Background:With increasing axial length(AL)and myopia progression,the micro-structure of the retina and choroid gradually changes.Our study describes the longitudinal changes in retinal and choroidal thickness in scho...Background:With increasing axial length(AL)and myopia progression,the micro-structure of the retina and choroid gradually changes.Our study describes the longitudinal changes in retinal and choroidal thickness in school-aged children with myopia and explores the relationship between changes in choroidal thickness and myopia progression.Methods:An exploratory analysis of a randomized trial was performed.Children(n=168,aged 7 to 12 years)with myopia from-0.75 diopter(D)to-4.00 D were enrolled in this prospective longitudinal study.Cycloplegic refraction,AL,retinal and choroidal thicknesses were measured at baseline and at 1-and 2-year follow-ups."Rapid progression myopia"was defined as increasing in myopia>1.00 D and'"stable progression myopia"was≤1.00 D during the 2-year follow-up.Factors affecting the changes in choroidal thickness were analysed using linear mixed models.Results:AL significantly increased by 0.67±0.24 mm with a myopic shift of-1.50±0.64 D over the 2 years.The overall retinal thickness increased from 251.12±15.91μm at baseline to 253.47±15.74μm at the 2-year followup(F=23.785,P<0.001).The subfoveal choroidal thickness decreased from 231.03±54.04μm at baseline to 206.53±59.71μm at the 2-year follow-up(F=73.358,P<0.001).Choroidal thinning was significantly associated with AL elongation(β=-43.579μm/mm,P=0.002)and sex(β=-17.258,P=0.001).Choroidal thickness continued to decrease in subjects with rapid progression(F=92.06,P<0.001)but not in those with steady progression(F=2.23,P=0.119).Conclusion:Significant choroidal thinning was observed and was associated with rapid progression and sex.These findings indicate a need to understand the role of the choroid in eye growth and myopia development.Synopsis/Precis:The macular choroidal thickness of myopic children is relevant to different degrees of myopic progression in this 2-year longitudinal study.These findings suggest that control of choroidal thickness might work to regulate human ocular growth.展开更多
4-hydroxyisoleucine(4-HIL)is a potential drug for diabetes and weight control.4-HIL was produced by expressing ido gene in L-isoleucine(Ile)-producing Corynebacterium glutamicum.But L-lysine(Lys)was also accumulated a...4-hydroxyisoleucine(4-HIL)is a potential drug for diabetes and weight control.4-HIL was produced by expressing ido gene in L-isoleucine(Ile)-producing Corynebacterium glutamicum.But L-lysine(Lys)was also accumulated as the main by-product in this recombinant strain SN02.To attenuate Lys synthesis,two genes in Lys synthetic pathway,i.e.,ddh encoding the diaminopimelic acid dehydrogenase and lysE encoding the specific Lys exporter were deleted in SN02.However,the deletion of ddh increased 4-HIL titer by 28.1%,but did not decrease Lys content;while the deletion of lysE significantly reduced Lys content by 66.7%,but 4-HIL titer also decreased by 19.3%.Therefore,we carried out transcriptome analysis to reveal the global variation in these mutants.Deletion of ddh and lysE(especially lysE)enhanced the transcription of key enzymes in succinylase branch of Lys synthesis pathway(DapD and DapC)and several enzymes involved in succinyl-CoA accessibility(SucC,SucD and OdhI),suggesting the compensatory synthesis of Lys via succinylase branch.In addition,the transcription of ilvBN in Ile synthesis pathway was improved,while the transcription of some genes in the 2-methylcitrate cycle and inositol metabolism pathway was weakened in these mutants.Mere deletion of ddh enhanced the transcription of aceA,ppc and pck,thus promoting oxaloacetate supply and 4-HIL synthesis.Deletion of lysE affected the transcription of some stress-related genes and transporter genes,suggesting that this mutant would be under stress,thus attenuating its 4-HIL synthesis.These findings will be helpful for systematic microbiology and bio-manufacturing of C.glutamicum.展开更多
基金This work was supported by the Zhejiang Provincial Key Research and Development Program(Grant No.2021C03102)International S&TCooperation Program of China(Grant No.2014DFA30940)with partial funding provided by Essilor International S.A.and Zhejiang Provincial Natural Science Foundation of China(GrantNo.LY19H120004).
