Radiation-induced brain injury(RIBI)represents a severe complication of cranial radiotherapy,substantially diminishing patients’quality of life.Unlike conventional brain injuries,RIBI evokes a unique chronic neuroinf...Radiation-induced brain injury(RIBI)represents a severe complication of cranial radiotherapy,substantially diminishing patients’quality of life.Unlike conventional brain injuries,RIBI evokes a unique chronic neuroinflammatory response that notably aggravates neurodegenerative processes.Despite significant progress in understanding the molecular mechanisms related to neuroinflammation,the specific and precise mechanisms that regulate neuroinflammation in RIBI and its associated toxicological effects remain largely unclear.Additionally,targeted neuroprotective strategies for RIBI are currently lacking.In this study,we systematically characterized the pathophysiology of RIBI using zebrafish(larvae/adults)and murine models.We established direct associations between neuronal damage and cognitive-behavioral deficits.Mechanistically,we proposed a ROS-mitochondrialimmune axis.Specifically,radiation-induced ROS lead to mitochondrial dysfunction,resulting in the leakage of mitochondrial DNA into the cytosol.This,in turn,activated the cGAS-STING pathway,thereby driving persistent microglia-mediated neuroinflammation.Furthermore,we engineered a dual-function nanotherapeutic agent,Pep-Cu_(5.4)O@H151.This agent integrates ultrasmall copper-based nanozymes(Cu_(5.4)O)for ROS scavenging and H151(a STING inhibitor)and is conjugated with peptides that can penetrate the blood-brain barrier and target microglia.This nanoplatform exhibited excellent synergistic therapeutic efficacy by simultaneously neutralizing oxidative stress and blocking inflammatory cascades.Our research provided an in-depth analysis of radiation-induced neurotoxicity,clarifying the crucial ROS-mitochondrial-immune axis.Moreover,we have developed a precise therapeutic strategy on the basis of this mechanism.展开更多
The concept of micro-total analysis systems(µTAS)introduced in the early 1990s revolutionized the development of lab-on-a-chip(LoC)technologies by miniaturizing and automating complex laboratory processes.Despite...The concept of micro-total analysis systems(µTAS)introduced in the early 1990s revolutionized the development of lab-on-a-chip(LoC)technologies by miniaturizing and automating complex laboratory processes.Despite their potential in diagnostics,drug development,and environmental monitoring,the widespread adoption of LoC systems has been hindered by challenges in scalability,integration,and cost-effective mass production.Traditional substrates like silicon,glass,and polymers struggle to meet the multifunctional requirements of practical applications.Lab-on-Printed Circuit Board(Lab-on-PCB)technology has emerged as a transformative solution,leveraging the cost-efficiency,scalability,and precision of PCB fabrication techniques.This platform facilitates the seamless integration of microfluidics,sensors,and actuators within a single device,enabling complex,multifunctional systems suitable for real-world deployment.Recent advancements have demonstrated Lab-on-PCB’s versatility across biomedical applications,such as point-of-care diagnostics,electrochemical biosensing,and molecular detection,as well as drug development and environmental monitoring.This review examines the evolution of Lab-on-PCB technology over the past eight years,focusing on its applications and impact within the research community.By analyzing recent progress in PCB-based microfluidics and biosensing,this work highlights how Lab-on-PCB systems address key technical barriers,paving the way for scalable and practical lab-on-chip solutions.The growing academic and industrial interest in Lab-on-PCB is underscored by a notable increase in publications and patents,signaling its potential for commercialization and broader adoption.展开更多
基金supported by the National Natural Science Foundation of China(82273577,82304079)the CAMS Innovation Fund for Medical Sciences(2023-I2M-3-018,2023-I2M-2-008,2021-I2M-1-042)+2 种基金the Natural Science Foundation of Tianjin Municipal Science and Technology Commission(23JCJQJC00230,24JCZDJC00580)the Fundamental Research Funds for the Central Universities(3332023066,3332024079)Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare.
文摘Radiation-induced brain injury(RIBI)represents a severe complication of cranial radiotherapy,substantially diminishing patients’quality of life.Unlike conventional brain injuries,RIBI evokes a unique chronic neuroinflammatory response that notably aggravates neurodegenerative processes.Despite significant progress in understanding the molecular mechanisms related to neuroinflammation,the specific and precise mechanisms that regulate neuroinflammation in RIBI and its associated toxicological effects remain largely unclear.Additionally,targeted neuroprotective strategies for RIBI are currently lacking.In this study,we systematically characterized the pathophysiology of RIBI using zebrafish(larvae/adults)and murine models.We established direct associations between neuronal damage and cognitive-behavioral deficits.Mechanistically,we proposed a ROS-mitochondrialimmune axis.Specifically,radiation-induced ROS lead to mitochondrial dysfunction,resulting in the leakage of mitochondrial DNA into the cytosol.This,in turn,activated the cGAS-STING pathway,thereby driving persistent microglia-mediated neuroinflammation.Furthermore,we engineered a dual-function nanotherapeutic agent,Pep-Cu_(5.4)O@H151.This agent integrates ultrasmall copper-based nanozymes(Cu_(5.4)O)for ROS scavenging and H151(a STING inhibitor)and is conjugated with peptides that can penetrate the blood-brain barrier and target microglia.This nanoplatform exhibited excellent synergistic therapeutic efficacy by simultaneously neutralizing oxidative stress and blocking inflammatory cascades.Our research provided an in-depth analysis of radiation-induced neurotoxicity,clarifying the crucial ROS-mitochondrial-immune axis.Moreover,we have developed a precise therapeutic strategy on the basis of this mechanism.
文摘The concept of micro-total analysis systems(µTAS)introduced in the early 1990s revolutionized the development of lab-on-a-chip(LoC)technologies by miniaturizing and automating complex laboratory processes.Despite their potential in diagnostics,drug development,and environmental monitoring,the widespread adoption of LoC systems has been hindered by challenges in scalability,integration,and cost-effective mass production.Traditional substrates like silicon,glass,and polymers struggle to meet the multifunctional requirements of practical applications.Lab-on-Printed Circuit Board(Lab-on-PCB)technology has emerged as a transformative solution,leveraging the cost-efficiency,scalability,and precision of PCB fabrication techniques.This platform facilitates the seamless integration of microfluidics,sensors,and actuators within a single device,enabling complex,multifunctional systems suitable for real-world deployment.Recent advancements have demonstrated Lab-on-PCB’s versatility across biomedical applications,such as point-of-care diagnostics,electrochemical biosensing,and molecular detection,as well as drug development and environmental monitoring.This review examines the evolution of Lab-on-PCB technology over the past eight years,focusing on its applications and impact within the research community.By analyzing recent progress in PCB-based microfluidics and biosensing,this work highlights how Lab-on-PCB systems address key technical barriers,paving the way for scalable and practical lab-on-chip solutions.The growing academic and industrial interest in Lab-on-PCB is underscored by a notable increase in publications and patents,signaling its potential for commercialization and broader adoption.