Linkages between aromatic structures in the Argonne Premium Coal Samples

The objective of this study is to elucidate the nature of the important linkages between aromatic clusters and variations of these links with coal rank. From studies using methods such as NMR and mass spectrometry, the authors have considerable information on the size and types of aromatic clusters in the Argonne coals. In this study, extracts, model polymers, extracted coals, and modified coals are examined by temperature resolved high resolution mass spectrometry. There is evidence that strong bond cleavage may be very important for volatile release in pyrolysis of higher rank coals

Smartphone Distraction: Italian Validation of the Smartphone Distraction Scale (SDS)

This work aimed to validate the use of the Smartphone Distraction Scale (SDS) in Italy. The SDS was devised to assess distraction related to smartphone use in adult populations. A cross-sectional study was conducted among n = 609 adults (females = 76.4%; mean age = 30.26; SD age = 9.90). An assessment of the factorial structure of the Italian version was carried out using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The four factors identified by Throuvala and colleagues were confirmed (i.e., attention impulsiveness, online vigilance, multitasking and emotion regulation). Reliability was assessed using Cronbach's alpha coefficient (0.703-0.889). The scale's scores showed significant linear correlations with validated instruments, including the Mobile Phone Problematic Use Scale (MPPUS)and the Cognitive Failures Questionnaire (CFQ). A multivariate analysis of variance showed significant differences in the means among participants belonging to different age groups (born before 1995 vs. born after 1996). In summary, the good psychometric properties observed led us to assume that this instrument can be applied and used in Italian studies to assess the cognitive dimension of distraction related to the use of smartphones

Observations of Coronal Mass Ejections with the Coronal Multichannel Polarimeter

The Coronal Multichannel Polarimeter (CoMP) measures not only the polarization of coronal emission, but also the full radiance profiles of coronal emission lines. For the first time, CoMP observations provide high-cadence image sequences of the coronal line intensity, Doppler shift and line width simultaneously in a large field of view. By studying the Doppler shift and line width we may explore more of the physical processes of CME initiation and propagation. Here we identify a list of CMEs observed by CoMP and present the first results of these observations. Our preliminary analysis shows that CMEs are usually associated with greatly increased Doppler shift and enhanced line width. These new observations provide not only valuable information to constrain CME models and probe various processes during the initial propagation of CMEs in the low corona, but also offer a possible cost-effective and low-risk means of space weather monitoring.Comment: 6 figures. Will appear in the special issue of Coronal Magnetism, Sol. Phy

Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection

Vinith Yathindranath,1,2 Nura Safa,1,2 Mateusz Marek Tomczyk,1,3 Vernon Dolinsky,1,3 Donald W Miller1,2 1Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada; 2PrairieNeuro Research Centre, Health Science Centre, Winnipeg, MB, Canada; 3Children’s Hospital Research Institute Manitoba, Health Science Centre, Winnipeg, MB, CanadaCorrespondence: Donald W Miller, Tel +1 204 789 3278, Email [email protected]: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lingering threat to public health has fueled the search for effective therapeutics to treat SARS-CoV-2. This study aimed to develop lipid nanoparticle (LNP) inhibitors of SARS-CoV-2 entry to reduce viral infection in the nose and upper airway.Methods: Two types of LNP formulations were prepared following a microfluidic mixing method. The LNP-Trap consisted of DOPC, DSPC, cholesterol, and DSPE-PEG-COOH modified with various spike protein binding ligands, including ACE2 peptide, recombinant human ACE2 (rhACE2) or monoclonal antibody to spike protein (mAb). The LNP-Trim consisted of ionizing cationic DLin-MC3-DMA, DSPC, cholesterol, and DMG-PEG lipids encapsulating siACE2 or siTMPRSS2. Both formulations were assayed for biocompatibility and cell uptake in airway epithelial cells (Calu-3). Functional assessment of activity was performed using SARS-CoV-2 spike protein binding assays (LNP-Trap), host receptor knockdown (LNP-Trim), and SARS-CoV-2 pseudovirus neutralization assay (LNP-Trap and LNP-Trim). Localization and tissue distribution of fluorescently labeled LNP formulations were assessed in mice following intranasal administration.Results: Both LNP formulations were biocompatible based on cell impedance and MTT cytotoxicity studies in Calu-3 cells at concentrations as high as 1 mg/mL. LNP-Trap formulations were able to bind spike protein and inhibit pseudovirus infection by 90% in Calu-3 cells. LNP-Trim formulations reduced ACE2 and TMPRSS2 at the mRNA (70% reduction) and protein level (50% reduction). The suppression of host targets in Calu-3 cells treated with LNP-Trim resulted in over 90% inhibition of pseudovirus infection. In vivo studies demonstrated substantial retention of LNP-Trap and LNP-Trim in the nasal cavity following nasal administration with minimal systemic exposure.Conclusion: Both LNP-Trap and LNP-Trim formulations were able to safely and effectively inhibit SARS-CoV-2 pseudoviral infection in airway epithelial cells. These studies provide proof-of-principle for a localized treatment approach for SARS-CoV-2 in the upper airway. Keywords: lipid nanoparticles, SARS-CoV-2, antiviral, gene knockdown, intranasal drug deliver

