Na Wu, En Wang, Daqiang Chen, Chao Lian, Yaxian Wang, Sheng Meng
Optical manipulation of spin-flip on a picosecond to femtosecond timescale has long been pursued to innovate next-generation electronic devices. However, understanding the ultrafast spin-electron-lattice coupled dynamics remains challenging, especially when the system is driven far from equilibrium. Here, we demonstrate an ultrafast light-induced spin-flip within 300 fs in Fe3GeTe2, a prototypical two-dimensional itinerant ferromagnet. Notably, by varying the laser fluence, we identify three distinct regimes that emerge assisted by a photoinduced single linear phonon mode, namely demagnetization, spin-flip, and spin-melting. We resolve the dominant role of displacively excited A1g phonons, while nonequilibrium electron occupation is essential to break the degeneracy of the spin up and down states and lower the spin-flip energy barrier. Accompanying the spin-flip, we also observe a sign change of the Berry curvature, implying involvement of nontrivial band topology. Our results provide a general guidance for optical manipulation of spin orders, holding promises for advancing future spintronics and information technology.
{"title":"Photoinduced femtosecond spin-flip assisted by a single-mode linear phonon","authors":"Na Wu, En Wang, Daqiang Chen, Chao Lian, Yaxian Wang, Sheng Meng","doi":"10.1126/sciadv.adv9616","DOIUrl":"10.1126/sciadv.adv9616","url":null,"abstract":"<div >Optical manipulation of spin-flip on a picosecond to femtosecond timescale has long been pursued to innovate next-generation electronic devices. However, understanding the ultrafast spin-electron-lattice coupled dynamics remains challenging, especially when the system is driven far from equilibrium. Here, we demonstrate an ultrafast light-induced spin-flip within 300 fs in Fe<sub>3</sub>GeTe<sub>2</sub>, a prototypical two-dimensional itinerant ferromagnet. Notably, by varying the laser fluence, we identify three distinct regimes that emerge assisted by a photoinduced single linear phonon mode, namely demagnetization, spin-flip, and spin-melting. We resolve the dominant role of displacively excited A<sub>1g</sub> phonons, while nonequilibrium electron occupation is essential to break the degeneracy of the spin up and down states and lower the spin-flip energy barrier. Accompanying the spin-flip, we also observe a sign change of the Berry curvature, implying involvement of nontrivial band topology. Our results provide a general guidance for optical manipulation of spin orders, holding promises for advancing future spintronics and information technology.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111411","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}
Zongyu Yue, Sheng Gou, Yexin Wang, Huacheng Li, Gregory Michael, Jianzhong Liu, Shujuan Sun, Yangting Lin, Kaichang Di, Qiuli Li, Yi Chen, Wei Yang, Bin Xie, Sen Hu, Shouding Li, Bo Zheng, Tianqiao Mao, Xianhua Li, Fuyuan Wu
The radiometric ages of the returned samples are the cornerstone of lunar cratering chronology models. However, all the previous samples were from the lunar nearside and the radiometric ages of those samples that can be associated with particular surfaces are <4.0 billion years. On 25 June 2024, Chang’e-6 successfully returned 1.935-kilogram samples from the lunar farside. The samples included local basalts with an age of 2807 ± 3 million years and the norites with an age of 4247 ± 5 million years likely corresponding to the age of the South Pole–Aitken basin. With these radiometric ages, we refined the lunar chronology function (CF) and verified that it is still consistent with a combination of an exponential decrease and a linear rate. We further derived the impacting rate and found it supports a smooth decay instead of abrupt changes of the impactor flux at early times. The refined lunar CF can be used to obtain more reliable ages for unsampled lunar areas and provide critical constraint for the lunar early impact history.
