Histone Modification of Osteogenesis Related Genes Triggered by Substrate Topography Promotes Human Mesenchymal Stem Cell Differentiation

The clinical success of orthopedic implants is closely related to their integration in the bone tissue promoted by rough device surfaces. The biological response of precursor cells to their artificial microenvironments plays a critical role in this process. In this study, we elucidated the relation between cell instructivity and surface microstructure of polycarbonate (PC)-based model substrates. The rough surface structure (hPC) with an average peak spacing (Sm) similar to the trabecular spacing of trabecular bone improved osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), as compared to the smooth surface (sPC) and the surface with a moderate Sm value (mPC). The hPC substrate promoted the cell adhesion and assembling of F-actin and enhanced cell contractile force by upregulating phosphorylated myosin light chain (pMLC) expression. The increased cell contractile force led to YAP nuclear translocation and the elongation of cell nuclei, presenting higher levels of active form of Lamin A/C. The nuclear deformation alternated the histone modification profile, particularly the decrease of H3K27me3 and increase of H3K9ac on the promoter region of osteogenesis related genes (ALPL, RUNX2, and OCN). Mechanism study using inhibitors and siRNAs elucidated the role of YAP, integrin, F-actin, myosin, and nuclear membrane proteins in such a regulatory process of surface topography on stem cell fate. These mechanistical insights on the epigenetic level give a new perspective in understanding of the interaction of substrate and stem cells as well as provide valuable criteria for designing bioinstructive orthopedic implants

Multiperspective Decoupling Analyses between Global Embodied Carbon Chains and Global Value Chains

Decoupling global economic growth from carbon emissions is essential for mitigating global climate change while maintaining continuous economic growth. Traditional production-side decoupling analysis alone is insufficient to capture the decoupling status between carbon emissions and the value added throughout global supply chains. This study investigates the decoupling status between value added and greenhouse gas (GHG) emissions during 1995–2019 from consumption and income perspectives. We find that the decoupling statuses of 17 regions (especially Russia, Australia, and Malta) show significant differences across multiple perspectives. For example, Malta’s direct GHG emissions decreased with its GDP growth from a production perspective (i.e., achieved strong decoupling). However, its consumption-based GHG emissions increased with the growth of consumption-based value added (i.e., expansive negative decoupling). Moreover, most international pairs have not yet achieved strong decoupling from consumption and income perspectives. International multilateral cooperation is crucial for decoupling global GHG emissions from economic growth across global supply chains. This study provides insights into the decoupling between embodied GHG emissions and value added from consumption and income perspectives. The findings of this study can complement existing policies on global GHG emission mitigation and sustainable development

Multiperspective Decoupling Analyses between Global Embodied Carbon Chains and Global Value Chains

Decoupling global economic growth from carbon emissions is essential for mitigating global climate change while maintaining continuous economic growth. Traditional production-side decoupling analysis alone is insufficient to capture the decoupling status between carbon emissions and the value added throughout global supply chains. This study investigates the decoupling status between value added and greenhouse gas (GHG) emissions during 1995–2019 from consumption and income perspectives. We find that the decoupling statuses of 17 regions (especially Russia, Australia, and Malta) show significant differences across multiple perspectives. For example, Malta’s direct GHG emissions decreased with its GDP growth from a production perspective (i.e., achieved strong decoupling). However, its consumption-based GHG emissions increased with the growth of consumption-based value added (i.e., expansive negative decoupling). Moreover, most international pairs have not yet achieved strong decoupling from consumption and income perspectives. International multilateral cooperation is crucial for decoupling global GHG emissions from economic growth across global supply chains. This study provides insights into the decoupling between embodied GHG emissions and value added from consumption and income perspectives. The findings of this study can complement existing policies on global GHG emission mitigation and sustainable development