Jiawei Tang, Weiwei Sun, Chaofan Chen, Lars Bannenberg, Xuehang Wang, Tingwei Zhu, Litao Sun, Jinlan Wang, Guobing Ying, Yu Xie, Naresh C. Osti, Alexander I. Kolesnikov, Eugene Mamontov, Madhusudan Tyagi, Jingsong Huang, Paul R. C. Kent
Nanoconfined water exhibits unique properties compared to bulk water due to limited quantities, frustrated hydrogen bonding, and surface interactions, which are fundamental for energy storage and transport applications. We integrate machine learning–accelerated ab initio molecular dynamics with x-ray diffraction (XRD) and inelastic neutron scattering (INS) to systematically analyze the thermodynamic and dynamic behavior of water confined between functionalized (-F, -O, and -OH) two-dimensional (2D) Ti 3 C 2 T x MXene layers. As water intercalates between layers, the interlayer spacing exhibits layer-dependent staging characteristics. The water polarization can be flipped by the count and morphology of intercalated molecules interacting with MXene surface groups, resulting in varying electrostatic potential profiles. On the basis of interfacial electrostatic potential, hydrogen bond lifetime, and molecular orientation, we establish a linear combination of exponential model describing water diffusivity. These computational insights align well with experimental x-ray and neutron measurements, suggesting strategies for tuning water morphology and transport by tailoring MXene surface chemistry and water content for electrochemical energy storage and nanofluidic applications.
与散装水相比，由于数量有限、氢键受挫和表面相互作用，纳米承压水表现出独特的性质，这是能量储存和传输应用的基础。我们将机器学习加速从头算分子动力学与x射线衍射（XRD）和非弹性中子散射（INS）相结合，系统地分析了水在功能化（-F， -O和-OH）二维（2D） Ti 3c2txmxene层之间的热力学和动力学行为。当水在层间穿插时，层间间距表现出与层相关的分期特征。通过与MXene表面基团相互作用的插层分子的数量和形态可以翻转水的极化，从而产生不同的静电势分布。在界面静电势、氢键寿命和分子取向的基础上，建立了描述水扩散系数的线性组合指数模型。这些计算见解与实验x射线和中子测量结果很好地吻合，为电化学储能和纳米流体应用提供了通过调整MXene表面化学和水含量来调整水形态和传输的策略。
{"title":"Altered morphology and diffusivity of water confined in MXenes: Machine learning–accelerated computations combined with experiments","authors":"Jiawei Tang, Weiwei Sun, Chaofan Chen, Lars Bannenberg, Xuehang Wang, Tingwei Zhu, Litao Sun, Jinlan Wang, Guobing Ying, Yu Xie, Naresh C. Osti, Alexander I. Kolesnikov, Eugene Mamontov, Madhusudan Tyagi, Jingsong Huang, Paul R. C. Kent","doi":"10.1126/sciadv.adz1780","DOIUrl":"https://doi.org/10.1126/sciadv.adz1780","url":null,"abstract":"Nanoconfined water exhibits unique properties compared to bulk water due to limited quantities, frustrated hydrogen bonding, and surface interactions, which are fundamental for energy storage and transport applications. We integrate machine learning–accelerated ab initio molecular dynamics with x-ray diffraction (XRD) and inelastic neutron scattering (INS) to systematically analyze the thermodynamic and dynamic behavior of water confined between functionalized (-F, -O, and -OH) two-dimensional (2D) Ti <jats:sub>3</jats:sub> C <jats:sub>2</jats:sub> T <jats:italic toggle=\"yes\"> <jats:sub>x</jats:sub> </jats:italic> MXene layers. As water intercalates between layers, the interlayer spacing exhibits layer-dependent staging characteristics. The water polarization can be flipped by the count and morphology of intercalated molecules interacting with MXene surface groups, resulting in varying electrostatic potential profiles. On the basis of interfacial electrostatic potential, hydrogen bond lifetime, and molecular orientation, we establish a linear combination of exponential model describing water diffusivity. These computational insights align well with experimental x-ray and neutron measurements, suggesting strategies for tuning water morphology and transport by tailoring MXene surface chemistry and water content for electrochemical energy storage and nanofluidic applications.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"190 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507242","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}