{"title":"Lunar chronology model with the Chang’e-6 farside samples and implications for the early impact history","authors":"Zongyu Yue, Sheng Gou, Yexin Wang, Huacheng Li, Gregory Michael, Jianzhong Liu, Shujuan Sun, Yangting Lin, Kaichang Di, Qiuli Li, Yi Chen, Wei Yang, Bin Xie, Sen Hu, Shouding Li, Bo Zheng, Tianqiao Mao, Xianhua Li, Fuyuan Wu","doi":"10.1126/sciadv.ady9265","DOIUrl":"10.1126/sciadv.ady9265","url":null,"abstract":"<div >The radiometric ages of the returned samples are the cornerstone of lunar cratering chronology models. However, all the previous samples were from the lunar nearside and the radiometric ages of those samples that can be associated with particular surfaces are <4.0 billion years. On 25 June 2024, Chang’e-6 successfully returned 1.935-kilogram samples from the lunar farside. The samples included local basalts with an age of 2807 ± 3 million years and the norites with an age of 4247 ± 5 million years likely corresponding to the age of the South Pole–Aitken basin. With these radiometric ages, we refined the lunar chronology function (CF) and verified that it is still consistent with a combination of an exponential decrease and a linear rate. We further derived the impacting rate and found it supports a smooth decay instead of abrupt changes of the impactor flux at early times. The refined lunar CF can be used to obtain more reliable ages for unsampled lunar areas and provide critical constraint for the lunar early impact history.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111426","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}
Mechanical stimuli originating from extracellular matrix have been proved to affect antitumor immunity by regulating dendritic cell (DC) locomotion. However, the immunological consequences of ultrasmall bioparticle–induced nanocollision remain largely an unexplored realm despite its ubiquitous and incessant occurrence within the in vivo milieu. Herein, we disclose that nanocollisions caused by endogenous bioparticles, such as extracellular vesicles, can induce localized membrane deformations. This spatially confined mechanical input activates Piezo1 at collision sites and promotes myosin IIA phosphorylation–mediated F-actin stabilization, enhancing DC intrinsic motility. Subsequent diffusion of Ca2+ up-regulates chemotaxis machinery, improving their capacity of tumor microenvironment patrolling and lymph node homing for antitumor immunity. This finding reveals a previously unidentified mechanoimmunological mechanism of immune surveillance. To accelerate the translation of this mechanism into clinical therapeutics, we developed an ultrasound-responsive nanocollision generator using gas-liquid-solid triphase conversion. This system achieves precise nanocollision to augment DC locomotion, promoting antitumor immunity in vivo.
{"title":"Nanocollision promotes locomotion of dendritic cells for tumor therapy","authors":"Qiangyuan Zhu, Shenglan Liu, Lei Chen, Xin Wang, Jiayi Liu, Cen Gao, Rongbing Tang","doi":"10.1126/sciadv.aeb7714","DOIUrl":"10.1126/sciadv.aeb7714","url":null,"abstract":"<div >Mechanical stimuli originating from extracellular matrix have been proved to affect antitumor immunity by regulating dendritic cell (DC) locomotion. However, the immunological consequences of ultrasmall bioparticle–induced nanocollision remain largely an unexplored realm despite its ubiquitous and incessant occurrence within the in vivo milieu. Herein, we disclose that nanocollisions caused by endogenous bioparticles, such as extracellular vesicles, can induce localized membrane deformations. This spatially confined mechanical input activates Piezo1 at collision sites and promotes myosin IIA phosphorylation–mediated F-actin stabilization, enhancing DC intrinsic motility. Subsequent diffusion of Ca<sup>2+</sup> up-regulates chemotaxis machinery, improving their capacity of tumor microenvironment patrolling and lymph node homing for antitumor immunity. This finding reveals a previously unidentified mechanoimmunological mechanism of immune surveillance. To accelerate the translation of this mechanism into clinical therapeutics, we developed an ultrasound-responsive nanocollision generator using gas-liquid-solid triphase conversion. This system achieves precise nanocollision to augment DC locomotion, promoting antitumor immunity in vivo.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111431","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}
Jason Boynewicz, Michael C. Thumann, Mark G. Raizen
Brownian motion is a foundational physical process characterized by a mean squared displacement that scales linearly in time in thermal equilibrium, known as diffusion. At short times, the mean squared displacement becomes ballistic, scaling as . This effect was predicted by Einstein in 1907 and recently observed experimentally. We report that this picture is only true on average; by conditioning specific initial velocities, we predict theoretically and confirm by experiment that the mean squared displacement becomes super-ballistic, with a power scaling law of . This result is due to the colored noise of incompressible fluids, resulting in a nonzero first moment for the thermal force when conditioned on nonzero initial velocities. These results are a step toward the unraveling of nonequilibrium dynamics of fluids.
