Pub Date : 2025-01-15DOI: 10.1038/s41467-025-55932-9
Sandra Viz-Lasheras, Alberto Gómez-Carballa, Xabier Bello, Irene Rivero-Calle, Ana Isabel Dacosta, Myrsini Kaforou, Dominic Habgood-Coote, Aubrey J. Cunnington, Marieke Emonts, Jethro A. Herberg, Victoria J. Wright, Enitan D. Carrol, Stephane C. Paulus, Werner Zenz, Daniela S. Kohlfürst, Nina Schweintzger, Michiel Van der Flier, Ronald de Groot, Luregn J. Schlapbach, Philipp Agyeman, Andrew J. Pollard, Colin Fink, Taco T. Kuijpers, Suzanne Anderson, Ulrich Von Both, Marko Pokorn, Dace Zavadska, María Tsolia, Henriëtte A. Moll, Clementien Vermont, Michael Levin, Federico Martinón-Torres, Antonio Salas
Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics. Using a LASSO regression simulation approach and blood microarray data from 107 children with pneumonia (including 30 M. pneumoniae) we identify eight different transcriptomic signatures, ranging from 3-10 transcripts, that differentiate mycoplasma pneumonia from other bacterial/viral pneumonias with high accuracy (AUC: 0.84–0.95). Additionally, we demonstrate that existing signatures for broadly distinguishing viral/bacterial infections and viral/bacterial pneumonias are ineffective in distinguishing M. pneumoniae from viral pneumonia. The new signatures are successfully validated in an independent RNAseq cohort of children with pneumonia, demonstrating their robustness. The high sensibility of these signatures presents a valuable opportunity to guide the treatment and management of M. pneumoniae pneumonia patients.
{"title":"A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment","authors":"Sandra Viz-Lasheras, Alberto Gómez-Carballa, Xabier Bello, Irene Rivero-Calle, Ana Isabel Dacosta, Myrsini Kaforou, Dominic Habgood-Coote, Aubrey J. Cunnington, Marieke Emonts, Jethro A. Herberg, Victoria J. Wright, Enitan D. Carrol, Stephane C. Paulus, Werner Zenz, Daniela S. Kohlfürst, Nina Schweintzger, Michiel Van der Flier, Ronald de Groot, Luregn J. Schlapbach, Philipp Agyeman, Andrew J. Pollard, Colin Fink, Taco T. Kuijpers, Suzanne Anderson, Ulrich Von Both, Marko Pokorn, Dace Zavadska, María Tsolia, Henriëtte A. Moll, Clementien Vermont, Michael Levin, Federico Martinón-Torres, Antonio Salas","doi":"10.1038/s41467-025-55932-9","DOIUrl":"https://doi.org/10.1038/s41467-025-55932-9","url":null,"abstract":"<p><i>Mycoplasma pneumoniae</i> causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics. Using a <i>LASSO</i> regression simulation approach and blood microarray data from 107 children with pneumonia (including 30 <i>M. pneumoniae</i>) we identify eight different transcriptomic signatures, ranging from 3-10 transcripts, that differentiate mycoplasma pneumonia from other bacterial/viral pneumonias with high accuracy (AUC: 0.84–0.95). Additionally, we demonstrate that existing signatures for broadly distinguishing viral/bacterial infections and viral/bacterial pneumonias are ineffective in distinguishing <i>M. pneumoniae</i> from viral pneumonia. The new signatures are successfully validated in an independent RNAseq cohort of children with pneumonia, demonstrating their robustness. The high sensibility of these signatures presents a valuable opportunity to guide the treatment and management of <i>M. pneumoniae</i> pneumonia patients.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"78 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-025-55978-9
Qing Yang, Weibin Wang, Yunfeng Yang, Pengyuan Li, Xinyi Yang, Fuquan Bai, Bo Zou
Metal-organic frameworks that feature hybrid fluorescence and phosphorescence offer unique advantages in white-emitting communities based on their multiple emission centers and high exciton utilization. However, it poses a substantial challenge to realize superior white-light emission in single-component metal-organic frameworks without encapsulating varying chromophores or integrating multiple phosphor subunits. Here, we achieve a high-performance white-light emission with photoluminescence quantum yield of 81.3% via boosting triplet excitons distribution through pressure treatment in single-component Zn-IPA metal-organic frameworks. A novel metal-ligand asymmetrical chelate coordination is successfully integrated into the Zn-IPA after a high-pressure treatment over ~20.0 GPa. This modification unexpectedly endows the targeted sample with a new emergent electronic state to narrow the singlet-triplet energy gap, which effectively accelerates the spin-flipping process for boosted triplet excitons population. Time delay phosphor-converted light-emitting diodes are fabricated with long emission time up to ~7 s after switching off, providing significant advancements for white-light and time-delay lighting applications.
