome, we conducted a cross-sectional study on a resident-based health checkup (n = 811; 58% women; 49.5 ± 15.1 years). Skin and serum carotenoid levels were measured via reflectance spectroscopy and high-performance liquid chromatography, respectively. Vegetable intake was estimated using a dietary questionnaire. Levels of 9 biomarkers (body mass index [BMI], brachial-ankle pulse wave velocity [baPWV], systolic and diastolic blood pressure [SBP and DBP], homeostasis model assessment as an index of insulin resistance [HOMA-IR], blood insulin, fasting blood glucose [FBG], triglycerides [TGs], and high-density lipoprotein cholesterol [HDL-C]) were determined. Skin carotenoid levels were significantly positively correlated with serum total carotenoids and vegetable intake (r = 0.678 and 0.210, respectively). In women, higher skin carotenoid levels were significantly associated with lower BMI, SBP, DBP, HOMA-IR, blood insulin, and TGs levels and higher HDL-C levels. In men, it was also significantly correlated with BMI and blood insulin levels. In conclusion, dermal carotenoid level may indicate vegetable intake, and the higher level of dermal carotenoids are associated with a lower risk of circulatory diseases and metabolic syndrome.

Anisotropic Quantum Transport through a Single Spin Channel in the Magnetic Semiconductor EuTiO3.

Magnetic semiconductors are a vital component in the understanding of quantum transport phenomena. To explore such delicate, yet fundamentally important, effects, it is crucial to maintain a high carrier mobility in the presence of magnetic moments. In practice, however, magnetization often diminishes the carrier mobility. Here, it is shown that EuTiO3 is a rare example of a magnetic semiconductor that can be desirably grown using the molecular beam epitaxy to possess a high carrier mobility exceeding 3000 cm2 V-1 s-1 at 2 K, while intrinsically hosting a large magnetization value, 7 µB per formula unit. This is demonstrated by measuring the Shubnikov-de Haas (SdH) oscillations in the ferromagnetic state of EuTiO3 films with various carrier densities. Using first-principles calculations, it is shown that the observed SdH oscillations originate genuinely from Ti 3d-t2g states which are fully spin-polarized due to their energetical proximity to the in-gap Eu 4f bands. Such an exchange coupling is further shown to have a profound effect on the effective mass and fermiology of the Ti 3d-t2g electrons, manifested by a directional anisotropy in the SdH oscillations. These findings suggest that EuTiO3 film is an ideal magnetic semiconductor, offering a fertile field to explore quantum phenomena suitable for spintronic applications.

Nonreciprocal transport in gate-induced polar superconductor SrTiO3.

Polar conductors/superconductors with Rashba-type spin-orbit interaction are potential material platforms for quantum transport and spintronic functionalities. One of their inherent properties is the nonreciprocal transport, where the rightward and leftward currents become inequivalent, reflecting spatial inversion/time-reversal symmetry breaking. Such a rectification effect originating from the polar symmetry has been recently observed at interfaces or bulk Rashba semiconductors, while its mechanism in a polar superconductor remains elusive. Here, we report the nonreciprocal transport in gate-induced two-dimensional superconductor SrTiO3, which is a Rashba superconductor candidate. In addition to the gigantic enhancement of nonreciprocal signals in the superconducting fluctuation region, we found kink and sharp peak structures around critical temperatures, which reflect the crossover behavior from the paraconductivity origin to the vortex origin, based on a microscopic theory. The present result proves that the nonreciprocal transport is a powerful tool for investigating the interfacial/polar superconductors without inversion symmetry, where rich exotic features are theoretically prognosticated.

Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology.

Reactive oxygen species (ROS) are byproducts of aerobic respiration and signaling molecules that control various cellular functions. Nrf2 governs the gene expression of endogenous antioxidant synthesis and ROS-eliminating enzymes in response to various electrophilic compounds that inactivate the negative regulator Keap1. Accumulating evidence has shown that mitochondrial ROS (mtROS) activate Nrf2, often mediated by certain protein kinases, and induce the expression of antioxidant genes and genes involved in mitochondrial quality/quantity control. Mild physiological stress, such as caloric restriction and exercise, elicits beneficial effects through a process known as "mitohormesis." Exercise induces NOX4 expression in the heart, which activates Nrf2 and increases endurance capacity. Mice transiently depleted of SOD2 or overexpressing skeletal muscle-specific UCP1 exhibit Nrf2-mediated antioxidant gene expression and PGC1α-mediated mitochondrial biogenesis. ATF4 activation may induce a transcriptional program that enhances NADPH synthesis in the mitochondria and might cooperate with the Nrf2 antioxidant system. In response to severe oxidative stress, Nrf2 induces Klf9 expression, which represses mtROS-eliminating enzymes to enhance cell death. Nrf2 is inactivated in certain pathological conditions, such as diabetes, but Keap1 down-regulation or mtROS elimination rescues Nrf2 expression and improves the pathology. These reports aid us in understanding the roles of Nrf2 in pathophysiological alterations involving mtROS.