{"title":"Observation of super-ballistic Brownian motion in liquid","authors":"Jason Boynewicz, Michael C. Thumann, Mark G. Raizen","doi":"10.1126/sciadv.aeb4579","DOIUrl":"10.1126/sciadv.aeb4579","url":null,"abstract":"<div >Brownian motion is a foundational physical process characterized by a mean squared displacement that scales linearly in time in thermal equilibrium, known as diffusion. At short times, the mean squared displacement becomes ballistic, scaling as <span><math><mrow><msup><mi>t</mi><mn>2</mn></msup></mrow></math></span>. This effect was predicted by Einstein in 1907 and recently observed experimentally. We report that this picture is only true on average; by conditioning specific initial velocities, we predict theoretically and confirm by experiment that the mean squared displacement becomes super-ballistic, with a power scaling law of <span><math><mrow><msup><mi>t</mi><mrow><mn>5</mn><mo>/</mo><mn>2</mn></mrow></msup></mrow></math></span>. This result is due to the colored noise of incompressible fluids, resulting in a nonzero first moment for the thermal force when conditioned on nonzero initial velocities. These results are a step toward the unraveling of nonequilibrium dynamics of fluids.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111437","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}
Increasing hydrostatic pressure induces the release of dissolved organic matter from rapidly settling marine particles and contributes to the depth attenuation of carbon fluxes.
不断增加的静水压力促使溶解的有机物从快速沉降的海洋颗粒中释放出来，并有助于碳通量的深度衰减。
{"title":"The ocean’s biological carbon pump under pressure","authors":"Jack J. Middelburg","doi":"10.1126/sciadv.aef3182","DOIUrl":"10.1126/sciadv.aef3182","url":null,"abstract":"<div >Increasing hydrostatic pressure induces the release of dissolved organic matter from rapidly settling marine particles and contributes to the depth attenuation of carbon fluxes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111422","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}
Liliane El Eid, Yusman Manchanda, Gregory Austin, Kieran Deane-Alder, Roxana-Maria Rujan, Zamara Mariam, Affiong I. Oqua, Matthew J. Belousoff, Jorge Bernardino de la Serna, Kyle W. Sloop, Guy A. Rutter, Alex Montoya, Dominic J. Withers, Steven J. Millership, Karim Bouzakri, Ben Jones, Christopher A. Reynolds, Patrick M. Sexton, Denise Wootten, Giuseppe Deganutti, Alejandra Tomas
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with GLP1R gene variation potentially linked to therapeutic outcomes. A GLP1R natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human GLP1R A316T mouse model. Human GLP1RA316T/A316T mice displayed lower fasting blood glucose versus wild-type littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion, and liver metabolism under a high-fat, high-sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in β cell models demonstrated that human GLP1R A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R–targeting therapies.
