The COVID-19 vaccine is now approved for individuals greater than 5 years of age, but vaccination rates remain lower than expected in the pediatric age group. Misinformation and widespread reporting ...of vaccine-related myocarditis are contributing to vaccine hesitancy. When compared to severe cardiac complications that are associated with COVID-19, vaccine-related myocarditis has a milder presentation, is easily treated, and has a good prognosis. Acute COVID-19 has been associated with higher rates of myocarditis and myocardial injury. Multisystem inflammatory syndrome in children occurs weeks after initial infection with SARS-CoV-2 and can be associated with severe cardiovascular complications and death. Cardiac complications associated with acute COVID-19 and MIS-C are more severe and occur more frequently than myocarditis after mRNA COVID-19 vaccination. Furthermore, some of the academic and social disruptions caused by the pandemic expect to be eased by widespread vaccination. For all these reasons, COVID-19 vaccination is strongly recommended for all eligible age groups.
► MicroRNA-181a (miR-181a) was frequently downregulated in oral squamous cell carcinoma (OSCC). ► Overexpression of miR-181a suppressed OSCC growth. ► K-ras is a novel target of miR-181a. ► Decreased ...miR-181a expression is attributed to its lower promoter activity in OSCC.
MicroRNAs (miRNAs) are epigenetic regulators of gene expression, and their deregulation plays an important role in human cancer, including oral squamous cell carcinoma (OSCC). Recently, we found that miRNA-181a (miR-181a) was upregulated during replicative senescence of normal human oral keratinocytes. Since senescence is considered as a tumor suppressive mechanism, we thus investigated the expression and biological role of miR-181a in OSCC. We found that miR-181a was frequently downregulated in OSCC. Ectopic expression of miR-181a suppressed proliferation and anchorage independent growth ability of OSCC. Moreover, miR-181a dramatically reduces the growth of OSCC on three dimensional organotypic raft culture. We also identified K-ras as a novel target of miR-181a. miR-181a decreased K-ras protein level as well as the luciferase activity of reporter vectors containing the 3′-untranslated region of K-ras gene. Finally, we defined a minimal regulatory region of miR-181a and found a positive correlation between its promoter activity and the level of miR-181a expression. In conclusion, miR-181a may function as an OSCC suppressor by targeting on K-ras oncogene. Thus, miR-181a should be considered for therapeutic application for OSCC.
Optical properties of nanoparticle assemblies reflect distinctive characteristics of their building blocks and spatial organization, giving rise to emergent phenomena. Integrated experimental and ...computational studies have established design principles connecting the structure to properties for assembled clusters and superlattices. However, conventional electromagnetic simulations are too computationally expensive to treat more complex assemblies. Here we establish a fast, materials agnostic method to simulate the optical response of large nanoparticle assemblies incorporating both structural and compositional complexity. This many-bodied, mutual polarization method resolves limitations of established approaches, achieving rapid, accurate convergence for configurations including thousands of nanoparticles, with some overlapping. We demonstrate these capabilities by reproducing experimental trends and uncovering far- and near-field mechanisms governing the optical response of plasmonic semiconductor nanocrystal assemblies including structurally complex gel networks and compositionally complex mixed binary superlattices. This broadly applicable framework will facilitate the design of complex, hierarchically structured, and dynamic assemblies for desired optical characteristics.
The role of anthropogenic NOx emissions in secondary organic aerosol (SOA) production is not fully understood but is important for understanding the contribution of emissions to air quality. Here, we ...examine the role of organic nitrates (RONO2) in SOA formation over the Korean Peninsula during the Korea–United States Air Quality field study in Spring 2016 as a model for RONO2 aerosol in cities worldwide. We use aircraft-based measurements of the particle phase and total (gas + particle) RONO2 to explore RONO2 phase partitioning. These measurements show that, on average, one-fourth of RONO2 are in the condensed phase, and we estimate that ≈15% of the organic aerosol (OA) mass can be attributed to RONO2. Furthermore, we observe that the fraction of RONO2 in the condensed phase increases with OA concentration, evidencing that equilibrium absorptive partitioning controls the RONO2 phase distribution. Lastly, we model RONO2 chemistry and phase partitioning in the Community Multiscale Air Quality modeling system. We find that known chemistry can account for one-third of the observed RONO2, but there is a large missing source of semivolatile, anthropogenically derived RONO2. We propose that this missing source may result from the oxidation of semi- and intermediate-volatility organic compounds and/or from anthropogenic molecules that undergo autoxidation or multiple generations of OH-initiated oxidation.
► TNFα increases CSC phenotype and tumorigenicity of oral squamous cell carcinoma (OSCC). ► TNFα enhances CSC property of OSCC by activating Notch-Hes1 pathway. ► Hes1 is upregulated in OSCC tissue ...in vivo.