Giant thermoelectric power factor in ultrathin FeSe superconductor.

The thermoelectric effect is attracting a renewed interest as a concept for energy harvesting technologies. Nanomaterials have been considered a key to realize efficient thermoelectric conversions owing to the low dimensional charge and phonon transports. In this regard, recently emerging two-dimensional materials could be promising candidates with novel thermoelectric functionalities. Here we report that FeSe ultrathin films, a high-Tc superconductor (Tc; superconducting transition temperature), exhibit superior thermoelectric responses. With decreasing thickness d, the electrical conductivity increases accompanying the emergence of high-Tc superconductivity; unexpectedly, the Seebeck coefficient α shows a concomitant increase as a result of the appearance of two-dimensional natures. When d is reduced down to ~1 nm, the thermoelectric power factor at 50 K and room temperature reach unprecedented values as high as 13,000 and 260 µW cm-1 K-2, respectively. The large thermoelectric effect in high Tc superconductors indicates the high potential of two-dimensional layered materials towards multi-functionalization.

Exceptionally High Electric Double Layer Capacitances of Oligomeric Ionic Liquids.

Electric double layer (EDL) capacitors are promising as next-generation energy accumulators if their capacitances and operation voltages are both high. However, only few electrolytes can simultaneously fulfill these two requisites. Here we report that an oligomeric ionic liquid such as IL4TFSI with four imidazolium ion units in its structure provides a wide electrochemical window of ∼5.0 V, similar to monomeric ionic liquids. Furthermore, electrochemical impedance measurements using Au working electrodes demonstrated that IL4TFSI exhibits an exceptionally high EDL capacitance of ∼66 µF/cm2, which is ∼6 times as high as those of monomeric ionic liquids so far reported. We also found that an EDL-based field effect transistor (FET) using IL4TFSI as a gate dielectric material and SrTiO3 as a channel material displays a very sharp transfer curve with an enhanced carrier accumulation capability of ∼64 µF/cm2, as determined by Hall-effect measurements.

Endeavor of Iontronics: From Fundamentals to Applications of Ion-Controlled Electronics.

Iontronics is a newly emerging interdisciplinary concept which bridges electronics and ionics, covering electrochemistry, solid-state physics, electronic engineering, and biological sciences. The recent developments of electronic devices are highlighted, based on electric double layers formed at the interface between ionic conductors (but electronically insulators) and various electronic conductors including organics and inorganics (oxides, chalcogenide, and carbon-based materials). Particular attention is devoted to electric-double-layer transistors (EDLTs), which are producing a significant impact, particularly in electrical control of phase transitions, including superconductivity, which has been difficult or impossible in conventional all-solid-state electronic devices. Besides that, the current state of the art and the future challenges of iontronics are also reviewed for many applications, including flexible electronics, healthcare-related devices, and energy harvesting.

Characterization of platelet-activating factor-induced cutaneous edema and erythema in dogs.

OBJECTIVE To characterize platelet-activating factor (PAF)-induced edema and erythema in the skin of dogs and compare those reactions with histamine-induced cutaneous reactions. ANIMALS 6 healthy Beagles. PROCEDURES Experiments were performed at ≥ 2-week intervals. Each dog received ID injections (5 µg/site) of PAF C16, PAF C18, lyso-PAF, and histamine. Edema (mean diameter) and erythema scores (none, mild, moderate, or severe) were assessed 30 minutes after the injections. Dogs received ID injections of PAF and histamine each with various concentrations of WEB 2086 (PAF receptor antagonist) or underwent ID testing with PAF and histamine before and 3 hours after oral administration of cetirizine hydrochloride or prednisolone (at 2 doses each). RESULTS ID injections of PAF C16 and PAF C18, but not lyso-PAF, induced comparable levels of edema and erythema. The PAF-induced edema and erythema peaked at 30 minutes and lasted for 6 hours after the injection; histamine-induced edema and erythema peaked at 30 minutes and lasted for 3 hours after the injection. Edema sizes and erythema scores were significantly smaller and lower, respectively, for PAF than for histamine. The WEB 2086 inhibited PAF-induced but not histamine-induced edema and erythema. Cetirizine slightly, but significantly, repressed PAF-induced edema and erythema as well as histamine-induced cutaneous reactions. Prednisolone suppressed both PAF-induced and histamine-induced edema and erythema. CONCLUSIONS AND CLINICAL RELEVANCE In canine skin, the duration of PAF-induced inflammation was longer than that of histamine-induced inflammation. The PAF- and histamine-induced cutaneous reactions were effectively suppressed by oral administration of prednisolone. The importance of PAF in dogs with anaphylaxis and allergic disorders warrants further investigation.