{"title":"In vivo functional profiling and structural characterization of the human GLP1R A316T variant","authors":"Liliane El Eid, Yusman Manchanda, Gregory Austin, Kieran Deane-Alder, Roxana-Maria Rujan, Zamara Mariam, Affiong I. Oqua, Matthew J. Belousoff, Jorge Bernardino de la Serna, Kyle W. Sloop, Guy A. Rutter, Alex Montoya, Dominic J. Withers, Steven J. Millership, Karim Bouzakri, Ben Jones, Christopher A. Reynolds, Patrick M. Sexton, Denise Wootten, Giuseppe Deganutti, Alejandra Tomas","doi":"10.1126/sciadv.adw0899","DOIUrl":"10.1126/sciadv.adw0899","url":null,"abstract":"<div >Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with <i>GLP1R</i> gene variation potentially linked to therapeutic outcomes. A <i>GLP1R</i> natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human <i>GLP1R</i> A316T mouse model. Human <i>GLP1R</i><sup>A316T/A316T</sup> mice displayed lower fasting blood glucose versus wild-type littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion, and liver metabolism under a high-fat, high-sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in β cell models demonstrated that human <i>GLP1R</i> A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R–targeting therapies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111430","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}
Peter Stief, Jutta Niggemann, Margot Bligh, Hagen Buck-Wiese, Urban Wünsch, Michael Steinke, Jan-Hendrik Hehemann, Ronnie N. Glud
Marine snow forms at the ocean surface, sinks to depth, and ultimately enables carbon sequestration in the seabed. Fast-sinking marine snow particles, such as diatom aggregates, encounter a rapid increase in hydrostatic pressure during their descent. Using incubations in rotating pressure tanks, we found that pressure levels corresponding to 2- to 6-kilometer water depth induce leakage of dissolved organic matter (DOM) from diatom aggregates equivalent to ~50% of their initial carbon contents. The leaked DOM proved to be diatom-derived and changed the amount and composition of DOM in the surrounding seawater substantially. Ultrahigh-resolution mass spectrometry, high protein-like fluorescence, and low carbon:nitrogen ratios classified the leaked DOM as labile. The bioavailability of leaked DOM was demonstrated by its rapid utilization by a pelagic microbial community, leaving mainly recalcitrant DOM behind. Pressure-induced DOM leakage likely weakens the gravitational “biological carbon pump” and supplies labile DOM to the pelagic microbiome of the deep ocean.
{"title":"Hydrostatic pressure induces strong leakage of dissolved organic matter from “marine snow” particles","authors":"Peter Stief, Jutta Niggemann, Margot Bligh, Hagen Buck-Wiese, Urban Wünsch, Michael Steinke, Jan-Hendrik Hehemann, Ronnie N. Glud","doi":"10.1126/sciadv.aec5677","DOIUrl":"10.1126/sciadv.aec5677","url":null,"abstract":"<div >Marine snow forms at the ocean surface, sinks to depth, and ultimately enables carbon sequestration in the seabed. Fast-sinking marine snow particles, such as diatom aggregates, encounter a rapid increase in hydrostatic pressure during their descent. Using incubations in rotating pressure tanks, we found that pressure levels corresponding to 2- to 6-kilometer water depth induce leakage of dissolved organic matter (DOM) from diatom aggregates equivalent to ~50% of their initial carbon contents. The leaked DOM proved to be diatom-derived and changed the amount and composition of DOM in the surrounding seawater substantially. Ultrahigh-resolution mass spectrometry, high protein-like fluorescence, and low carbon:nitrogen ratios classified the leaked DOM as labile. The bioavailability of leaked DOM was demonstrated by its rapid utilization by a pelagic microbial community, leaving mainly recalcitrant DOM behind. Pressure-induced DOM leakage likely weakens the gravitational “biological carbon pump” and supplies labile DOM to the pelagic microbiome of the deep ocean.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111419","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}
The idea that better cognitive functioning helps to close the gap between goals and behavior seems self-evident, yet empirical work has found unusually weak interindividual associations between cognitive task performance and real-world, goal-relevant outcomes. Here, we resolve this paradox by shifting from trait-level to state-level analysis. Leveraging a microtask design to measure daily fluctuations in cognitive function, goal setting and goal progress, mood, sleep, and motivation over a 12-week intensive longitudinal study of university students (N = 184, time points = 9248), we show that within-person upswings in domain-general cognitive processing precision precede and predict same-day self-reported goal setting and achievement across both academic and nonacademic domains, even controlling for other factors. A one-standard-deviation change in cognitive precision had an effect statistically equivalent to ~40 min of work, with similar or larger predictive effects compared to fluctuations in mood/motivation and no moderation by trait-level self-control or conscientiousness. Our work addresses long-standing controversies and highlights the power of intraindividual analysis to reveal relationships missed by cross-sectional approaches.
