Ergothioneine: an underrecognised dietary micronutrient required for healthy ageing?

Ergothioneine is a naturally occurring amino acid and thiol antioxidant found in high amounts in mushrooms and fermented foods. Humans and animals acquire ergothioneine from the diet through the pH-dependent activity of a membrane transporter, the large solute carrier 22A member 4 (SLC22A4), expressed on the apical membrane of the small intestine. The SLC22A4 transporter also functions in the renal reabsorption of ergothioneine in the kidney, with avid absorption and retention of ergothioneine from the diet observed in both animals and humans. Ergothioneine is capable of scavenging a diverse range of reactive oxygen and nitrogen species, has metal chelation properties, and is predicted to directly regulate nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Although not lethal, the genetic knockout of the SLC22A4 gene in multiple organisms increases susceptibility to oxidative stress, damage and inflammation; in agreement with a large body of preclinical data suggesting the physiological function of ergothioneine is as a cellular antioxidant and cytoprotectant agent. In humans, blood levels of ergothioneine decline after the age of 60 years, and lower levels of ergothioneine are associated with more rapid cognitive decline. Conversely, high plasma ergothioneine levels have been associated with significantly reduced cardiovascular mortality and overall mortality risks. In this horizon’s manuscript, we review evidence suggesting critical roles for dietary ergothioneine in healthy ageing and the prevention of cardiometabolic disease. We comment on some of the outstanding research questions in the field and consider the question of whether or not ergothioneine should be considered a conditionally essential micronutrient

Fault tolerant control for nonlinear systems using sliding mode and adaptive neural network estimator

This paper proposes a new fault tolerant control scheme for a class of nonlinear systems including robotic systems and aeronautical systems. In this method, a sliding mode control is applied to maintain system stability under the post-fault dynamics. A neural network is used as on-line estimator to reconstruct the change rate of the fault and compensate for the impact of the fault on the system performance. The control law and the neural network learning algorithms are derived using the Lyapunov method, so that the neural estimator is guaranteed to converge to the fault change rate, while the entire closed-loop system stability and tracking control is guaranteed. Compared with the existing methods, the proposed method achieved fault tolerant control for time-varying fault, rather than just constant fault. This greatly expands the industrial applications of the developed method to enhance system reliability. The main contribution and novelty of the developed method is that the system stability is guaranteed and the fault estimation is also guaranteed for convergence when the system subject to a time-varying fault. A simulation example is used to demonstrate the design procedure and the effectiveness of the method. The simulation results demonstrated that the post-fault is stable and the performance is maintained

Combining Antigen-Based Therapy with GABA Treatment Synergistically Prolongs Survival of Transplanted ß-Cells in Diabetic NOD Mice

Antigen-based therapies (ABTs) very effectively prevent the development of type 1 diabetes (T1D) when given to young nonobese diabetic (NOD) mice, however, they have little or no ability to reverse hyperglycemia in newly diabetic NOD mice. More importantly, ABTs have not yet demonstrated an ability to effectively preserve residual ß-cells in individuals newly diagnosed with type 1 diabetes (T1D). Accordingly, there is great interest in identifying new treatments that can be combined with ABTs to safely protect ß-cells in diabetic animals. The activation of γ-aminobutyric acid (GABA) receptors (GABA-Rs) on immune cells has been shown to prevent T1D, experimental autoimmune encephalomyelitis (EAE) and rheumatoid arthritis in mouse models. Based on GABA's ability to inhibit different autoimmune diseases and its safety profile, we tested whether the combination of ABT with GABA treatment could prolong the survival of transplanted ß-cells in newly diabetic NOD mice. Newly diabetic NOD mice were untreated, or given GAD/alum (20 or 100 µg) and placed on plain drinking water, or water containing GABA (2 or 6 mg/ml). Twenty-eight days later, they received syngenic pancreas grafts and were monitored for the recurrence of hyperglycemia. Hyperglycemia reoccurred in the recipients given plain water, GAD monotherapy, GABA monotherapy, GAD (20 µg)+GABA (2 mg/ml), GAD (20 µg)+GABA (6 mg/ml) and GAD (100 µg)+GABA (6 mg/ml) about 1, 2-3, 3, 2-3, 3-8 and 10-11 weeks post-transplantation, respectively. Thus, combined GABA and ABT treatment had a synergistic effect in a dose-dependent fashion. These findings suggest that co-treatment with GABA (or other GABA-R agonists) may provide a new strategy to safely enhance the efficacy of other therapeutics designed to prevent or reverse T1D, as well as other T cell-mediated autoimmune diseases

QCD-like theories at nonzero temperature and density

We investigate the properties of hot and/or dense matter in QCD-like theories with quarks in a (pseudo)real representation of the gauge group using the Nambu-Jona-Lasinio model. The gauge dynamics is modeled using a simple lattice spin model with nearest-neighbor interactions. We first keep our discussion as general as possible, and only later focus on theories with adjoint quarks of two or three colors. Calculating the phase diagram in the plane of temperature and quark chemical potential, it is qualitatively confirmed that the critical temperature of the chiral phase transition is much higher than the deconfinement transition temperature. At a chemical potential equal to half of the diquark mass in the vacuum, a diquark Bose-Einstein condensation (BEC) phase transition occurs. In the two-color case, a Ginzburg-Landau expansion is used to study the tetracritical behavior around the intersection point of the deconfinement and BEC transition lines, which are both of second order. We obtain a compact expression for the expectation value of the Polyakov loop in an arbitrary representation of the gauge group (for any number of colors), which allows us to study Casimir scaling at both nonzero temperature and chemical potential.Comment: JHEP class, 31 pages, 7 eps figures; v2: error in Eq. (3.11) fixed, two references added; matches published versio

In situ interface engineering for probing the limit of quantum dot photovoltaic devices.

