Growing urban populations and deteriorating infrastructure are driving unprecedented demands for concrete, a material for which there is no alternative that can meet its functional capacity. The production of concrete, more particularly the hydraulic cement that glues the material together, is one of the worlds largest sources of greenhouse gas (GHG) emissions. While this is a well-studied source of emissions, the consequences of efficient structural design decisions on mitigating these emissions are not yet well known. Here, we show that a combination of manufacturing and engineering decisions have the potential to reduce over 76% of the GHG emissions from cement and concrete production, equivalent to 3.6 Gt CO2-eq lower emissions in 2100. The studied methods similarly result in more efficient utilization of resources by lowering cement demand by up to 65%, leading to an expected reduction in all other environmental burdens. These findings show that the flexibility within current concrete design approaches can contribute to climate mitigation without requiring heavy capital investment in alternative manufacturing methods or alternative materials.

Sotatercept is an activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein that improves cardiopulmonary function in patients with pulmonary arterial hypertension (PAH) by selectively trapping activins and growth differentiation factors. However, the cellular and molecular mechanisms of ActRIIA-Fc action are incompletely understood. Here, we determined through genome-wide expression profiling that inflammatory and immune responses are prominently upregulated in the lungs of a Sugen-hypoxia rat model of severe angio-obliterative PAH, concordant with profiles observed in PAH patients. Therapeutic treatment with ActRIIA-Fc-but not with a vasodilator-strikingly reversed proinflammatory and proliferative gene expression profiles and normalized macrophage infiltration in diseased rodent lungs. Furthermore, ActRIIA-Fc normalized pulmonary macrophage infiltration and corrected cardiopulmonary structure and function in Bmpr2 haploinsufficient mice subjected to hypoxia, a model of heritable PAH. Three high-affinity ligands of ActRIIA-Fc each induced macrophage activation in vitro, and their combined immunoneutralization in PAH rats produced cardiopulmonary benefits comparable to those elicited by ActRIIA-Fc. Our results in complementary experimental and genetic models of PAH reveal therapeutic anti-inflammatory activities of ActRIIA-Fc that, together with its known anti-proliferative effects on vascular cell types, could underlie clinical activity of sotatercept as either monotherapy or add-on to current PAH therapies.