In the trachea and bronchi of the mouse, airway smooth muscle (SM) and cartilage are localized to complementary domains surrounding the airway epithelium. Proper juxtaposition of these tissues ensures a balance of elasticity and rigidity that is critical for effective air passage. It is unknown how this tissue complementation is established during development. Here we dissect the developmental relationship between these tissues by genetically disrupting SM formation (through Srf inactivation) or cartilage formation (through Sox9 inactivation) and assessing the impact on the remaining lineage. We found that, in the trachea and main bronchi, loss of SM or cartilage resulted in an increase in cell number of the remaining lineage, namely the cartilage or SM, respectively. However, only in the main bronchi, but not in the trachea, did the loss of SM or cartilage lead to a circumferential expansion of the remaining cartilage or SM domain, respectively. In addition to SM defects, cartilage-deficient tracheas displayed epithelial phenotypes, including decreased basal cell number, precocious club cell differentiation, and increased secretoglobin expression. These findings together delineate the mechanisms through which a cell-autonomous disruption of one structural tissue can have widespread consequences on upper airway function.airway development | tracheomalacia T he trachea and the main bronchi, here collectively termed the upper airways, are essential conduits of air before and after gas exchange (1, 2). Normal upper airways offer the correct balance of elasticity and rigidity, which together maintain air pressure and prevent airway collapse. The elasticity is primarily provided by smooth muscle (SM) and the rigidity by cartilage. The balance is achieved via a precise juxtaposition of these tissues that together encircle and support the endoderm-derived upper airway epithelium. Clinical evidence suggests that malformation of the SM or cartilage leads to respiratory deficiencies. For example, patients with tracheomalacia and bronchomalacia exhibit airway collapse upon exhalation as a result of softened and disorganized cartilage (3). This collapse causes breathing difficulties that contribute to sleep apnea, respiratory infections, and possibly sudden infant death (4). Despite the importance of a proper SM and cartilage balance, how it is achieved during development is not understood.In mouse upper airways, SM is localized to the dorsal side of the trachea and the medial (inner) sides of the main bronchi. The lower conducting airways lack cartilage and instead SM surrounds the circumference of the epithelial tube. Data suggest that airway SM develops from fibroblast growth factor 10 (Fgf10)-expressing cells found in the distal mesenchyme (5). As the epithelial buds elongate, the Fgf10-expressing cells are thought to translocate proximally along the airway and begin to express SM-specific genes, including SM α-actin-2 (Acta2, also known as SM actin), one of the earliest markers of SM. Additionally, a recent study has u...

Highlights d Inactivating Myocd prevented airway smooth muscle differentiation and peristalsis d Preventing airway smooth muscle differentiation did not alter epithelial branching d Preventing airway smooth muscle differentiation disrupted tracheal architecture d Preventing airway smooth muscle differentiation led to reduced airway diameter

In this study, an ultrasonic cavitation based dispersion technique was used to fabricate Al-7Si-0.3Mg alloyed with Cu and reinforced with 1 wt pct Al 2 O 3 nanoparticles, in order to investigate their influence on the mechanical properties and microstructures of Al-7Si-0.3Mg alloy. The combined addition of 0.5 pct Cu with 1 pct Al 2 O 3 nanoparticles increased the yield strength, tensile strength, and ductility of the as-cast Al-7Si-0.3Mg alloy, mostly due to grain refinement and modification of the eutectic Si and h-CuAl 2 phases. Moreover, Al-7Si-0.3Mg-0.5Cu-1 pct Al 2 O 3 nanocomposites after T6 heat treatment showed a significant enhancement of ductility (increased by 512 pct) and tensile strength (by 22 pct). The significant enhancement of properties is attributed to the suppression of pore formation and modification of eutectic Si phases due to the addition of Al 2 O 3 nanoparticles. However, the yield strength of the T6 heat-treated nanocomposites was limited in enhancement due to a reaction between Mg and Al 2 O 3 nanoparticles.

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