Downregulated BMP-Smad1/5/8 signaling causes emphysema via dysfunction of alveolar type II epithelial cells.

Bone morphogenetic protein (BMP)-Smad1/5/8 signaling plays a crucial regulatory role in lung development and adult lung homeostasis. However, it remains elusive whether BMP-Smad1/5/8 signaling is involved in the pathogenesis of emphysema. In this study, we downregulated BMP-Smad1/5/8 signaling by overexpressing its antagonist Noggin in adult mouse alveolar type II epithelial cells (AT2s), resulting in an emphysematous phenotype mimicking the typical pathological features of human emphysema, including distal airspace enlargement, pulmonary inflammation, extracellular matrix remodeling, and impaired lung function. Dysregulation of BMP-Smad1/5/8 signaling in AT2s leads to inflammatory destruction dominated by macrophage infiltration, associated with reduced secretion of surfactant proteins and inhibition of AT2 proliferation and differentiation. Reactivation of BMP-Smad1/5/8 signaling by genetics or chemotherapy significantly attenuated the morphology and pathophysiology of emphysema and improved the lung function in Noggin-overexpressing lungs. We also found that BMP-Smad1/5/8 signaling was downregulated in cigarette smoke-induced emphysema, and that enhancing its activity in AT2s prevented or even reversed emphysema in the mouse model. Our data suggest that BMP-Smad1/5/8 signaling, located at the top of the signaling cascade that regulates lung homeostasis, represents a key molecular regulator of alveolar stem cell secretory and regenerative function, and could serve as a potential target for future prevention and treatment of pulmonary emphysema. © 2023 The Pathological Society of Great Britain and Ireland.

Enhanced iron(III) reduction following amendment of paddy soils with biochar and glucose modified biochar.

Although biochar application to paddy fields has been widely studied, its effects on Fe(III) reduction have not yet been investigated. Paddy soil slurry and soil microbial inoculation incubation were conducted with unmodified biochar (UMB) or glucose-modified biochar (GMB) additions at different particle sizes. The Fe(II) concentration and pH value were determined regularly, and Fe(III) reducing capacity (FeRC) was evaluated by modeling. Fe(III) reduction potential (a) was increased by 0-1.96 mg g-1 in response to UMBs addition, and a more remarkable increase in a was related to the decrease of particle size. The dissolved organic carbon of UMBs was responsible for the majority of the biochar reducing capacity. UMBs addition increased the contribution of free Fe and nitrate nitrogen to FeRC, while it decreased that of available phosphorus. Moreover, GMBs led to greater promotion of FeRC than the corresponding UMBs, with an increase in a of 2.9-16% in soil slurry and reduction rate of 13-35% in microbial inoculation incubation. The maximum Fe(III) reduction rate (V max) with GMBs addition was faster or invariable than UMBs, while the time to V max (T Vmax) was shorter or stable. The effect of GMBs on Fe(III) reduction was less sensitive as GMB particle size increased. Compared with UMBs addition, pH declined remarkably in response to GMBs. These findings suggest that GMBs can effectively stimulate Fe(III) reduction in paddy fields, while simultaneously alleviating the pH increase usually caused by pristine biochar application.