Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion.

Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.

Application of breast ultrasound in a mammography-based Chinese breast screening study.

We evaluated the clinical significance of the combined use of mammography + ultrasound as a new breast screening strategy. The inclusion criteria were: (1) females aged >40yrs; (2) breast cancer diagnosis by the breast image screening personnel at FUSCC; (3) screening by both ultrasound and mammography; (4) mammographic/sonographic images analyzed independently by different radiologists; and (5) follow-up for at least 1 year. Fifty-four women were enrolled. The analysis included diagnostic sensitivity of mammography, ultrasound, and mammography + ultrasound. The sensitivities of mammography and mammography + ultrasound were compared overall as well as among different age groups/breast densities. The screening sensitivity of mammography, ultrasound, and mammography + ultrasound was 79.6, 57.4, and 92.6 %, respectively. The difference between mammography and mammography + ultrasound was significant (P < 0.05). The benefit of including ultrasound with mammography as a new breast image screening strategy was found statistically significant in patients with dense breast on mammogram while it was non-significant in younger (<50 years) women. We, therefore, concluded that mammography + ultrasound increased the diagnostic sensitivity of breast screening; hence it was more desirable for women with dense breast on mammography.