Villadsenacosta0159

These results showcase that lipid 1 can serve as a promising ROS-responsive liposomal delivery platform for controlled release.A novel Hadamard-transform excitation-emission matrix (EEM) spectrometer generates two-dimensional (2D) fluorescence matrices at a data acquisition rate of over 6 EEMs per minute and with a spectral resolution of 5.3 nm. Using Fresnel reflections from the sample cell, we could record optical transmission spectra synchronously with the 2D EEMs. The spectrometer was integrated into a custom-designed stopped-flow injection device to collect visible absorption and fluorescence EEM spectra of reacting solutions. Two different kinetic studies on two rapidly evolving chemical reactions with multiple overlapping spectral components were conducted by collecting over 8400 absorption spectra and EEMs. The third-order rate constant for the demetalation of chlorophyll-a to pheophytin-a was experimentally determined to be 450 ± 20 M-2·s-1 as derived from a parallel factor (PARAFAC) analysis where absorption and fluorescence data were combined. A PARAFAC analysis of data collected from the insertion of a copper atom into pheophytin-a resulted in several absorbing components and only a single fluorescing component. A reaction model with an association complex and a sitting-a-top (SAT) complex as intermediates explained the absorption data, resulting in a sequence of second-order reactions with rate constants of 4.0 ± 0.4, 2.7 ± 0.3, and 0.28 ± 0.02 M-1·s-1, respectively. The rate constant of the fluorescence decrease was determined to be 1.7 ± 0.2 M-1·s-1, which is consistent with the fluorescence component being attributed to both the pheophytin-a and the association complex.Flexible bioelectronics for biomedical applications requires a stretchable, conductive, self-healable, and biocompatible material that can be obtained by cost-effective chemicals and strategies. Herein, we synthesized polypyrrole or Zn-functionalized chitosan molecules, which are cross-linked with poly(vinyl alcohol) to form a hydrogel through dynamic di-diol complexations, hydrogen bonding, and zinc-based coordination bonds. These multiple dynamic interactions endow the material with excellent stretchability and autonomous self-healing ability. The choice of Food and Drug Administration (FDA)-approved materials (poly(vinyl alcohol) and chitosan) as the matrix materials ensures the good biocompatibility of the hydrogel. The conductivity contributed by the polypyrrole allowed the hydrogel to sense strain and temperature, and the coordinated Zn significantly enhanced the antibacterial activity of the hydrogel. Moreover, using a diabetic rat model, we have proved that this hydrogel is capable of promoting the healing of the infected chronic wounds with electrical stimulation.The promising alkaline anion exchange membrane fuel cell suffers from sluggish kinetics of the hydrogen oxidation reaction (HOR). However, the puzzling HOR mechanism hinders the further development of highly active catalysts in alkaline media. In this work, we conducted detailed first-principles calculations to acquire a deep understanding of the alkaline HOR mechanism on PtNi bulk alloys [Pt3Ni(111), Pt2Ni2(111), and PtNi3(111)] and its surface alloy [PtNisurf(111)]. CP43 The full free energy profiles suggest that the HOR on PtNi alloys proceeds via the Tafel-Volmer mechanism, that is, the direct decomposition of H2 into two adsorbed H, followed by its reaction with OH- in the electrolyte, as the rate-determining step, to form H2O. Therefore, the HOR activity of PtNi alloys is solely impacted by the adsorption of hydrogen, rather than hydroxyl species, though the oxophilicity is also enhanced by alloying Pt with Ni. Thermodynamically, a moderate H adsorption free energy, ΔGH* ≈ 0.414 eV, is calculated to be an optimal candidate for the HOR at pH = 13. Alloying Pt with Ni can elevate the d-band center (εd), push the value of ΔGH* closer to 0.414 eV, and thus lower the free energy barrier (Ea) of the rate-determining Volmer reaction, leading to the highest HOR activity of PtNi3(111) among all considered PtNi alloys. This situation is further confirmed by both the microkinetic model and the Tafel plot, where PtNi3(111) exhibits the highest reaction rate (r = 9.42 × 103 s-1 site-1) and the largest exchange current density (i0 = 1.42 mA cm-2) for HOR in alkaline media. This work provides a fundamental understanding of the HOR mechanism and theoretical guidance for rational design of electrocatalysts for HOR in alkaline media.The products of most secondary metabolite biosynthetic gene clusters (BGCs) have yet to be discovered, in part due to low expression levels in laboratory cultures. Reporter-guided mutant selection (RGMS) has recently been developed for this purpose a mutant library is generated and screened, using genetic reporters to a chosen BGC, to select transcriptionally active mutants that then enable the characterization of the "cryptic" metabolite. The requirement for genetic reporters limits the approach to a single pathway within genetically tractable microorganisms. Herein, we utilize untargeted metabolomics in conjunction with transposon mutagenesis to provide a global read-out of secondary metabolism across large numbers of mutants. We employ self-organizing map analytics and imaging mass spectrometry to identify and characterize seven cryptic metabolites from mutant libraries of two different Burkholderia species. Applications of the methodologies reported can expand our understanding of the products and regulation of cryptic BGCs across phylogenetically diverse bacteria.