Wensai Shang, Ji Liu, Zigong Xu, Chao Yue, Ruilong Guo, Chao Xiao, Quanqi Shi, Robert F. Wimmer-Schweingruber, Jingnan Guo, Alexander W. Degeling, Robert Rankin, Anmin Tian, Qiu-Gang Zong, Chenyao Han, Jong-Sun Park, Huizi Wang, Wenlong Liu, Suiyan Fu, L. M. Zhai, D. Chen, Sulan Ni, T. L. Chen
In regions of the Solar System distant from planetary magnetic fields, galactic cosmic rays (GCRs) have generally been assumed to be uniformly distributed over the Earth-Moon distance. However, our analysis of data from the LND (Lunar Lander Neutron and Dosimetry) experiment onboard the Chang’E-4 lander revealed a region of reduced GCR flux in the prenoon sector of the lunar orbit. Further investigation suggests the presence of an energetic particle cavity, formed by Earth’s magnetic field acting as an obstacle to GCR propagation. This cavity indicates that the influence of Earth’s magnetic field within the space environment extends unexpectedly up to and far beyond the lunar orbit. This finding offers the potential to avoid high radiation levels during future lunar exploration and deep-space missions.
{"title":"A galactic cosmic ray cavity in Earth-Moon space","authors":"Wensai Shang, Ji Liu, Zigong Xu, Chao Yue, Ruilong Guo, Chao Xiao, Quanqi Shi, Robert F. Wimmer-Schweingruber, Jingnan Guo, Alexander W. Degeling, Robert Rankin, Anmin Tian, Qiu-Gang Zong, Chenyao Han, Jong-Sun Park, Huizi Wang, Wenlong Liu, Suiyan Fu, L. M. Zhai, D. Chen, Sulan Ni, T. L. Chen","doi":"10.1126/sciadv.adv1908","DOIUrl":"https://doi.org/10.1126/sciadv.adv1908","url":null,"abstract":"In regions of the Solar System distant from planetary magnetic fields, galactic cosmic rays (GCRs) have generally been assumed to be uniformly distributed over the Earth-Moon distance. However, our analysis of data from the LND (Lunar Lander Neutron and Dosimetry) experiment onboard the Chang’E-4 lander revealed a region of reduced GCR flux in the prenoon sector of the lunar orbit. Further investigation suggests the presence of an energetic particle cavity, formed by Earth’s magnetic field acting as an obstacle to GCR propagation. This cavity indicates that the influence of Earth’s magnetic field within the space environment extends unexpectedly up to and far beyond the lunar orbit. This finding offers the potential to avoid high radiation levels during future lunar exploration and deep-space missions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"16 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507260","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}
Han Fang, Meagan Mulcair, Jia-Peng Han, Bo Zhang, Brian Space, Shi-Qiang Wang, Mei-Hui Yu, Ze Chang, Xian-He Bu
The pursuit of selective adsorption for separating molecules with similar shapes and interactions remains a formidable challenge. This work harnesses a powerful, previously unrecognized mechanism in a flexible metal-organic framework (Flex-Cd-MOF-3) to achieve switchable adsorption selectivity. Specifically, Flex-Cd-MOF-3, a descendant of Flex-Cd-MOF-2 with increased linker rigidity and functionalization, exhibits both local rearrangements and reversible framework expansion or shrinkage, showing phase-dependent propylene/propane selectivity. Considering propane, mutually beneficial conformational changes in the material and sorbate co-occur that are not possible with rigid propylene, reshaping the energy landscapes. These distinct interaction mechanisms, for otherwise very similar molecules, directly lead to pore swelling and shrinking at different pressures and phase switchable selectivity. An innovative modeling approach was developed that describes the full desorption pathway, explaining the relative binding energies and the sorbate-dependent mechanism of pore shrinkage. This work establishes cooperative sorbate-sorbent adaptation as a generalizable adsorption mechanism for achieving precise separation of similar molecules through distinct intermolecular interactions.
