Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues.

Synthetic Notch (SynNotch) receptors function like natural Notch proteins and can be used to install customized sense-and-respond capabilities into mammalian cells. Here, we introduce an adaptor-based strategy for regulating SynNotch activity via fluorescein isomers and analogs. Using an optimized fluorescein-binding SynNotch receptor, we describe ways to chemically control SynNotch signaling, including an approach based on a bio-orthogonal chemical ligation and a spatially controllable strategy via the photo-patterned uncaging of an o-nitrobenzyl-caged fluorescein conjugate.

Gestational exposure to PM, NO, and sex steroid hormones: Identifying critical windows of exposure in the Rochester UPSIDE Cohort.

Background: Sex steroid hormones are critical for maintaining pregnancy and optimal fetal development. Air pollutants are potential endocrine disruptors that may disturb sex steroidogenesis during pregnancy, potentially leading to adverse health outcomes.

Methods: In the Environmental influences on Child Health Outcomes Understanding Pregnancy Signals and Infant Development pregnancy cohort (Rochester, NY), sex steroid concentrations were collected at study visits in early-, mid-, and late-pregnancy in 299 participants.

Automated proximal coronary artery calcium identification using artificial intelligence: advancing cardiovascular risk assessment.

Aims: Proximal coronary artery calcium (CAC) may improve prediction of major adverse cardiac events (MACE) beyond the CAC score, particularly in patients with low CAC burden. We investigated whether the proximal CAC can be detected on gated cardiac computer tomography (CT) and whether it provides prognostic significance with artificial intelligence (AI).

Methods And Results: A total of 2016 asymptomatic adults with baseline CAC CT scans from a single site were followed up for MACE for 14 years.

Keratinocyte-derived extracellular vesicles in painful diabetic neuropathy.

Painful diabetic neuropathy (PDN) is a challenging complication of diabetes with patients experiencing a painful and burning sensation in their extremities. Existing treatments provide limited relief without addressing the underlying mechanisms of the disease. PDN involves the gradual degeneration of nerve fibers in the skin.