To date, no consensus has been reached on the optimal management of congenital lung abnormalities, and factors predicting postnatal outcome have not been identified. We developed an objective quantitative computed tomography (CT) scoring method, and assessed its value for clinical decision-making.

Volumetric CT-scans of all patients born with a congenital lung abnormality between January 1999 and 2018 were assessed. Lung disease was quantified using the newly-developed congenital lung abnormality quantification (CLAQ) scoring method. In 20 equidistant axial slices, cells of a square grid were scored according to the abnormality within. The scored CT parameters were used to predict development of symptoms, and SD scores for spirometry and exercise tolerance (Bruce treadmill test) at 8 years of age.

CT-scans of 124 patients with a median age of 5 months were scored. Clinical diagnoses included congenital pulmonary airway malformation (49%), bronchopulmonary sequestration (27%), congenital lobar overinflation (22%), and bronchogenic cyst (1%). Forty-four patients (35%) developed symptoms requiring surgery of whom 28 (22%) patients became symptomatic before a CT-scan was scheduled. Lesional hyperdensity was found as an important predictor of symptom development and decreased exercise tolerance. Using receiver operating characteristic analysis, an optimal cut-off value for developing symptoms was found at 18% total disease.

CT-quantification of congenital lung abnormalities using the CLAQ method is an objective and reproducible system to describe congenital lung abnormalities on chest CT. The risk for developing symptoms may increase when more than a single lung lobe is affected.

CT-quantification of congenital lung abnormalities using the CLAQ method is an objective and reproducible system to describe congenital lung abnormalities on chest CT. The risk for developing symptoms may increase when more than a single lung lobe is affected.Alcohol-related dementia (ARD) is a common and severe co-morbidity in alcohol use disorder (AUD). We propose brain iron overload (BIO) to be an important and previously neglected pathogenic process, accelerating cognitive decline in AUD. Furthermore, we suggest thiamine, which is frequently depleted in AUD, to be a key modulator in this process Thiamine deficiency impairs the integrity of the blood-brain barrier, thereby enabling iron to pass through and accumulate in the brain. This hypothesis is based on findings from animal, translational, and neuroimaging studies, discussed in this article. To validate this hypothesis, translational studies focusing on brain iron homeostasis in AUD, as well as prospective clinical studies investigating prevalence and clinical impact of BIO in AUD, should be conducted. If proven right, this would change the understanding of ARD and may lead to novel therapeutic interventions in prevention and treatment of ARD.Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4) c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 [46%] in cases vs. 449/1495 [30%] in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.

Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.

We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures.

SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant.

In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.

In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.Multifactor and multistep processes were elucidated to participate in the progression of non-small-cell lung cancer (NSCLC). Circular RNA 0031250 (circ-PRMT5) was a vital factor in NSCLC. However, the role of circ-PRMT5 in cisplatin (DDP)-resistance needed to be further highlighted. Expression profiles of circ-PRMT5, microRNA (miR)-4458, and EV3-like DNA-directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real-time polymerase chain reaction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were performed to determine the half-maximal inhibitory concentration of DDP, cell viability, apoptosis, and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined by adopting western blot. Dual-luciferase reporter assay was performed to analyze the interaction between miR-4458 and circ-PRMT5 or REV3L. The functional role of circ-PRMT5 was explored using a xenograft tumor model. Levels of circ-PRMT5 and REV3L were markedly increased, while miR-4458 was downregulated in resistant tissues and cells.