综合性期刊最新文献

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Extensive glacier loss in the coterminous United States. 毗邻美国的冰川大面积消失。
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-12 DOI: 10.1073/pnas.2600941123
Andrew G Fountain, Bryce Glenn, Christopher McNeil, Brian Menounos
{"title":"Extensive glacier loss in the coterminous United States.","authors":"Andrew G Fountain, Bryce Glenn, Christopher McNeil, Brian Menounos","doi":"10.1073/pnas.2600941123","DOIUrl":"https://doi.org/10.1073/pnas.2600941123","url":null,"abstract":"<p><p>Glaciers populate the mountain ranges of the western conterminous United States and despite their importance to alpine hydrology, their area and volume change have never been comprehensively evaluated. Our study shows that since the mid-twentieth century about one-quarter of the glaciers have disappeared and the overall area and volume are reduced by one-third. The pattern of glacier shrinkage suggests most glaciers in the conterminous United States are largely maintained by local topographic influences due to their small size. These results improve our understanding of evolving high alpine hydrology and importance to ecosystem processes.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2600941123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171128","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}
引用次数: 0
Catalytic reactive-hydrogen membranes for rapid capture and hydrodefluorination of six PFAS of regulatory concern.
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-19 DOI: 10.1073/pnas.2613985123
Min Long, Ai-Shi Wang, Welman C Elias, Chen Zhou, Thomas P Senftle, Michael S Wong, Jie Cheng, Bruce E Rittmann
{"title":"Catalytic reactive-hydrogen membranes for rapid capture and hydrodefluorination of six PFAS of regulatory concern.","authors":"Min Long, Ai-Shi Wang, Welman C Elias, Chen Zhou, Thomas P Senftle, Michael S Wong, Jie Cheng, Bruce E Rittmann","doi":"10.1073/pnas.2613985123","DOIUrl":"https://doi.org/10.1073/pnas.2613985123","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) persist in aquatic environments due to their ultrastable C-F bonds and poor susceptibility to conventional treatment. Here, we report an H<sub>2</sub>-based catalytic-film membrane that enables PFAS destruction in ambient conditions by generating highly reactive surface (H<sub>ads</sub><sup>*</sup>) and subsurface hydrogen (H<sub>sub</sub><sup>*</sup>), the latter stored as β-phase palladium hydride (β-PdHx). Solid-state analyses evidenced β-PdHx formation and related lattice expansion with elevated H<sub>2</sub> chemical potential, revealing a structural mechanism that links hydrogen storage to catalytic defluorination. Mechanistically, the two hydrogen species play complementary roles: H<sub>ads</sub><sup>*</sup>-rich Pd<sup>0</sup> surface enabled PFAS capture through parallel adsorption to maximize interfacial contact with active H, whereas sustained H<sub>sub</sub><sup>*</sup> supplied the energetic driving force for stepwise hydrodefluorination consistent with sequential C-F scission. As a result, across six PFAS of regulatory concern-PFOA, PFOS, PFNA, PFHxS, PFBS, and GenX-the catalytic membrane converted all contaminants toward fully defluorinated products. Long-chain PFAS were removed and defluorinated more rapidly than short-chain analogs, while GenX showed greater recalcitrance due to its ether linkage, weaker adsorption, and higher average C-F bond dissociation energy; nonetheless, GenX still exhibited removal and defluorination, with the production of 2-propoxypropanoic acid. The system also enabled continuous coremoval of all six PFAS in ambient conditions, with up to 96% removal and 83% defluorination over 58 d. These findings provide a mechanistic framework for how active hydrogen is generated, stored, and deployed in catalytic membranes, and identify engineered H<sub>2</sub>-catalytic membranes as a promising low-energy technology for destructive PFAS treatment.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2613985123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224829","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}
引用次数: 0
Reply to Gorelick and Kunst: Paying reviewers will increase publication costs and could exacerbate inequities. 回复Gorelick和Kunst:付钱给审稿人会增加出版成本,并可能加剧不公平。
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-16 DOI: 10.1073/pnas.2628160123
Angela Moles, Stephen Bonser, Nigel Andrew, Daniel Falster, Russell Bonduriansky
{"title":"Reply to Gorelick and Kunst: Paying reviewers will increase publication costs and could exacerbate inequities.","authors":"Angela Moles, Stephen Bonser, Nigel Andrew, Daniel Falster, Russell Bonduriansky","doi":"10.1073/pnas.2628160123","DOIUrl":"https://doi.org/10.1073/pnas.2628160123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2628160123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207911","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}
引用次数: 0
Modeling the global potential of smart farming innovations.
