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Summary: Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. Methods: We conducted a retrospective cohort study of individuals

Abstract Background A major focus in cystic fibrosis (CF) care aims to increase weight gain. Rates of overweight and obese people with CF have gradually increased over the past decade. Obesity could be a risk for restriction of lung volumes and airway obstruction as well as increase rates of pulmonary exacerbations in people with CF. Aim To assess the relationship between weight categories and pulmonary outcomes in children and adults with CF. Methods Patients 6 years of age and older were categorized into weight categories based on the Centers for Disease Control and Prevention (CDC) definitions. A retrospective chart review was conducted to obtain lung function testing and other outcomes. Results One hundred five patients with a median age of 20.6 years were included in this analysis. 8.4%, 64%, 18%, and 10% of patients were underweight, normal/healthy weight, overweight, and obese, respectively. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (% predicted) did not differ between patients with weights in the normal range versus patients in the overweight/obese categories. Linear regression analysis showed a direct correlation between body mass index (BMI) and FEV1 that continued as BMI entered overweight and obese categories in both pediatric and adult patients. Overweight/obese patients did not have increased rates of pulmonary exacerbations compared to those in the normal/healthy weight category. Conclusion As CF therapies continue to improve, an increasing number of people with CF are exceeding the CDC's normal‐weight range. Gaining weight past the normal range does not appear to negatively impact pulmonary health of people with CF. If this trend of increased weight gain continues, it remains to be seen if it will eventually negatively affect lung health.

Abstract Bioenergy from photosynthetic living organisms is a potential solution for energy‐harvesting and bioelectricity‐generation issues. With the emerging interest in biophotovoltaics, extracting electricity from photosynthetic organisms remains challenging because of the low electron‐transition rate and photon collection efficiency due to membrane shielding. In this study, the concept of “photosynthetic resonator” to amplify biological nanoelectricity through the confinement of living microalgae (Chlorella sp.) in an optical micro/nanocavity is demonstrated. Strong energy coupling between the Fabry–Perot cavity mode and photosynthetic resonance offers the potential of exploiting optical resonators to amplify photocurrent generation as well as energy harvesting. Biomimetic models and living photosynthesis are explored in which the power is increased by almost 600% and 200%, respectively. Systematic studies of photosystem fluorescence and photocurrent are simultaneously carried out. Finally, an optofluidic‐based photosynthetic device is developed. It is envisaged that the key innovations proposed in this study can provide comprehensive insights in biological‐energy sciences, suggesting a new avenue to amplify electrochemical signals using an optical cavity. Promising applications include photocatalysis, photoelectrochemistry, biofuel devices, and sustainable optoelectronics.

Real-world management decisions for acute cough in children in primary care practice are not well understood. This study is an analysis of 560 encounters for children with cough, 19 days to 18 years of age, seen in a predominantly suburban academic pediatric practice, over 1 year. Past history, cough duration, and cough characteristics significantly affected treatment decisions. Children with cough frequently had a history of preterm birth, allergies, asthma, and neurological conditions. Most common therapies were bronchodilators, antibiotics, and oral corticosteroids. Children prescribed antibiotics were older, more likely to have a wet or productive cough, history of sinusitis, pneumonia or dysphagia, and longer cough duration. Children prescribed oral corticosteroids were younger, less likely to be wet or productive and more likely to have history of asthma or dysphagia. Children prescribed bronchodilators were more likely to have fever, nasal congestion, and wheezing and history of previous asthma, pneumonia, or dysphagia.

