超分辨率径向波动(SRRF)作为一种无需特殊硬件的计算成像方法,为活细胞超分辨率成像提供了有力工具,然而该技术的成像效果高度依赖参数设置。为建立针对活细胞线粒体的SRRF成像优化方案,该研究以HeLa细胞为模型,利用Abberior Live Orang...超分辨率径向波动(SRRF)作为一种无需特殊硬件的计算成像方法,为活细胞超分辨率成像提供了有力工具,然而该技术的成像效果高度依赖参数设置。为建立针对活细胞线粒体的SRRF成像优化方案,该研究以HeLa细胞为模型,利用Abberior Live Orange Mito染料标记线粒体,通过转盘共聚焦显微镜获取时间序列图像,并使用NanoJ-SRRF系统评估了环半径、径向放大倍数、时序分析模式等关键参数对成像质量的影响。重建图像的分辨率与质量分别采用半高全宽和NanoJ-SQUIRREL的分辨率尺度皮尔逊相关系数与分辨率尺度误差进行定量评估。结果表明,环半径是最关键参数,较小取值(0.1~1.0)可实现超越衍射极限的分辨率;径向放大倍数与环内轴数对结构质量影响较小;在时序分析模式中,时序径向性平均法能提供最稳定且无伪影的重建结果;而梯度加权会引入明显伪影并显著降低图像质量。该研究针对转盘共聚焦成像、Abberior Live Orange Mito标记、108 nm像素尺寸、20 Hz采集、100帧时间序列的实验条件,提供了经量化评估的NanoJ-SRRF参数优化方案,为该条件下的活细胞线粒体纳米级成像提供了经量化评估的参数优化起点。展开更多
Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a s...Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.展开更多
文摘超分辨率径向波动(SRRF)作为一种无需特殊硬件的计算成像方法,为活细胞超分辨率成像提供了有力工具,然而该技术的成像效果高度依赖参数设置。为建立针对活细胞线粒体的SRRF成像优化方案,该研究以HeLa细胞为模型,利用Abberior Live Orange Mito染料标记线粒体,通过转盘共聚焦显微镜获取时间序列图像,并使用NanoJ-SRRF系统评估了环半径、径向放大倍数、时序分析模式等关键参数对成像质量的影响。重建图像的分辨率与质量分别采用半高全宽和NanoJ-SQUIRREL的分辨率尺度皮尔逊相关系数与分辨率尺度误差进行定量评估。结果表明,环半径是最关键参数,较小取值(0.1~1.0)可实现超越衍射极限的分辨率;径向放大倍数与环内轴数对结构质量影响较小;在时序分析模式中,时序径向性平均法能提供最稳定且无伪影的重建结果;而梯度加权会引入明显伪影并显著降低图像质量。该研究针对转盘共聚焦成像、Abberior Live Orange Mito标记、108 nm像素尺寸、20 Hz采集、100帧时间序列的实验条件,提供了经量化评估的NanoJ-SRRF参数优化方案,为该条件下的活细胞线粒体纳米级成像提供了经量化评估的参数优化起点。
基金supported by grants from The National Natural Science Foundation of China(82472611)The“14th Five Year Plan”Scientific Research and Innovation Team of Chengdu Sport University(23CXTD02)Sports Medicine Key Laboratory of Sichuan Province/Key Laboratory of Sports Medicine,General Administration of Sport of China(2025-A028)。
文摘Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.