Quantum dot (QD) photovoltaic devices are attractive for their low-cost synthesis, tunable band gap and potentially high power conversion efficiency (PCE). However, the experimentally achieved efficiency to date remains far from ideal. Here, we report an in-situ fabrication and investigation of single TiO2-nanowire/CdSe-QD heterojunction solar cell (QDHSC) using a custom-designed photoelectric transmission electron microscope (TEM) holder. A mobile counter electrode is used to precisely tune the interface area for in situ photoelectrical measurements, which reveals a strong interface area dependent PCE. Theoretical simulations show that the simplified single nanowire solar cell structure can minimize the interface area and associated charge scattering to enable an efficient charge collection. Additionally, the optical antenna effect of nanowire-based QDHSCs can further enhance the absorption and boost the PCE. This study establishes a robust 'nanolab' platform in a TEM for in situ photoelectrical studies and provides valuable insight into the interfacial effects in nanoscale solar cells

Expression of a diverse array of Ca²⁺-activated K⁺ channels (SK1/3, IK1, BK) that functionally couple to the mechanosensitive TRPV4 channel in the collecting duct system of kidney

The voltage- and Ca2+-activated, large conductance K+ channel (BK, maxi-K) is expressed in the collecting duct system of kidney where it underlies flow- and Ca2+-dependent K+ excretion. To determine if other Ca2+-activated K+ channels (KCa) may participate in this process, mouse kidney and the K+-secreting mouse cortical collecting duct (CCD) cell line, mCCDcl1, were assessed for TRPV4 and KCa channel expression and cross-talk. qPCR mRNA analysis and immunocytochemical staining demonstrated TRPV4 and KCa expression in mCCDcl1 cells and kidney connecting tubule (CNT) and CCD. Three subfamilies of KCa channels were revealed: the high Ca2+-binding affinity small-conductance SK channels, SK1and SK3, the intermediate conductance channel, IK1, and the low Ca2+-binding affinity, BK channel (BKα subunit). Apparent expression levels varied in CNT/CCD where analysis of CCD principal cells (PC) and intercalated cells (IC) demonstrated differential staining: SK1:PCIC, IK1:PC>IC, BKα:PC = IC, and TRPV4:PC>IC. Patch clamp analysis and fluorescence Ca2+ imaging of mCCDcl1 cells demonstrated potent TRPV4-mediated Ca2+ entry and strong functional cross-talk between TRPV4 and KCa channels. TRPV4-mediated Ca2+ influx activated each KCa channel, as evidenced by selective inhibition of KCa channels, with each active KCa channel enhancing Ca2+ entry (due to membrane hyperpolarization). Transepithelial electrical resistance (TEER) analysis of confluent mCCDcl1 cells grown on permeable supports further demonstrated this cross-talk where TRPV4 activation induce a decrease in TEER which was partially restored upon selective inhibition of each KCa channel. It is concluded that SK1/SK3 and IK1 are highly expressed along with BKα in CNT and CCD and are closely coupled to TRPV4 activation as observed in mCCDcl1 cells. The data support a model in CNT/CCD segments where strong cross talk between TRPV4-mediated Ca2+ influx and each KCa channel leads to enhance Ca2+ entry which will support activation of the low Ca2+-binding affinity BK channel to promote BK-mediated K+ secretion

Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study

Background Ergothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome. Methods We have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables. Discussion The ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial. Trial registration ISRCTN, ISRCTN25890011 Registered February 10th, 202

State Transfer Between a Mechanical Oscillator and Microwave Fields in the Quantum Regime

Recently, macroscopic mechanical oscillators have been coaxed into a regime of quantum behavior, by direct refrigeration [1] or a combination of refrigeration and laser-like cooling [2, 3]. This exciting result has encouraged notions that mechanical oscillators may perform useful functions in the processing of quantum information with superconducting circuits [1, 4-7], either by serving as a quantum memory for the ephemeral state of a microwave field or by providing a quantum interface between otherwise incompatible systems [8, 9]. As yet, the transfer of an itinerant state or propagating mode of a microwave field to and from a mechanical oscillator has not been demonstrated owing to the inability to agilely turn on and off the interaction between microwave electricity and mechanical motion. Here we demonstrate that the state of an itinerant microwave field can be coherently transferred into, stored in, and retrieved from a mechanical oscillator with amplitudes at the single quanta level. Crucially, the time to capture and to retrieve the microwave state is shorter than the quantum state lifetime of the mechanical oscillator. In this quantum regime, the mechanical oscillator can both store and transduce quantum information

Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China

© 2013 Tan 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.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239