Human YRNA 4 (HY4) plasma levels are a prognostic indicator of SARS-CoV-2 infection clinical severity.

SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome.

Nuclear FAK in endothelium: An intrinsic inhibitor of NF-κB activation in atherosclerosis.

BACKGROUND AND AIMS: Hyperlipidemia leads to the accumulation of oxidized low-density lipoprotein (oxLDL) within the vessel wall where it causes chronic inflammation in endothelial cells (ECs) and drives atherosclerotic lesions. Although focal adhesion kinase (FAK) is critical in proinflammatory NF-κB activation in ECs, it is unknown if hyperlipidemia alters FAK-mediated NF-κB activity in vivo to affect atherosclerosis progression. METHODS: We investigated changes in EC FAK and NF-κB activation using Apoe-/- mice fed a western diet (WD). Both pharmacological FAK inhibition and EC-specific FAK inhibited mouse models were utilized. FAK and NF-κB localization and activity were also analyzed in human atherosclerotic samples. RESULTS: ECs of hyperlipidemic mice clearly showed much higher levels of FAK activation in the cytoplasm, which was associated with increased NF-κB activation compared to normal diet (ND) group. On the contrary, FAK is mostly localized in the nucleus and inactive in ECs under healthy conditions with a low NF-κB activity. Both pharmacological and EC-specific genetic FAK inhibition in WD fed Apoe-/- mice exhibited a significant decrease in FAK activity and cytoplasmic localization, NF-κB activation, macrophage recruitment, and atherosclerotic lesions compared to the vehicle or FAK wild-type groups. Analyses of human atherosclerotic specimens revealed a positive correlation between increased active cytoplasmic FAK within ECs and NF-κB activation in the lesions. CONCLUSIONS: Hyperlipidemic conditions activate NF-κB pathway by increasing EC FAK activity and cytoplasmic localization in mice and human atherosclerotic samples. As FAK inhibition can efficiently reduce vascular inflammation and atherosclerotic lesions in mice by reversing EC FAK localization and NF-κB activation, these findings support a potential use for FAK inhibitors in treating atherosclerosis.

Solvothermal synthesis of TiO2nanospheres for non-volatile memory and synaptic learning applications.

In this study, we used the one-pot solvothermal method to synthesize the TiO2nanospheres (NSs) and used them for non-volatile memory and neuromorphic computing applications. Several analytical tools were used to understand the structural, optical, morphological, and compositional characteristics of synthesized TiO2NSs. The tetragonal crystal structure of anatase TiO2was formed, according to the Rietveld refined x-ray diffraction results. The NS morphology was confirmed by field emission scanning electron microscopy and transmission electron microscopy images. X-ray photoelectron spectroscopy was probed to understand the elemental composition and electronic states of the TiO2NSs. We specifically looked at the impact of reaction time on the structural, optical, morphological, compositional, and resistive switching (RS) properties of TiO2NSs. The fabricated devices (Ag/TiO2NSs/FTO) exhibit bipolar RS behavior. The optimized RS device shows good endurance (5000 cycles) and memory retention (5000 s) properties. Moreover, fabricated devices showed double-valued charge-flux characteristics, whereas charge transport was caused by the Ohmic and space charge-limited current mechanisms. Additionally, the optimized device can mimic various synaptic characteristics including potentiation-depression, excitatory post-synaptic current, and paired-pulse facilitation.

Real-time tracking of bioluminescent influenza A virus infection in mice.

Despite the availability of vaccines and antiviral therapies, seasonal influenza infections cause 400,000 human deaths on average per year. Low vaccine coverage and the occurrence of drug-resistant viral strains highlight the need for new and improved countermeasures. While influenza A virus (IAV) engineered to express a reporter gene may serve as a valuable tool for real-time tracking of viral infection, reporter gene insertion into IAV typically attenuates viral pathogenicity, hindering its application to research. Here, we demonstrate that lethal or even sublethal doses of bioluminescent IAV carrying the NanoLuc gene in the C-terminus of PB2 can be tracked in real-time in live mice without compromising pathogenicity. Real-time tracking of this bioluminescent IAV enables spatiotemporal viral replication tracking in animals that will facilitate the development of countermeasures by enhancing the interpretation of clinical signs and prognosis while also allowing less animal usage.

