The consolidation recycled AZ80 billets were successfully fabricated through the cold press and hot press sintering of the AZ80 metal chips.The consolidation recycled billets sintered at 350℃present the comparable co...The consolidation recycled AZ80 billets were successfully fabricated through the cold press and hot press sintering of the AZ80 metal chips.The consolidation recycled billets sintered at 350℃present the comparable compressive properties and inferior tensile properties compared with the initial cast billets.The defects in the consolidation recycled billet were inclined to propagate along the bond interface between the metal chips during tension,which resulted in the inferior tensile properties of the recycled billets.The recycled billets were then subjected to the integrated extrusion-shear(ES) process.The homogeneous finer dynamic recrystallization grains with an average grain size of 6 μm can be obtained in the shear deformation zone and extrusion sizing zone through integrated ES process at 300℃with an extrusion velocity of 0.6 mm/s.The recycled billets after integrated ES forming process present rival tensile properties compared with the initial cast billets after integrated ES forming with the same extrusion parameters,which can be ascribed to that the integrated ES forming can nearly eliminate the defects through the severe compressive and shear strain.The solid-state recycling process through hot press sintering and subsequent integrated ES process can fabricate the consolidation recycled AZ80 rod,which demonstrates the comparable tensile properties with the cast-extrusion rod.展开更多
Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contrib...Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA,the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis;however, it conferred high cardiovascular risk in clinical trials. Furthermore,romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.展开更多
基金financially supported by the National Natural Science Foundation of China (No. 51875127).
文摘The consolidation recycled AZ80 billets were successfully fabricated through the cold press and hot press sintering of the AZ80 metal chips.The consolidation recycled billets sintered at 350℃present the comparable compressive properties and inferior tensile properties compared with the initial cast billets.The defects in the consolidation recycled billet were inclined to propagate along the bond interface between the metal chips during tension,which resulted in the inferior tensile properties of the recycled billets.The recycled billets were then subjected to the integrated extrusion-shear(ES) process.The homogeneous finer dynamic recrystallization grains with an average grain size of 6 μm can be obtained in the shear deformation zone and extrusion sizing zone through integrated ES process at 300℃with an extrusion velocity of 0.6 mm/s.The recycled billets after integrated ES forming process present rival tensile properties compared with the initial cast billets after integrated ES forming with the same extrusion parameters,which can be ascribed to that the integrated ES forming can nearly eliminate the defects through the severe compressive and shear strain.The solid-state recycling process through hot press sintering and subsequent integrated ES process can fabricate the consolidation recycled AZ80 rod,which demonstrates the comparable tensile properties with the cast-extrusion rod.
基金supported by the National Key R&D Program of China (2018YFA0800802)Hong Kong General Research Fund (HKBU 12114416,HKBU 12101117,HKBU 12100918,HKBU 12101018,HKBU 12103519,HKBU 14100218,CUHK 14108816,CUHK 14100218,CUHK 14103420,China)+3 种基金Direct Grant of The Chinese University of Hong Kong (2018.094,China)Interdisciplinary Research Clusters Matching Scheme of Hong Kong Baptist University (RC-IRCs/17-18/02,China)Guangdong Basic and Applied Basic Research Foundation (2019B1515120089,China)Science and Technology Innovation Commission of Shenzhen Municipality Funds (JCYJ20160229210357960,China)。
文摘Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA,the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis;however, it conferred high cardiovascular risk in clinical trials. Furthermore,romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.
