The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk ...factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to attenuate disease progression.
•Oxidative stress in neurodegenerative diseases•The Keap1-Nrf2-ARE pathway in brain•Changes in Nrf2 and Nrf2-dependent genes in diseased brain tissue•Transgenic, viral, and chemical-mediated activation of Nrf2 in animal models•Effect of Nrf2 activation on progression of neurodegeneration in animal models
An emerging body of data suggests that lipid metabolism has an important role to play in the aging process. Indeed, a plethora of dietary, pharmacological, genetic, and surgical lipid‐related ...interventions extend lifespan in nematodes, fruit flies, mice, and rats. For example, the impairment of genes involved in ceramide and sphingolipid synthesis extends lifespan in both worms and flies. The overexpression of fatty acid amide hydrolase or lysosomal lipase prolongs life in Caenorhabditis elegans, while the overexpression of diacylglycerol lipase enhances longevity in both C. elegans and Drosophila melanogaster. The surgical removal of adipose tissue extends lifespan in rats, and increased expression of apolipoprotein D enhances survival in both flies and mice. Mouse lifespan can be additionally extended by the genetic deletion of diacylglycerol acyltransferase 1, treatment with the steroid 17‐α‐estradiol, or a ketogenic diet. Moreover, deletion of the phospholipase A2 receptor improves various healthspan parameters in a progeria mouse model. Genome‐wide association studies have found several lipid‐related variants to be associated with human aging. For example, the epsilon 2 and epsilon 4 alleles of apolipoprotein E are associated with extreme longevity and late‐onset neurodegenerative disease, respectively. In humans, blood triglyceride levels tend to increase, while blood lysophosphatidylcholine levels tend to decrease with age. Specific sphingolipid and phospholipid blood profiles have also been shown to change with age and are associated with exceptional human longevity. These data suggest that lipid‐related interventions may improve human healthspan and that blood lipids likely represent a rich source of human aging biomarkers.
A growing body of evidence suggests that lipid metabolism regulates aging. Various dietary, pharmacological, surgical, and genetic lipid‐related interventions have been shown to extend lifespan in model organisms. These lifespan studies have implicated several specific lipid pathways as regulators of aging and health. Current data suggest that lipid‐specific interventions have the potential to extend human healthspan. Moreover, blood‐based lipids represent a promising source of aging biomarkers.
With many commodity and financial markets reportedly experiencing poor performances during this COVID-19 pandemic, this study intends to examine the effect of the pandemic on the connectedness among ...the markets. There are several reasons that suggest that apart from the pandemic affecting the performances of the markets, it can also be a driver of their connectedness, coming from the perspective of the global financial cycle channel. Therefore, we first employ the recently developed time-varying parameter vector autoregressions (TVP-VAR) technique to examine the volatility spillover among the commodity and financial assets. We find evidence of strong volatility across the markets, with gold and USD being net receivers of shocks, and others, net transmitters. With this evidence, we proceed to the evaluation of the influence of the COVID-19 pandemic on the connectedness across the markets using both the linear and non-linear (causality-in-quantiles) causality tests. The causality-in-quantiles test outperforms the linear Granger-causality test, and the results show significant causal impacts of the two measures of COVID-19 pandemic (infectious diseases-based equity market volatility and the growth rate of the U.S. COVID-19 reported cases) on the connectedness across the markets, especially at the lower and middle-level quantiles. Overall, these findings prove that the pandemic has been largely responsible for risks transmission across various commodity and financial markets. This is because it has significantly raised investors’ and policy uncertainties and immensely altered global financial cycle which in turn results in global flows of capital, and movements in the prices of assets across different financial markets.
•Impact of COVID-19 pandemic on connectedness across commodity and financial markets.•TVP-VAR reveals strong volatility spillover across the markets with gold and USD being net receivers of shocks.•Causality-in-quantiles test shows that the connectedness across the markets are principally driven by COVID-19 pandemic.•Causality effect is established mostly at lower and middle-level quantiles.•Significant policy implications for investors, portfolio managers, policy makers and future researches are drawn.
The use of light to mediate controlled radical polymerization has emerged as a powerful strategy for rational polymer synthesis and advanced materials fabrication. This review provides a ...comprehensive survey of photocontrolled, living radical polymerizations (photo-CRPs). From the perspective of mechanism, all known photo-CRPs are divided into either (1) intramolecular photochemical processes or (2) photoredox processes. Within these mechanistic regimes, a large number of methods are summarized and further classified into subcategories based on the specific reagents, catalysts, etc., involved. To provide a clear understanding of each subcategory, reaction mechanisms are discussed. In addition, applications of photo-CRP reported so far, which include surface fabrication, particle preparation, photoresponsive gel design, and continuous flow technology, are summarized. We hope this review will not only provide informative knowledge to researchers in this field but also stimulate new ideas and applications to further advance photocontrolled reactions.