{"title":"Harnessing cooperative sorbate-sorbent adaptation in a flexible metal-organic framework for switchable hydrocarbon separation","authors":"Han Fang, Meagan Mulcair, Jia-Peng Han, Bo Zhang, Brian Space, Shi-Qiang Wang, Mei-Hui Yu, Ze Chang, Xian-He Bu","doi":"10.1126/sciadv.aee4346","DOIUrl":"https://doi.org/10.1126/sciadv.aee4346","url":null,"abstract":"The pursuit of selective adsorption for separating molecules with similar shapes and interactions remains a formidable challenge. This work harnesses a powerful, previously unrecognized mechanism in a flexible metal-organic framework (Flex-Cd-MOF-3) to achieve switchable adsorption selectivity. Specifically, Flex-Cd-MOF-3, a descendant of Flex-Cd-MOF-2 with increased linker rigidity and functionalization, exhibits both local rearrangements and reversible framework expansion or shrinkage, showing phase-dependent propylene/propane selectivity. Considering propane, mutually beneficial conformational changes in the material and sorbate co-occur that are not possible with rigid propylene, reshaping the energy landscapes. These distinct interaction mechanisms, for otherwise very similar molecules, directly lead to pore swelling and shrinking at different pressures and phase switchable selectivity. An innovative modeling approach was developed that describes the full desorption pathway, explaining the relative binding energies and the sorbate-dependent mechanism of pore shrinkage. This work establishes cooperative sorbate-sorbent adaptation as a generalizable adsorption mechanism for achieving precise separation of similar molecules through distinct intermolecular interactions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"60 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507263","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}
Seismicity is primarily driven by tectonics, but stress variations of natural or human-made origin can induce detectable modulations, offering insights into earthquake physics. Here, we identify regions in California exhibiting significant seasonal modulations of seismicity rate linked to hydrological surface loading but no significant semidiurnal tidal modulation. The peak seismicity rate lags behind the peak stressing rate by half a month. Assuming instantaneous nucleation substantially overpredicts the response, whereas time-dependent nucleation governed by rate-and-state friction accurately captures both the amplitude and the time delay with friction-stress parameter a σ ~ 1 to 10 kilopascals (kPa) and characteristic relaxation time ta ~ 0.05 to 1 year. The seismicity response to tidal and seasonal stress perturbations allows us to probe fault mechanical properties, providing a way to improve seismic hazard assessment.
{"title":"Seismic rhythms: Earthquake response to tectonic, hydrological, and tidal forcing in California","authors":"Krittanon Sirorattanakul, Jean-Philippe Avouac","doi":"10.1126/sciadv.adz5711","DOIUrl":"https://doi.org/10.1126/sciadv.adz5711","url":null,"abstract":"Seismicity is primarily driven by tectonics, but stress variations of natural or human-made origin can induce detectable modulations, offering insights into earthquake physics. Here, we identify regions in California exhibiting significant seasonal modulations of seismicity rate linked to hydrological surface loading but no significant semidiurnal tidal modulation. The peak seismicity rate lags behind the peak stressing rate by half a month. Assuming instantaneous nucleation substantially overpredicts the response, whereas time-dependent nucleation governed by rate-and-state friction accurately captures both the amplitude and the time delay with friction-stress parameter <jats:italic toggle=\"yes\">a</jats:italic> σ ~ 1 to 10 kilopascals (kPa) and characteristic relaxation time <jats:italic toggle=\"yes\">t</jats:italic> <jats:sub> <jats:italic toggle=\"yes\">a</jats:italic> </jats:sub> ~ 0.05 to 1 year. The seismicity response to tidal and seasonal stress perturbations allows us to probe fault mechanical properties, providing a way to improve seismic hazard assessment.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"17 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507266","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}
Yao Shi, Göran Widmalm, Charlotte Sorieul, Thomas J. Roodsant, Jeffrey S. Rush, Natalia Korotkova, Manouk Vrieling, Antonius A. C. Jacobs, Mirlin Spaninks, Ries Grommen, C. Coral Domínguez-Medina, Irene M. Schimmel, Nicole N. van der Wel, Cameron W. Kenner, Christian Heiss, Parastoo Azadi, Li Tan, Jeroen D. C. Codée, Arjan Stegeman, Constance Schultsz, Lindert Benedictus, Nina M. van Sorge