Cancer stem-like cell (CSC; also known as tumor initiating cell) is defined as a small subpopulation of cancer cells within a tumor and isolated from various primary tumors and cancer cell lines. CSCs are highly tumorigenic and resistant to anticancer treatments. In this study, we found that prolonged exposure to tumor necrosis factor alpha (TNFα), a major proinflammatory cytokine, enhances CSC phenotype of oral squamous cell carcinoma (OSCC) cells, such as an increase in tumor sphere-forming ability, stem cell-associated genes expression, chemo-radioresistance, and tumorigenicity. Moreover, activation of Notch1 signaling was detected in the TNFα-exposed cells, and suppression of Notch1 signaling inhibited CSC phenotype. Furthermore, we demonstrated that inhibition of a Notch downstream target, Hes1, led to suppression of CSC phenotype in the TNFα-exposed cells. We also found that Hes1 expression is commonly upregulated in OSCC lesions compared to precancerous dysplastic lesions, suggesting the possible involvement of Hes1 in OSCC progression and CSC in vivo. In conclusion, inflammatory cytokine exposure may enhance CSC phenotype of OSCC, in part by activating the Notch-Hes1 pathway.
Abstract
Tourette syndrome (TS) is a childhood-onset disorder in which tics are often preceded by premonitory sensory urges. More severe urges correlate with worse tics and can render behavioral ...therapies less effective. The supplementary motor area (SMA) is a prefrontal region believed to influence tic performance. To determine whether cortical physiological properties correlate with urges and tics, we evaluated, in 8–12-year-old right-handed TS children (n = 17), correlations of urge and tic severity scores and compared both to cortical excitability (CE) and short- and long-interval cortical inhibition (SICI and LICI) in both left and right M1. We also modeled these M1 transcranial magnetic stimulation measures with SMA gamma-amino butyric acid (GABA) levels in TS and typically developing control children (n = 16). Urge intensity correlated strongly with tic scores. More severe urges correlated with lower CE and less LICI in both right and left M1. Unexpectedly, in right M1, lower CE and less LICI correlated with less severe tics. We found that SMA GABA modulation of right, but not left, M1 CE and LICI differed in TS. We conclude that in young children with TS, lower right M1 CE and LICI, modulated by SMA GABA, may reflect compensatory mechanisms to diminish tics in response to premonitory urges.
Tryptophan and tyrosine can form radical intermediates that enable long-range, multistep electron transfer (ET) reactions in proteins. This report describes the mechanisms of formation and quenching ...of a neutral tryptophan radical in azurin, a blue-copper protein that contains native tyrosine (Y108 and Y72) and tryptophan (W48) residues. A long-lived neutral tryptophan radical W48• is formed upon UV-photoexcitation of a zinc(II)-substituted azurin mutant in the presence of an external electron acceptor. The quantum yield of W48• formation (Φ) depends upon the tyrosine residues in the protein. A tyrosine-deficient mutant, ZnIIAz48W, exhibited a value of Φ = 0.080 with a Co(III) electron acceptor. A nearly identical quantum yield was observed when the electron acceptor was the analogous tyrosine-free, copper(II) mutant; this result for the ZnIIAz48W:CuIIAz48W mixture suggests there is an interprotein ET path. A single tyrosine residue at one of the native positions reduced the quantum yield to 0.062 (Y108) or 0.067 (Y72). Wild-type azurin with two tyrosine residues exhibited a quantum yield of Φ = 0.045. These data indicate that tyrosine is able to quench the tryptophan radical in azurin.
Deficient safety learning has been implicated in the pathogenesis of anxiety disorders. Despite increased translational interest, there has been limited research on the basis of safety learning in ...humans. Here, we examined safety learning in seventy-three healthy participants via a modified Pavlovian conditioned inhibition paradigm, featuring a conditioned threat stimulus that was reinforced alone (A+), but not when combined with a second stimulus (the conditioned inhibitor, AX-). During a test phase, X and a control safety cue (C) were combined with a second threat stimulus to assess their inhibition of threat responses, measured via skin conductance (SCRs) and US-expectancy ratings. Both stimuli exhibited conditioned inhibition, but X suppressed ratings by a greater magnitude than C. Trait anxiety also predicted increased US-expectancy ratings of X. These findings suggest that a Pavlovian inhibitor accrues greater safety value than a merely unreinforced safety signal. Conditioned inhibition paradigms may have utility in the ongoing study of safety learning and its relevance to anxious psychopathology.
•Safety learning was compared between a conditioned inhibitor and a conventional CS-.•Both inhibited threat responses at test, but the inhibitor showed greater suppression of US-expectancy ratings.•The inhibitor was easily re-learned as threatening when subsequently reinforced, contrary to conventional theory.•US-expectancy to the conditioned inhibitor was associated with higher trait anxiety.
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