Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Na...Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.展开更多
It is important to improve residential thermal comfort in the high dense cities,in which wind environment is crucial.Waterside buildings take an advantage of micro-hydrological-climate in summer that should be used to...It is important to improve residential thermal comfort in the high dense cities,in which wind environment is crucial.Waterside buildings take an advantage of micro-hydrological-climate in summer that should be used to enhance residential thermal comfort especially in the subtropical region.In order to propose design approaches according to the outdoor thermal comfort of the waterside residential,a case study of Shenzhen She Kou residential district has been made.It focused on various factors that could have influence on wind environment for improving thermal comfort.Using wind velocity ratio(ΔRi)criterion,factors of building development volume,building direction and layout pattern,open space arrangement etc.have been broadly explored using FLUENT simulation.To planning parameters,the Floor Area Ratio(FAR)is significantly influence wind environment,the smaller FAR is better.To the vertical layout of the buildings,multi-storey layout and multi-storey&sub high-rise mixed layout would provide better wind environment.To the horizontal layout,the determinant is better than the peripheral.Other factors such as the buildings’direction towards the road,buildings’height,and open space setting,have influence on wind environment yet.In general,the more benefit of design layout for wind breezing,the better wind environment it could get.展开更多
Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss(NIHL). Given that cellular defense against oxidative stress is an energyconsuming process, the aim of the present study was to ...Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss(NIHL). Given that cellular defense against oxidative stress is an energyconsuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noiseinduced formation of reactive oxygen species(ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H_2O_2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.展开更多
基金supported by the National Natural Science Foundation of China,No.82101327(to YY)President Foundation of Nanfang Hospital,Southern Medical University,No.2020A001(to WL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,Nos.2019A1515110150,2022A1515012362(both to YY)Guangzhou Science and Technology Project,No.202201020111(to YY).
文摘Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.
文摘It is important to improve residential thermal comfort in the high dense cities,in which wind environment is crucial.Waterside buildings take an advantage of micro-hydrological-climate in summer that should be used to enhance residential thermal comfort especially in the subtropical region.In order to propose design approaches according to the outdoor thermal comfort of the waterside residential,a case study of Shenzhen She Kou residential district has been made.It focused on various factors that could have influence on wind environment for improving thermal comfort.Using wind velocity ratio(ΔRi)criterion,factors of building development volume,building direction and layout pattern,open space arrangement etc.have been broadly explored using FLUENT simulation.To planning parameters,the Floor Area Ratio(FAR)is significantly influence wind environment,the smaller FAR is better.To the vertical layout of the buildings,multi-storey layout and multi-storey&sub high-rise mixed layout would provide better wind environment.To the horizontal layout,the determinant is better than the peripheral.Other factors such as the buildings’direction towards the road,buildings’height,and open space setting,have influence on wind environment yet.In general,the more benefit of design layout for wind breezing,the better wind environment it could get.
基金supported by the National Natural Science Foundation of China (81570916, 81771018, and 81873699)。
文摘Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss(NIHL). Given that cellular defense against oxidative stress is an energyconsuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noiseinduced formation of reactive oxygen species(ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H_2O_2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.