BackgroundThe somatic mutation in the FOXL2 gene c.402C>G (p.Cys134Trp) has recently been identified in the vast majority of adult ovarian granulosa cell tumors (OGCTs) studied. In addition, this mutation seems to be specific to adult OGCTs and is likely to be a driver of malignant transformation. However, its pathogenic mechanisms remain elusive.Methodology/principal findingsWe have sequenced the FOXL2 open reading frame in a panel of tumor cell lines (NCI-60, colorectal carcinoma cell lines, JEG-3, and KGN cells). We found the FOXL2 c.402C>G mutation in the adult OGCT-derived KGN cell line. All other cell lines analyzed were negative for the mutation. In order to gain insights into the pathogenic mechanism of the p.Cys134Trp mutation, the subcellular localization and mobility of the mutant protein were studied and found to be no different from those of the wild type (WT). Furthermore, its transactivation ability was in most cases similar to that of the WT protein, including in conditions of oxidative stress. A notable exception was an artificial promoter known to be coregulated by FOXL2 and Smad3, suggesting a potential modification of their interaction. We generated a 3D structural model of the p.Cys134Trp variant and our analysis suggests that homodimer formation might also be disturbed by the mutation.Conclusions/significanceHere, we confirm the specificity of the FOXL2 c.402C>G mutation in adult OGCTs and begin the exploration of its molecular significance. This is the first study demonstrating that the p.Cys134Trp mutant does not have a strong impact on FOXL2 localization, solubility, and transactivation abilities on a panel of proven target promoters, behaving neither as a dominant-negative nor as a loss-of-function mutation. Further studies are required to understand the specific molecular effects of this outstanding FOXL2 mutation.

As aortic valve stenosis (AVS) progresses, the valve tissue also stiffens. This increase in tissue stiffness causes the valvular interstitial cells (VICs) to transform into myofibroblasts in response. VIC-to-myofibroblast differentiation is critically involved in the development of AVS. Herein, we investigated the role of mechanosensitive Ca 2+ -permeant transient receptor potential vanilloid 4 (Trpv4) channels in matrix stiffness- and transforming growth factor β1 (TGFβ1)-induced VIC-myofibroblast activation. We confirmed Trpv4 functionality in primary mouse wild-type VICs compared to Trpv4 null VICs using live Ca 2+ influx detection during application of its selective agonist and antagonist. Using physiologically relevant hydrogels of varying stiffness that respectively mimic healthy or diseased aortic valve tissue stiffness, we found that genetic ablation of Trpv4 blocked matrix stiffness- and TGFβ1-induced VIC-myofibroblast activation as determined by changes in morphology, alterations of expression of α-smooth muscle actin, and modulations of F-actin generation. Our results showed that N-terminal residues 30-130 in Trpv4 were crucial for cellular force generation and VIC-myofibroblast activation, while deletion of residues 1-30 had no noticeable negative effect on these processes. Collectively, these data suggest a differential regulatory role for Trpv4 in stiffness/TGFβ1-induced VIC-myofibroblast activation. Our data further showed that Trpv4 regulates stiffness/TGFβ1-induced PI3K-AKT activity that is required for VIC-myofibroblast differentiation and cellular force generation, suggesting a mechanism by which Trpv4 activity regulates VIC-myofibroblast activation. Altogether, these data identify a novel role for Trpv4 mechanotransduction in regulating VIC-myofibroblast activation, implicating Trpv4 as a potential therapeutic target to slow and/or reverse AVS development., Competing Interests: CONFLICT OF INTEREST: The authors declare that there are no conflicts of interest.