Streptococcus suis is a largely neglected but emerging bacterial zoonotic pathogen of global concern for animal welfare, antibiotic resistance development, and human health. No effective vaccines are now available. Here, we identified and characterized the function and structure of two cell wall polysaccharide variants in pathogenic S. suis strains using genetic deletion and (heterologous) complementation, lectin staining, glycan composition analysis, and specialized NMR spectroscopy. Both glycan variants were anionic polymers that differed in the presence of glucose in the side chain as a result of allelic variation in a glycosyltransferase gene. Deletion of this variable glycosyltransferase revealed an identical glycan “core” and affected S. suis morphology and lysozyme resistance. Immunization of pigs with this core domain elicited antibodies that recognized antigenically diverse pathogenic S. suis strains and induced complement deposition on encapsulated pathogenic S. suis strains. This study provides valuable insights for developing next-generation glycoconjugate vaccines, whereby a single-glycan target could protect against the emerging zoonotic pathogen S. suis .
{"title":"A conserved glycan motif induces broadly reactive functional antibodies against the zoonotic pathogen Streptococcus suis","authors":"Yao Shi, Göran Widmalm, Charlotte Sorieul, Thomas J. Roodsant, Jeffrey S. Rush, Natalia Korotkova, Manouk Vrieling, Antonius A. C. Jacobs, Mirlin Spaninks, Ries Grommen, C. Coral Domínguez-Medina, Irene M. Schimmel, Nicole N. van der Wel, Cameron W. Kenner, Christian Heiss, Parastoo Azadi, Li Tan, Jeroen D. C. Codée, Arjan Stegeman, Constance Schultsz, Lindert Benedictus, Nina M. van Sorge","doi":"10.1126/sciadv.adz1854","DOIUrl":"https://doi.org/10.1126/sciadv.adz1854","url":null,"abstract":"<jats:italic toggle=\"yes\">Streptococcus suis</jats:italic> is a largely neglected but emerging bacterial zoonotic pathogen of global concern for animal welfare, antibiotic resistance development, and human health. No effective vaccines are now available. Here, we identified and characterized the function and structure of two cell wall polysaccharide variants in pathogenic <jats:italic toggle=\"yes\">S. suis</jats:italic> strains using genetic deletion and (heterologous) complementation, lectin staining, glycan composition analysis, and specialized NMR spectroscopy. Both glycan variants were anionic polymers that differed in the presence of glucose in the side chain as a result of allelic variation in a glycosyltransferase gene. Deletion of this variable glycosyltransferase revealed an identical glycan “core” and affected <jats:italic toggle=\"yes\">S. suis</jats:italic> morphology and lysozyme resistance. Immunization of pigs with this core domain elicited antibodies that recognized antigenically diverse pathogenic <jats:italic toggle=\"yes\">S. suis</jats:italic> strains and induced complement deposition on encapsulated pathogenic <jats:italic toggle=\"yes\">S. suis</jats:italic> strains. This study provides valuable insights for developing next-generation glycoconjugate vaccines, whereby a single-glycan target could protect against the emerging zoonotic pathogen <jats:italic toggle=\"yes\">S. suis</jats:italic> .","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"18 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507234","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}
Václav Krupička, Florent Grélard, Landry Blanc, Aleksandra Popowich, José Luis Lazarte Luna, Nicolas Desbenoit, Julie Arslanoglu, Caroline Tokarski
Layer-by-layer characterization of modern and historic paintings is essential for understanding how an artwork was created and how it has changed over time. This information can reveal historical or societal insights, inform attribution and classification, and support preservation efforts. The determination of the identity, structure, and composition of art material remains challenging due to the complex, multilayered nature of paintings. These structures often contain mixtures of organic and inorganic components, with unknown in situ chemical interactions, that create cross-linked and chemically modified molecular networks and assemblies. In this work, we have developed a method with high chemical specificity to identify and map organic and inorganic components in modern and historic multilayered paint systems. Our approach achieves an unprecedented level of molecular detail using a single technique. In addition, we have designed the method for automated composition assignment of individual layer through high-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) and a dedicated composition prediction model.
