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No biomarkers showed a significant association in multivariate analysis.<br /><br /> Less than half of the patients presented an exacerbation during the one-year follow-up. CAT scores, FEV1(%) and previous exacerbations were the only variables associated with increased risk of exacerbations. Routine biomarkers did not provide additional information to evaluate the risk of exacerbations.<br /><br />Less than half of the patients presented an exacerbation during the one-year follow-up. CAT scores, FEV1(%) and previous exacerbations were the only variables associated with increased risk of exacerbations. Routine biomarkers did not provide additional information to evaluate the risk of exacerbations.Nanoplastics derived from degradation of micro- or macroplastics are emerging contaminants in aquatic environments, where their fate and transport as well as toxicity are affected by aggregation. This study employed time-resolved dynamic light scattering to investigate the aggregation kinetics of polystyrene nanoplastics (PSNPs) in the presence of four macromolecules (sodium alginate (SA), bovine serum albumin (BSA), extracellular polymeric substance (EPS), and Suwannee River humic acid (HA)) in solutions containing monovalent (NaCl) and divalent (CaCl2) salts at different pH. Our results showed that the macromolecules enhanced PSNP stability in NaCl solutions but destabilized PSNPs in CaCl2 solutions at pH 6. In NaCl solutions, macromolecules inhibited PSNP aggregation due to steric hindrance originated from macromolecular layer adsorbed on PSNPs. The strongest stabilization effect was observed for BSA having the greatest hydrodynamic adsorption layer thickness of 21.9 nm, followed by HA, EPS, and SA. In CaCl2 solutions, SA significantly destabilized PSNPs via alginate bridging with Ca2+, which enhanced with concentrations of SA and CaCl2. The destabilization effects of other three macromolecules in CaCl2 solutions were governed by the interplay among molecular bridging, charge screening, and steric hindrance. [https://www.selleckchem.com/HSP-90.html find protocol] An increased pH in NaCl or CaCl2 solutions containing macromolecules all stabilized PSNPs due to elevated electrostatic repulsion, except that SA destabilized PSNPs in CaCl2 solutions via enhanced molecular bridging. The stabilization effect of macromolecules may also compete with the destabilization effect under seawater condition. This study suggested that PSNP aggregation in aquatic environments could be strongly affected by macromolecules and solution chemistry.Ocular scarring after surgery, trauma, or infection leads to vision loss. The transparent cornea is an excellent model system to test anti-scarring therapies. Cholesterol-conjugated fully modified asymmetric small interfering RNAs (siRNAs) (self-deliverable siRNAs [sdRNAs]) are a novel modality for in vivo gene knockdown, transfecting cells and tissues without any additional formulations. Myofibroblasts are a main contributor to scarring and fibrosis. αv integrins play a central role in myofibroblast pathological adhesion, overcontraction, and transforming growth factor β (TGF-β) activation. Previously, we demonstrated that αv integrins are protected from intracellular degradation after wounding by upregulation of the deubiquitinase (DUB) ubiquitin-specific protease 10 (USP10), leading to integrin cell surface accumulation. In this study, we tested whether knockdown of USP10 with a USP10-targeting sdRNA (termed US09) will reduce scarring after wounding a rabbit cornea in vivo. The wounded corneal stroma was treated once with US09 or non-targeting control (NTC) sdRNA. At 6 weeks US09 treatment resulted in faster wound closure, limited scarring, and suppression of fibrotic markers and immune response. Specifically, fibronectin-extra domain A (EDA), collagen III, and a-smooth muscle actin (p less then 0.05), CD45+ cell infiltration (p less then 0.01), and apoptosis at 24 (p less then 0.01) and 48 h (p less then 0.05) were reduced post-wounding. Corneal thickness and cell proliferation were restored to unwounded parameters. Targeting the DUB, USP10 is a novel strategy to reduce scarring. This study indicates that ubiquitin-mediated pathways should be considered in the pathogenesis of fibrotic healing.MicroRNAs (miRNAs) have been reported to serve as silencers to repress gene expression at post-transcriptional levels. Multiple miRNAs have been demonstrated to play important roles in osteogenesis. MicroRNA (miR)-378, a conserved miRNA, was reported to mediate bone metabolism and influence bone development, but the detailed function and underlying mechanism remain obscure. In this study, the miR-378 transgenic (TG) mouse was developed to study the role of miR-378 in osteogenic differentiation as well as bone formation. The abnormal bone tissues and impaired bone quality were displayed in the miR-378 TG mice, and a delayed healing effect was observed during bone fracture of the miR-378 TG mice. link2 The osteogenic differentiation of mesenchymal stem cells (MSCs) derived from this TG mouse was also inhibited. We also found that miR-378 mimics suppressed, whereas anti-miR-378 promoted osteogenesis of human MSCs. Two Wnt family members, Wnt6 and Wnt10a, were identified as bona fide targets of miR-378, and their expression was decreased by this miRNA, which eventually induced the inactivation of Wnt/β-catenin signaling. Finally, the short hairpin (sh)-miR-378-modified MSCs were locally injected into the fracture sites in an established mouse fracture model. The results indicated that miR-378 inhibitor therapy could promote bone formation and stimulate the healing process in vivo. In conclusion, miR-378 suppressed osteogenesis and bone formation via inactivating Wnt/β-catenin signaling, suggesting that miR-378 may be a potential therapeutic target for bone diseases.