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-19 DOI: 10.1073/pnas.2530081123
Shahrear Roman, Hadi Hadi, Wyclife Agumba Oluoch, David Zilberman, Robert Finger, David Wuepper
{"title":"Modeling the global potential of smart farming innovations.","authors":"Shahrear Roman, Hadi Hadi, Wyclife Agumba Oluoch, David Zilberman, Robert Finger, David Wuepper","doi":"10.1073/pnas.2530081123","DOIUrl":"https://doi.org/10.1073/pnas.2530081123","url":null,"abstract":"<p><p>Smart farming innovations can improve agricultural productivity, resilience, and environmental sustainability, yet their real-world impact hinges on their diffusion dynamics, which in turn depend on their economic viability. We present here a global assessment of the profitability of smart farming innovation across croplands at a spatial resolution of ~5 km from the farmers' and the societal perspectives. We cover application mapping for precision agriculture, automated application of inputs, autonomous weeding machines, GPS steering assistance systems, and autonomous irrigation systems. For this, we compiled a globally comprehensive dataset of smart farming innovation adoption locations (N = 4,422) based on a combination of a survey (N = 2,677) and a meta-analysis (N = 1,745) and combined them with remotely sensed and statistical data to train an ensemble of five geospatial machine learning models (generalized linear models, random forests, support vector machines, maximum entropy, and boosted regression trees), which show the global distribution of the different innovations' profitability and its overlap with major environmental issues the innovations can help to mitigate. Simulations of future socioeconomic pathways combined with assumptions about future agri-environmental policies reveal that, especially in middle-income countries, the potential of smart farming will grow over time.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2530081123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224550","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}
引用次数: 0
Immense but not immutable: A sudden and sustained decline in deep-pelagic life in a large oceanic ecosystem.
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-19 DOI: 10.1073/pnas.2616554123
Tracey T Sutton, Rosanna J Milligan, April B Cook, Kevin M Boswell, Heather Bracken-Grissom, Tamara Frank, Heather Judkins, Jon A Moore, Isabel C Romero, Michael Vecchione, Marta D'Elia, Matthew W Johnston, Pedro A Peres, Nina M Pruzinsky, John A Quinlan, Joseph D Warren, Daniel R Hahn
{"title":"Immense but not immutable: A sudden and sustained decline in deep-pelagic life in a large oceanic ecosystem.","authors":"Tracey T Sutton, Rosanna J Milligan, April B Cook, Kevin M Boswell, Heather Bracken-Grissom, Tamara Frank, Heather Judkins, Jon A Moore, Isabel C Romero, Michael Vecchione, Marta D'Elia, Matthew W Johnston, Pedro A Peres, Nina M Pruzinsky, John A Quinlan, Joseph D Warren, Daniel R Hahn","doi":"10.1073/pnas.2616554123","DOIUrl":"https://doi.org/10.1073/pnas.2616554123","url":null,"abstract":"<p><p>The deep-pelagic habitat of the Gulf of Mexico comprises 90.4% of its volume and houses an exceptionally diverse deep-pelagic animal community that provides numerous ecosystem services, including carbon cycling and prey provisioning for oceanic predators. Here, we report sudden, severe, and persistent declines in the abundance of deep-pelagic fishes, crustaceans, and cephalopods that have persisted for over a decade. Over a 3.5-y period, animal abundances declined by 60 to 85%, taxon depending. Particularly hard-hit were ecologically foundational taxa such as euphausiids and lanternfishes. The magnitude of population-level decline that occurred during this 3.5-y period was greater than any observed over a 60-y period in the California Current system, the only comparable dataset, making this the fastest and most severe faunal decline reported for Earth's largest ecosystem type. These declines were detected both via direct sampling and acoustic sensing, providing independent corroboration. Genomic analyses indicate reductions in genetic diversity among dominant taxa, both a corroboration and a consequence of the decline. Furthermore, resource managers report that these trends parallel those of managed or protected Gulf species that are dependent on deep-pelagic prey, including endangered species (e.g., beaked whales, Rice's whale). No naturally occurring factors (e.g., temperature, oxygen, food supply) correlated with the observed declines, suggesting an anthropogenic proximate cause. That the declines began shortly after the <i>Deepwater Horizon</i> oil spill points to that event as the most parsimonious explanation. These findings suggest that despite its immense size the deep-pelagic biome is vulnerable to human-induced disturbance and possesses limited resilience to facilitate recovery.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2616554123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224603","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}
引用次数: 0
Unique features of EIGHT fold-Proteins with the most complex 83 knotted topology.