Editorial: Pharmacology of Plant Polyphenols in Human Health and Diseases

Polyphenols are one of the most abundant classes of secondary metabolites in plants and particularly relevant in leafy vegetables, fruits, berries, tea, and other beverages, with a wide range of health-promoting activities reported. They are also among the most widely studied natural products regarding their biosynthesis, chemical properties, and pharmacological activities. Different polyphenols such as anthocyanins, coumarins, carotenoids, flavonoids, and xanthones have been reported to be promising anti-inflammatory, anticancer, antidiabetic, antihyperlipidemic, antioxidant, and neuroprotective agents (Ganesan and Xu, 2017; Khan et al., 2019). In recent years, there is a growing number of papers that deal with the isolation, characterization, and bioactivity evaluation of polyphenols. However, many published results are mostly based on in vitro evidence. At the same time, there is less focus on the bioavailability, study of detailedmechanisms of action using animal models, and possible toxicities. There have also been concerns about the specificity of the compounds’ effects and the dose levels needed to achieve such outcomes. Althoughmany polyphenols show potent bioactivity during testing with in vitro evaluation systems, there are various challenges at an in vivo level. The in vitro results often cannot be translated to similar effects in animal models and clinical studies (Hu, 2007).https://www.frontiersin.org/journals/pharmacologyam2023Plant Production and Soil Scienc

CYP3A variation, premenopausal estrone levels, and breast cancer risk.

BACKGROUND: Epidemiological studies have provided strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women. METHODS: We measured urinary levels of estrone glucuronide (E1G) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle in 729 healthy premenopausal women. We genotyped 642 single-nucleotide polymorphisms (SNPs) in these women; a single SNP, rs10273424, was further tested for association with the risk of breast cancer using data from 10 551 breast cancer case patients and 17 535 control subjects. All statistical tests were two-sided. RESULTS: rs10273424, which maps approximately 50 kb centromeric to the cytochrome P450 3A (CYP3A) gene cluster at chromosome 7q22.1, was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI] = 27.8% to 15.3% reduction; P = 2.7 × 10(-9)) and a modest reduction in the risk of breast cancer in case patients who were diagnosed at or before age 50 years (odds ratio [OR] = 0.91, 95% CI = 0.83 to 0.99; P = .03) but not in those diagnosed after age 50 years (OR = 1.01, 95% CI = 0.93 to 1.10; P = .82). CONCLUSIONS: Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. This association may have wider implications given that the most predominantly expressed CYP3A gene, CYP3A4, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents used in the treatment of breast cancer

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Gas phase stability of Protein Ions in a Cyclic Ion Mobility Spectrometry Traveling Wave Device

Ion mobility mass spectrometry (IM-MS) allows separation of native protein ions into “conformational families”. Increasing the IM resolving power should allow finer structural information to be obtained and can be achieved by increasing the length of the IM separator. This, however, increases the time that protein ions spend in the gas phase and previous experiments have shown that the initial conformations of small proteins can be lost within tens of milliseconds. Here, we report on investigations of protein ion stability using a multipass traveling wave (TW) cyclic IM (cIM) device. Using this device, minimal structural changes were observed for Cytochrome C after hundreds of milliseconds, while no changes were observed for a larger multimeric complex (Concanavalin A). The geometry of the instrument (Q-cIM-ToF) also enables complex tandem IM experiments to be performed, which were used to obtain more detailed collision-induced unfolding pathways for Cytochrome C. The instrument geometry provides unique capabilities with the potential to expand the field of protein analysis via IM-MS

Plant uptake of explosives from contaminated soil at the Joliet Army Ammunition Plant

Explosives and their degradation products may enter the animal and human food chains through plants grown on soils contaminated with explosives. Soil and plant samples were collected from the Group 61 area at the Joliet Army Ammunition Plant and analyzed to determine the extent to which 2,4,6-trinitrotoluene (TNT) and its degradation products are taken up by existing vegetation and crops growing on contaminated soils. Neither TNT nor its degradation products was detected in any of the aboveground plant organs of existing vegetation. Oat (Avena sativa L.) and perennial ryegrass (Lolium perenne L.) were planted on TNT-contaminated soils amended with three levels of chopped grass hay. Extractable TNT concentrations in hay-amended soils were monitored for almost 1 year. Crop establishment and growth improved with increased levels of hay amendment, but TNT uptake was not affected or detected in any aboveground crop organs. Evidence was found to indicate that soil manipulation and hay addition may reduce extractable TNT concentration in soils, but the wide variations in TNT concentrations in these soils prevented development of conclusive evidence regarding reduction of extractable TNT concentrations. Results from this study suggest that vegetation grown on TNT-contaminated soils is not a major health concern because TNT and its degradation products were not detected in aboveground plant organs. However, low concentrations of TNT, 4-amino-2,6-dinitrotoluene, and 2-amino-4,6-dinitrotoluene were detected in or on some existing vegetation and crop roots. 21 refs., 10 figs., 26 tabs

Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014

During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks