We synthesized and characterized photoactivatable phospholipidic probes 1-3.These probes have the perfluorinated aryl azide function at the polar head of phospholipid.They are stable in dark and become highly reactive...We synthesized and characterized photoactivatable phospholipidic probes 1-3.These probes have the perfluorinated aryl azide function at the polar head of phospholipid.They are stable in dark and become highly reactive upon photoirradiation.The preliminary results suggest that they are promising tools to study the topology of membrane proteins and protein-lipid interactions using photolabeling approach.展开更多
Dengue vector is responsible for millions of deaths every year and has caused disastrous impacts on health systems. The continuous use of chemical insecticides, such as carbamates, pyrethroids and organophosphates gen...Dengue vector is responsible for millions of deaths every year and has caused disastrous impacts on health systems. The continuous use of chemical insecticides, such as carbamates, pyrethroids and organophosphates generates resistant populations of the mosquito, therefore, new control methods must be investigated. The joint action of the population and guidelines for preventing the reproduction of the mosquito associated with the use of photoactivatable insecticides can be the alternative for the control of epidemiological outbreaks in affected regions. In this study, the photo-larvicidal activity of Photogem^（PG）, a derivative of hematoporphyrin, was investigated against 2nd-early 3rd instar of Aedes aegypti larvae （Diptera： Culicidae） under different lighting conditions （artificial lighting system and sunlight）. The dynamics of PG accumulation was characterized by CLSM （confocal laser scanning microscopy） and total time PG eliminationin solution was investigated by ultraviolet-visible spectrophotometry. The maximum photo-activity of PG was observed in 0.5 h under sunlight exposure which achieved 100% larval mortality. Fluorescence images showed a uniform distribution of PG along the digestive tract. PG remained stable in the sunlight for 48 h and in an artificial lighting system for longer periods, therefore, it can be used for the control ofAedes aegypti larvae as a new alternative to chemical insecticides. The method is considered environmentally friendly due to its rapid degradation in the presence of light. Further studies are required, so that the potential of the technique can be explored in real breeding places.展开更多
Dear Editor,It is now well established that optogenetic stimulation can achieve precise intervention and modulate the activity of local neurons or neural circuits in the brain.Although this technique holds promise for...Dear Editor,It is now well established that optogenetic stimulation can achieve precise intervention and modulate the activity of local neurons or neural circuits in the brain.Although this technique holds promise for clinical therapy for neurological and psychiatric disorders,it requires the expression of lightsensitive proteins(such as channel rhodopsin)or photoactivatable chemicals(such as caged neurotransmitters)in the targeted brain regions[1].展开更多
Precisely monitoring the distribution and local fluctuation of metal ions,which play vital roles in many physiological and pathological processes,contributes largely to the study of metal ion-induced pathogenesis.Howe...Precisely monitoring the distribution and local fluctuation of metal ions,which play vital roles in many physiological and pathological processes,contributes largely to the study of metal ion-induced pathogenesis.However,current reactive fluorescent sensors can hardly realize the monitoring of metal ions in situ due to the premature activation and aimless dispersion of the sensors,which hinder their applications in biological samples.Herein,we report a photoactivatable cell-surface DNAzyme sensor to monitor metal ions in the microenvironment of living cells or tissues with high spatial resolution and temporal control.The sensor can efficiently anchor to the cell membrane through amphipathic interaction,and the activity of the sensor can be restored after the irradiation by light,which avoids false positive signals from the reaction with metal cofactors during delivery.First,the properties of the sensor were investigated either in buffer or on amodel cell surface,inwhich the sensor responded to Zn2+with superior temporal and spatial resolution under light activation.Then,the sensor was applied tomonitor the dynamic changes ofmetal ions during the formation of Aβaggregates in the cellular microenvironment of brain cells and brain tissues.This strategy provides a potential tool to understand the roles ofmetal ions in the progression of diseases,such as Alzheimer’s disease.展开更多
Intensity-based quantitative fluorescence resonance energy transfer(FRET)is a technique to measure the distance of molecules in scale of a few nanometers which is far beyond optical diffraction limit.This widely used ...Intensity-based quantitative fluorescence resonance energy transfer(FRET)is a technique to measure the distance of molecules in scale of a few nanometers which is far beyond optical diffraction limit.This widely used technique needs complicated experimental process and manual image analyses to obtain precise results,which take a long time and restrict the application of quantitative FRET especially in living cells.In this paper,a simplified and automatic quanti-tative FRET(saqFRET)method with high efficiency is presented.In saqFRET,photo-activatable acceptor PA-mCherry and optimized excitation wavelength of donor enhanced green fluorescent protein(EGFP)are used to simplify FRET crosstalk elimination.Traditional manual image analyses are time consuming when the dataset is large.The proposed automatic image analyses based on deep learning can analyze 100 samples within 30 s and demonstrate the same precision as manual image analyses.展开更多
Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumors. However, poor solubility, serious side effects, and more importantl...Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumors. However, poor solubility, serious side effects, and more importantly, the intrinsic and acquired resistance limit their clinical applications. These factors motivate scientists to design and synthesize novel and more potent analogues lacking disadvantages of clinical platinum drugs. Platinum (IV) complexes are one of representatives. In this review, we summarized the investigations undertaken into Platinum (IV) antitumor compounds since Rosenberg first noted their antitumor activity. The synthesis method and mechanism of action of Platinum (IV) complexes are outlined, as well as their chemical and pharmacological properties. Recent advances in Platinum (IV) anticancer agents that have been in clinical trials and photoactivatable Platinum (IV) complexes are also summarized, and the purpose here is to provide insight into the requirements for the antitumor activity of Platinum (IV) complexes and a basis for progressing in a new platinum compound.展开更多
Recent advancements in single-molecule biophysics have been driven by breakthroughs in advanced fluorescence microscopy techniques and the development of nextgeneration organic fluorophores.These cutting-edge fluoroph...Recent advancements in single-molecule biophysics have been driven by breakthroughs in advanced fluorescence microscopy techniques and the development of nextgeneration organic fluorophores.These cutting-edge fluorophores,coupled through tailored biolabeling strategies,offer single-molecule brightness,photostability,and phototunability(i.e.,photoswitchable,photoactivatable),contributing to enhancing spatial and temporal imaging resolution for studying biomolecular interactions and dynamics at single-event precision.This review examines the progress made over the past decade in the development of next-generation fluorophores,along with their site-specific labeling methods for proteins,nucleic acids,and biomolecular complexes.It also explores their applications in single-molecule fluorescencebased dynamic structural biology and super-resolution microscopy imaging.Furthermore,it examines ongoing efforts to address challenges associated with fluorophore photostability,photobleaching,and the integration of advanced photophysical and photochemical functionalities.The integration of state-of-the-art fluorophores with advanced labeling strategies aim to deliver complementary correlative data,holding promise for revolutionizing single-molecule biophysics by pushing the boundaries of temporal and spatial imaging resolution to unprecedented limits.展开更多
基金support from the National KeyProject for Basic Research 2003CB114400the Hi-Tech Research and Development Program of China No.2003AA2Z3506,Wuhan University and the CNRS is gratefully acknowledged.
文摘We synthesized and characterized photoactivatable phospholipidic probes 1-3.These probes have the perfluorinated aryl azide function at the polar head of phospholipid.They are stable in dark and become highly reactive upon photoirradiation.The preliminary results suggest that they are promising tools to study the topology of membrane proteins and protein-lipid interactions using photolabeling approach.
文摘Dengue vector is responsible for millions of deaths every year and has caused disastrous impacts on health systems. The continuous use of chemical insecticides, such as carbamates, pyrethroids and organophosphates generates resistant populations of the mosquito, therefore, new control methods must be investigated. The joint action of the population and guidelines for preventing the reproduction of the mosquito associated with the use of photoactivatable insecticides can be the alternative for the control of epidemiological outbreaks in affected regions. In this study, the photo-larvicidal activity of Photogem^（PG）, a derivative of hematoporphyrin, was investigated against 2nd-early 3rd instar of Aedes aegypti larvae （Diptera： Culicidae） under different lighting conditions （artificial lighting system and sunlight）. The dynamics of PG accumulation was characterized by CLSM （confocal laser scanning microscopy） and total time PG eliminationin solution was investigated by ultraviolet-visible spectrophotometry. The maximum photo-activity of PG was observed in 0.5 h under sunlight exposure which achieved 100% larval mortality. Fluorescence images showed a uniform distribution of PG along the digestive tract. PG remained stable in the sunlight for 48 h and in an artificial lighting system for longer periods, therefore, it can be used for the control ofAedes aegypti larvae as a new alternative to chemical insecticides. The method is considered environmentally friendly due to its rapid degradation in the presence of light. Further studies are required, so that the potential of the technique can be explored in real breeding places.
基金supported by grants from the Key Strategic Science and Technology Cooperation Project of the Ministry of Science and Technology of China(2023YFE0206800)the National Natural Science Foundation of China(81625006,31820103005,32200620,32170976,81971874)+1 种基金Zhejiang Province Natural Science Foundation of China(LZ24C090003 and LY21C090003)the Peak Discipline Cultivation Program of Zhejiang University School of Basic Medicine.