Atherosclerosis, a chronic inflammatory disease of aorta, remains the major cause of morbidity and mortality among cardiovascular disease patients. Macrophage foam cell formation and inflammation are critically involved in early stages of atherosclerosis, hence chemopreventive targeting of foam cell formation by nutraceuticals may be a promising approach to curbing the progression of atherosclerosis. However, many nutraceuticals including berberine and ginkgetin have low stability, tissue/cell penetration and bioavailability resulting in inadequate chemotherapeutic effects of these nutraceuticals. We have used avocado-derived extracellular vesicles (EV) isolated from avocado (EV Avo ) as a novel carrier of nutraceuticals, in a strategy to alleviate the build-up of macrophage foam cells and expression of inflammatory genes. Our key findings are: (i) Avocado is a natural source of plant-derived EVs as shown by the results from transmission electron microscopy, dynamic light scattering and NanoBrook Omni analysis and atomic force microscopy; (ii) EV Avo are taken up by macrophages, a critical cell type in atherosclerosis; (iii) EV Avo can be loaded with high amounts of ginkgetin and berberine; (iv) ginkgetin plus berberine-loaded EV Avo (EV Avo(B+G) ) suppress activation of NFκB and NLRP3, and inhibit expression of pro-inflammatory and atherogenic genes, specifically Cd36, Tnfα, Il1β and Il6; (v) EV Avo(B+G) attenuate oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation and (vi) EV Avo(B+G) inhibit oxLDL uptake but not its cell surface binding during foam cell formation. Overall, our results suggest that using EV Avo as a natural carrier of nutraceuticals may improve strategies to curb the progression of atherosclerosis by limiting inflammation and pro-atherogenic responses., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The present study was designed to evaluate the anti-obesity and anti-hyperglycemic activity of Thymoquinone (ThyQ) isolated from Nigella sativa seeds. Male Wistar rats were randomly divided into five groups and fed either normal pellet diet or high-fat diet (HFD) for 18 weeks and water ad-libitum . Group I: normal pellet diet (NPD)-fed, Group II: high-fat diet (HFD)-fed, Group III: HFD-fed-ThyQ (20 mg)-treated, Group IV: HFD-fed-ThyQ (40 mg)-treated and Group V: HFD-fed-Orlistat (5 mg)-treated group. Intervention with ThyQ started from 12th week onwards to HFD-fed rats of group III and IV. ThyQ administration significantly ( p  < 0.01) mitigated body weight gain, blood glucose, insulin level, serum and liver lipids (except HDL) and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose tolerance test (OGTT), homeostasis model assessment-insulin resistance (HOMA-IR) and insulin tolerance test (ITT). Furthermore, ThyQ significantly ( p  < 0.01) diminished serum aspartate transaminase (AST), alanine transaminase (ALT), acetyl-CoA carboxylase (ACC), plasma leptin, resistin and visfatin levels but enhanced lipoprotein lipase (LPL) and adiponectin levels. RT-PCR analysis demonstrated down-regulated mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), CCAAT/enhancer-binding protein-α (C/EBP-α) and fatty acid synthase (FAS) but upregulation of Insulin receptor substrate-1 (IRS-1).Western blot analysis displayed phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in ThyQ-treated rats. Liver microtome sections of HFD-fed rats showed degenerated hepatocytes with high lipid stores while that of adipose tissue sections displayed large, fat-laden adipocytes, however, these histological changes were considerably attenuated in ThyQ-treated groups. Together these findings demonstrate that ThyQ can be a valuable therapeutic compound to potentially alleviate diet-induced obesity, hyperglycemia and insulin resistance., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03847-x., Competing Interests: Conflict of interestThere are no competing financial interests declared by the authors., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Epithelial-mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA-MB-231 and MCF-7 breast cancer cells. The apparent anticancer activity of UA on MDA-MB-231 and MCF-7 cells was evident from IC50 values of 14.98 and 15.99 μg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA-MB-231 and MCF-7 cells were treated with 20 μg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G 0 /G 1 phase, S phase, G 2 /M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum-polarized-ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with -53.865, -48.971 and -40.617 MMGBSA (ΔG bind ) scores, respectively. The long-range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent., (© 2023 Wiley Periodicals LLC.)