A Mixed-Methods Study of Early Childhood Education and Care in South Korea: Policies and Practices During COVID-19.

This study of South Korea's response to COVID-19 has three purposes. First, it uses document analysis to examine policies, strategies, and resources offered by the South Korean government and public organizations to support young children and families during the first 6 months of the pandemic. Next, it uses open-ended surveys with 30 directors of early childhood institutions to explore institutional-level supports and needs during the pandemic. Finally, it looks at the discrepancies between stated policies outlining the South Korea's response to COVID-19 and the lived experiences of early childhood educators as a route to arriving at recommendations for education policymakers and other stakeholders. To that end, we reviewed government documents (n = 84) containing early childhood education-related responses to Covid-19 established by the Ministry of Education, the Ministry of Health and Welfare, and other relevant government sectors. An online survey with 17 kindergarten and 13 child care center directors was also analyzed. Using content analysis, the findings revealed that the government's policies and guidance for Early Childhood Education and Care (ECEC) as well as the institutional supports for children and families were overall comprehensive in its scope. The analysis, based on the five tenets of the Whole Child approach, also indicated that the government's policy responses and services for ECEC focused mainly on the 'Safe' and 'Supported' tenets, while 'Challenged' was given the least amount of consideration. The survey responses demonstrated different measures taken by kindergartens and child care centers highlighting the separate nature of 'education' and 'care' in South Korea, while also indicating limited resources for supporting children's psychological well-being and for children and families in need. This overview provides a foundation for further discussion and research on the impact of Covid-19 on ECEC in South Korea and beyond.

Probability of Immobilization on Host Cell Surface Regulates Viral Infectivity.

The efficiency of a virus to establish its infection in host cells varies broadly among viruses. It remains unclear if there is a key step in this process that controls viral infectivity. To address this question, we use single-particle tracking and Brownian dynamics simulation to examine human immunodeficiency virus type 1 (HIV-1) infection in cell culture. We find that the frequency of viral-cell encounters is consistent with diffusion-limited interactions. However, even under the most favorable conditions, only 1% of the viruses can become immobilized on cell surface and subsequently enter the cell. This is a result of weak interaction between viral surface gp120 and CD4 receptor, which is insufficient to form a stable complex the majority of the time. We provide the first direct quantitation for efficiencies of these events relevant to measured HIV-1 infectivity and demonstrate that immobilization on host cell surface post-virion-diffusion is the key step in viral infection. Variation of its probability controls the efficiency of a virus to infect its host cells. These results explain the low infectivity of cell-free HIV-1 in vitro and offer a potential rationale for the pervasive high efficiency of cell-to-cell transmission of animal viruses.

Trap-Free Heterostructure of PbS Nanoplatelets on InP(001) by Chemical Epitaxy.

Semiconductor nanocrystalline heterostructures can be produced by the immersion of semiconductor substrates into an aqueous precursor solution, but this approach usually leads to a high density of interfacial traps. In this work, we study the effect of a chemical passivation of the substrate prior to the nanocrystalline growth. PbS nanoplatelets grown on sulfur-treated InP (001) surfaces at temperatures as low as 95 °C exhibit abrupt crystalline interfaces that allow a direct and reproducible electron transfer to the InP substrate through the nanometer-thick nanoplatelets with scanning tunnelling spectroscopy. It is in sharp contrast with the less defined interface and the hysteresis of the current-voltage characteristics found without the passivation step. Based on a tunnelling effect occurring at energies below the bandgap of PbS, we show the formation of a type II, trap-free, epitaxial heterointerface, with a quality comparable to that grown on a nonreactive InP (110) substrate by molecular beam epitaxy. Our scheme offers an attractive alternative to the fabrication of semiconductor heterostructures in the gas phase.

The association between body mass index and academic performance.

[No Abstract Available].

The Single-Molecule Centroid Localization Algorithm Improves the Accuracy of Fluorescence Binding Assays.

Here, we demonstrate that the use of the single-molecule centroid localization algorithm can improve the accuracy of fluorescence binding assays. Two major artifacts in this type of assay, i.e., nonspecific binding events and optically overlapping receptors, can be detected and corrected during analysis. The effectiveness of our method was confirmed by measuring two weak biomolecular interactions, the interaction between the B1 domain of streptococcal protein G and immunoglobulin G and the interaction between double-stranded DNA and the Cas9-RNA complex with limited sequence matches. This analysis routine requires little modification to common experimental protocols, making it readily applicable to existing data and future experiments.

Risk for Hip Fracture due to Alpha Blocker Treatment in Korean Women: National Health Insurance Database Study.

OBJECTIVE: The aim of this study is to evaluate the risk for hip fracture associated with adverse drug reactions caused by α1-adrenergic (alpha) blockers to treat female voiding dysfunction. METHODS: Information from the Health Insurance Review and Assessment Service database from January 1, 2008 to December 31, 2012 was used. Hip fracture women patients who received a prescription for an alpha blocker due to voiding dysfunction were the cases. A 30-day hazard period after administration of an alpha blocker was set. The 30-day control period was defined as 360 days before administration. The standardized incidence ratio and hazard ratio for the risk of hip bone fracture as related to alpha blocker use were analyzed. RESULTS: The study cohort included 287 383 subjects having a mean age of 65.1 ± 9.7 years in the study cohort. A total of 170 and 79 hip fracture cases were diagnosed in the hazard period and control period, respectively. The incidence of newly diagnosed hip fractures per 100 000 person-years was 763.4 in the hazard period and 348.5 in the control period. The hazard ratio for hip fracture after use of an alpha blocker was 2.19 (95% confidence interval, 1.74-2.77). CONCLUSIONS: Alpha blockers to treat voiding dysfunction may have association with the risk for hip fracture in elderly women.

Effects of personality traits on collaborative performance in problem-based learning tutorials.

[No Abstract Available].

An innovative concept of use of redox-active electrolyte in asymmetric capacitor based on MWCNTs/MnO2 and Fe2O3 thin films.

In present investigation, we have prepared a nanocomposites of highly porous MnO2 spongy balls and multi-walled carbon nanotubes (MWCNTs) in thin film form and tested in novel redox-active electrolyte (K3[Fe(CN)6] doped aqueous Na2SO4) for supercapacitor application. Briefly, MWCNTs were deposited on stainless steel substrate by "dip and dry" method followed by electrodeposition of MnO2 spongy balls. Further, the supercapacitive properties of these hybrid thin films were evaluated in hybrid electrolyte ((K3[Fe(CN)6 doped aqueous Na2SO4). Thus, this is the first proof-of-design where redox-active electrolyte is applied to MWCNTs/MnO2 hybrid thin films. Impressively, the MWCNTs/MnO2 hybrid film showed a significant improvement in electrochemical performance with maximum specific capacitance of 1012 Fg-1 at 2 mA cm-2 current density in redox-active electrolyte, which is 1.5-fold higher than that of conventional electrolyte (Na2SO4). Further, asymmetric capacitor based on MWCNTs/MnO2 hybrid film as positive and Fe2O3 thin film as negative electrode was fabricated and tested in redox-active electrolytes. Strikingly, MWCNTs/MnO2//Fe2O3 asymmetric cell showed an excellent supercapacitive performance with maximum specific capacitance of 226 Fg-1 and specific energy of 54.39 Wh kg-1 at specific power of 667 Wkg-1. Strikingly, actual practical demonstration shows lightning of 567 red LEDs suggesting "ready-to sell" product for industries.

Quantitative Correlation between Infectivity and Gp120 Density on HIV-1 Virions Revealed by Optical Trapping Virometry.

The envelope glycoprotein (Env) gp120/gp41 is required for HIV-1 infection of host cells. Although in general it has been perceived that more Env gives rise to higher infectivity, the precise quantitative dependence of HIV-1 virion infectivity on Env density has remained unknown. Here we have developed a method to examine this dependence. This method involves 1) production of a set of single-cycle HIV-1 virions with varied density of Env on their surface, 2) site-specific labeling of Env-specific antibody Fab with a fluorophore at high efficiency, and 3) optical trapping virometry to measure the number of gp120 molecules on individual HIV-1 virions. The resulting gp120 density per virion is then correlated with the infectivity of the virions measured in cell culture. In the presence of DEAE-dextran, the polycation known to enhance HIV-1 infectivity in cell culture, virion infectivity follows gp120 density as a sigmoidal dependence and reaches an apparent plateau. This quantitative dependence can be described by a Hill equation, with a Hill coefficient of 2.4 ± 0.6. In contrast, in the absence of DEAE-dextran, virion infectivity increases monotonically with gp120 density and no saturation is observed under the experimental conditions. These results provide the first quantitative evidence that Env trimers cooperate on the virion surface to mediate productive infection by HIV-1. Moreover, as a result of the low number of Env trimers on individual virions, the number of additional Env trimers per virion that is required for the optimal infectivity will depend on the inclusion of facilitating agents during infection.

Interaction effect of serum 25-hydroxyvitamin D levels and CYP1A1, CYP1B1 polymorphisms on blood pressure in an elderly population.

OBJECTIVE: Hypertension and vitamin D deficiency are prevalent worldwide, especially in the elderly. Considering the possibility of gene-environment contributions to disease development, we evaluated the influence of certain cytochrome P450 polymorphisms and vitamin D levels on blood pressure (BP). METHODS: We measured serum 25-hydroxyvitamin D levels [25(OH)D] and BP in 535 individuals over 60 years old and identified single-nucleotide polymorphisms (SNPs) of CYP1A1 and CYP1B1 in lymphocyte DNA. Repeated measure analyses were used to determine the statistical association. RESULTS: The relationship between 25(OH)D and SBP or DBP was inversely significant, and influence of several CYP1A1 and CYP1B1 SNPs on BP was found across different genotypes. Estimated effect of 25(OH)D levels on BP in the group with higher risky genotype scores of selected SNPs (rs4646421, rs2551188, and rs1056836) was greater (ß = -2.841, P = 0.004 for SBP; ß = -2.035, P = 0.001 for DBP) than the group with lower genotype score (ß = -0.878, P = 0.347 for SBP; ß = 0.037, P = 0.947 for DBP), and synergistic interaction between vitamin D levels and genotype variations was observed (P-interaction = 0.081 for SBP and 0.008 for DBP). When stratified by the hypertension medication status, interaction effect was found only in individuals taking medication (P-interaction = 0.004 for SBP and 0.001 for DBP). CONCLUSION: Genetic variations in CYP1A1 and CYP1B1 and the serum levels of 25(OH)D showed synergistic effect on BP, especially in individuals currently in treatment for hypertension.

High performing smart electrochromic device based on honeycomb nanostructured h-WO3 thin films: hydrothermal assisted synthesis.

Herein, we report honeycomb nanostructured single crystalline hexagonal WO(3) (h-WO(3)) thin films in order to improve electrochromic performance. In the present investigation, honeycomb nanostructured WO(3) with different unit size and nanowire array with highly nanocrystalline frameworks have been synthesized via a hydrothermal technique. The influence of hydrothermal reaction time on the honeycomb unit cells, crystallite size, lithium ion diffusion coefficient and switching time for coloration/bleaching were studied systematically. The electrochromic study reveals that the honeycomb unit cell size has a significant impact on the electrochromic performance. Small unit cells in the honeycomb lead to large optical modulation and fast switching response. A large optical modulation in the visible spectral region (60.74% at λ = 630 nm) at a potential of -1.2 V with fast switching time (4.29 s for coloration and 3.38 s for bleaching) and high coloration efficiency (87.23 cm(2) C(-1)) is observed in the honeycomb WO(3) thin films with a unit cell diameter of 1.7 µm. The variation in color on reduction of WO(3) with applied potential has been plotted on an xy-chromaticity diagram and the color space coordinate shows the transition from a colorless to deep blue state.

Macrophage depletion ameliorates glycerol-induced acute kidney injury in mice.

BACKGROUND: This study was conducted to elucidate the role of renal macrophages in the development of acute kidney injury (AKI) in a glycerol (Gly)-induced rhabdomyolysis mouse model. METHODS: The experimental model of rhabdomyolysis requires injecting 50% Gly (10 ml/kg) intramuscularly into mice. Control mice were injected into the tail vein with the liposomal vehicle. Liposome-encapsulated clodronate (LEC)-only mice were injected with LEC. Gly-only mice were injected with Gly into a hind limb. LEC+Gly-treated mice were injected intravenously with 100 µl of LEC 24 h prior to Gly injection. Mice were sacrificed 24 h after Gly injection. RESULTS: Gly injection increased the serum creatinine level, and induced tubular damage. Renal CD45(+)CD11b(+)Ly6c(+) or CD45(+)CD11b(+)Ly6c(+)F4/80(+) macrophages were decreased by pretreatment with LEC in both normal and injured kidneys. Macrophage depletion prevented Gly-induced apoptotic death of tubular epithelial cells by decreasing caspase-9, ERK and p53, while increasing Bcl-2 expression. Expression of the inflammatory mediators NF-κB, MCP-1, ICAM-1, iNOS and COX-2 were also decreased with LEC pretreatment of mice injected with Gly. CONCLUSION: These results support the hypothesis that depletion of macrophages prevents renal dysfunction by abrogating apoptosis and attenuating inflammation during AKI.

