Doganduran4866

Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause). These effects involved brain regions subserving higher-order cognitive processes and were specific to menopausal endocrine aging rather than chronological aging, as determined by comparison to age-matched males. Brain biomarkers largely stabilized post-menopause, and gray matter volume (GMV) recovered in key brain regions for cognitive aging. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance post-menopause, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri-menopausal and post-menopausal women carrying apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer's disease, relative to genotype-matched males. These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine aging of the female brain.In bone regeneration induced by the combination of mesenchymal stromal cells (MSCs) and calcium-phosphate (CaP) materials, osteoclasts emerge as a pivotal cell linking inflammation and bone formation. Favorable outcomes are observed despite short-term engraftments of implanted MSCs, highlighting their major paracrine function and the possible implication of cell death in modulating their secretions. In this work, we focused on the communication from MSCs towards osteoclasts-like cells in vitro. MSCs seeded on a CaP biomaterial or undergoing induced apoptosis produced a conditioned media favoring the development of osteoclasts from human CD14+ monocytes. On the contrary, MSCs' apoptotic secretion inhibited the development of inflammatory multinucleated giant cells formed after IL-4 stimulation. Components of MSCs' secretome before and after apoptotic stress were compared using mass spectrometry-based quantitative proteomics and a complementary immunoassay for major cytokines. CXCR-1 and CXCR-2 ligands, primarily IL-8/CXCL-8 but also the growth-regulated proteins CXCL-1, -2 or -3, were suggested as the major players of MSCs' pro-osteoclastic effect. These findings support the hypothesis that osteoclasts are key players in bone regeneration and suggest that apoptosis plays an important role in MSCs' effectiveness.Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery.The last decades have witnessed a sudden increase in myopia incidence among youngsters that have been related to modern lifestyle along with the use of emerging technologies affecting visual exposure. Increasing exposures to known risk factors for myopia, such as time spent indoors, close-distance work, or low-light conditions are thought to be responsible for this public health issue. In most cases, development of myopia is secondary to a vitreous chamber enlargement, although the related mechanisms and the potential interaction between central and peripheral retinal area remain unclear. For a better understanding, we performed a classical twin study where objective refractive error along 70° of horizontal retinal arc was measured in 100 twin pairs of university students, 78% of which showed manifest myopia. We found the variance of shared environmental origin (range 0.34 to 0.67) explained most of the objective refractive error variance within central 42° of the retina (22° temporal to 19° nasal), whereas additive genetic variance (range 0.34 to 0.76) was predominant in the peripheral retinal areas measured. In this sample of millennial university students, with a large prevalence of myopia, environmental exposures were mostly responsible for inter-individual variation in the retinal horizontal area surrounding the macula, while their relative weight on phenotypic variance was gradually descending, and replaced by the variance of genetic origin, towards the retinal periphery.The stochastic model for epidemic spreading of the novel coronavirus disease based on the data set supply by the public health agencies in countries as Brazil, United States and India is investigated. We perform a numerical analysis using the stochastic differential equation in Itô's calculus for the estimating of novel cases daily, as well as analytical calculations solving the correspondent Fokker-Planck equation for the probability density distribution of novel cases, P(N(t), t). Our results display that the model based in the Itô's diffusion fits well to the results due to uncertainty in the official data and to the number of tests realized in populations of each country.Dietary compounds play an important role in the prevention and treatment of many cancers, although their specific molecular mechanism is not yet known. In the present study, thirty dietary agents were analyzed on nine drug targets through in silico studies. However, nine dietary scaffolds, such as silibinin, flavopiridol, oleandrin, ursolic acid, α-boswellic acid, β-boswellic acid, triterpenoid, guggulsterone, and oleanolic acid potentially bound to the cavity of PI3K-α, PKC-η, H-Ras, and Ras with the highest binding energy. Particularly, the compounds silibinin and flavopiridol have been shown to have broad spectrum anticancer activity. Interestingly, flavopiridol was embedded in the pockets of PI3K-α and PKC-η as bound crystal inhibitors in two different conformations and showed significant interactions with ATP binding pocket residues. However, complex-based pharmacophore modeling achieved two vital pharmacophoric features namely, two H-bond acceptors for PI3K-α, while three are hydrophobic, one cat-donor and one H-bond donor and acceptor for PKC-η, respectively. The database screening with the ChemBridge core library explored potential hits on a valid pharmacophore query. Nor-NOHA datasheet Therefore, to optimize perspective lead compounds from the hits, which were subjected to various constraints such as docking, MM/GBVI, Lipinski rule of five, ADMET and toxicity properties. Henceforth, the top ligands were sorted out and examined for vital interactions with key residues, arguably the top three promising lead compounds for PI3K-α, while seven for PKC-η, exhibiting binding energy from - 11.5 to - 8.5 kcal mol-1. Therefore, these scaffolds could be helpful in the development of novel class of effective anticancer agents.Urban greening is an effective mitigation option for climate change in urban areas. In this contribution, a European Union (EU)-wide assessment is presented to quantify the benefits of urban greening in terms of availability of green water, reduction of cooling costs and CO2 sequestration from the atmosphere, for different climatic scenarios. Results show that greening of 35% of the EU's urban surface (i.e. more than 26,000 km2) would avoid up to 55.8 Mtons year-1 CO2 equivalent of greenhouse gas emissions, reducing energy demand for the cooling of buildings in summer by up to 92 TWh per year, with a net present value (NPV) of more than 364 billion Euro. It would also transpire about 10 km3 year-1 of rain water, turning into "green" water about 17.5% of the "blue" water that is now urban runoff, helping reduce pollution of the receiving water bodies and urban flooding. The greening of urban surfaces would decrease their summer temperature by 2.5-6 °C, with a mitigation of the urban heat island effect estimated to have a NPV of 221 billion Euro over a period of 40 years. The monetized benefits cover less than half of the estimated costs of greening, having a NPV of 1323 billion Euro on the same period. Net of the monetized benefits, the cost of greening 26,000 km2 of urban surfaces in Europe is estimated around 60 Euro year-1 per European urban resident. The additional benefits of urban greening related to biodiversity, water quality, health, wellbeing and other aspects, although not monetized in this study, might be worth such extra cost. When this is the case, urban greening represents a multifunctional, no-regret, cost-effective solution.Purine rich element binding protein A (Purα), encoded by the Purα gene, is an important transcriptional regulator that binds to DNA and RNA and is involved in processes such as DNA replication and RNA translation. Purα also plays an important role in the nervous system. To identify the function of Pura, we performed RNA sequence (RNA-seq) analysis of Purɑ-KO mouse hippocampal neuron cell line (HT22) to analyze the effect of Purα deletion on neuronal expression profiles. And combined with ChIP-seq analysis to explore the mechanism of Purα on gene regulation. In the end, totaly 656 differentially expressed genes between HT22 and Purα-KO HT22 cells have been found, which include 7 Alzheimer's disease (AD)-related genes and 5 Aβ clearance related genes. 47 genes were regulated by Purα directly, the evidence based on CHIP-seq, which include Insr, Mapt, Vldlr, Jag1, etc. Our study provides the important informations of Purα in neuro-development. The possible regulative effects of Purα on AD-related genes consist inthe direct and indirect pathways of Purα in the pathogenesis of AD.