3-Pyridinealdazine was synthesized and characterized by FT-IR, (1)H, (13)C NMR and mass spectroscopy. The conformations of azine was determined theoretically besides selected geometrical parameters, HOMO-LUMO energies, polarizability, hyperpolarizability, natural bond orbital (NBO), atomic charges, Mulliken charges and atom in molecule (AIM) analysis were also calculated. The optimized geometry of the symmetrical azine, HOMO-LUMO and molecular electrostatic potential (MEP) surface were also evaluated using B3LYP/6-31G(d,p) basis set. (13)C NMR data were also computed using Gaussian-03 package and compared with the observed values according to density functional theory (DFT) method and analyzed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A novel unsymmetrical azine 2-(4-methoxybenzylidene)-1-(1-(4-isobutylphenyl) ethylidene) hydrazine (UA) was prepared and characterized by IR, (1)H and (13)C NMR spectral studies. A 2D - potential energy scan (PES) of p-isobutylacetophenone (IBAP) was the portal to the conformational analysis of UA by density functional theory (DFT) methods using 6-31G(d,p) basis set by Gaussian 03 program. The theoretical IR frequencies were found to be in good agreement with the experimental values. The IR frequencies of UA were analyzed by means of Potential energy Distribution (PED %) calculation using Vibrational Energy Distribution Analysis (VEDA 4) program. The experimental NMR chemical shift values of UA were compared with the theoretical values obtained by DFT method. Nonlinear optical behavior of the unsymmetrical azine is also examined by the theoretically predicted values of dipole moment (μ), polarizability (α0) and first hyperpolarizability (βtot). Stability of the UA molecule has been analyzed using NBO analysis. The electrochemistry of UA studied experimentally by cyclic voltammetry is complemented by the computational analysis of the anionic form of the molecule UA. The determination of various global and local reactivity descriptors in the context of chemical reactivity is also performed and the electrophilicity at the vital atomic sites in UA is revealed. Bader's Atoms in molecules (AIM) theory of UA indicated the presence of intramolecular hydrogen bonding in the molecule. The molecular electrostatic potential (MEP) and HOMO-LUMO orbital analysis are also performed for the molecule UA., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the present study a novel series of 1-(1-(4-isobutylphenyl)ethylidene)-2-(4-phenylthiazol-2-yl)hydrazine 2a and its derivatives 2b-2f have been synthesized by the cyclization of 1-(1-(4-isobutylphenyl)ethylidene)thiosemicarbazide with 2-bromoacetophenone/ 4-substituted 2-bromoacetophenones. The structures of the synthesized thiazolyl hydrazones 2a-2f were characterized by FT-IR, (1)H, (13)C NMR, 2D NMR and mass spectral techniques. The molecular geometries were also investigated theoretically using B3LYP functional with 6-311G(d,p) basis set. To explain the molecular properties energy gap (Eg), electronegativity (χ), hardness (g), electrophilicity (ω) and softness (S) were computed, natural bonding orbital (NBO) analysis and molecular electrostatic potential (MEP) were also performed at the same level of theory. All the synthesized thiazolyl hydrazones 2a-2f were screened for their in vitro antimicrobial activity against selected bacterial and fungal strains. The results showed that the heterocyclic thiazolyl hydrazone derivatives exhibit a promising selective inhibitory activity against various bacterial and fungal strains., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A series of novel unsymmetrical azines 2-8 are prepared and characterized by FT-IR, (1)H, (13)C NMR, Mass and UV spectral studies. The Gaussian-03 B3LYP/6-311+G(d,p) calculations on these azines are used to evaluate the heat of formation of the different conformers, identify the stable conformation, to determine dipole moment (μ), polarizability (α0), first hyperpolarizability (βtot), selected geometrical parameters, MEP surface, frontier molecular orbital energies (HOMO-LUMO) and their energy gap. The μ, α0, βtot values clearly depict that the unsymmetrical azine 8 is found to have a good NLO property compared to other azines 1-7. The SHG measurement of unsymmetrical azine 8 was performed by Kurtz and Perry powder method and the results indicated that the azine 8 is having comparable efficiency as that of potassium dihydrogen phosphate (KDP) crystal. The natural bond orbital (NBO) analysis of the unsymmetrical azines 2-8 are also made using B3LYP/6-31G(d,p) basis set., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the title compound, C(22)H(17)N(3), the 1H-indole unit is essentially planar, with a dihedral angle of 0.95 (10)° between the pyrrole ring and the fused benzene ring. The dihedral angle between the two phenyl rings is 65.09 (10)°. In the crystal, an inter-molecular N-H⋯N hydrogen bond forms an infinite chain in the b-axis direction.

In the title mol-ecule, C(26)H(18)N(2), the 9H-fluorene unit is almost planar, as the cyclo-penta-diene ring makes dihedral angles of 1.12 (6) and 1.46 (6)° with the fused benzene rings. The dihedral angle between the two phenyl rings of the diphenyl-methyl-ene residue is 61.78 (6)°.