{"title":"Layer-by-layer decoding of contemporary and historic painting composition using MALDI mass spectrometry imaging and machine learning","authors":"Václav Krupička, Florent Grélard, Landry Blanc, Aleksandra Popowich, José Luis Lazarte Luna, Nicolas Desbenoit, Julie Arslanoglu, Caroline Tokarski","doi":"10.1126/sciadv.adz4427","DOIUrl":"https://doi.org/10.1126/sciadv.adz4427","url":null,"abstract":"Layer-by-layer characterization of modern and historic paintings is essential for understanding how an artwork was created and how it has changed over time. This information can reveal historical or societal insights, inform attribution and classification, and support preservation efforts. The determination of the identity, structure, and composition of art material remains challenging due to the complex, multilayered nature of paintings. These structures often contain mixtures of organic and inorganic components, with unknown in situ chemical interactions, that create cross-linked and chemically modified molecular networks and assemblies. In this work, we have developed a method with high chemical specificity to identify and map organic and inorganic components in modern and historic multilayered paint systems. Our approach achieves an unprecedented level of molecular detail using a single technique. In addition, we have designed the method for automated composition assignment of individual layer through high-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) and a dedicated composition prediction model.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"15 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507246","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}
Sazzad Mahmood, Stephen Lu, Ana Beatriz Barletta Ferreira, Markus Berger, Oladele A. Oluwayiose, Christine A. Schneider, Jacqueline M. Leung, Melina Garcia Guizzo, Yixiang Zhang, Randall Johnson, Kevin W. Cormier, Motoshi Suzuki, Nathan T. Brandes, Gwendolyn Cooper, Joshua Gold, Benjamin Schwarz, Lisa R. Olano, Justin Lack, Carolina Barillas-Mury, José M. Ribeiro, Lucas Tirloni
Ticks transmit a wide range of pathogens to humans. During blood feeding, they inject salivary proteins that suppress host immune responses, enabling prolonged feeding and pathogen transmission. A hallmark of this process is the dynamic reprogramming of salivary gene expression, known as the sialome switch. Here, we describe a previously unrecognized cellular mechanism underlying this phenomenon in two medically important tick species. Using integrated multi-omics and imaging approaches, we identified a conserved population of undifferentiated salivary gland precursor cells in unfed ticks. Upon host attachment, these precursors undergo terminal differentiation into specialized secretory subtypes through a conserved transcriptional and signaling framework that drives salivary gland activation and maturation. Unlike other blood-feeding arthropods, tick salivary glands dynamically remodel in response to host contact, producing saliva with a shifting composition. This study suggests the cellular basis of adult female tick salivary gland maturation and offers targets to disrupt feeding and pathogen transmission.
