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Introduction
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Free radical scavenging
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Scavenging superoxide and other ROS
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Scavenging hydroxyl radical and other ROS
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Stable radical scavenging
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Metal ion (Fe2+, Fe3+, Cu2+ and Cu+) ...chelating
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Inhibition of free radical generating enzymes
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Activation of internal antioxidant enzymes
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Prevention of lipid peroxidation
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Prevention of DNA damage
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Prevention of protein modification
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Conclusions
Free radicals derived from oxygen, nitrogen and sulphur molecules in the biological system are highly active to react with other molecules due to their unpaired electrons. These radicals are important part of groups of molecules called reactive oxygen/nitrogen species (ROS/RNS), which are produced during cellular metabolism and functional activities and have important roles in cell signalling, apoptosis, gene expression and ion transportation. However, excessive ROS attack bases in nucleic acids, amino acid side chains in proteins and double bonds in unsaturated fatty acids, and cause oxidative stress, which can damage DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and intake of dietary antioxidants may help to maintain an adequate antioxidant status in the body. In the past decades, new molecular techniques, cell cultures and animal models have been established to study the effects and mechanisms of antioxidants on ROS. The chemical and molecular approaches have been used to study the mechanism and kinetics of antioxidants and to identify new potent antioxidants. Antioxidants can decrease the oxidative damage directly via reacting with free radicals or indirectly by inhibiting the activity or expression of free radical generating enzymes or enhancing the activity or expression of intracellular antioxidant enzymes. The new chemical and cell‐free biological system has been applied in dissecting the molecular action of antioxidants. This review focuses on the research approaches that have been used to study oxidative stress and antioxidants in lipid peroxidation, DNA damage, protein modification as well as enzyme activity, with emphasis on the chemical and cell‐free biological system.
In the present paper, we investigate the dark energy equation of state using the Gaussian processes analysis method, without confining a particular parametrization. The reconstruction is carried out ...by adopting the background data including supernova and Hubble parameter, and perturbation data from the growth rate. It suggests that the background and perturbation data both present a hint of dynamical dark energy. However, the perturbation data have a more promising potential to distinguish non-evolution dark energy including the cosmological constant model. We also test the influence of some parameters on the reconstruction. We find that the matter density parameter
Ω
m
0
has a slight effect on the background data reconstruction, but has a notable influence on the perturbation data reconstruction. While the Hubble constant presents a significant influence on the reconstruction from background data.
Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, ...we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.
Depression is a chronic, recurring, and serious mood disorder that afflicts up to 20% of the global population. The monoamine hypothesis has dominated our understanding of the pharmacotherapy of ...depression for more than half a century; however, our understanding of the pathophysiology and pathogenesis of major depression has lagged far behind. Astrocytes are the most abundant and versatile cells in the brain, participating in most, if not all, of brain functions as both a passive housekeeper and an active player. Mounting evidence from clinical, preclinical and post‐mortem studies has revealed a decrease in the number or density of astrocytes and morphological and functional astroglial atrophy in patients with major depressive disorder (MDD) and in animal models of depression. Furthermore, currently available antidepressant treatments at least partially exert their therapeutic effects on astrocytes. More importantly, dysfunctional astrocytes lead to depressive‐like phenotypes in animals. Together, current studies point to astroglial pathology as the potential root cause of MDD. Thus, a shift from a neuron‐centric to an astrocyte‐centric cause of MDD has gained increasing attention during the past two decades. Here we will summarize the current evidence supporting the hypothesis that MDD is a disease of astrocyte pathology and highlight previous studies on promising strategies that directly target astrocytes for the development of novel antidepressant treatments.
Main Points
Astrocytes display morphological and functional atrophy in patients with depression.
Dysfunctional astrocytes lead to depressive‐like phenotypes.
Antidepressant treatments may exert their therapeutic effects on astrocytes.
Earth's habitability is closely tied to its late-stage accretion, during which impactors delivered the majority of life-essential volatiles. However, the nature of these final building blocks remains ...poorly constrained. Nickel (Ni) can be a useful tracer in characterizing this accretion as most Ni in the bulk silicate Earth (BSE) comes from the late-stage impactors. Here, we apply Ni stable isotope analysis to a large number of meteorites and terrestrial rocks, and find that the BSE has a lighter Ni isotopic composition compared to chondrites. Using first-principles calculations based on density functional theory, we show that core-mantle differentiation cannot produce the observed light Ni isotopic composition of the BSE. Rather, the sub-chondritic Ni isotopic signature was established during Earth's late-stage accretion, probably through the Moon-forming giant impact. We propose that a highly reduced sulfide-rich, Mercury-like body, whose mantle is characterized by light Ni isotopic composition, collided with and merged into the proto-Earth during the Moon-forming giant impact, producing the sub-chondritic Ni isotopic signature of the BSE, while delivering sulfur and probably other volatiles to the Earth.
Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications. Ginsenosides, the major pharmacologically active ...ingredients of ginseng, appear to be responsible for most of the activities of ginseng including vasorelaxation, antioxidation, anti-inflammation and anti-cancer. Approximately 40 ginsenoside compounds have been identified. Researchers now focus on using purified individual ginsenoside to reveal the specific mechanism of functions of ginseng instead of using whole ginseng root extracts. Individual ginsenosides may have different effects in pharmacology and mechanisms due to their different chemical structures. Among them the most commonly studied ginsenosides are Rb1, Rg1, Rg3, Re, Rd and Rh1. The molecular mechanisms and medical applications of ginsenosides have attracted much attention and hundreds of papers have been published in the last few years. The general purpose of this update is to provide information of recently described effects of ginsenosides on antioxidation, vascular system, signal transduction pathways and interaction with receptors. Their therapeutic applications in animal models and humans as well as the pharmacokinetics and toxicity of ginsenosides are also discussed in this review. This review concludes with some thoughts for future directions in the further development of ginseng compounds as effective therapeutic agents.
A
bstract
We introduce superdensity operators as a tool for analyzing quantum information in spacetime. Superdensity operators encode spacetime correlation functions in an operator framework, and ...support a natural generalization of Hilbert space techniques and Dirac’s transformation theory as traditionally applied to standard density operators. Superdensity operators can be measured experimentally, but accessing their full content requires novel procedures. We demonstrate these statements on several examples. The superdensity formalism suggests useful definitions of spacetime entropies and spacetime quantum channels. For example, we show that the von Neumann entropy of a super-density operator is related to a quantum generalization of the Kolmogorov-Sinai entropy, and compute this for a many-body system. We also suggest experimental protocols for measuring spacetime entropies.
An electrical-thermal co-simulation based on the finite element method is presented for analysis of high-power RF/microwave circuits. The co-simulation integrates a full-wave electromagnetic analysis ...and a transient thermal analysis through an iterative scheme, and is devised for the design and analysis of RF/microwave circuits operated at high frequencies and high power levels. To enhance the efficiency in solving large-scale problems, a domain decomposition scheme called the finite element tearing and interconnecting and an adaptive time-stepping scheme based on the algorithm of proportional-integral-derivative control are incorporated into the co-simulation. Temperature stability analysis is performed with the proposed co-simulation for a matching network in high-power RF amplifiers and for a substrate integrated waveguide filter.
Abstract
Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these ...vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.
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