{"title":"Pressure treatment enables white-light emission in Zn-IPA MOF via asymmetrical metal-ligand chelate coordination","authors":"Qing Yang, Weibin Wang, Yunfeng Yang, Pengyuan Li, Xinyi Yang, Fuquan Bai, Bo Zou","doi":"10.1038/s41467-025-55978-9","DOIUrl":"https://doi.org/10.1038/s41467-025-55978-9","url":null,"abstract":"<p>Metal-organic frameworks that feature hybrid fluorescence and phosphorescence offer unique advantages in white-emitting communities based on their multiple emission centers and high exciton utilization. However, it poses a substantial challenge to realize superior white-light emission in single-component metal-organic frameworks without encapsulating varying chromophores or integrating multiple phosphor subunits. Here, we achieve a high-performance white-light emission with photoluminescence quantum yield of 81.3% via boosting triplet excitons distribution through pressure treatment in single-component Zn-IPA metal-organic frameworks. A novel metal-ligand asymmetrical chelate coordination is successfully integrated into the Zn-IPA after a high-pressure treatment over ~20.0 GPa. This modification unexpectedly endows the targeted sample with a new emergent electronic state to narrow the singlet-triplet energy gap, which effectively accelerates the spin-flipping process for boosted triplet excitons population. Time delay phosphor-converted light-emitting diodes are fabricated with long emission time up to ~7 s after switching off, providing significant advancements for white-light and time-delay lighting applications.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"2 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-025-56117-0
Dobromir Rahnev
One of the most important aspects of research on metacognition is the measurement of metacognitive ability. However, the properties of existing measures of metacognition have been mostly assumed rather than empirically established. Here I perform a comprehensive empirical assessment of 17 measures of metacognition. First, I develop a method of determining the validity and precision of a measure of metacognition and find that all 17 measures are valid and most show similar levels of precision. Second, I examine how measures of metacognition depend on task performance, response bias, and metacognitive bias, finding only weak dependences on response and metacognitive bias but many strong dependencies on task performance. Third, I find that all measures have very high split-half reliabilities, but most have poor test-retest reliabilities. This comprehensive assessment paints a complex picture: no measure of metacognition is perfect and different measures may be preferable in different experimental contexts.
{"title":"A comprehensive assessment of current methods for measuring metacognition","authors":"Dobromir Rahnev","doi":"10.1038/s41467-025-56117-0","DOIUrl":"https://doi.org/10.1038/s41467-025-56117-0","url":null,"abstract":"<p>One of the most important aspects of research on metacognition is the measurement of metacognitive ability. However, the properties of existing measures of metacognition have been mostly assumed rather than empirically established. Here I perform a comprehensive empirical assessment of 17 measures of metacognition. First, I develop a method of determining the validity and precision of a measure of metacognition and find that all 17 measures are valid and most show similar levels of precision. Second, I examine how measures of metacognition depend on task performance, response bias, and metacognitive bias, finding only weak dependences on response and metacognitive bias but many strong dependencies on task performance. Third, I find that all measures have very high split-half reliabilities, but most have poor test-retest reliabilities. This comprehensive assessment paints a complex picture: no measure of metacognition is perfect and different measures may be preferable in different experimental contexts.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"89 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-025-55960-5
Nina McTiernan, Ine Kjosås, Thomas Arnesen
N-terminal acetylation is a highly abundant protein modification in eukaryotic cells. This modification is catalysed by N-terminal acetyltransferases acting co- or post-translationally. Here, we review the eukaryotic N-terminal acetylation machinery: the enzymes involved and their substrate specificities. We also provide an overview of the impact of N-terminal acetylation, including its effects on protein folding, subcellular targeting, protein complex formation, and protein turnover. In particular, there may be competition between N-terminal acetyltransferases and other enzymes in defining protein fate. At the organismal level, N-terminal acetylation is highly influential, and its impairment was recently linked to cardiac dysfunction and neurodegenerative diseases.