{"title":"Blood feeding triggers the terminal differentiation of precursor cells in tick salivary glands","authors":"Sazzad Mahmood, Stephen Lu, Ana Beatriz Barletta Ferreira, Markus Berger, Oladele A. Oluwayiose, Christine A. Schneider, Jacqueline M. Leung, Melina Garcia Guizzo, Yixiang Zhang, Randall Johnson, Kevin W. Cormier, Motoshi Suzuki, Nathan T. Brandes, Gwendolyn Cooper, Joshua Gold, Benjamin Schwarz, Lisa R. Olano, Justin Lack, Carolina Barillas-Mury, José M. Ribeiro, Lucas Tirloni","doi":"10.1126/sciadv.aec7620","DOIUrl":"https://doi.org/10.1126/sciadv.aec7620","url":null,"abstract":"Ticks transmit a wide range of pathogens to humans. During blood feeding, they inject salivary proteins that suppress host immune responses, enabling prolonged feeding and pathogen transmission. A hallmark of this process is the dynamic reprogramming of salivary gene expression, known as the sialome switch. Here, we describe a previously unrecognized cellular mechanism underlying this phenomenon in two medically important tick species. Using integrated multi-omics and imaging approaches, we identified a conserved population of undifferentiated salivary gland precursor cells in unfed ticks. Upon host attachment, these precursors undergo terminal differentiation into specialized secretory subtypes through a conserved transcriptional and signaling framework that drives salivary gland activation and maturation. Unlike other blood-feeding arthropods, tick salivary glands dynamically remodel in response to host contact, producing saliva with a shifting composition. This study suggests the cellular basis of adult female tick salivary gland maturation and offers targets to disrupt feeding and pathogen transmission.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"17 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507261","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}
Autoimmune T cells orchestrate joint inflammation and pain in concert with synovial macrophages; however, the mechanisms governing the development and functional diversification of these macrophages remain unclear. Using a model of T helper 17 cell (T H 17 cell)–mediated autoimmune arthritis, we show that joint-infiltrating Ly6C hi monocytes in response to autoimmune T H 17 cells, rather than resident synovial macrophages, are the primary mediators of disease pathogenesis. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical component of the pathogenic circuit driven by arthritogenic T H 17 cells, does not contribute to monocyte recruitment to the synovium but facilitates their subsequent differentiation into functionally distinct synovial macrophage subsets, thereby amplifying joint inflammation. Single-cell RNA sequencing identified two GM-CSF–dependent subpopulations of pathogenic synovial macrophages—Arginase-1 + and epithelial cell adhesion molecule (EpCAM) + clusters—both expressing proinflammatory cytokines and matrix metalloproteinases. Notably, EpCAM + macrophages uniquely express Ccl17 , a pronociceptive mediator implicated in arthritic pain. Collectively, these findings delineate a GM-CSF–driven program of macrophage diversification that underpins both joint inflammation and pain, implicating this axis in the chronic activation of inflammatory and nociceptive pathways in autoimmune arthritis.
{"title":"Pathogenic GM-CSF drives functional diversification of inflammatory macrophages in autoimmune arthritis","authors":"Hiroki Mukoyama, Yusuke Takeuchi, Daiya Ohara, Yoonha Lee, Hitomi Watanabe, Hiroki Kato, Gen Kondoh, Akio Morinobu, Keiji Hirota","doi":"10.1126/sciadv.aec0986","DOIUrl":"https://doi.org/10.1126/sciadv.aec0986","url":null,"abstract":"Autoimmune T cells orchestrate joint inflammation and pain in concert with synovial macrophages; however, the mechanisms governing the development and functional diversification of these macrophages remain unclear. Using a model of T helper 17 cell (T <jats:sub>H</jats:sub> 17 cell)–mediated autoimmune arthritis, we show that joint-infiltrating Ly6C <jats:sup>hi</jats:sup> monocytes in response to autoimmune T <jats:sub>H</jats:sub> 17 cells, rather than resident synovial macrophages, are the primary mediators of disease pathogenesis. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical component of the pathogenic circuit driven by arthritogenic T <jats:sub>H</jats:sub> 17 cells, does not contribute to monocyte recruitment to the synovium but facilitates their subsequent differentiation into functionally distinct synovial macrophage subsets, thereby amplifying joint inflammation. Single-cell RNA sequencing identified two GM-CSF–dependent subpopulations of pathogenic synovial macrophages—Arginase-1 <jats:sup>+</jats:sup> and epithelial cell adhesion molecule (EpCAM) <jats:sup>+</jats:sup> clusters—both expressing proinflammatory cytokines and matrix metalloproteinases. Notably, EpCAM <jats:sup>+</jats:sup> macrophages uniquely express <jats:italic toggle=\"yes\">Ccl17</jats:italic> , a pronociceptive mediator implicated in arthritic pain. Collectively, these findings delineate a GM-CSF–driven program of macrophage diversification that underpins both joint inflammation and pain, implicating this axis in the chronic activation of inflammatory and nociceptive pathways in autoimmune arthritis.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"16 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507236","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}
