Systemic Hypoxemia Induces Cardiomyocyte Hypertrophy and Right Ventricular Specific Induction of Proliferation.

BACKGROUND: A recent study suggests that systemic hypoxemia in adult male mice can induce cardiac myocytes to proliferate. The goal of the present experiments was to confirm these results, provide new insights on the mechanisms that induce adult cardiomyocyte cell cycle reentry, and to determine if hypoxemia also induces cardiomyocyte proliferation in female mice. METHODS: EdU-containing mini pumps were implanted in 3-month-old, male and female C57BL/6 mice. Mice were placed in a hypoxia chamber, and the oxygen was lowered by 1% every day for 14 days to reach 7% oxygen. The animals remained in 7% oxygen for 2 weeks before terminal studies. Myocyte proliferation was also studied with a mosaic analysis with double markers mouse model. RESULTS: Hypoxia induced cardiac hypertrophy in both left ventricular (LV) and right ventricular (RV) myocytes, with LV myocytes lengthening and RV myocytes widening and lengthening. Hypoxia induced an increase (0.01±0.01% in normoxia to 0.11±0.09% in hypoxia) in the number of EdU+ RV cardiomyocytes, with no effect on LV myocytes in male C57BL/6 mice. Similar results were observed in female mice. Furthermore, in mosaic analysis with double markers mice, hypoxia induced a significant increase in RV myocyte proliferation (0.03±0.03% in normoxia to 0.32±0.15% in hypoxia of RFP+ myocytes), with no significant change in LV myocyte proliferation. RNA sequencing showed upregulation of mitotic cell cycle genes and a downregulation of Cullin genes, which promote the G1 to S phase transition in hypoxic mice. There was significant proliferation of nonmyocytes and mild cardiac fibrosis in hypoxic mice that did not disrupt cardiac function. Male and female mice exhibited similar gene expression following hypoxia. CONCLUSIONS: Systemic hypoxia induces a global hypertrophic stress response that was associated with increased RV proliferation, and while LV myocytes did not show increased proliferation, our results minimally confirm previous reports that hypoxia can induce cardiomyocyte cell cycle activity in vivo.

Time lag effects of COVID-19 policies on transportation systems: A comparative study of New York City and Seattle.

The unprecedented challenges caused by the COVID-19 pandemic demand timely action. However, due to the complex nature of policy making, a lag may exist between the time a problem is recognized and the time a policy has its impact on a system. To understand this lag and to expedite decision making, this study proposes a change point detection framework using likelihood ratio, regression structure and a Bayesian change point detection method. The objective is to quantify the time lag effect reflected in transportation systems when authorities take action in response to the COVID-19 pandemic. Using travel patterns as an indicator of policy effectiveness, the length of policy lag and magnitude of policy impacts on the road system, mass transit, and micromobility are investigated through the case studies of New York City (NYC), and Seattle-two U.S. cities significantly affected by COVID-19. The quantitative findings show that the National declaration of emergency had no policy lag while stay-at-home and reopening policies had a lead effect on mobility. The magnitude of impact largely depended on the land use and sociodemographic characteristics of the area, as well as the type of transportation system.

miR-182/183-Rasa1 axis induced macrophage polarization and redox regulation promotes repair after ischemic cardiac injury.

Few therapies have produced significant improvement in cardiac structure and function after ischemic cardiac injury (ICI). Our possible explanation is activation of local inflammatory responses negatively impact the cardiac repair process following ischemic injury. Factors that can alter immune response, including significantly altered cytokine levels in plasma and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI is a valid strategy for reducing infarct size and damage after myocardial injury. Our previous studies showed that cortical bone stem cells (CBSCs) possess reparative effects after ICI. In our current study, we have identified that the beneficial effects of CBSCs appear to be mediated by miRNA in their extracellular vesicles (CBSC-EV). Our studies showed that CBSC-EV treated animals demonstrated reduced scar size, attenuated structural remodeling, and improved cardiac function versus saline treated animals. These effects were linked to the alteration of immune response, with significantly altered cytokine levels in plasma, and polarization of macrophages and T cells towards a pro-reparative phenotype in the myocardium post-MI. Our detailed in vitro studies demonstrated that CBSC-EV are enriched in miR-182/183 that mediates the pro-reparative polarization and metabolic reprogramming in macrophages, including enhanced OXPHOS rate and reduced ROS, via Ras p21 protein activator 1 (RASA1) axis under Lipopolysaccharides (LPS) stimulation. In summary, CBSC-EV deliver unique molecular cargoes, such as enriched miR-182/183, that modulate the immune response after ICI by regulating macrophage polarization and metabolic reprogramming to enhance repair.

No-Reference Quality Assessment for Screen Content Images Using Visual Edge Model and AdaBoosting Neural Network.

In this paper, a competitive no-reference metric is proposed to assess the perceptive quality of screen content images (SCIs), which uses the human visual edge model and AdaBoosting neural network. Inspired by the existing theory that the edge information which reflects the visual quality of SCI is effectively captured by the human visual difference of the Gaussian (DOG) model, we compute two types of multi-scale edge maps via the DOG operator firstly. Specifically, two types of edge maps contain contour and edge information respectively. Then after locally normalizing edge maps, L -moments distribution estimation is utilized to fit their DOG coefficients, and the fitted L -moments parameters can be regarded as edge features. Finally, to obtain the final perceptive quality score, we use an AdaBoosting back-propagation neural network (ABPNN) to map the quality-aware features to the perceptual quality score of SCIs. The reason why the ABPNN is regarded as the appropriate approach for the visual quality assessment of SCIs is that we abandon the regression network with a shallow structure, try a regression network with a deep architecture, and achieve a good generalization ability. The proposed method delivers highly competitive performance and shows high consistency with the human visual system (HVS) on the public SCI-oriented databases.