PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD ...PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD domains are crucial for the Pi transport,but the role of PiT2-loop7 remains unclear.In PFBC patients,mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion.To date,six missense mutations have been identified in PiT2-loop7;however,the mechanisms by which these mutations cause PFBC are poorly understood.Here,we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2.Furthermore,we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase(AMPK)-or protein kinase B(AKT)-mediated PiT2 phosphorylation.In contrast,the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities.These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2.This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.展开更多
The electrochemical performance of 317L stainless steel used in medicineunder different conditions of passivation (different contents of HNO_3 solution, differentpassivation time and different passivation temperatures...The electrochemical performance of 317L stainless steel used in medicineunder different conditions of passivation (different contents of HNO_3 solution, differentpassivation time and different passivation temperatures) was studied. The results show that thepitting potential of 317L stainless steel used in medicine can reach about 1.0 V (SCE) whenelectrochemically tested in 0.9% NaCl solution after the steel was passivated in 30% HNO_3 solutionat 35℃ for 6 h, which indicates that the passivation film has a relatively strong resistance tocorrosion. The results also show that the corrosion resistance of the passivation film on thesurface of 317SS can be increased after suitable amount of K_2Cr_2O_7 is added into HNO_3passivation solution.展开更多
基金supported by the National Natural Science Foundation of China(31871262)a Shanghai Municipal Science and Technology Major Project(2018SHZDZX05).
文摘PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD domains are crucial for the Pi transport,but the role of PiT2-loop7 remains unclear.In PFBC patients,mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion.To date,six missense mutations have been identified in PiT2-loop7;however,the mechanisms by which these mutations cause PFBC are poorly understood.Here,we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2.Furthermore,we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase(AMPK)-or protein kinase B(AKT)-mediated PiT2 phosphorylation.In contrast,the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities.These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2.This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
文摘The electrochemical performance of 317L stainless steel used in medicineunder different conditions of passivation (different contents of HNO_3 solution, differentpassivation time and different passivation temperatures) was studied. The results show that thepitting potential of 317L stainless steel used in medicine can reach about 1.0 V (SCE) whenelectrochemically tested in 0.9% NaCl solution after the steel was passivated in 30% HNO_3 solutionat 35℃ for 6 h, which indicates that the passivation film has a relatively strong resistance tocorrosion. The results also show that the corrosion resistance of the passivation film on thesurface of 317SS can be increased after suitable amount of K_2Cr_2O_7 is added into HNO_3passivation solution.
基金Project(ZR2021QE136)supported by the Natural Science Foundation of Shandong Province,ChinaProject(2020B010186002)supported by the Key Research and Development Program of Guangdong Province,China。