Optical trapping of individual human immunodeficiency viruses in culture fluid reveals heterogeneity with single-molecule resolution.

Optical tweezers use the momentum of photons to trap and manipulate microscopic objects, contact-free, in three dimensions. Although this technique has been widely used in biology and nanotechnology to study molecular motors, biopolymers and nanostructures, its application to study viruses has been very limited, largely due to their small size. Here, using optical tweezers that can simultaneously resolve two-photon fluorescence at the single-molecule level, we show that individual HIV-1 viruses can be optically trapped and manipulated, allowing multi-parameter analysis of single virions in culture fluid under native conditions. We show that individual HIV-1 differs in the numbers of envelope glycoproteins by more than one order of magnitude, which implies substantial heterogeneity of these virions in transmission and infection at the single-particle level. Analogous to flow cytometry for cells, this fluid-based technique may allow ultrasensitive detection, multi-parameter analysis and sorting of viruses and other nanoparticles in biological fluid with single-molecule resolution.

Chemically and biologically synthesized CPP-modified gelonin for enhanced anti-tumor activity.

The ineffectiveness of small molecule drugs against cancer has generated significant interest in more potent macromolecular agents. Gelonin, a plant-derived toxin that inhibits protein translation, has attracted much attention in this regard. Due to its inability to internalize into cells, however, gelonin exerts only limited tumoricidal effect. To overcome this cell membrane barrier, we modified gelonin, via both chemical conjugation and genetic recombination methods, with low molecular weight protamine (LMWP), a cell-penetrating peptide (CPP) which was shown to efficiently ferry various cargoes into cells. Results confirmed that gelonin-LMWP chemical conjugate (cG-L) and recombinant gelonin-LMWP chimera (rG-L) possessed N-glycosidase activity equivalent to that of unmodified recombinant gelonin (rGel); however, unlike rGel, both gelonin-LMWPs were able to internalize into cells. Cytotoxicity studies further demonstrated that cG-L and rG-L exhibited significantly improved tumoricidal effects, with IC50 values being 120-fold lower than that of rGel. Moreover, when tested against a CT26 s.c. xenograft tumor mouse model, significant inhibition of tumor growth was observed with rG-L doses as low as 2 µg/tumor, while no detectable therapeutic effects were seen with rGel at 10-fold higher doses. Overall, this study demonstrated the potential of utilizing CPP-modified gelonin as a highly potent anticancer drug to overcome limitations of current chemotherapeutic agents.

Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells.

The infectivity of retroviruses such as HIV-1 in plasma or cultured media is less than 0.1% in general, the mechanisms of which are not yet fully understood. One possible explanation among others is the potential presence of large numbers of defective virions in a virus pool, which limits the apparent infectivity of HIV virions. To test this hypothesis, we have varied the culture conditions used to generate single-cycle HIV-1 virions. Among these culture variables, virion harvest time, media change after transfection, and envelope plasmid input can all improve HIV-1 infectivity by reducing the number of defective virions. A harvest time of 18-24 hours post transfection as opposed to 48 hours, and a media change six hours post transfection both improve viral infectivity. An optimal quantity of envelope plasmid input during transfection was also found. Collectively, these conditions increased the infectivity of HIV-1 virions by sevenfold compared to normally reported values in TZM-bl indicator cell lines. These conditions also increased the infectivity of HIV-1 in CD4(+) T cells, suggesting that these conditions work by increasing the intrinsic infectivity of a virus pool. Nevertheless, these improvements on virion infectivity were marginal compared to the impact of host cells on HIV infection, which can decrease the apparent infectivity by 19-fold even for the most optimized viruses. These results suggest that the infectivity of HIV-1 virions can be optimized by reducing the number of defective virions; however, viral-cell interactions may pose a major barrier for HIV-1 infectivity.