Tau oligomers are recognized for their critical role in causing neuronal toxicity and synaptic dysfunction in a diverse array of neurodegenerative diseases collectively referred to as tauopathies.However,the discovery...Tau oligomers are recognized for their critical role in causing neuronal toxicity and synaptic dysfunction in a diverse array of neurodegenerative diseases collectively referred to as tauopathies.However,the discovery of drugs that specifically target tau oligomers has been impeded by the absence of appropriate screening methods.Here,we suggest a drug screening platform based on tau amyloid corona-shelled nanoparticles(TACONs)to assess the efficacy of tau oligomer-degrading agents through aggregation-induced colorimetric responses of TACONs.TACONs were engineered via the encapsulation of gold nanoparticles(AuNPs)with homogeneous tau oligomers by leveraging heparin as a co-factor.Our TACON-based strategy harnesses two primary functions of AuNPs:(i)catalytic activators for the selective isolation of tau oligomers and(ii)optical reporters for quantifying colorimetric responses induced by tau oligomer-degrading agents.To validate this approach,we employed proteases that can degrade tau oligomers(protease XIV and plasmin)along with various small molecules known to aid in the treatment of tauopathies.Furthermore,we significantly enhanced screening efficiency by integrating a time-series deep learning architecture,enabling rapid identification of effective agents within 1 h.These results highlight the great potential of a deep learning-assisted TACON-based drug screening platform as a powerful strategy for streamlining drug discovery in tauopathies.展开更多
Palladium is the most prominent material in both scientific and industrial research on gas storage,purification,detection,and catalysis due to its unique properties as a catalyst and hydrogen absorber.Advancing the dy...Palladium is the most prominent material in both scientific and industrial research on gas storage,purification,detection,and catalysis due to its unique properties as a catalyst and hydrogen absorber.Advancing the dynamic optical phenomena of palladium reacting with hydrogen,transduction of the gas-matter reaction into light-matter interaction is attempted to visualize the dynamic surface chemistry and reaction behaviors.The simple geometry of the metal-dielectric-metal structure,Fabry-Perot etalon,is employed for a colorimetric reactor,to display the catalytic reaction of the exposed gas via water-film/bubble formation at the dielectric/palladium interface.The adsorption/desorption behavior and catalytic reaction of hydrogen and oxygen on the palladium surface display highly repeatable and dramatic color changes based on two distinct water formation trends:the foggy effect by water bubbles and the whiteout effect by water film formation.Simulations and experiments demonstrate the robustness of the proposed Fabry-Perot etalon as an excellent platform for monitoring the opto-physical phenomena driven by heterogeneous catalysis.展开更多
基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean Government(MSIP)(Grant Numbers:RS-2025-00553786,RS-2024-00400563,RS-2024-00409958,RS-2025-02263504,RS-2025-02263404,and RS-2025-00519761)the BK21 FOUR Institute of Precision Public Health,the Science and Technology Commercialization Agency(Grant Number:RS-2024-00423580)+1 种基金Soseon Foundationsupported by Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health and Welfare(Grant Numbers:RS-2023-00274152 and RS-2023-00265159).
文摘Tau oligomers are recognized for their critical role in causing neuronal toxicity and synaptic dysfunction in a diverse array of neurodegenerative diseases collectively referred to as tauopathies.However,the discovery of drugs that specifically target tau oligomers has been impeded by the absence of appropriate screening methods.Here,we suggest a drug screening platform based on tau amyloid corona-shelled nanoparticles(TACONs)to assess the efficacy of tau oligomer-degrading agents through aggregation-induced colorimetric responses of TACONs.TACONs were engineered via the encapsulation of gold nanoparticles(AuNPs)with homogeneous tau oligomers by leveraging heparin as a co-factor.Our TACON-based strategy harnesses two primary functions of AuNPs:(i)catalytic activators for the selective isolation of tau oligomers and(ii)optical reporters for quantifying colorimetric responses induced by tau oligomer-degrading agents.To validate this approach,we employed proteases that can degrade tau oligomers(protease XIV and plasmin)along with various small molecules known to aid in the treatment of tauopathies.Furthermore,we significantly enhanced screening efficiency by integrating a time-series deep learning architecture,enabling rapid identification of effective agents within 1 h.These results highlight the great potential of a deep learning-assisted TACON-based drug screening platform as a powerful strategy for streamlining drug discovery in tauopathies.
基金National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2021R1A2C2009236 and No.2020M3H5A108110413)Y.-S.R.acknowledges support from a grant of the Information and Communications Promotion Fund(ICT promotion fund)through the National IT Industry Promotion Agency(NIPA),and Korea University Grant(K2311801)Y.P acknowledges support from KIST Institutional grants(No.2E32451 and 2V09640).
文摘Palladium is the most prominent material in both scientific and industrial research on gas storage,purification,detection,and catalysis due to its unique properties as a catalyst and hydrogen absorber.Advancing the dynamic optical phenomena of palladium reacting with hydrogen,transduction of the gas-matter reaction into light-matter interaction is attempted to visualize the dynamic surface chemistry and reaction behaviors.The simple geometry of the metal-dielectric-metal structure,Fabry-Perot etalon,is employed for a colorimetric reactor,to display the catalytic reaction of the exposed gas via water-film/bubble formation at the dielectric/palladium interface.The adsorption/desorption behavior and catalytic reaction of hydrogen and oxygen on the palladium surface display highly repeatable and dramatic color changes based on two distinct water formation trends:the foggy effect by water bubbles and the whiteout effect by water film formation.Simulations and experiments demonstrate the robustness of the proposed Fabry-Perot etalon as an excellent platform for monitoring the opto-physical phenomena driven by heterogeneous catalysis.
