Tuning mucoadhesion and mucopenetration in self-assembled poly(lactic acid)-block-poly(oligoethylene glycol methacrylate) block copolymer nanoparticles by controlling side-chain lengths.

The capacity to tune the degree of mucoadhesion and mucopenetration of nanoparticles is essential to improving drug bioavailability, transport, and efficacy at mucosal interfaces. Herein, self-assembled nanoparticles (NPs) fabricated from amphiphilic block copolymers of poly(lactic acid) (PLA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA) with various side chain lengths (PLA-POEGMA) are reported to facilitate tunable mucosal interactions. PLA-POEGMA nanoparticles with long PEG side chain lengths ( = 20, or 40) demonstrated mucoadhesive properties based on rheological synergism, calorimetric tracking of mucin-nanoparticle interactions, and the formation of larger NP-mucin hybrid structures; in contrast, NPs fabricated from block copolymers with shorter PEG side chains ( = 2/8-9 or = 8,9) showed poor mucoadhesion but penetrated through the mucin layer with significantly higher permeation rates (>80%).

Terminal complement inhibition and control of hemolysis in patients with paroxysmal nocturnal hemoglobinuria who switched from high-dose eculizumab to ravulizumab: a phase IV, single-arm clinical trial.

Not available.

Decoding the transcriptomic signatures of psychological trauma in human cortex and amygdala.

Psychological trauma has profound effects on brain function and precipitates psychiatric disorders in vulnerable individuals, however, the molecular mechanisms linking trauma with psychiatric risk remain incompletely understood. Using RNA-seq data postmortem brain tissue of a cohort of 304 donors (N=136 with trauma exposure), we investigated transcriptional signatures of trauma exposures in two cortical regions (dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex) and two amygdala regions (medial amygdala and basolateral amygdala) associated with stress processing and regulation. We focused on dissecting heterogeneity of traumatic experiences in these transcriptional signatures by investigating exposure to several trauma types (childhood, adulthood, complex, single acute, combat, and interpersonal traumas) and interactions with sex.

Gluconeogenesis and glycogenolysis required in metastatic breast cancer cells.

Introduction: Metabolic adaptability, including glucose metabolism, enables cells to survive multiple stressful environments. Glycogen may serve as a critical storage depot to provide a source of glucose during times of metabolic demand during the metastatic cascade; therefore, understanding glycogen metabolism is critical. Our goal was to determine mechanisms driving glycogen accumulation and its role in metastatic (MCF10CA1a) compared to nonmetastatic (MCF10A-) human breast cancer cells.

Features Associated With the Presence of Specific Bacterial Strains in Pediatric Tracheostomy.

Background: Tracheostomy bypasses physical barriers that decrease microbial access to the lower airway, which can lead to changes to the lung microbiota. Patients often become chronically colonized with potential pathogens. This study described the incidence and prevalence of specific organisms in a 5-y cohort of children with tracheostomy.