文摘Background:With increasing axial length(AL)and myopia progression,the micro-structure of the retina and choroid gradually changes.Our study describes the longitudinal changes in retinal and choroidal thickness in school-aged children with myopia and explores the relationship between changes in choroidal thickness and myopia progression.Methods:An exploratory analysis of a randomized trial was performed.Children(n=168,aged 7 to 12 years)with myopia from-0.75 diopter(D)to-4.00 D were enrolled in this prospective longitudinal study.Cycloplegic refraction,AL,retinal and choroidal thicknesses were measured at baseline and at 1-and 2-year follow-ups."Rapid progression myopia"was defined as increasing in myopia>1.00 D and'"stable progression myopia"was≤1.00 D during the 2-year follow-up.Factors affecting the changes in choroidal thickness were analysed using linear mixed models.Results:AL significantly increased by 0.67±0.24 mm with a myopic shift of-1.50±0.64 D over the 2 years.The overall retinal thickness increased from 251.12±15.91μm at baseline to 253.47±15.74μm at the 2-year followup(F=23.785,P<0.001).The subfoveal choroidal thickness decreased from 231.03±54.04μm at baseline to 206.53±59.71μm at the 2-year follow-up(F=73.358,P<0.001).Choroidal thinning was significantly associated with AL elongation(β=-43.579μm/mm,P=0.002)and sex(β=-17.258,P=0.001).Choroidal thickness continued to decrease in subjects with rapid progression(F=92.06,P<0.001)but not in those with steady progression(F=2.23,P=0.119).Conclusion:Significant choroidal thinning was observed and was associated with rapid progression and sex.These findings indicate a need to understand the role of the choroid in eye growth and myopia development.Synopsis/Precis:The macular choroidal thickness of myopic children is relevant to different degrees of myopic progression in this 2-year longitudinal study.These findings suggest that control of choroidal thickness might work to regulate human ocular growth.
基金funded by the program of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201904)national first-class discipline program of Light Industry Technology and Engineering(LITE2018-10).
文摘4-hydroxyisoleucine(4-HIL)is a potential drug for diabetes and weight control.4-HIL was produced by expressing ido gene in L-isoleucine(Ile)-producing Corynebacterium glutamicum.But L-lysine(Lys)was also accumulated as the main by-product in this recombinant strain SN02.To attenuate Lys synthesis,two genes in Lys synthetic pathway,i.e.,ddh encoding the diaminopimelic acid dehydrogenase and lysE encoding the specific Lys exporter were deleted in SN02.However,the deletion of ddh increased 4-HIL titer by 28.1%,but did not decrease Lys content;while the deletion of lysE significantly reduced Lys content by 66.7%,but 4-HIL titer also decreased by 19.3%.Therefore,we carried out transcriptome analysis to reveal the global variation in these mutants.Deletion of ddh and lysE(especially lysE)enhanced the transcription of key enzymes in succinylase branch of Lys synthesis pathway(DapD and DapC)and several enzymes involved in succinyl-CoA accessibility(SucC,SucD and OdhI),suggesting the compensatory synthesis of Lys via succinylase branch.In addition,the transcription of ilvBN in Ile synthesis pathway was improved,while the transcription of some genes in the 2-methylcitrate cycle and inositol metabolism pathway was weakened in these mutants.Mere deletion of ddh enhanced the transcription of aceA,ppc and pck,thus promoting oxaloacetate supply and 4-HIL synthesis.Deletion of lysE affected the transcription of some stress-related genes and transporter genes,suggesting that this mutant would be under stress,thus attenuating its 4-HIL synthesis.These findings will be helpful for systematic microbiology and bio-manufacturing of C.glutamicum.