No abstract

Stem cells are fundamental units of tissue remodeling whose functions are dictated by lineage-specific transcription factors. Home to epidermal stem cells and their upward-stratifying progenies, skin relies on its secretory functions to form the outermost protective barrier, of which a transcriptional orchestrator has been elusive. KLF5 is a Krüppel-like transcription factor broadly involved in development and regeneration whose lineage specificity, if any, remains unclear. Here we report KLF5 specifically marks the epidermis, and its deletion leads to skin barrier dysfunction in vivo. Lipid envelopes and secretory lamellar bodies are defective in KLF5-deficient skin, accompanied by preferential loss of complex sphingolipids. KLF5 binds to and transcriptionally regulates genes encoding rate-limiting sphingolipid metabolism enzymes. Remarkably, skin barrier defects elicited by KLF5 ablation can be rescued by dietary interventions. Finally, we found that KLF5 is widely suppressed in human diseases with disrupted epidermal secretion, and its regulation of sphingolipid metabolism is conserved in human skin. Altogether, we established KLF5 as a disease-relevant transcription factor governing sphingolipid metabolism and barrier function in the skin, likely representing a long-sought secretory lineage-defining factor across tissue types.

To further characterize the anxiolytic activities of CJ, its action on human neuroblastoma cells were assessed. The CJ extract dose-dependently increased chloride ion (Cl -) influx, which was blocked by coadministration of the GABA A receptor competitive antagonist, bicuculline, suggesting a GABA A receptor -Cl -channel mechanism of action. Taken altogether, the present study demonstrates that the ethanol extract of CJ has anxiolytic effects, probably mediated through GABAergic neurotransmission.

Background: Several recent studies have reported that deep learning reconstruction “TrueFidelity” (TF) improves computed tomography (CT) image quality. However, no study has compared adaptive statistical repeated reconstruction (ASIR-V) using TF in pediatric cardiac CT angiography (CTA) with a low peak kilovoltage. Objective: This study aimed to determine whether ASIR-V or TF CTA image quality is superior in children with congenital heart disease (CHD). Materials and methods: Fifty children (median age, 2 months; interquartile range, 0–5 months; 28 men) with CHD who underwent CTA were enrolled between June and September 2020. Images were reconstructed using 2 ASIR-V blending factors (80% and 100% [AV-100]) and 3 TF settings (low, medium, and high [TF-H] strength levels). For the quantitative analyses, 3 objective image qualities (attenuation, noise, and signal-to-noise ratio [SNR]) were measured of the great vessels and heart chambers. The contrast-to-noise ratio (CNR) was also evaluated between the left ventricle and the dial wall. For the qualitative analyses, the degree of quantum mottle and blurring at the upper level to the first branch of the main pulmonary artery was assessed independently by 2 radiologists. Results: When the ASIR-V blending factor level and TF strength were higher, the noise was lower, and the SNR was higher. The image noise and SNR of TF-H were significantly lower and higher than those of AV-100 ( P < .01), except for noise in the right atrium and left pulmonary artery and SNR of the right ventricle. Regarding CNR, TF-H was significantly better than AV-100 ( P < .01). In addition, in the objective assessment of the degree of quantum mottle and blurring, TF-H had the best score among all examined image sets ( P < .01). Conclusion: TF-H is superior to AV-100 in terms of objective and subjective image quality. Consequently, TF-H was the best image set for cardiac CTA in children with CHD.