{"title":"Illuminating the impact of N-terminal acetylation: from protein to physiology","authors":"Nina McTiernan, Ine Kjosås, Thomas Arnesen","doi":"10.1038/s41467-025-55960-5","DOIUrl":"https://doi.org/10.1038/s41467-025-55960-5","url":null,"abstract":"<p>N-terminal acetylation is a highly abundant protein modification in eukaryotic cells. This modification is catalysed by N-terminal acetyltransferases acting co- or post-translationally. Here, we review the eukaryotic N-terminal acetylation machinery: the enzymes involved and their substrate specificities. We also provide an overview of the impact of N-terminal acetylation, including its effects on protein folding, subcellular targeting, protein complex formation, and protein turnover. In particular, there may be competition between N-terminal acetyltransferases and other enzymes in defining protein fate. At the organismal level, N-terminal acetylation is highly influential, and its impairment was recently linked to cardiac dysfunction and neurodegenerative diseases.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"53 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-024-55701-0
Jiangang Chen, Zhixing Wen, Fan Yang, Renji Bian, Qirui Zhang, Er Pan, Yuelei Zeng, Xiao Luo, Qing Liu, Liang-Jian Deng, Fucai Liu
Neural reuse can drive organisms to generalize knowledge across various tasks during learning. However, existing devices mostly focus on architectures rather than network functions, lacking the mimic capabilities of neural reuse. Here, we demonstrate a rational device designed based on ferroionic CuInP2S6, to accomplish the neural reuse function, enabled by dynamic allocation of the ferro-ionic phase. It allows for dynamic refresh and collaborative work between volatile and non-volatile modes to support the entire neural reuse process. Notably, ferroelectric polarization can remain consistent even after undergoing the refresh process, providing a foundation for the shared functionality across multiple tasks. By implementing neural reuse, the classification accuracy of neuromorphic hardware can improve by 17%, while the consumption is reduced by 40%; in multi-task scenarios, its training speed is accelerated by 2200%, while its generalization ability is enhanced by 21%. Our results are promising towards building refreshable hardware platforms based on ferroelectric-ionic combination capable of accommodating more efficient algorithms and architectures.
{"title":"Refreshable memristor via dynamic allocation of ferro-ionic phase for neural reuse","authors":"Jiangang Chen, Zhixing Wen, Fan Yang, Renji Bian, Qirui Zhang, Er Pan, Yuelei Zeng, Xiao Luo, Qing Liu, Liang-Jian Deng, Fucai Liu","doi":"10.1038/s41467-024-55701-0","DOIUrl":"https://doi.org/10.1038/s41467-024-55701-0","url":null,"abstract":"<p>Neural reuse can drive organisms to generalize knowledge across various tasks during learning. However, existing devices mostly focus on architectures rather than network functions, lacking the mimic capabilities of neural reuse. Here, we demonstrate a rational device designed based on ferroionic CuInP<sub>2</sub>S<sub>6</sub>, to accomplish the neural reuse function, enabled by dynamic allocation of the ferro-ionic phase. It allows for dynamic refresh and collaborative work between volatile and non-volatile modes to support the entire neural reuse process. Notably, ferroelectric polarization can remain consistent even after undergoing the refresh process, providing a foundation for the shared functionality across multiple tasks. By implementing neural reuse, the classification accuracy of neuromorphic hardware can improve by 17%, while the consumption is reduced by 40%; in multi-task scenarios, its training speed is accelerated by 2200%, while its generalization ability is enhanced by 21%. Our results are promising towards building refreshable hardware platforms based on ferroelectric-ionic combination capable of accommodating more efficient algorithms and architectures.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"26 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-024-55704-x
Marine N. Fleury, Lawrence P. Binding, Peter Taylor, Fenglai Xiao, Davide Giampiccolo, Sarah Buck, Gavin P. Winston, Pamela J. Thompson, Sallie Baxendale, Andrew W. McEvoy, Matthias J. Koepp, John S. Duncan, Meneka K. Sidhu
Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery. We assess memory network changes, from 3–12 months to 10 years postoperatively, in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal task-based functional MRI and standard neuropsychology assessments. We observe key adaptive changes in memory networks of a predominantly seizure-free cohort. Ongoing neuroplasticity in posterior medial temporal regions and contralesional cingulum or pallidum contribute to long-term verbal and visual memory recovery. Here, we show the potential for sustained cognitive improvement and importance of strategic approaches in epilepsy treatment, advocating for conservative surgeries and long-term use of cognitive rehabilitation for ongoing recovery.