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-19 DOI: 10.1073/pnas.2523017123
Mariusz Mozajew, Maciej Sikora, Mateusz Fortunka, Agata P Perlinska, Anna Kluza, Szymon Niewieczerzal, Fernando Bruno da Silva, Maciej Lukaszewicz, Julia A Sikorska, Lena J Mikulska, Sophie E Jackson, Joanna I Sulkowska
{"title":"Unique features of EIGHT fold-Proteins with the most complex 8<sub>3</sub> knotted topology.","authors":"Mariusz Mozajew, Maciej Sikora, Mateusz Fortunka, Agata P Perlinska, Anna Kluza, Szymon Niewieczerzal, Fernando Bruno da Silva, Maciej Lukaszewicz, Julia A Sikorska, Lena J Mikulska, Sophie E Jackson, Joanna I Sulkowska","doi":"10.1073/pnas.2523017123","DOIUrl":"https://doi.org/10.1073/pnas.2523017123","url":null,"abstract":"<p><p>Herein, we present three crystal structures of the most complex knotted protein to date, an [Formula: see text] knot with eight crossings, which belongs to a clasp knot family. The fold of this protein is also unique, and we call it the EIGHT fold (Extraordinarily Intricate Globular Helical Tangled fold). The [Formula: see text] knot is found only in a certain group of bacteria, where it is strictly conserved, despite sequence identities as low as 10%. The [Formula: see text] structure shows a high level of internal symmetry, with structurally analogous halves. It is possible that the EIGHT fold evolved from a single unknotted \"half\" that duplicated and formed a complex protein. Based on an in vitro study of three selected [Formula: see text] proteins, we estimated their thermal and thermodynamic stability, and showed that they follow a two-state unfolding model under equilibrium conditions and their refolding occurs to a compact, nonnative state. Unfolding kinetics of [Formula: see text] knotted proteins reveal a complex, multiphase process spanning milliseconds to days. Six kinetic phases were resolved using stopped-flow fluorescence and far-ultraviolet absorbance circular dichroism spectroscopy, highlighting both rapid early events and slower rearrangements in secondary and tertiary structures. Finally, with a structure-based model, we showed that proteins with an [Formula: see text] knot can self-tie through a [Formula: see text] knotted intermediate state. They can also self-untie, albeit via an additional intermediate knot such as [Formula: see text]. Nevertheless, these proteins do not seem to fit with current folding theories known to date and require the development of a new approach.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2523017123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224622","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}
引用次数: 0
The honey bee stinger: An unusual pump with collapsible double pistons. 蜜蜂刺:一种不寻常的泵,有可折叠的双活塞。
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-12 DOI: 10.1073/pnas.2603916123
Fiorella Ramirez-Esquivel, Claudia Klose, Hyun Chai Lee, Quinn Graco, Ajay Narendra, Sridhar Ravi
{"title":"The honey bee stinger: An unusual pump with collapsible double pistons.","authors":"Fiorella Ramirez-Esquivel, Claudia Klose, Hyun Chai Lee, Quinn Graco, Ajay Narendra, Sridhar Ravi","doi":"10.1073/pnas.2603916123","DOIUrl":"https://doi.org/10.1073/pnas.2603916123","url":null,"abstract":"<p><p>Most stinging animals deliver venom by contracting muscles around a venom reservoir, but honey bees employ a fundamentally different strategy. The stingers of worker bees have the unique ability to autotomize, separating from the body, to continue to sting independently. Despite more than a century of anatomical descriptions, the mechanics of venom pumping have remained unresolved due to the challenges of observing them in action. We recorded high-speed videos of active, autotomized stingers, combined with micro computed tomography-based three-dimensional reconstruction to characterize the biomechanics of stinging in the honey bee <i>Apis mellifera</i>. We reveal that the stinger functions as a unique double-piston micro-pump. Two lancets, each possessing a deformable valve, slide in antiphase within a bulb chamber. These valves dynamically deform to alternately form a seal during the downstroke and collapse during the upstroke, enabling pressure generation for pumping while potentially minimizing backflow during refilling. The inverted tear-drop shape of the bulb facilitates refill even while pumping proceeds. We explored valve deformations and flow behavior by constructing a dynamically scaled physical model of the bulb chamber confirming key features of the pumping cycle and propose mechanisms for valve deformations. The double piston design adds significant design complexity but enables continuous venom delivery in a compact, autonomous unit. These findings provide deeper understanding of venom pumping in honey bees and other Hymenoptera. This study also provides evidence of an axial piston pump within a biological system and offers inspiration for the design of microfluidic pumping devices.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2603916123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168539","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}
引用次数: 0
Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer.
