Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF.Experimental Design/Results: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-tomesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)-specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFb-R1/Smad signaling was dependent on HIF1a expression. A novel HIF1a inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1a-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1a-related EndMT was observed also in human RIPF tissues.Conclusions: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage.

The deep learning algorithm could diagnose maxillary sinusitis on Waters' view radiograph with superior AUC and comparable sensitivity and specificity to those of radiologists.

T he glymphatic system, which is a glial-dependent waste clearance pathway, is an emerging circulatory model in the brain and is characteristically devoid of authentic lymphatic vessels (1). The key component of the glymphatic system is the perivascular space. At the periarterial space, cerebrospinal fluid (CSF) enters the interstitial space of the brain through the aquaporin-4 water channels at the end feet of astrocytes (2). CSF mixed with interstitial fluid then exits the brain via the perivenous space along with metabolic waste products. The waste clearance pathway downstream to the glymphatic system comprises meningeal lymphatic vessels, an authentic lymphatic network found at the dura, cranial nerves, and large vessels at the skull exits (3).Accumulating evidence suggests the clearance of metabolites, such as t protein, amyloid-b, and lactate from the brain through the glymphatic system (2,4,5). Impairment of the glymphatic system is an important pathophysiology of various abnormal conditions, including Background: Evaluation of the glymphatic system with intrathecal contrast material injection has limited clinical use. Purpose:To investigate the feasibility of using serial intravenous contrast-enhanced T1 mapping in the quantitative evaluation of putative dynamic glymphatic activity in various brain regions and to demonstrate the effect of sleep on glymphatic activity in humans. Materials and Methods:In this prospective study from May 2019 to February 2020, 25 healthy participants (mean age, 25 years 6 2 [standard deviation]; 15 men) underwent two cycles of MRI (day and night cycles). For each cycle, T1 maps were acquired at baseline and 0.5, 1, 1.5, 2, and 12 hours after intravenous contrast material injection. For the night cycle, participants had a normal night of sleep between 2 and 12 hours. The time (t min ) to reach the minimum T1 value (T1 min ), the absolute difference between baseline T1 and T1 min (peak DT1), and the slope between two measurements at 2 and 12 hours (slope [2h-12h] ) were determined from T1 value-time curves in cerebral gray matter (GM), cerebral white matter (WM), cerebellar GM, cerebellar WM, and putamen. Mixed-model analysis of variance (ANOVA), Friedman test, and repeated-measures ANOVA were used to assess the effect of sleep on slope (2h-12h) and to compare t min and peak DT1 among different regions. Results:The slope (2h-12h) increased from the day to night cycles in cerebral GM, cerebellar GM, and putamen (geometric mean ratio [night/day]