{"title":"Long-term memory plasticity in a decade-long connectivity study post anterior temporal lobe resection","authors":"Marine N. Fleury, Lawrence P. Binding, Peter Taylor, Fenglai Xiao, Davide Giampiccolo, Sarah Buck, Gavin P. Winston, Pamela J. Thompson, Sallie Baxendale, Andrew W. McEvoy, Matthias J. Koepp, John S. Duncan, Meneka K. Sidhu","doi":"10.1038/s41467-024-55704-x","DOIUrl":"https://doi.org/10.1038/s41467-024-55704-x","url":null,"abstract":"<p>Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery. We assess memory network changes, from 3–12 months to 10 years postoperatively, in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal task-based functional MRI and standard neuropsychology assessments. We observe key adaptive changes in memory networks of a predominantly seizure-free cohort. Ongoing neuroplasticity in posterior medial temporal regions and contralesional cingulum or pallidum contribute to long-term verbal and visual memory recovery. Here, we show the potential for sustained cognitive improvement and importance of strategic approaches in epilepsy treatment, advocating for conservative surgeries and long-term use of cognitive rehabilitation for ongoing recovery.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"20 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-024-53780-7
Friedemann Reum, Julia Marshall, Henry C. Bittig, Lutz Bretschneider, Göran Broström, Anusha L. Dissanayake, Theo Glauch, Klaus-Dirk Gottschaldt, Jonas Gros, Heidi Huntrieser, Astrid Lampert, Michael Lichtenstern, Scot M. Miller, Martin Mohrmann, Falk Pätzold, Magdalena Pühl, Gregor Rehder, Anke Roiger
The Nord Stream pipeline leaks on 26 September 2022 released 465 ± 20 kt of methane into the atmosphere, which is the largest recorded transient anthropogenic methane emission event. While most of the gas escaped directly to the atmosphere, a fraction dissolved in the water. So far, studies on the fate of this dissolved methane rely on pipeline volumetric estimates or spatially sparse concentration measurements and ocean models. Here, we use atmospheric measurements with broad spatial coverage obtained from an airborne platform to estimate outgassing of 19-48 t h−1 on 5 October 2022. Our results broadly agree with ocean models but reveal uncertainties such as inaccuracies in their spatial emission distribution. Thus, we provide a data-driven constraint on the fate of the methane from the Nord Stream pipelines in the Baltic Sea. These results demonstrate the benefit of a fast-response airborne mission to track a dynamic methane emission event.
