Search

Abstract Changing the perception of defects as imperfections in crystalline frameworks into correlated domains amenable to chemical control and targeted design might offer opportunities for the design of porous materials with superior performance or distinctive behavior in catalysis, separation, storage, or guest recognition. From a chemical standpoint, the establishment of synthetic protocols adapted to control the generation and growth of correlated disorder is crucial to consider defect engineering a practicable route towards adjusting framework function. By using UiO-66 as experimental platform, we systematically explored the framework chemical space of the corresponding defective materials. Periodic disorder arising from controlled generation and growth of missing cluster vacancies can be chemically controlled by the relative concentration of linker and modulator, which has been used to isolate a crystallographically pure “disordered” reo phase. Cs-corrected scanning transmission electron microscopy is used to proof the coexistence of correlated domains of missing linker and cluster vacancies, whose relative sizes are fixed by the linker concentration. The relative distribution of correlated disorder in the porosity and catalytic activity of the material reveals that, contrarily to the common belief, surpassing a certain defect concentration threshold can have a detrimental effect.

Introduction: Adult patients with atrial septal defects (ASD), the most common form of adult congenital heart disease, often die of arrhythmias, and the immaturity of cardiomyocytes contributes significantly to arrhythmias. ASD typically induces a left-to-right shunt, which then leads to the right atrium (RA) volume overload (VO). Whether or not VO contributes to RA cardiomyocyte immaturity and thereby causes arrhythmias in adult patients with ASD remains unclear.Methods: Here, we developed the first neonatal RA VO mouse model by creating a fistula between the inferior vena cava and abdominal aorta on postnatal day 7. RA VO was confirmed by increases in the mean flow velocity, mean pressure gradient, and velocity time integral across the tricuspid valve, and an increase in the RA diameter and RA area middle section.Results: We found that VO decreased the regularity and length of sarcomeres, and decreased the T-element density, regularity, and index of integrity of T-tubules in RA cardiomyocytes, suggesting that the two most important maturation hallmarks (sarcomere and T-tubules) of RA cardiomyocytes were impaired by VO. Accordingly, the calcium handling capacity of cardiomyocytes from postnatal day 21 (P21) RA was decreased by VO. VO caused a significant elongation of the PR interval. The expression of connexin 43 (Cx43) was decreased in RA VO. Moreover, gene ontology (GO) analysis of the downregulated genes in RA demonstrated that there was an abundance of enriched terms associated with sarcomeres and T-tubules exposed to VO. The results were further verified by qRT-PCR.Conclusions: In conclusion, the first neonatal RA VO mouse model was developed; furthermore, using this neonatal RA VO mouse model, we revealed that VO impeded RA sarcomere and T-tubule maturation, which may be the underlying causes of atrial arrhythmias in adult patients with ASD.