Vascular endothelial growth factor receptor inhibition enhances chronic obstructive pulmonary disease picture in mice exposed to waterpipe smoke

Background: Chronic obstructive pulmonary disease (COPD) is marked by destruction of alveolar architecture. Preclinical modelling for COPD is challenging. Chronic cigarette smoke exposure, the reference animal model of COPD, is time-inefficient, while exposure to waterpipe smoke (WPS), a surging smoking modality, was not fully tested for its histopathological pulmonary consequences. Since alveolar damage and pulmonary vascular endothelial dysfunction are integral to COPD pathology, lung histopathological effects of WPS were temporally evaluated, alone or in combination with vascular endothelial growth factor receptor (VEGFR) inhibition in mice.Materials and methods: Mice were exposed to WPS, 3 hours/day, 5 days/week, for 1, 2, 3, or 4 months. Another group of mice was exposed to WPS for 1 month, while being subjected to injections with the VEGFR blocker Sugen5416 (SU, 20 mg/kg) 3 times weekly. Control mice were exposed to fresh air in a matching inhalation chamber. Histopathological assessment of COPD was performed. Alveolar destructive index (DI) was counted as the percentage of abnormally enlarged alveoli with damaged septa per all alveoli counted. Mean linear intercept (MLI) was calculated as a measure of airspace enlargement.Results: Exposure to WPS resulted in significant increases in alveolar DI and MLI only after 4 months. Lung inflammatory score was minimal across all time-points. Importantly, combination of WPS and SU resulted in significantly increased DI, MLI, and inflammatory scores as early as 1 month post exposure.Conclusions: Combined exposure to WPS and SU results in COPD picture, highlighting the role of pulmonary vascular endothelial dysfunction in the disease

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7