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-19 DOI: 10.1073/pnas.2609893123
Nishant Joshi, Xuan Yan, Niccoló Calcini, Payam Safavi, Asli Ak, Koen Kole, Sven van der Burg, Tansu Celikel, Fleur Zeldenrust
{"title":"Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer.","authors":"Nishant Joshi, Xuan Yan, Niccoló Calcini, Payam Safavi, Asli Ak, Koen Kole, Sven van der Burg, Tansu Celikel, Fleur Zeldenrust","doi":"10.1073/pnas.2609893123","DOIUrl":"https://doi.org/10.1073/pnas.2609893123","url":null,"abstract":"<p><p>Neuromodulatory systems such as dopamine and acetylcholine enable cortical circuits to rapidly shift between behavioral states, yet it remains unclear how receptor-specific signaling reshapes what single neurons compute. Here, we combined whole-cell recordings from excitatory and inhibitory neurons in layer 2/3 of mouse somatosensory cortex with information-theoretic analyses under frozen-noise stimulation. We quantified stimulus-to-spike information transfer and profiled each neuron across four functional domains: passive membrane biophysics, action potential dynamics, intrinsic adaptation currents, and input feature selectivity captured by spike-triggered averages. Activation of D1, D2, or M1 receptors revealed three main findings. First, neuromodulators altered fractional information and firing output in a cell-type- and receptor-specific manner, demonstrating selective regulation of encoding. Second, unsupervised clustering based on functional attribute sets showed that receptor activation reorganizes baseline functional grouping, consistent with a dynamic computational phenotype. Third, multiset correlation and factor analysis revealed that neuromodulation systematically reorganizes covariance among functional domains. In excitatory neurons, dopaminergic activation decreased coordination between input feature selectivity and other functional properties while strengthening coordination among response-based features such as spike dynamics and adaptation. Inhibitory neurons, by contrast, generally exhibited increased coordination across domains. In unison, these findings identify neuromodulation as a reconfiguration signal that reshapes not only individual cellular properties, but also the statistical architecture linking them across the recorded cohort, thereby revealing a higher-dimensional mode of single-neuron regulatory control in the cortex.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2609893123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224559","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}
引用次数: 0
Compensate peer reviewers; do not conscript them. 补偿同行审稿人;不要征召他们。
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-16 DOI: 10.1073/pnas.2619714123
Daniel A Gorelick, Jonas Kunst
{"title":"Compensate peer reviewers; do not conscript them.","authors":"Daniel A Gorelick, Jonas Kunst","doi":"10.1073/pnas.2619714123","DOIUrl":"https://doi.org/10.1073/pnas.2619714123","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2619714123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207843","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}
引用次数: 0
Identification and characterization of neoplastic cells in keratin-positive giant cell-rich tumors.
IF 9.5 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2026-10-27 Epub Date: 2026-10-19 DOI: 10.1073/pnas.2611959123
Maarten van der Linde, John S A Chrisinger, Elizabeth G Demicco, Carina A Dehner, Gregory W Charville, Inge H Briaire-de Bruijn, Sushama Varma, ChunFang Zhu, Magdalena Matusiak, Judith V M G Bovée, Matt van de Rijn, David Gp van IJzendoorn
{"title":"Identification and characterization of neoplastic cells in keratin-positive giant cell-rich tumors.","authors":"Maarten van der Linde, John S A Chrisinger, Elizabeth G Demicco, Carina A Dehner, Gregory W Charville, Inge H Briaire-de Bruijn, Sushama Varma, ChunFang Zhu, Magdalena Matusiak, Judith V M G Bovée, Matt van de Rijn, David Gp van IJzendoorn","doi":"10.1073/pnas.2611959123","DOIUrl":"https://doi.org/10.1073/pnas.2611959123","url":null,"abstract":"<p><p>Keratin-positive giant cell-rich tumor (KPGCT) is a newly described bone and soft tissue tumor. The tumor is characterized by scattered keratin-positive cells and the presence of <i>HMGA2::NCOR2</i> fusions. It is not known if the <i>HMGA2::NCOR2</i> fusion is located in the keratin-positive cells, and little is known about how KPGCT develops. KPGCT shares some histologic features with tenosynovial giant cell tumor (TGCT), a soft tissue tumor with <i>CSF1</i> rearrangements. Single-nuclei RNA sequencing and Xenium spatial transcriptomics were used to elucidate the most likely mechanisms driving KPGCT and compare KPGCT to TGCT. We identified a population of cells coexpressing keratin, <i>HMGA2</i>, and <i>CSF1</i> as the likely neoplastic cells; these cells constitute the minority of the cells in the tumor. These cells express no synovial markers, confirming KPGCT as a distinct entity, separate from TGCT. The bulk of the tumor consists of <i>CSF1R</i>-expressing macrophages and multinucleated giant cells (MNGCs), suggesting an important role for CSF1-CSF1R signaling. In addition, we find that the likely neoplastic cell population shows activation of the hippo signaling pathway, a possible central pathway in KPGCT tumorigenesis. The CSF1-CSF1R axis likely stimulates the migration and proliferation of macrophages, which form the majority of cells in the tumor, as well as their differentiation into MNGCs. These results provide a rationale for the use of CSF1R inhibitors, which have already shown efficacy in TGCT, as a therapy for KPGCT.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"123 43","pages":"e2611959123"},"PeriodicalIF":9.5,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224327","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}
引用次数: 0
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