Laser powder bed fusion(L-PBF)of magnesium(Mg)alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects.However,one of t...Laser powder bed fusion(L-PBF)of magnesium(Mg)alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects.However,one of the key technical difficulties lies in the poor L-PBF process performance of Mg,contributed by the high susceptibility to oxidation,vaporization,thermal expansion,and powder attachment etc.This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder,and characterized the microstructure,mechanical properties,biocompatibility,biodegradation and osteogenic effect of the as-built WE43 porous scaffolds.With the customized energy input and scanning strategy,the relative density of struts reached over 99.5%,and the geometrical error between the designed and the fabricated porosity declined to below 10%.Massive secondary phases including intermetallic precipitates and oxides were observed.The compressive strength(4.37-23.49 MPa)and elastic modulus(154.40-873.02 MPa)were comparable to those of cancellous bone.Good biocompatibility was observed by in vitro cell viability and in vivo implantation.The biodegradation of as-built porous scaffolds promoted the osteogenic effect,but the structural integrity devastated after 12 h by the immersion tests in Hank’s solution and after 4 weeks by the implantation in rabbits’femur,indicating an excessively rapid degradation rate.展开更多
Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as nove...Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.展开更多
The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work...The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work, we found that high temperature oxidation improves the corrosion resistance of magnesium scaffold. And the effects of pore size on the mechanical characteristics and biodegradation of scaffolds, as well as new bone formation, were investigated using magnesium scaffolds with three different pore sizes, namely, 500, 800, and 1400 μm (P500, P800, and P1400). We discovered that the mechanical characteristics of the P500 group were much better than those of the other two groups. In vitro and in vivo investigations showed that WE43 magnesium alloy scaffolds supported the survival of mesenchymal stem cells and did not cause any local toxicity. Due to their larger specific surface area, the scaffolds in the P500 group released more magnesium ions within reasonable range and improved the osteogenic differentiation of bone mesenchymal stem cells compared with the other two scaffolds. In a rabbit femoral condyle defect model, the P500 group demonstrated unique performance in promoting new bone formation, indicating its great potential for use in bone defect regeneration therapy.展开更多
In this paper,we propose a new directional multi-resolution ridgelet network(DMRN)based on the ridgelet frame theory,which uses the ridgelet as the activation function in a hidden layer.For the multi-resolution proper...In this paper,we propose a new directional multi-resolution ridgelet network(DMRN)based on the ridgelet frame theory,which uses the ridgelet as the activation function in a hidden layer.For the multi-resolution properties of the ridgelet function in the direction besides scale and position,DMRN has great capabilities in catching essential features of direction-rich data.It proves to be able to approximate any multivariate function in a more stable and efficient way,and optimal in approximating functions with spatial inhomogeneities.Besides,using binary ridgelet frame as the mathematical foundation in its construction,DMRN is more flexible with a simple structure.The construction and the learning algorithm of DMRN are given.Its approximation capacity and approximation rate are also analyzed in detail.Possibilities of applications to regression and recognition are included to demonstrate its superiority to other methods and feasibility in practice.Both theory analysis and simulation results prove its high efficiency.展开更多
基金funded by the National Key Research and Development Program of China(2018YFE0104200)National Natural Science Foundation of China(51875310,52175274,82172065)and AO Foundation(AOTAP21-47).
文摘Laser powder bed fusion(L-PBF)of magnesium(Mg)alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects.However,one of the key technical difficulties lies in the poor L-PBF process performance of Mg,contributed by the high susceptibility to oxidation,vaporization,thermal expansion,and powder attachment etc.This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder,and characterized the microstructure,mechanical properties,biocompatibility,biodegradation and osteogenic effect of the as-built WE43 porous scaffolds.With the customized energy input and scanning strategy,the relative density of struts reached over 99.5%,and the geometrical error between the designed and the fabricated porosity declined to below 10%.Massive secondary phases including intermetallic precipitates and oxides were observed.The compressive strength(4.37-23.49 MPa)and elastic modulus(154.40-873.02 MPa)were comparable to those of cancellous bone.Good biocompatibility was observed by in vitro cell viability and in vivo implantation.The biodegradation of as-built porous scaffolds promoted the osteogenic effect,but the structural integrity devastated after 12 h by the immersion tests in Hank’s solution and after 4 weeks by the implantation in rabbits’femur,indicating an excessively rapid degradation rate.
基金supported by National Natural Science Foundation of China(Grant Nos.81620108029,81974083,and 81330074)Beijing Natural Science Foundation grant 7172113(China)
文摘Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.
文摘The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work, we found that high temperature oxidation improves the corrosion resistance of magnesium scaffold. And the effects of pore size on the mechanical characteristics and biodegradation of scaffolds, as well as new bone formation, were investigated using magnesium scaffolds with three different pore sizes, namely, 500, 800, and 1400 μm (P500, P800, and P1400). We discovered that the mechanical characteristics of the P500 group were much better than those of the other two groups. In vitro and in vivo investigations showed that WE43 magnesium alloy scaffolds supported the survival of mesenchymal stem cells and did not cause any local toxicity. Due to their larger specific surface area, the scaffolds in the P500 group released more magnesium ions within reasonable range and improved the osteogenic differentiation of bone mesenchymal stem cells compared with the other two scaffolds. In a rabbit femoral condyle defect model, the P500 group demonstrated unique performance in promoting new bone formation, indicating its great potential for use in bone defect regeneration therapy.
基金supported by the National Natural Science Foundation of China (Grant No.60601029)the National Basic Research Program of China (No.A 50105020025).
文摘In this paper,we propose a new directional multi-resolution ridgelet network(DMRN)based on the ridgelet frame theory,which uses the ridgelet as the activation function in a hidden layer.For the multi-resolution properties of the ridgelet function in the direction besides scale and position,DMRN has great capabilities in catching essential features of direction-rich data.It proves to be able to approximate any multivariate function in a more stable and efficient way,and optimal in approximating functions with spatial inhomogeneities.Besides,using binary ridgelet frame as the mathematical foundation in its construction,DMRN is more flexible with a simple structure.The construction and the learning algorithm of DMRN are given.Its approximation capacity and approximation rate are also analyzed in detail.Possibilities of applications to regression and recognition are included to demonstrate its superiority to other methods and feasibility in practice.Both theory analysis and simulation results prove its high efficiency.