文摘Dear Editor,It is now well established that optogenetic stimulation can achieve precise intervention and modulate the activity of local neurons or neural circuits in the brain.Although this technique holds promise for clinical therapy for neurological and psychiatric disorders,it requires the expression of lightsensitive proteins(such as channel rhodopsin)or photoactivatable chemicals(such as caged neurotransmitters)in the targeted brain regions[1].
基金supported by the National Natural Science Foundation of China(Grant nos.21974039,21890744,51872088,21804039,and 22104032)Hunan Provincial Natural Science Foundation of China(grant no.2018JJ3092)+1 种基金China Postdoctoral Science Foundation(grant no.2020M672470)the China National Postdoctoral Program for Innovative Talents(grant no.BX20200118).
文摘Precisely monitoring the distribution and local fluctuation of metal ions,which play vital roles in many physiological and pathological processes,contributes largely to the study of metal ion-induced pathogenesis.However,current reactive fluorescent sensors can hardly realize the monitoring of metal ions in situ due to the premature activation and aimless dispersion of the sensors,which hinder their applications in biological samples.Herein,we report a photoactivatable cell-surface DNAzyme sensor to monitor metal ions in the microenvironment of living cells or tissues with high spatial resolution and temporal control.The sensor can efficiently anchor to the cell membrane through amphipathic interaction,and the activity of the sensor can be restored after the irradiation by light,which avoids false positive signals from the reaction with metal cofactors during delivery.First,the properties of the sensor were investigated either in buffer or on amodel cell surface,inwhich the sensor responded to Zn2+with superior temporal and spatial resolution under light activation.Then,the sensor was applied tomonitor the dynamic changes ofmetal ions during the formation of Aβaggregates in the cellular microenvironment of brain cells and brain tissues.This strategy provides a potential tool to understand the roles ofmetal ions in the progression of diseases,such as Alzheimer’s disease.
基金supported in part by the National Natural Science Foundation of China(61871251 and 61871022)Sichuan Science and Technology Program(2019YFSY0048)
文摘Intensity-based quantitative fluorescence resonance energy transfer(FRET)is a technique to measure the distance of molecules in scale of a few nanometers which is far beyond optical diffraction limit.This widely used technique needs complicated experimental process and manual image analyses to obtain precise results,which take a long time and restrict the application of quantitative FRET especially in living cells.In this paper,a simplified and automatic quanti-tative FRET(saqFRET)method with high efficiency is presented.In saqFRET,photo-activatable acceptor PA-mCherry and optimized excitation wavelength of donor enhanced green fluorescent protein(EGFP)are used to simplify FRET crosstalk elimination.Traditional manual image analyses are time consuming when the dataset is large.The proposed automatic image analyses based on deep learning can analyze 100 samples within 30 s and demonstrate the same precision as manual image analyses.
文摘Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumors. However, poor solubility, serious side effects, and more importantly, the intrinsic and acquired resistance limit their clinical applications. These factors motivate scientists to design and synthesize novel and more potent analogues lacking disadvantages of clinical platinum drugs. Platinum (IV) complexes are one of representatives. In this review, we summarized the investigations undertaken into Platinum (IV) antitumor compounds since Rosenberg first noted their antitumor activity. The synthesis method and mechanism of action of Platinum (IV) complexes are outlined, as well as their chemical and pharmacological properties. Recent advances in Platinum (IV) anticancer agents that have been in clinical trials and photoactivatable Platinum (IV) complexes are also summarized, and the purpose here is to provide insight into the requirements for the antitumor activity of Platinum (IV) complexes and a basis for progressing in a new platinum compound.
基金financial support from the National Natural Science Foundation of China(No.22374075)the Start-up Research Fund of Southeast University(4031002412).
文摘Recent advancements in single-molecule biophysics have been driven by breakthroughs in advanced fluorescence microscopy techniques and the development of nextgeneration organic fluorophores.These cutting-edge fluorophores,coupled through tailored biolabeling strategies,offer single-molecule brightness,photostability,and phototunability(i.e.,photoswitchable,photoactivatable),contributing to enhancing spatial and temporal imaging resolution for studying biomolecular interactions and dynamics at single-event precision.This review examines the progress made over the past decade in the development of next-generation fluorophores,along with their site-specific labeling methods for proteins,nucleic acids,and biomolecular complexes.It also explores their applications in single-molecule fluorescencebased dynamic structural biology and super-resolution microscopy imaging.Furthermore,it examines ongoing efforts to address challenges associated with fluorophore photostability,photobleaching,and the integration of advanced photophysical and photochemical functionalities.The integration of state-of-the-art fluorophores with advanced labeling strategies aim to deliver complementary correlative data,holding promise for revolutionizing single-molecule biophysics by pushing the boundaries of temporal and spatial imaging resolution to unprecedented limits.
