Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone res...Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone resorption. Here, we identified Calca,encoding the sepsis biomarker procalcitonin(ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.展开更多
Monolithic integration of quantum dot(QD)gain materials onto Si photonic platforms via direct epitaxial growth is a promising solution for on-chip light sources.Recent developments have demonstrated superior device re...Monolithic integration of quantum dot(QD)gain materials onto Si photonic platforms via direct epitaxial growth is a promising solution for on-chip light sources.Recent developments have demonstrated superior device reliability in blanket hetero-epitaxy ofⅡ-Ⅴdevices on Si at elevated temperatures.Yet,thick,defect management epi designs prevent vertical light coupling from the gain region to the Si-on-lnsulator waveguides.Here,we demonstrate the frst electrically pumped QD lasers grown by molecular beam epitaxy on a 300 mm patterned(001)Si wafer with a buttcoupled configuration.Unique growth and fabrication challenges imposed by the template architecture have been resolved,contributing to continuous wave lasing to 60℃and a maximum double-side output power of 126.6 mW at 20℃with a double-side wall-plug efficiency of 8.6%.The potential for robust on-chip laser operation and effcient lowloss light coupling to Si photonic circuits makes this heteroepitaxial integration platform on Si promising for scalable and low-cost mass production.展开更多
基金funded by grants from the Else-Kr?ner-Fresenius-Stiftung (EKFS 2017_A22)the German Research Foundation (DFG KE 2179/4-1)+3 种基金the Berlin Institute of Health to JKfrom the Hertie-Stiftung (Hertie Academy of Clinical Neuroscience)the German Research Foundation (DFGgrant numbers: DFG FOR 2879 [project LU 1924/1-]) to PL.
文摘Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone resorption. Here, we identified Calca,encoding the sepsis biomarker procalcitonin(ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.
基金We thank W.Jin,Z.Zhang,J.C.Norman,M.Dumont,MJ.Kennedy,and C.Xiang for useful discussions and help with the fabrication and testing.This material is based on research sponsored by Defense Advanced Research Projects Agency(No.HR0011-20-C-0142)Air Force Research Laboratory under AIM Photonics(agreement number FA8650-21-2-1000).
文摘Monolithic integration of quantum dot(QD)gain materials onto Si photonic platforms via direct epitaxial growth is a promising solution for on-chip light sources.Recent developments have demonstrated superior device reliability in blanket hetero-epitaxy ofⅡ-Ⅴdevices on Si at elevated temperatures.Yet,thick,defect management epi designs prevent vertical light coupling from the gain region to the Si-on-lnsulator waveguides.Here,we demonstrate the frst electrically pumped QD lasers grown by molecular beam epitaxy on a 300 mm patterned(001)Si wafer with a buttcoupled configuration.Unique growth and fabrication challenges imposed by the template architecture have been resolved,contributing to continuous wave lasing to 60℃and a maximum double-side output power of 126.6 mW at 20℃with a double-side wall-plug efficiency of 8.6%.The potential for robust on-chip laser operation and effcient lowloss light coupling to Si photonic circuits makes this heteroepitaxial integration platform on Si promising for scalable and low-cost mass production.
