Nucleoporin93 limits Yap activity to prevent endothelial cell senescence.

As the innermost lining of the vasculature, endothelial cells (ECs) are constantly subjected to systemic inflammation and particularly vulnerable to aging. Endothelial health is hence vital to prevent age-related vascular disease. Healthy ECs rely on the proper localization of transcription factors via nuclear pore complexes (NPCs) to govern cellular behavior. Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age-associated EC dysfunction. We herein identify nucleoporin93 (Nup93), a crucial structural NPC protein, as an indispensable player in vascular protection. Endothelial Nup93 protein levels are significantly reduced in the vasculature of aged mice, paralleling observations of Nup93 loss when using in vitro models of EC senescence. The loss of Nup93 in human ECs induces cell senescence and promotes the expression of inflammatory adhesion molecules, where restoring Nup93 protein in senescent ECs reverses features of endothelial aging. Mechanistically, we find that both senescence and loss of Nup93 impair endothelial NPC transport, leading to nuclear accumulation of Yap and downstream inflammation. Pharmacological studies indicate Yap hyperactivation as the primary consequence of senescence and Nup93 loss in ECs. Collectively, our findings indicate that the maintenance of endothelial Nup93 is a key determinant of EC health, where aging targets endothelial Nup93 levels to impair NPC function as a novel mechanism of EC senescence and vascular aging.

Nucleoporin93 (Nup93) Limits Yap Activity to Prevent Endothelial Cell Senescence.

Endothelial cells (ECs) form the innermost lining of the vasculature and serve a pivotal role in preventing age-related vascular disease. Endothelial health relies on the proper nucleocytoplasmic shuttling of transcription factors via nuclear pore complexes (NPCs). Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age-related EC dysfunction. We herein identify nucleoporin93 (Nup93), a crucial structural NPC protein, as an indispensable player for vascular protection. Endothelial Nup93 protein levels are significantly reduced in the vasculature of aged mice, paralleling observations of Nup93 loss when using in vitro models of endothelial aging. Mechanistically, we find that loss of Nup93 impairs NPC transport, leading to the nuclear accumulation of Yap and downstream inflammation. Collectively, our findings indicate maintenance of endothelial Nup93 as a key determinant of EC health, where aging targets endothelial Nup93 levels to impair NPC function as a novel mechanism for EC senescence and vascular aging.

Relationship Between Grocery Shopping Frequency and Home- and Individual-Level Diet Quality Among Low-Income Racial or Ethnic Minority Households With Preschool-Aged Children.

BACKGROUND: The home food environment can shape the diets of young children. However, little is known about modifiable factors that influence home food availability and dietary intake. OBJECTIVE: The purpose of this study was to examine the relationship between grocery shopping frequency with home- and individual-level diet quality. DESIGN: This was a secondary, cross-sectional analyses of data from the Study on Children's Home Food Availability Using TechNology. Data were collected in the homes of participants from November 2014 through March 2016. PARTICIPANTS/SETTINGS: A purposive sample of 97 low-income African American and Hispanic or Latinx parent-child dyads residing in Chicago, IL, enrolled in the study. MAIN OUTCOME MEASURES: The main outcomes were home- and individual-level diet quality. Healthy Eating Index-2010 (HEI-2010) scores were calculated from home food inventory data collected in participants' homes to assess home-level diet quality. To assess individual-level diet quality, HEI-2010 scores were based on multiple 24-hour diet recalls from parent-child dyads. STATISTICAL ANALYSES: Grocery shopping frequency was examined in relation to diet quality at the home and individual levels. Grocery shopping frequency was defined as the number of times households shopped on a monthly basis (ie, once a month, twice a month, 3 times a month, or 4 times or more a month). Multivariable linear regression analysis, controlling for covariates, tested the relationships between grocery shopping frequency and HEI-2010 total and component scores at the home and individual levels. RESULTS: Grocery shopping frequency was positively associated with home-level HEI-2010 scores for total diet, whole grains, and empty calories (higher scores reflect better diet quality) and with individual-level HEI-2010 scores for total and whole fruit (parents only), vegetables (children only), and sodium (children only). CONCLUSIONS: Grocery shopping frequency was associated with multiple dimensions of diet quality at the home and individual levels. These results offer a potential strategy to intervene on home food availability and individual dietary intake.

Pilon fractures.

The nature of the pilon fracture has caused evolution of treatment methods and its historically high rate of complication and poor outcome continue to direct choice of treatment. Attention to the delicate soft tissue envelope surrounding the ankle and recognition of the severity of the initial injury is crucial to ensure a satisfactory outcome and to minimize complications. Understanding the importance of staging surgical interventions will help to improve outcomes, but even optimal treatment may result in less than satisfactory results.