Mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes.A nuclear gene HPDL(4-hydroxyphenylpyruvate dioxygenase-like),which encodes an intermembrane mitochondrial protein,has been recen...Mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes.A nuclear gene HPDL(4-hydroxyphenylpyruvate dioxygenase-like),which encodes an intermembrane mitochondrial protein,has been recently implicated in causing a neurodegenerative disease characterized by pediatric-onset spastic movement phenotypes.Here,we report six Chinese patients with bi-allelic HPDL pathogenic variants from four unrelated families showing neuropathic symptoms of variable severity,including developmental delay/intellectual disability,spasm,and hypertonia.Seven different pathogenic variants are identified,of which five are novel.Both fibroblasts and immortalized lymphocytes derived from patients show impaired mitochondrial respiratory function,which is also observed in HPDL-knockdown(KD)He La cells.In these He La cells,overexpression of a wild-type HPDL gene can rescue the respiratory phenotype of oxygen consumption rate.In addition,a decreased activity of the oxidative phosphorylation(OXPHOS)complex II is observed in patient-derived lymphocytes and HPDL-KD He La cells,further supporting an essential role of HPDL in the mitochondrial respiratory chain.Collectively,our data expand the clinical and mutational spectra of this mitochondrial neuropathy and further delineate the possible disease mechanism involving the impairment of the OXPHOS complex II activity due to the bi-allelic inactivations of HPDL.展开更多
In order to reduce the cost of the austenitic stainless steels(ASSs),the expensive austenite former(nickel) is often substituted by manganese.However,manganese is generally seen to have a detrimental effect on the cor...In order to reduce the cost of the austenitic stainless steels(ASSs),the expensive austenite former(nickel) is often substituted by manganese.However,manganese is generally seen to have a detrimental effect on the corrosion resistance.In the present study,the feasibility of laser surface modification of a lean-alloyed ASS(FeCrMn) for enhancing pitting corrosion resistance was investigated.Laser surface modification of FeCrMn was successfully achieved by a 2.3 kW high power diode laser(HPDL).Cyclic polarization tests for FeCrMn after laser surface modification in 3.5% NaCl solution at 25 ℃ were performed by using a potentiostat.The pitting resistance of the laser-modified specimens was found to be significantly improved as reflected by the noble shift in pitting potential.This could be attributed to redistribution of manganese sulphide leading to a more homogenous and refined microstructure.Pitting corrosion resistance of the laser-treated FeCrMn followed by subsequent citric acid passivation was found to be further improved as reflected by the noble shift in pitting potential to 0.18 V.展开更多
基金funded by the Precision Medical Research of National Key Research and Development Program(2018YFC1002200,2019YFC1005100 to Y.Yu,2018YFC1002400 to Y.Sun,and 2018YFC1002501 to Y.Shen)National Natural Science Foundation of China(81873633 and 82071276 to Y.Shen,81830071 to J.Lyu,81873724 to Y.Sun,and 82070914 and 81873671 to Y.Yu)+7 种基金Shanghai Shen Kang Hospital Development Center(SHDC12017109 to Y.Yu)the Shanghai Science and Technology Commission(19140904500 to Y.Yu)Jiaotong University Cross Biomedical Engineering(YG2017MS72 to Y.Yu)the“Eastern Scholar”Fundthe“Guangxi Bagui Scholar”fund(to Y.Shen)the Major Research Plan of the Provincial Science and Technology Foundation of Guangxi(AB16380214 to Y.Shen)Foundation of Shanghai Municipal Health Commission(shslczdzk05702,to Y.Yu and Y.Sun)Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20191908,to Y.Yu)。
文摘Mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes.A nuclear gene HPDL(4-hydroxyphenylpyruvate dioxygenase-like),which encodes an intermembrane mitochondrial protein,has been recently implicated in causing a neurodegenerative disease characterized by pediatric-onset spastic movement phenotypes.Here,we report six Chinese patients with bi-allelic HPDL pathogenic variants from four unrelated families showing neuropathic symptoms of variable severity,including developmental delay/intellectual disability,spasm,and hypertonia.Seven different pathogenic variants are identified,of which five are novel.Both fibroblasts and immortalized lymphocytes derived from patients show impaired mitochondrial respiratory function,which is also observed in HPDL-knockdown(KD)He La cells.In these He La cells,overexpression of a wild-type HPDL gene can rescue the respiratory phenotype of oxygen consumption rate.In addition,a decreased activity of the oxidative phosphorylation(OXPHOS)complex II is observed in patient-derived lymphocytes and HPDL-KD He La cells,further supporting an essential role of HPDL in the mitochondrial respiratory chain.Collectively,our data expand the clinical and mutational spectra of this mitochondrial neuropathy and further delineate the possible disease mechanism involving the impairment of the OXPHOS complex II activity due to the bi-allelic inactivations of HPDL.
基金supported by research grant from the Science and Technology Development Fund(FDCT)of MacauSAR(Grant No.070/2011/A3)
文摘In order to reduce the cost of the austenitic stainless steels(ASSs),the expensive austenite former(nickel) is often substituted by manganese.However,manganese is generally seen to have a detrimental effect on the corrosion resistance.In the present study,the feasibility of laser surface modification of a lean-alloyed ASS(FeCrMn) for enhancing pitting corrosion resistance was investigated.Laser surface modification of FeCrMn was successfully achieved by a 2.3 kW high power diode laser(HPDL).Cyclic polarization tests for FeCrMn after laser surface modification in 3.5% NaCl solution at 25 ℃ were performed by using a potentiostat.The pitting resistance of the laser-modified specimens was found to be significantly improved as reflected by the noble shift in pitting potential.This could be attributed to redistribution of manganese sulphide leading to a more homogenous and refined microstructure.Pitting corrosion resistance of the laser-treated FeCrMn followed by subsequent citric acid passivation was found to be further improved as reflected by the noble shift in pitting potential to 0.18 V.