<br /><br /> Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disorder. Most studies involve white children in developed countries in the northern hemisphere. The authors aimed to describe the clinical course and prognostic of a cohort of adult patients with ADEM from Rio de Janeiro city, where most of the population is Afro-descendant.<br /><br /> We performed a longitudinal study with retrospective data collection of patients with ADEM seen from 1999 to 2016 at a reference center for demyelinating diseases, identifying demographic, clinical, and laboratory data. Then we compared our findings with data from an extensive review of previously published reports. The literature review was carried out using Google Scholar, PubMed, and the reference lists of included studies. Searches were limited to English language original manuscripts published between 2000 and 2019.<br /><br /> Among 1396 registers, we identified 23 cases of ADEM, mostly women (78.3%), Afro-descendant (52.4%) with a mean age of 30.8±11.9 years at onset. One quarter had a previous viral infection and, 4.3% vaccination. link3 The presentation was polyfocal, characterized by the association of pyramidal 82.6%, brainstem 69.6%, mental 65.2%, cerebellar 39.1%, sensory 39.1%, sphincter 43.5%, and visual 34.8% syndromes with severe disability in 86.6%. The breakdown of the blood-brain barrier occurred at 60%. MRI was suggestive of ADEM in 87%, with good radiological evolution. A majority had a significant recovery after treatment.<br /><br /> ADEM in adults is a rare, severe, polyfocal disease with a favorable prognosis. The absence of encephalopathy does not exclude the diagnosis.<br /><br />ADEM in adults is a rare, severe, polyfocal disease with a favorable prognosis. The absence of encephalopathy does not exclude the diagnosis.Blister beetles owe their name to their ability to release cantharidin, a blistering terpene, the highest concentration of which is retained in male accessory glands. The anatomy and ultrastructure of the three pairs of male reproductive accessory glands and the glandular region of the two vasa deferentia of Meloe proscarabaeus were investigated using light, electron and ion beam microscopy. All of the mesodermal glands here analysed share a common structural organization with an outer muscular layer and an inner glandular epithelium facing a broad lumen in which the secretory products are released. Developed rough endoplasmic reticulum, Golgi systems, abundant mitochondria, numerous secretory vesicles and a microvillated apical membrane are commonly found in the cells of different glandular epithelia, suggesting that all accessory gland pairs as well as the vasa deferentia are involved in an active synthesis. Nevertheless, each pair of glands appears specialized in the production of a specific set of substances, as suggested by the peculiarities in cellular ultrastructure and by the different aspect of the secretions stored in their glandular lumen. The above cited features of male accessory glands of M. proscarabaeus are compared with those of other beetles and some hints on their potential role in producing and/or concentrating cantharidin are provided.Aggregation of reduced graphene oxide (RGO) due to π-π stacking is a recurrent problem in graphene-based electrochemistry, decreasing the effective working area and therefore the performance of the RGO electrodes. Dispersing RGO on three-dimensional (3D) carbon paper electrodes is one strategy towards overcoming this challenge, with partial relief aggregation. In this report, we describe the grafting of negatively charged 4-aminobenzoic acid (4-ABA) onto a graphene functionalized carbon paper electrode surface. 4-ABA functionalization induces separation of the RGO layers, at the same time leading to favorable orientation of the blue multi-copper enzyme Myrothecium verrucaria bilirubin oxidase (MvBOD) for direct electron transfer (DET) in the dioxygen reduction reaction (ORR) at neutral pH. Simultaneous electroreduction of graphene oxide to RGO and covalent attachment of 4-ABA are achieved by applying alternating cathodic and anodic electrochemical potential pulses, leading to a high catalytic current density (Δjcat193 ± 4 μA cm-2) under static conditions. Electrochemically grafted 4-ABA not only leads to a favorable orientation of BOD as validated by fitting a kinetic model to the electrocatalytic data, but also acts to alleviate RGO aggregation as disclosed by scanning electron microscopy, most likely due to the electrostatic repulsion between 4-ABA-grafted graphene layers. With a half-lifetime of 55 h, the bioelectrode also shows the highest operational stability for DET-type MvBOD-based bioelectrodes reported to date. The bioelectrode was finally shown to work well as a biocathode of a membrane-less glucose/O2 enzymatic biofuel cell with a maximum power density of 22 μW cm-2 and an open circuit voltage of 0.51 V.Cardiac conduction is an important function of the heart. To date, accurate measurement of conduction velocity (CV) in vitro is hindered by the low spatial resolution and poor signal-to-noise ratio of microelectrode arrays (MEAs), or the cytotoxicity and end-point analysis of fluorescence optical imaging. Here, we have developed a new label-free method based on defocused brightfield imaging to quantify CV by analyzing centroid displacements and contraction trajectories of each cardiomyocyte in a monolayer of human stem cell-derived cardiomyocytes (iPSC-CMs). Our data revealed that the time delay between intracellular calcium release and the initiation of cell contraction is highly consistent across cardiomyocytes; however, the duration a cell takes to reach its maximum beating magnitude varies significantly, proving that the time delay in excitation-contraction coupling is largely constant in iPSC-CMs. Standard calcium imaging of the same iPSC-CM populations (~106 cells) was conducted for comparison with our label-free method.