Gate-Tuned Thermoelectric Power in Black Phosphorus.

The electric field effect is a useful means of elucidating intrinsic material properties as well as for designing functional devices. The electric-double-layer transistor (EDLT) enables the control of carrier density in a wide range, which is recently proved to be an effective tool for the investigation of thermoelectric properties. Here, we report the gate-tuning of thermoelectric power in a black phosphorus (BP) single crystal flake with the thickness of 40 nm. Using an EDLT configuration, we successfully control the thermoelectric power (S) and find that the S of ion-gated BP reached +510 µV/K at 210 K in the hole depleted state, which is much higher than the reported bulk single crystal value of +340 µV/K at 300 K. We compared this experimental data with the first-principles-based calculation and found that this enhancement is qualitatively explained by the effective thinning of the conduction channel of the BP flake and nonuniformity of the channel owing to the gate operation in a depletion mode. Our results provide new opportunities for further engineering BP as a thermoelectric material in nanoscale.

Influence of glucocorticoids on a time-of-day-dependent variation in intradermal reactivity to histamine in dogs.

The objectives of this study were to determine daily variation in intradermal reactivity to histamine in dogs and to evaluate a potential influence of glucocorticoids on reactivity. Wheal sizes formed after intradermal injections of histamine were measured every 6 h during a single 24 h period in six healthy dogs. To determine whether glucocorticoids were implicated in daily variation, intradermal reactivity to histamine was evaluated at 9:00 h and at 21:00 h during a single day in dogs that received oral prednisolone (a synthetic glucocorticoid) or oral trilostane (an inhibitor of endogenous glucocorticoid synthesis). Finally, the time required for the histamine reaction to diminish after an intravenous injection of hydrocortisone was also assessed. A significant time-of-day-dependent variation in intradermal reactivity to histamine was detected in dogs, with a larger wheal size observed at 9:00 h than at 21:00 h. Administration of prednisolone or trilostane disrupted this variation. Intradermal reactivity to histamine was significantly reduced 6 h after an intravenous injection of hydrocortisone. These results suggest that glucocorticoid secretion from the adrenal glands could be involved in the regulation of daily variation in histamine-mediated reactions in dogs.

Enhanced thermopower in ZnO two-dimensional electron gas.

Control of dimensionality has proven to be an effective way to manipulate the electronic properties of materials, thereby enabling exotic quantum phenomena, such as superconductivity, quantum Hall effects, and valleytronic effects. Another example is thermoelectricity, which has been theoretically proposed to be favorably controllable by reducing the dimensionality. Here, we verify this proposal by performing a systematic study on a gate-tuned 2D electron gas (2DEG) system formed at the surface of ZnO. Combining state-of-the-art electric-double-layer transistor experiments and realistic tight-binding calculations, we show that, for a wide range of carrier densities, the 2DEG channel comprises a single subband, and its effective thickness can be reduced to [Formula: see text] 1 nm at sufficiently high gate biases. We also demonstrate that the thermoelectric performance of the 2DEG region is significantly higher than that of bulk ZnO. Our approach opens up a route to exploit the peculiar behavior of 2DEG electronic states and realize thermoelectric devices with advanced functionalities.

Thermoelectric Detection of Multi-Subband Density of States in Semiconducting and Metallic Single-Walled Carbon Nanotubes.

Thermoelectric detection of a multi-subband density of states in semiconducting and metallic single-walled carbon nanotubes is demonstrated by scanning the Fermi energy from electron-doped to hole-doped regions. The Fermi energy is systematically controlled by utilizing the strong electric field induced in electric-double-layer transistor configurations, resulting in the optimization of the thermoelectric power factor.