The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our socie...The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.展开更多
This paper introduces the related concepts of the hybrid spherical-shaped dataset and proposes a new discriminant analysis method based on the spherical-shaped dataset (SDAM), then SDAM is further improved by the idea...This paper introduces the related concepts of the hybrid spherical-shaped dataset and proposes a new discriminant analysis method based on the spherical-shaped dataset (SDAM), then SDAM is further improved by the idea of the class cover and presents the nonlinear discriminant analysis method (NDAM). To demonstrate the effectiveness of these two methods, this work constructs seven hybrid spherical-shaped datasets and uses nine UCI datasets. Numerical experiments on these examples indicate that SDAM can preferably solve the discriminant problem for the hybrid sphericalshaped dataset, but this method does not always work well for real datasets;NDAM overcomes the drawbacks of SDAM and better solves the discriminative problem of real datasets. Besides, it has better stability.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:82241058,31922045,31771031Natural Science Foundation of Tianjin Province of China,Grant/Award Number:21JCZDJC00290+2 种基金State Key Laboratory of Medicinal Chemical Biology in Nankai University,Grant/Award Number:2020017State Key Laboratory of Biochemical EngineeringOpen Funding Project of State Key Laboratory of Biochemical Engineering,Grant/Award Number:2021KF-01。
文摘The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.
基金Supported by he National Natural Science Foundation of China(52070119)the Natural Science Foundation of Fujian Province(2021J01970)。
文摘This paper introduces the related concepts of the hybrid spherical-shaped dataset and proposes a new discriminant analysis method based on the spherical-shaped dataset (SDAM), then SDAM is further improved by the idea of the class cover and presents the nonlinear discriminant analysis method (NDAM). To demonstrate the effectiveness of these two methods, this work constructs seven hybrid spherical-shaped datasets and uses nine UCI datasets. Numerical experiments on these examples indicate that SDAM can preferably solve the discriminant problem for the hybrid sphericalshaped dataset, but this method does not always work well for real datasets;NDAM overcomes the drawbacks of SDAM and better solves the discriminative problem of real datasets. Besides, it has better stability.