Polymer networks, which are materials composed of many smaller components—referred to as “junctions” and “strands”—connected together via covalent or non‐covalent/supramolecular interactions, are ...arguably the most versatile, widely studied, broadly used, and important materials known. From the first commercial polymers through the plastics revolution of the 20th century to today, there are almost no aspects of modern life that are not impacted by polymer networks. Nevertheless, there are still many challenges that must be addressed to enable a complete understanding of these materials and facilitate their development for emerging applications ranging from sustainability and energy harvesting/storage to tissue engineering and additive manufacturing. Here, we provide a unifying overview of the fundamentals of polymer network synthesis, structure, and properties, tying together recent trends in the field that are not always associated with classical polymer networks, such as the advent of crystalline “framework” materials. We also highlight recent advances in using molecular design and control of topology to showcase how a deep understanding of structure–property relationships can lead to advanced networks with exceptional properties.
Polymer networks are materials composed of linear strands connected by multifunctional junctions. These strands and junctions can be flexible or rigid (macro)molecules, and the connections between strands and junctions can be covalent or non‐covalent. Thus, polymer networks comprise a vast array of useful materials ranging from elastomers and gels to porous crystalline frameworks.
Scalable production of all-electronic DNA biosensors with high sensitivity and selectivity is a critical enabling step for research and applications associated with detection of DNA hybridization. We ...have developed a scalable and very reproducible (>90% yield) fabrication process for label-free DNA biosensors based upon graphene field effect transistors (GFETs) functionalized with single-stranded probe DNA. The shift of the GFET sensor Dirac point voltage varied systematically with the concentration of target DNA. The biosensors demonstrated a broad analytical range and limit of detection of 1 fM for 60-mer DNA oligonucleotide. In control experiments with mismatched DNA oligomers, the impact of the mismatch position on the DNA hybridization strength was confirmed. This class of highly sensitive DNA biosensors offers the prospect of detection of DNA hybridization and sequencing in a rapid, inexpensive, and accurate way.
Ultralow friction can be achieved with 2D materials, particularly graphene and MoS2. The nanotribological properties of these different 2D materials have been measured in previous atomic force ...microscope (AFM) experiments sequentially, precluding immediate and direct comparison of their frictional behavior. Here, friction is characterized at the nanoscale using AFM experiments with the same tip sliding over graphene, MoS2, and a graphene/MoS2 heterostructure in a single measurement, repeated hundreds of times, and also measured with a slowly varying normal force. The same material systems are simulated using molecular dynamics (MD) and analyzed using density functional theory (DFT) calculations. In both experiments and MD simulations, graphene consistently exhibits lower friction than the MoS2 monolayer and the heterostructure. In some cases, friction on the heterostructure is lower than that on the MoS2 monolayer. Quasi-static MD simulations and DFT calculations show that the origin of the friction contrast is the difference in energy barriers for a tip sliding across each of the three surfaces.
Alpha synuclein (SYN) is a central player in the pathogenesis of sporadic and familial Parkinson's disease (PD). SYN aggregation and oxidative stress are associated and enhance each other's toxicity. ...It is unknown whether the redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a role against the toxicity of SYN. To examine this, mice selectively overexpressing Nrf2 in astrocytes (GFAP-Nrf2) were crossed with mice selectively expressing human mutant SYN (hSYN(A53T)) in neurons. Increased astrocytic Nrf2 delayed the onset and extended the life span of the hSYN(A53T) mice. This correlated with increased motor neuron survival, reduced oxidative stress, and attenuated gliosis in the spinal cord, as well as a dramatic decrease in total hSYN(A53T) and phosphorylated (Ser129) hSYN(A53T) in Triton-insoluble aggregates. Furthermore, Nrf2 in astrocytes delayed chaperone-mediated autophagy and macroautophagy dysfunction observed in the hSYN(A53T) mice. Our data suggest that Nrf2 in astrocytes provides neuroprotection against hSYN(A53T)-mediated toxicity by promoting the degradation of hSYN(A53T) through the autophagy-lysosome pathway in vivo. Thus, activation of the Nrf2 pathway in astrocytes is a potential target to develop therapeutic strategies for treating pathologic synucleinopathies including PD.
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