Yu Wang, Runxin Zhou, Xiao Zeng, Dingyuan Guo, Nan Li, Shuangli Li, Xu Zhang, Mingxuan Shi, Li Jiang, Mingzhu Fan, Shan Feng, Lili He, Anbing Shi, Ke Liu, Yusong R. Guo, Lichun He, Mingchang Li, Yugang Wang
Circadian CLOCK (circadian locomotor output cycles kaput) can mediate chromatin remodeling events implicated in gene transcription. The acetyltransferase roles of CLOCK are well studied, but CLOCK-mediated chromatin remodeling events are not well understood. We report that CLOCK can use glutaryl–coenzyme A to catalyze glutarylation at histone H3 Lys 37 (H3K37glut). H3K37glut is undocumented. The glutaryl moiety of H3K37glut can be pulled by its neighboring H3H39 and H3R40 residues via electrostatic interactions and bent over the pyrrolidine ring of the neighboring H3P38 residue, forming a conformation to block SETD2 binding to the N-terminal tail of histone H3. It reduces SETD2-catalyzed H3K36 trimethylation (H3K36me3) and the H3K36me3-regulated downstream pathways in cells. In glioblastoma, both CLOCK protein and CLOCK-mediated H3K37glut are abnormally up-regulated. H3K37glut significantly correlates with suppressed H3K36me3 level in human glioblastoma tissues, tumor progression, and survival of patients with glioblastoma. This study expands the repertoire of histone modification and diversifies the mechanisms underlying CLOCK-implicated chromatin dynamics. It also unearths an undocumented mechanistic link between dysregulated circadian CLOCK and decreased H3K36me3 pathways in glioblastoma.
{"title":"CLOCK-catalyzed histone H3K37 glutarylation suppresses H3K36 trimethylation pathways in glioblastoma","authors":"Yu Wang, Runxin Zhou, Xiao Zeng, Dingyuan Guo, Nan Li, Shuangli Li, Xu Zhang, Mingxuan Shi, Li Jiang, Mingzhu Fan, Shan Feng, Lili He, Anbing Shi, Ke Liu, Yusong R. Guo, Lichun He, Mingchang Li, Yugang Wang","doi":"10.1126/sciadv.aea1127","DOIUrl":"https://doi.org/10.1126/sciadv.aea1127","url":null,"abstract":"Circadian CLOCK (circadian locomotor output cycles kaput) can mediate chromatin remodeling events implicated in gene transcription. The acetyltransferase roles of CLOCK are well studied, but CLOCK-mediated chromatin remodeling events are not well understood. We report that CLOCK can use glutaryl–coenzyme A to catalyze glutarylation at histone H3 Lys <jats:sup>37</jats:sup> (H3K37glut). H3K37glut is undocumented. The glutaryl moiety of H3K37glut can be pulled by its neighboring H3H39 and H3R40 residues via electrostatic interactions and bent over the pyrrolidine ring of the neighboring H3P38 residue, forming a conformation to block SETD2 binding to the N-terminal tail of histone H3. It reduces SETD2-catalyzed H3K36 trimethylation (H3K36me3) and the H3K36me3-regulated downstream pathways in cells. In glioblastoma, both CLOCK protein and CLOCK-mediated H3K37glut are abnormally up-regulated. H3K37glut significantly correlates with suppressed H3K36me3 level in human glioblastoma tissues, tumor progression, and survival of patients with glioblastoma. This study expands the repertoire of histone modification and diversifies the mechanisms underlying CLOCK-implicated chromatin dynamics. It also unearths an undocumented mechanistic link between dysregulated circadian CLOCK and decreased H3K36me3 pathways in glioblastoma.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"15 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507237","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}
Pengfei Bai, Minh Huy Vu, Chiaki Komatsu, Ophelia Papoulas, Kazuo Ebine, Akira Nozawa, Tatsuya Sawasaki, Takashi Ueda, Edward M. Marcotte, Keiko U. Torii
Receptor kinases are pivotal for growth, development, and environmental response of plants. Yet, their regulatory mechanisms and spatial dynamics remain underexplored. The ERECTA-family receptor kinases coordinate diverse developmental processes, including stomatal development. To understand the proteomic landscape of the ERECTA-mediated signaling pathways, we report comparative analyses of the ERECTA interactome and proximitome by epitope-tagged affinity-purification (ET-AP) and TurboID-based proximity labeling (TbID-PL) mass spectrometry, respectively. While ET-AP recovered receptor complex components (e.g., TOO MANY MOUTHS), TbID-PL effectively captured transient associations with the components of endosomal trafficking, i.e., clathrin-mediated endocytosis machinery. We further identify that specific subfamily members of phosphatidylinositol-binding clathrin assembly proteins (PICALMs) interact with and synergistically regulate ERECTA internalization. Mutations in PICALMs impair ERECTA endocytosis and lead to excessive stomatal clustering by dampening the downstream signaling output. Together, we provide a proteomic atlas of the ERECTA signaling network and demonstrate that timely removal of receptor kinase by the endocytosis machinery is essential for active signal transduction enforcing stomatal patterning.