{"title":"Airborne observations reveal the fate of the methane from the Nord Stream pipelines","authors":"Friedemann Reum, Julia Marshall, Henry C. Bittig, Lutz Bretschneider, Göran Broström, Anusha L. Dissanayake, Theo Glauch, Klaus-Dirk Gottschaldt, Jonas Gros, Heidi Huntrieser, Astrid Lampert, Michael Lichtenstern, Scot M. Miller, Martin Mohrmann, Falk Pätzold, Magdalena Pühl, Gregor Rehder, Anke Roiger","doi":"10.1038/s41467-024-53780-7","DOIUrl":"https://doi.org/10.1038/s41467-024-53780-7","url":null,"abstract":"<p>The Nord Stream pipeline leaks on 26 September 2022 released 465 ± 20 kt of methane into the atmosphere, which is the largest recorded transient anthropogenic methane emission event. While most of the gas escaped directly to the atmosphere, a fraction dissolved in the water. So far, studies on the fate of this dissolved methane rely on pipeline volumetric estimates or spatially sparse concentration measurements and ocean models. Here, we use atmospheric measurements with broad spatial coverage obtained from an airborne platform to estimate outgassing of 19-48 t h<sup>−1</sup> on 5 October 2022. Our results broadly agree with ocean models but reveal uncertainties such as inaccuracies in their spatial emission distribution. Thus, we provide a data-driven constraint on the fate of the methane from the Nord Stream pipelines in the Baltic Sea. These results demonstrate the benefit of a fast-response airborne mission to track a dynamic methane emission event.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"68 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-024-55687-9
Moritz Lehners, Hannes Schmidt, Maria T. K. Zaldivia, Daniel Stehle, Michael Krämer, Andreas Peter, Julia Adler, Robert Lukowski, Susanne Feil, Robert Feil
A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions. Correlative profiling of pathway activity and VSMC phenotype at the single-cell level shows that phenotypic modulation of contractile VSMCs to chondrocyte-like plaque cells during atherogenesis is associated with a switch from ANP/GC‑A to CNP/GC‑B signaling. Silencing of the CNP/GC-B axis in VSMCs results in an increase of chondrocyte-like plaque cells. These findings indicate that the CNP/GC-B/cGMP pathway is a marker and atheroprotective regulator of modulated VSMCs, limiting their transition to chondrocyte-like cells. Overall, this study highlights the plasticity of cGMP signaling in VSMCs and suggests analogies between CNP-dependent remodeling of bone and blood vessels.
{"title":"Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis","authors":"Moritz Lehners, Hannes Schmidt, Maria T. K. Zaldivia, Daniel Stehle, Michael Krämer, Andreas Peter, Julia Adler, Robert Lukowski, Susanne Feil, Robert Feil","doi":"10.1038/s41467-024-55687-9","DOIUrl":"https://doi.org/10.1038/s41467-024-55687-9","url":null,"abstract":"<p>A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions. Correlative profiling of pathway activity and VSMC phenotype at the single-cell level shows that phenotypic modulation of contractile VSMCs to chondrocyte-like plaque cells during atherogenesis is associated with a switch from ANP/GC‑A to CNP/GC‑B signaling. Silencing of the CNP/GC-B axis in VSMCs results in an increase of chondrocyte-like plaque cells. These findings indicate that the CNP/GC-B/cGMP pathway is a marker and atheroprotective regulator of modulated VSMCs, limiting their transition to chondrocyte-like cells. Overall, this study highlights the plasticity of cGMP signaling in VSMCs and suggests analogies between CNP-dependent remodeling of bone and blood vessels.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"29 4 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-025-56097-1
Sung-Hyun Yoon, Chae youn Kim, Eunju Lee, Changjun Lee, Kyung-Seo Lee, Jaeho Lee, Hana Park, Bokeum Choi, Inhwa Hwang, Junhan Kim, Tae-Gyun Kim, Junghyun Son, Young-Min Hyun, Seunghee Hong, Je-Wook Yu
Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain. Using a mouse model with cell-specific hyperactivation of NLRP3, we identify microglial NLRP3 activation as essential for peripheral inflammation-induced BBB disruption. Conversely, NLRP3 and microglial gasdermin D (GSDMD) deficiency markedly attenuates lipopolysaccharide-induced BBB breakdown. Notably, IL-1β is not required for NLRP3-GSDMD-mediated BBB disruption. Instead, microglial NLRP3-GSDMD axis upregulates CXCL chemokines and matrix metalloproteinases around BBB via producing GDF-15, promoting the recruitment of CXCR2-containing neutrophils. Inhibition of neutrophil infiltration and matrix metalloproteinase activity significantly reduces NLRP3-mediated BBB impairment. Collectively, these findings reveal the important role of NLRP3-driven chemokine production in BBB disintegration, suggesting potential therapeutic targets to mitigate neuroinflammation.