{"title":"Day-to-day fluctuations in cognitive precision predict the domain-general intention-behavior gap","authors":"Daniel J. Wilson, Cendri A. Hutcherson","doi":"10.1126/sciadv.aea8697","DOIUrl":"10.1126/sciadv.aea8697","url":null,"abstract":"<div >The idea that better cognitive functioning helps to close the gap between goals and behavior seems self-evident, yet empirical work has found unusually weak interindividual associations between cognitive task performance and real-world, goal-relevant outcomes. Here, we resolve this paradox by shifting from trait-level to state-level analysis. Leveraging a microtask design to measure daily fluctuations in cognitive function, goal setting and goal progress, mood, sleep, and motivation over a 12-week intensive longitudinal study of university students (<i>N</i> = 184, time points = 9248), we show that within-person upswings in domain-general cognitive processing precision precede and predict same-day self-reported goal setting and achievement across both academic and nonacademic domains, even controlling for other factors. A one-standard-deviation change in cognitive precision had an effect statistically equivalent to ~40 min of work, with similar or larger predictive effects compared to fluctuations in mood/motivation and no moderation by trait-level self-control or conscientiousness. Our work addresses long-standing controversies and highlights the power of intraindividual analysis to reveal relationships missed by cross-sectional approaches.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111420","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}
Aize Pellon, Shervin Dokht Sadeghi Nasab, Gholamreza Bidkhori, James S. Griffiths, Stefania Vaga, Neelu Begum, Mariana Blagojevic, Nitesh Kumar Sigh, Natalia K. Kotowicz, Ifeanyi Uzochukwu, Adrien Le Guennec, Rhonda Henley-Smith, Harry Gregson-Williams, Frederick Clasen, Miranda Pryce, Nadia Karimpour, Richard Cook, Juan Anguita, Jonathan P. Richardson, Selvam Thavaraj, Julian R. Naglik, Saeed Shoaie, David L. Moyes
Candida albicans–induced immunometabolic changes drive complex responses in immune cells. However, whether and how C. albicans causes remodeling of oral epithelial cell (OEC) metabolism is unclear. Here, we use in vitro experiments and patient biopsies to demonstrate that OECs undergo metabolic reprogramming when infected by C. albicans independently of candidalysin secretion, increasing glycolysis and decreasing tricarboxylic acid (TCA) cycle activity. Glycolysis and glucose transport inhibition show that these pathways support OEC cytokine release, highlighting the partial control of antifungal epithelial immunity by cellular metabolism. However, glucose supplementation disrupts OEC responses both in vitro and in vivo, suggesting that the fungus benefits from these metabolic shifts and that increased aerobic glycolysis in OECs is detrimental. Genome-scale metabolic modeling predicted a shutdown of the TCA cycle and a previously unidentified role for glutamic-oxaloacetic transaminase 1 (GOT1) in response to C. albicans, which was subsequently shown to be important for OEC survival during infection. This study reveals a fundamental role for hexose metabolism and identifies a GOT1-mediated TCA cycle shunt in regulating OEC survival and immune responses during mucosal fungal infections.