受体激酶是植物生长发育和环境反应的关键。然而，它们的调控机制和空间动态仍未得到充分探索。erecta家族受体激酶协调多种发育过程，包括气孔发育。为了了解ERECTA介导的信号通路的蛋白质组学特征，我们分别通过表位标记亲和纯化（ET-AP）和基于turboid的接近标记（TbID-PL）质谱法对ERECTA相互作用组和邻近组进行了比较分析。虽然ET-AP恢复了受体复合物组分（例如，TOO MANY mouth），但TbID-PL有效地捕获了与内体运输组分的短暂关联，即网格蛋白介导的内吞机制。我们进一步确定了磷脂酰肌醇结合网格蛋白组装蛋白（PICALMs）的特定亚家族成员与ERECTA内化相互作用并协同调节。picalm的突变会损害ERECTA的内吞作用，并通过抑制下游信号输出导致过度的气孔聚集。总之，我们提供了ERECTA信号网络的蛋白质组学图谱，并证明了内吞机制及时去除受体激酶对于加强气孔模式的主动信号转导至关重要。
{"title":"Comparative proteomic profiling of receptor kinase signaling reveals key trafficking components enforcing plant stomatal development","authors":"Pengfei Bai, Minh Huy Vu, Chiaki Komatsu, Ophelia Papoulas, Kazuo Ebine, Akira Nozawa, Tatsuya Sawasaki, Takashi Ueda, Edward M. Marcotte, Keiko U. Torii","doi":"10.1126/sciadv.aeb6464","DOIUrl":"https://doi.org/10.1126/sciadv.aeb6464","url":null,"abstract":"Receptor kinases are pivotal for growth, development, and environmental response of plants. Yet, their regulatory mechanisms and spatial dynamics remain underexplored. The ERECTA-family receptor kinases coordinate diverse developmental processes, including stomatal development. To understand the proteomic landscape of the ERECTA-mediated signaling pathways, we report comparative analyses of the ERECTA interactome and proximitome by epitope-tagged affinity-purification (ET-AP) and TurboID-based proximity labeling (TbID-PL) mass spectrometry, respectively. While ET-AP recovered receptor complex components (e.g., TOO MANY MOUTHS), TbID-PL effectively captured transient associations with the components of endosomal trafficking, i.e., clathrin-mediated endocytosis machinery. We further identify that specific subfamily members of phosphatidylinositol-binding clathrin assembly proteins (PICALMs) interact with and synergistically regulate ERECTA internalization. Mutations in <jats:italic toggle=\"yes\">PICALMs</jats:italic> impair ERECTA endocytosis and lead to excessive stomatal clustering by dampening the downstream signaling output. Together, we provide a proteomic atlas of the ERECTA signaling network and demonstrate that timely removal of receptor kinase by the endocytosis machinery is essential for active signal transduction enforcing stomatal patterning.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"17 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506994","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}
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