{"title":"Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice","authors":"Sung-Hyun Yoon, Chae youn Kim, Eunju Lee, Changjun Lee, Kyung-Seo Lee, Jaeho Lee, Hana Park, Bokeum Choi, Inhwa Hwang, Junhan Kim, Tae-Gyun Kim, Junghyun Son, Young-Min Hyun, Seunghee Hong, Je-Wook Yu","doi":"10.1038/s41467-025-56097-1","DOIUrl":"https://doi.org/10.1038/s41467-025-56097-1","url":null,"abstract":"<p>Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain. Using a mouse model with cell-specific hyperactivation of NLRP3, we identify microglial NLRP3 activation as essential for peripheral inflammation-induced BBB disruption. Conversely, NLRP3 and microglial gasdermin D (GSDMD) deficiency markedly attenuates lipopolysaccharide-induced BBB breakdown. Notably, IL-1β is not required for NLRP3-GSDMD-mediated BBB disruption. Instead, microglial NLRP3-GSDMD axis upregulates CXCL chemokines and matrix metalloproteinases around BBB via producing GDF-15, promoting the recruitment of CXCR2-containing neutrophils. Inhibition of neutrophil infiltration and matrix metalloproteinase activity significantly reduces NLRP3-mediated BBB impairment. Collectively, these findings reveal the important role of NLRP3-driven chemokine production in BBB disintegration, suggesting potential therapeutic targets to mitigate neuroinflammation.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"2 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41467-025-56021-7
Yudong Ren, Kangpeng Ye, Qiaolu Chen, Fujia Chen, Li Zhang, Yuang Pan, Wenhao Li, Xinrui Li, Lu Zhang, Hongsheng Chen, Yihao Yang
Topological phases have prevailed across diverse disciplines, spanning electronics, photonics, and acoustics. Hitherto, the understanding of these phases has centred on energy (frequency) bandstructures, showcasing topological boundary states at spatial interfaces. Recent strides have uncovered a unique category of bandstructures characterised by gaps in momentum, referred to as momentum bandgaps or k gaps, notably driven by breakthroughs in photonic time crystals. This discovery hints at abundant topological phases defined within momentum bands, alongside a wealth of topological boundary states in the time domain. Here, we report the experimental observation of k-gap topology in a large-scale optical temporal synthetic lattice, manifesting as temporal topological boundary states. These boundary states are uniquely situated at temporal interfaces between two subsystems with distinct k-gap topology. Counterintuitively, despite the exponential amplification of k-gap modes within both subsystems, these topological boundary states exhibit decay in both temporal directions [i.e., with energy growing (decaying) before (after) the temporal interfaces]. Our findings mark a significant pathway for delving into k gaps, temporal topological states, and time-varying physics.
{"title":"Observation of momentum-gap topology of light at temporal interfaces in a time-synthetic lattice","authors":"Yudong Ren, Kangpeng Ye, Qiaolu Chen, Fujia Chen, Li Zhang, Yuang Pan, Wenhao Li, Xinrui Li, Lu Zhang, Hongsheng Chen, Yihao Yang","doi":"10.1038/s41467-025-56021-7","DOIUrl":"https://doi.org/10.1038/s41467-025-56021-7","url":null,"abstract":"<p>Topological phases have prevailed across diverse disciplines, spanning electronics, photonics, and acoustics. Hitherto, the understanding of these phases has centred on energy (frequency) bandstructures, showcasing topological boundary states at spatial interfaces. Recent strides have uncovered a unique category of bandstructures characterised by gaps in momentum, referred to as momentum bandgaps or <i>k</i> gaps, notably driven by breakthroughs in photonic time crystals. This discovery hints at abundant topological phases defined within momentum bands, alongside a wealth of topological boundary states in the time domain. Here, we report the experimental observation of <i>k</i>-gap topology in a large-scale optical temporal synthetic lattice, manifesting as temporal topological boundary states. These boundary states are uniquely situated at temporal interfaces between two subsystems with distinct <i>k</i>-gap topology. Counterintuitively, despite the exponential amplification of <i>k</i>-gap modes within both subsystems, these topological boundary states exhibit decay in both temporal directions [i.e., with energy growing (decaying) before (after) the temporal interfaces]. Our findings mark a significant pathway for delving into <i>k</i> gaps, temporal topological states, and time-varying physics.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"31 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}