Background:Microglial activation is a hallmark of retinal neurodegeneration.However,whether microglia predominantly drive inflammatory damage or support tissue adaptation after acute photoreceptor injury remains uncle...Background:Microglial activation is a hallmark of retinal neurodegeneration.However,whether microglia predominantly drive inflammatory damage or support tissue adaptation after acute photoreceptor injury remains unclear.Resolving this issue is critical for defining therapeutic strategies.As colony-stimulating factor 1 receptor(CSF1R)signaling is essential for microglial survival,its pharmacological inhibition enables selective microglial depletion in vivo.Here,we used the CSF1R inhibitor PLX5622 in the N-methyl-N-nitrosourea(MNU)model to directly test the contribution of microglia to inflammation and photoreceptor degeneration.Methods:C57BL/6J mice received PLX5622 for 14 days before and throughout a 5-day MNU regimen.Retinal structure was assessed by fundus photography,optical coherence tomography(OCT),and hematoxylin and eosin(H&E)histology.Visual function was evaluated via electroretinography(ERG).Global transcriptomic alterations were profiled by RNA-seq,and selected inflammatory and complement mediators were assessed by Western blot.Results:PLX5622 treatment resulted in near-complete depletion of TMEM119+/Iba1+microglia in MNU-injured retinas.Microglia depletion was associated with reduced fundus white lesions,preserved outer nuclear layer(ONL)thickness and nuclei density,and significantly rescued ERG a-and b-wave amplitudes.Transcriptomic analysis further revealed broad attenuation of pro-inflammatory and innate immune pathways,accompanied by modulation of antioxidant responses,mitochondrial/metabolic alterations,neuron-related signaling,and macroglial activation-related programs.Consistently,Western blot analysis confirmed that MNU-induced upregulation of IL-1β,C3,and C1qa was markedly reduced following PLX5622 treatment.Conclusions:Pharmacological CSF1R inhibition leading to efficient retinal microglial depletion attenuated neuroinflammatory responses and preserved photoreceptor structure and visual function in acute toxic retinal degeneration.These findings indicate that microglial activation functions predominantly as a pathogenic amplifier rather than an adaptive response in this context,and identify CSF1R-dependent myeloid signaling as a key mechanistic driver of injury-associated retinal degeneration.展开更多
The NIST Cybersecurity Framework (NIST CSF) serves as a voluntary guideline aimed at helping organizations, tiny and medium-sized enterprises (SMEs), and critical infrastructure operators, effectively manage cyber ris...The NIST Cybersecurity Framework (NIST CSF) serves as a voluntary guideline aimed at helping organizations, tiny and medium-sized enterprises (SMEs), and critical infrastructure operators, effectively manage cyber risks. Although comprehensive, the complexity of the NIST CSF can be overwhelming, especially for those lacking extensive cybersecurity resources. Current implementation tools often cater to larger companies, neglecting the specific needs of SMEs, which can be vulnerable to cyber threats. To address this gap, our research proposes a user-friendly, open-source web platform designed to simplify the implementation of the NIST CSF. This platform enables organizations to assess their risk exposure and continuously monitor their cybersecurity maturity through tailored recommendations based on their unique profiles. Our methodology includes a literature review of existing tools and standards, followed by a description of the platform’s design and architecture. Initial tests with SMEs in Burkina Faso reveal a concerning cybersecurity maturity level, indicating the urgent need for improved strategies based on our findings. By offering an intuitive interface and cross-platform accessibility, this solution aims to empower organizations to enhance their cybersecurity resilience in an evolving threat landscape. The article concludes with discussions on the practical implications and future enhancements of the tool.展开更多
基金supported by National Natural Science Foundation of China(82322016,82271095)Guangdong Provincial Key Area R&D Program(2023B1111050004)+1 种基金Natural Science Foundation of Guangdong Province,China(2023A1515012656)Guangzhou Science and Technology Plan Project(2025A03J3981,2024B01J1121,2025A03J3988).
摘要Background:Microglial activation is a hallmark of retinal neurodegeneration.However,whether microglia predominantly drive inflammatory damage or support tissue adaptation after acute photoreceptor injury remains unclear.Resolving this issue is critical for defining therapeutic strategies.As colony-stimulating factor 1 receptor(CSF1R)signaling is essential for microglial survival,its pharmacological inhibition enables selective microglial depletion in vivo.Here,we used the CSF1R inhibitor PLX5622 in the N-methyl-N-nitrosourea(MNU)model to directly test the contribution of microglia to inflammation and photoreceptor degeneration.Methods:C57BL/6J mice received PLX5622 for 14 days before and throughout a 5-day MNU regimen.Retinal structure was assessed by fundus photography,optical coherence tomography(OCT),and hematoxylin and eosin(H&E)histology.Visual function was evaluated via electroretinography(ERG).Global transcriptomic alterations were profiled by RNA-seq,and selected inflammatory and complement mediators were assessed by Western blot.Results:PLX5622 treatment resulted in near-complete depletion of TMEM119+/Iba1+microglia in MNU-injured retinas.Microglia depletion was associated with reduced fundus white lesions,preserved outer nuclear layer(ONL)thickness and nuclei density,and significantly rescued ERG a-and b-wave amplitudes.Transcriptomic analysis further revealed broad attenuation of pro-inflammatory and innate immune pathways,accompanied by modulation of antioxidant responses,mitochondrial/metabolic alterations,neuron-related signaling,and macroglial activation-related programs.Consistently,Western blot analysis confirmed that MNU-induced upregulation of IL-1β,C3,and C1qa was markedly reduced following PLX5622 treatment.Conclusions:Pharmacological CSF1R inhibition leading to efficient retinal microglial depletion attenuated neuroinflammatory responses and preserved photoreceptor structure and visual function in acute toxic retinal degeneration.These findings indicate that microglial activation functions predominantly as a pathogenic amplifier rather than an adaptive response in this context,and identify CSF1R-dependent myeloid signaling as a key mechanistic driver of injury-associated retinal degeneration.
摘要The NIST Cybersecurity Framework (NIST CSF) serves as a voluntary guideline aimed at helping organizations, tiny and medium-sized enterprises (SMEs), and critical infrastructure operators, effectively manage cyber risks. Although comprehensive, the complexity of the NIST CSF can be overwhelming, especially for those lacking extensive cybersecurity resources. Current implementation tools often cater to larger companies, neglecting the specific needs of SMEs, which can be vulnerable to cyber threats. To address this gap, our research proposes a user-friendly, open-source web platform designed to simplify the implementation of the NIST CSF. This platform enables organizations to assess their risk exposure and continuously monitor their cybersecurity maturity through tailored recommendations based on their unique profiles. Our methodology includes a literature review of existing tools and standards, followed by a description of the platform’s design and architecture. Initial tests with SMEs in Burkina Faso reveal a concerning cybersecurity maturity level, indicating the urgent need for improved strategies based on our findings. By offering an intuitive interface and cross-platform accessibility, this solution aims to empower organizations to enhance their cybersecurity resilience in an evolving threat landscape. The article concludes with discussions on the practical implications and future enhancements of the tool.