{"title":"Fungal infection drives metabolic reprogramming in epithelial cells via aerobic glycolysis and an alternative TCA cycle shunt","authors":"Aize Pellon, Shervin Dokht Sadeghi Nasab, Gholamreza Bidkhori, James S. Griffiths, Stefania Vaga, Neelu Begum, Mariana Blagojevic, Nitesh Kumar Sigh, Natalia K. Kotowicz, Ifeanyi Uzochukwu, Adrien Le Guennec, Rhonda Henley-Smith, Harry Gregson-Williams, Frederick Clasen, Miranda Pryce, Nadia Karimpour, Richard Cook, Juan Anguita, Jonathan P. Richardson, Selvam Thavaraj, Julian R. Naglik, Saeed Shoaie, David L. Moyes","doi":"10.1126/sciadv.aea0405","DOIUrl":"10.1126/sciadv.aea0405","url":null,"abstract":"<div ><i>Candida albicans</i>–induced immunometabolic changes drive complex responses in immune cells. However, whether and how <i>C. albicans</i> causes remodeling of oral epithelial cell (OEC) metabolism is unclear. Here, we use in vitro experiments and patient biopsies to demonstrate that OECs undergo metabolic reprogramming when infected by <i>C. albicans</i> independently of candidalysin secretion, increasing glycolysis and decreasing tricarboxylic acid (TCA) cycle activity. Glycolysis and glucose transport inhibition show that these pathways support OEC cytokine release, highlighting the partial control of antifungal epithelial immunity by cellular metabolism. However, glucose supplementation disrupts OEC responses both in vitro and in vivo, suggesting that the fungus benefits from these metabolic shifts and that increased aerobic glycolysis in OECs is detrimental. Genome-scale metabolic modeling predicted a shutdown of the TCA cycle and a previously unidentified role for glutamic-oxaloacetic transaminase 1 (GOT1) in response to <i>C. albicans</i>, which was subsequently shown to be important for OEC survival during infection. This study reveals a fundamental role for hexose metabolism and identifies a GOT1-mediated TCA cycle shunt in regulating OEC survival and immune responses during mucosal fungal infections.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111432","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}
Gurpreet Kaur, Sue E. Crawford, Sara Javornik Cregeen, Anil Surathu, B. Vijayalakshmi Ayyar, Carmen V. Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E. Blutt, Harsha Doddapaneni, Donna M. Muzny, Cristian Coarfa, Ramakrishnan Anish, B. V. Venkataram Prasad, Robert L. Atmar, Sasirekha Ramani, Mary K. Estes
The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed one consensus change in the major capsid protein and several dynamic adaptations, suggesting emergence of variants. TAK-779 also enhanced replication of GI.1 and GII.17 strains, but not GII.4, suggesting strain-specific host interactions. This breakthrough in passaging provides insight into HuNoV-host interactions, establishes a scalable in vitro system for virus propagation, and opens avenues for structural, biochemical, and therapeutic studies.
{"title":"Overcoming host restrictions to enable continuous passaging of GII.3 human norovirus in human intestinal enteroids","authors":"Gurpreet Kaur, Sue E. Crawford, Sara Javornik Cregeen, Anil Surathu, B. Vijayalakshmi Ayyar, Carmen V. Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E. Blutt, Harsha Doddapaneni, Donna M. Muzny, Cristian Coarfa, Ramakrishnan Anish, B. V. Venkataram Prasad, Robert L. Atmar, Sasirekha Ramani, Mary K. Estes","doi":"10.1126/sciadv.aeb0455","DOIUrl":"10.1126/sciadv.aeb0455","url":null,"abstract":"<div >The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed one consensus change in the major capsid protein and several dynamic adaptations, suggesting emergence of variants. TAK-779 also enhanced replication of GI.1 and GII.17 strains, but not GII.4, suggesting strain-specific host interactions. This breakthrough in passaging provides insight into HuNoV-host interactions, establishes a scalable in vitro system for virus propagation, and opens avenues for structural, biochemical, and therapeutic studies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111433","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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