Background:Alzheimer’s disease(AD)is a progressive and irreversible neurodegenerative brain disorder,which is the most common form of dementia.Intensive efforts have been made to find effective and safe treatment aga...Background:Alzheimer’s disease(AD)is a progressive and irreversible neurodegenerative brain disorder,which is the most common form of dementia.Intensive efforts have been made to find effective and safe treatment against AD.Acetylcholinesterase inhibitors(AChEIs)have been widely used for the treatment of mild to moderate AD.In this study,we investigated the effect of Bis(9)-(−)-Meptazinol(B9M),a novel potential dual-binding acetylcholinesterase(AChE)inhibitor,on learning and memory abilities,as well as the underlying mechanism in the APP/PS1 mouse model of AD.Methods:B9M(0.1μg/kg,0.3μg/kg,and 1μg/kg)was administered by subcutaneous injection into eight-month-old APP/PS1 transgenic mice for four weeks.Morris water maze,nest-building and novel object recognition were used to examine learning and memory ability.Aβ levels and Aβplaque were evaluated by ELISA and immunochemistry.Results:Our results showed that chronic treatment with B9M significantly improved the cognitive function of APP/PS1 transgenic mice in the Morris water maze test,nest-building test and novel object recognition test.Moreover,B9M improved cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of the AChE activity,Aβ plaque burden,levels of Aβ and the consequent activation of astrocytes and microglia in the brain of APP/PS1 transgenic mice.Most of important,the most effective dose of B9M in the present study is 1μg/kg,which is one thousand of the dosage of Donepezil acted as the control treatment.Furthermore,B9M reduced Aβ plaque burden better than Donepezil.Conclusion:These results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties.展开更多
Thermally activated delayed fluorescence(TADF)organic light-emitting diodes(OLEDs)have been demonstrated in applications such as displays and solid-state lightings.However,weak stability and ineffi-cient emission of b...Thermally activated delayed fluorescence(TADF)organic light-emitting diodes(OLEDs)have been demonstrated in applications such as displays and solid-state lightings.However,weak stability and ineffi-cient emission of blue TADF OLEDs are two key bottlenecks limiting the development of solution processable displays and white light sources.This work presents a solution-processed OLED using a blue-emitting TADF small molecule bis[4-(9,9-dimethyl-9,10-dihydroacridine)phenyl]sulfone(DMAC-DPS)as an emitter.We comparatively investigated the effects of single host poly(Nvinylcarbazole)(PVK)and a co-host of 60%PVK and 30%2,2′-(1,3-phenylene)-bis[5-(4-tert-butylphenyl)-1,3,4-oxadiazole](OXD-7)on the device performance(the last 10%is emitter DMAC-DPS).The co-host device shows lower turn-on voltage,similar maximum luminance,and much slower external quantum efficiency(EQE)rolloff.In other words,device stability improved by doping OXD-7 into PVK,and the device impedance simultaneously and significantly reduced from 8.6103 to 4.2103 W at 1000 Hz.Finally,the electroluminescent stability of the co-host device was significantly enhanced by adjusting the annealing temperature.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(No.81503174,81573415,81573401,81503044,81373395)for financial support.
文摘Background:Alzheimer’s disease(AD)is a progressive and irreversible neurodegenerative brain disorder,which is the most common form of dementia.Intensive efforts have been made to find effective and safe treatment against AD.Acetylcholinesterase inhibitors(AChEIs)have been widely used for the treatment of mild to moderate AD.In this study,we investigated the effect of Bis(9)-(−)-Meptazinol(B9M),a novel potential dual-binding acetylcholinesterase(AChE)inhibitor,on learning and memory abilities,as well as the underlying mechanism in the APP/PS1 mouse model of AD.Methods:B9M(0.1μg/kg,0.3μg/kg,and 1μg/kg)was administered by subcutaneous injection into eight-month-old APP/PS1 transgenic mice for four weeks.Morris water maze,nest-building and novel object recognition were used to examine learning and memory ability.Aβ levels and Aβplaque were evaluated by ELISA and immunochemistry.Results:Our results showed that chronic treatment with B9M significantly improved the cognitive function of APP/PS1 transgenic mice in the Morris water maze test,nest-building test and novel object recognition test.Moreover,B9M improved cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of the AChE activity,Aβ plaque burden,levels of Aβ and the consequent activation of astrocytes and microglia in the brain of APP/PS1 transgenic mice.Most of important,the most effective dose of B9M in the present study is 1μg/kg,which is one thousand of the dosage of Donepezil acted as the control treatment.Furthermore,B9M reduced Aβ plaque burden better than Donepezil.Conclusion:These results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties.
基金The National Natural Science Foundation of China(51072008,51172006)the Natural Science Foundation of Beijing(2102006)+3 种基金the Project of New Star of Science and Technology of Beijing(2007A014)the Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing MunicipalityPHR(IHLB)(PHR201008012,201007101)the Postgraduate Science and Technology Foundation of Beijing University of Technology(ykj-2011-6371)
基金the National Key Research and Development Program of China(No.2017YFB0404404)the Open Fund of State Key Laboratory of Luminescent Materials and Devices(South China University of Technology),China。
文摘Thermally activated delayed fluorescence(TADF)organic light-emitting diodes(OLEDs)have been demonstrated in applications such as displays and solid-state lightings.However,weak stability and ineffi-cient emission of blue TADF OLEDs are two key bottlenecks limiting the development of solution processable displays and white light sources.This work presents a solution-processed OLED using a blue-emitting TADF small molecule bis[4-(9,9-dimethyl-9,10-dihydroacridine)phenyl]sulfone(DMAC-DPS)as an emitter.We comparatively investigated the effects of single host poly(Nvinylcarbazole)(PVK)and a co-host of 60%PVK and 30%2,2′-(1,3-phenylene)-bis[5-(4-tert-butylphenyl)-1,3,4-oxadiazole](OXD-7)on the device performance(the last 10%is emitter DMAC-DPS).The co-host device shows lower turn-on voltage,similar maximum luminance,and much slower external quantum efficiency(EQE)rolloff.In other words,device stability improved by doping OXD-7 into PVK,and the device impedance simultaneously and significantly reduced from 8.6103 to 4.2103 W at 1000 Hz.Finally,the electroluminescent stability of the co-host device was significantly enhanced by adjusting the annealing temperature.
