Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutic...Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.展开更多
In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed metho...In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.展开更多
目的为评价CEREC椅旁CAD/CAM系统制作的IPS e.max CAD玻璃陶瓷高嵌体应用于根管治疗后牙缺损病例的临床效果。方法选择42例根管治疗后牙,应用高嵌体的牙体预备方式,采用CEREC椅旁CAD/CAM修复系统和IPS e.max CAD玻璃陶瓷,即刻完成修复...目的为评价CEREC椅旁CAD/CAM系统制作的IPS e.max CAD玻璃陶瓷高嵌体应用于根管治疗后牙缺损病例的临床效果。方法选择42例根管治疗后牙,应用高嵌体的牙体预备方式,采用CEREC椅旁CAD/CAM修复系统和IPS e.max CAD玻璃陶瓷,即刻完成修复体并粘接;修复1年后复查,参照改良修正后的美国公众健康服务标准(US Public Health Service Criteria,USPHS),在修复体边缘染色、边缘继发龋、修复体边缘适合性、修复体崩瓷折裂或脱落、修复体颜色、牙龈健康状况、修复体邻接关系、患者满意度8个方面进行评价。结果修复体边缘染色C级病例1例,成功率97.6%;边缘继发龋C级病例1例,成功率97.6%;修复体邻接关系欠佳C级病例1例,成功率97.6%;在边缘适合性、修复体崩瓷折裂或脱落、修复体颜色、牙龈健康状况、患者满意方面表现优秀,成功率均为100%。结论椅旁CAD/CAM系统制作的IPS e.maxCAD高嵌体修复体在短期内可取得良好的修复效果。展开更多
基金funded by grants from the Novo Nordisk Foundation (NNF18OC0052699) (M.S.H.) and NNF18OC0055047 (M.F.)the Region of Southern Denmark (ref: 18/17553 (M.S.H.))+3 种基金Odense University Hospital (ref: A3147) (M.F.)a faculty fellowship from the University of Southern Denmark (K.M.), the Lundbeck Foundation (ref: R335-2019-2195) (K.M.and A.R.)an Academy of Medical Sciences Springboard Award supported by the British Heart Foundation, Diabetes UK, the Global Challenges Research Fund, the Government Department of Business, Energy and Industrial Strategy and the Wellcome Trust (ref: SBF004 | 1034, C.M.G)a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 224155/Z/21/Z to C.M.G.).
文摘Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.
基金supported by the National Science Fund for Distinguished Young Scholars (62225303)the Fundamental Research Funds for the Central Universities (buctrc202201)+1 种基金China Scholarship Council,and High Performance Computing PlatformCollege of Information Science and Technology,Beijing University of Chemical Technology。
文摘In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.
文摘目的为评价CEREC椅旁CAD/CAM系统制作的IPS e.max CAD玻璃陶瓷高嵌体应用于根管治疗后牙缺损病例的临床效果。方法选择42例根管治疗后牙,应用高嵌体的牙体预备方式,采用CEREC椅旁CAD/CAM修复系统和IPS e.max CAD玻璃陶瓷,即刻完成修复体并粘接;修复1年后复查,参照改良修正后的美国公众健康服务标准(US Public Health Service Criteria,USPHS),在修复体边缘染色、边缘继发龋、修复体边缘适合性、修复体崩瓷折裂或脱落、修复体颜色、牙龈健康状况、修复体邻接关系、患者满意度8个方面进行评价。结果修复体边缘染色C级病例1例,成功率97.6%;边缘继发龋C级病例1例,成功率97.6%;修复体邻接关系欠佳C级病例1例,成功率97.6%;在边缘适合性、修复体崩瓷折裂或脱落、修复体颜色、牙龈健康状况、患者满意方面表现优秀,成功率均为100%。结论椅旁CAD/CAM系统制作的IPS e.maxCAD高嵌体修复体在短期内可取得良好的修复效果。
