Hyperthermia-induced decline in cognitive performance is a moderate complication that poses challenges to the maintenance of safety. Although the underlying mechanism can be attributed to the disruption of brain netwo...Hyperthermia-induced decline in cognitive performance is a moderate complication that poses challenges to the maintenance of safety. Although the underlying mechanism can be attributed to the disruption of brain networks, the propensity remains unclear. This study aimed to test the hypothesis that the extent of the alterations in cognitive performance is governed by the activity of deep brain structures, including monoaminergic neural systems. A decline in cognitive performance during mild hyperthermia and the beneficial effects of neck cooling were demonstrated using the Continuous Performance Test as a battery of cognitive tasks. Aspects of cognitive performance were characterized using the deep-brain activity (DBA) index as a neural activity parameter and the State-Trait Anxiety Inventory to assess the extent of alterations in cognitive performance as an individual measure. It was found that a higher average DBA index during tasks is essential for high cognitive performance in the heat. This beneficial effect of DBA is governed by the upper brainstem. This DBA benefit is more significant for individuals with higher average DBA indices at rest in a normal environment. Individual differences in cognitive performance in the heat are governed by differences in DBA. In addition, the beneficial effect of DBA on cognitive performance in heat only applies under conditions including neck cooling. This limited neck-cooling effect is attributed to anti-homeostatic thermoregulatory responses to cognitive tasks regulated by DBA.展开更多
Three-photon(3P)fluorescence imaging(FLI)utilizing excitation wavelengths within the near-infrared-Ⅲ (NIR-Ⅲ,1600-1870 nm)window has emerged as a transformative modality for intravital imaging,owing to its combined a...Three-photon(3P)fluorescence imaging(FLI)utilizing excitation wavelengths within the near-infrared-Ⅲ (NIR-Ⅲ,1600-1870 nm)window has emerged as a transformative modality for intravital imaging,owing to its combined advantages of excellent spatiotemporal resolution and remarkable tissue penetration.High-performance fluorescent probes are the cornerstone of highquality NIR-Ⅲ3P FLI.However,the construction of such probes is often hindered by inherent trade-offs in molecular design principles,posing significant challenges for their performance optimization and practical application.Here,we propose a straightforward and effective strategy based onπ-bridge manipulation to reconcile those competing molecular design parameters and substantially enhance 3P fluorescence properties.Leveraging this approach,a robust AIE-active small molecule,named TSSID,was developed,which exhibits bright NIR-I(700-950 nm)emission under 1665 nm NIR-Ⅲ3P excitation when formulated into nanoparticles(NPs).Remarkably,upon retro-orbital injection into mice following craniotomy,TSSID NPs achieved the best performance in deep-brain angiography among all reported organic 3P materials in terms of vascular imaging depth,signalto-background ratio,spatial resolution,and hemodynamic imaging depth.Additionally,TSSID NPs demonstrated outstanding biocompatibility through systematic biosafety evaluations.This study provides an excellent imaging agent and useful molecular design philosophy,facilitating the development of advanced organic 3P FLI probes.展开更多
文摘Hyperthermia-induced decline in cognitive performance is a moderate complication that poses challenges to the maintenance of safety. Although the underlying mechanism can be attributed to the disruption of brain networks, the propensity remains unclear. This study aimed to test the hypothesis that the extent of the alterations in cognitive performance is governed by the activity of deep brain structures, including monoaminergic neural systems. A decline in cognitive performance during mild hyperthermia and the beneficial effects of neck cooling were demonstrated using the Continuous Performance Test as a battery of cognitive tasks. Aspects of cognitive performance were characterized using the deep-brain activity (DBA) index as a neural activity parameter and the State-Trait Anxiety Inventory to assess the extent of alterations in cognitive performance as an individual measure. It was found that a higher average DBA index during tasks is essential for high cognitive performance in the heat. This beneficial effect of DBA is governed by the upper brainstem. This DBA benefit is more significant for individuals with higher average DBA indices at rest in a normal environment. Individual differences in cognitive performance in the heat are governed by differences in DBA. In addition, the beneficial effect of DBA on cognitive performance in heat only applies under conditions including neck cooling. This limited neck-cooling effect is attributed to anti-homeostatic thermoregulatory responses to cognitive tasks regulated by DBA.
基金the financial support from the National Natural Science Foundation of China(22275124,22475134,62475160,T2421003,62075135)Shenzhen University 2035 Program for Excellent Research(868-000003011036)Start-up Grant from Shenzhen University(868-000001032113,868-000001032219).
文摘Three-photon(3P)fluorescence imaging(FLI)utilizing excitation wavelengths within the near-infrared-Ⅲ (NIR-Ⅲ,1600-1870 nm)window has emerged as a transformative modality for intravital imaging,owing to its combined advantages of excellent spatiotemporal resolution and remarkable tissue penetration.High-performance fluorescent probes are the cornerstone of highquality NIR-Ⅲ3P FLI.However,the construction of such probes is often hindered by inherent trade-offs in molecular design principles,posing significant challenges for their performance optimization and practical application.Here,we propose a straightforward and effective strategy based onπ-bridge manipulation to reconcile those competing molecular design parameters and substantially enhance 3P fluorescence properties.Leveraging this approach,a robust AIE-active small molecule,named TSSID,was developed,which exhibits bright NIR-I(700-950 nm)emission under 1665 nm NIR-Ⅲ3P excitation when formulated into nanoparticles(NPs).Remarkably,upon retro-orbital injection into mice following craniotomy,TSSID NPs achieved the best performance in deep-brain angiography among all reported organic 3P materials in terms of vascular imaging depth,signalto-background ratio,spatial resolution,and hemodynamic imaging depth.Additionally,TSSID NPs demonstrated outstanding biocompatibility through systematic biosafety evaluations.This study provides an excellent imaging agent and useful molecular design philosophy,facilitating the development of advanced organic 3P FLI probes.
