Pub Date : 2026-02-11DOI: 10.1038/s41586-026-10129-y
Huigang Shi, Xiaorong Wang, Clinton Yu, Haibin Mao, Fenglong Jiao, Merav Braitbard, Ben Shor, Zhongsheng Zhang, Thomas R. Hinds, Shiyun Cao, Erkang Fan, Dina Schneidman-Duhovny, Lan Huang, Ning Zheng
Orthosteric inhibitors block enzyme active sites and prevent substrates from binding1. Enhancing their specificity through substrate dependence seems inherently unlikely, as their mechanism hinges on direct competition rather than selective recognition. Here we show that a molecular glue mechanism unexpectedly imparts substrate-dependent potency to CSN5i-3, an orthosteric inhibitor of the COP9 signalosome (CSN). We first confirm that CSN5i-3 inhibits CSN, which catalyses NEDD8 (N8) deconjugation from the cullin-RING ubiquitin ligases, by occupying the active site of its catalytic subunit, CSN5, and directly competing with the iso-peptide bond substrate. Notably, the orthosteric inhibitor binds free CSN with only micromolar affinity, yet achieves nanomolar potency in blocking its deneddylase activity. Cryogenic electron microscopy structures of the enzyme–substrate–inhibitor complex reveal that active site-engaged CSN5i-3 occludes the substrate iso-peptide linkage while simultaneously extending an N8-binding exosite of CSN5, acting as a molecular glue to cement the N8–CSN5 interaction. The cooperativity of this trimolecular CSN5i-3–N8–CSN5 assembly, in turn, sequesters CSN5i-3 at its binding site, conferring high potency to the orthosteric inhibitor despite its low affinity for the free enzyme. Together, our findings highlight the modest affinity requirements of molecule glues for individual target proteins and establish orthosteric molecular glue inhibitors as a new class of substrate-dependent enzyme antagonists.
{"title":"CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome","authors":"Huigang Shi, Xiaorong Wang, Clinton Yu, Haibin Mao, Fenglong Jiao, Merav Braitbard, Ben Shor, Zhongsheng Zhang, Thomas R. Hinds, Shiyun Cao, Erkang Fan, Dina Schneidman-Duhovny, Lan Huang, Ning Zheng","doi":"10.1038/s41586-026-10129-y","DOIUrl":"https://doi.org/10.1038/s41586-026-10129-y","url":null,"abstract":"Orthosteric inhibitors block enzyme active sites and prevent substrates from binding1. Enhancing their specificity through substrate dependence seems inherently unlikely, as their mechanism hinges on direct competition rather than selective recognition. Here we show that a molecular glue mechanism unexpectedly imparts substrate-dependent potency to CSN5i-3, an orthosteric inhibitor of the COP9 signalosome (CSN). We first confirm that CSN5i-3 inhibits CSN, which catalyses NEDD8 (N8) deconjugation from the cullin-RING ubiquitin ligases, by occupying the active site of its catalytic subunit, CSN5, and directly competing with the iso-peptide bond substrate. Notably, the orthosteric inhibitor binds free CSN with only micromolar affinity, yet achieves nanomolar potency in blocking its deneddylase activity. Cryogenic electron microscopy structures of the enzyme–substrate–inhibitor complex reveal that active site-engaged CSN5i-3 occludes the substrate iso-peptide linkage while simultaneously extending an N8-binding exosite of CSN5, acting as a molecular glue to cement the N8–CSN5 interaction. The cooperativity of this trimolecular CSN5i-3–N8–CSN5 assembly, in turn, sequesters CSN5i-3 at its binding site, conferring high potency to the orthosteric inhibitor despite its low affinity for the free enzyme. Together, our findings highlight the modest affinity requirements of molecule glues for individual target proteins and establish orthosteric molecular glue inhibitors as a new class of substrate-dependent enzyme antagonists.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"35 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-025-10068-0
Olena Bukalo, Ruairi O’Sullivan, Yuta Tanisumi, Adriana Mendez, Chase Weinholtz, Sydney Zimmerman, Victoria Offenberg, Olivia Carpenter, Hrishikesh Bhagwat, Sophie Mosley, John J. O’Malley, Kerri Lyons, Yulan Fang, Jess Goldschlager, Linnaea E. Ostroff, Mario A. Penzo, Hiroaki Wake, Lindsay R. Halladay, Andrew Holmes
Brain systems mediating responses to previously encountered threats provide critical survival functions. Fear memory and extinction are underpinned by neural representations in the basolateral amygdala (BLA)1,2,3,4,5,6,7, but the contribution of non-neuronal cells, including astrocytes, to these processes remains unresolved. Here, using in vivo calcium (Ca2+) imaging and causal astrocyte manipulations, we find that BLA astrocytes dynamically track fear state and support fear memory retrieval and extinction. By combining astrocyte manipulations with in vivo BLA neuronal Ca2+ imaging and electrophysiological recordings, we show that astrocyte Ca2+ signalling enables neuronal encoding of fear memory retrieval and extinction, and readout through a BLA–prefrontal circuit. Our findings reveal a key role for astrocytes in the generation and adaptation of fear-state-related neural representations, revising neurocentric models of critical amygdala-mediated adaptive functions.
{"title":"Astrocytes enable amygdala neural representations supporting memory","authors":"Olena Bukalo, Ruairi O’Sullivan, Yuta Tanisumi, Adriana Mendez, Chase Weinholtz, Sydney Zimmerman, Victoria Offenberg, Olivia Carpenter, Hrishikesh Bhagwat, Sophie Mosley, John J. O’Malley, Kerri Lyons, Yulan Fang, Jess Goldschlager, Linnaea E. Ostroff, Mario A. Penzo, Hiroaki Wake, Lindsay R. Halladay, Andrew Holmes","doi":"10.1038/s41586-025-10068-0","DOIUrl":"https://doi.org/10.1038/s41586-025-10068-0","url":null,"abstract":"Brain systems mediating responses to previously encountered threats provide critical survival functions. Fear memory and extinction are underpinned by neural representations in the basolateral amygdala (BLA)1,2,3,4,5,6,7, but the contribution of non-neuronal cells, including astrocytes, to these processes remains unresolved. Here, using in vivo calcium (Ca2+) imaging and causal astrocyte manipulations, we find that BLA astrocytes dynamically track fear state and support fear memory retrieval and extinction. By combining astrocyte manipulations with in vivo BLA neuronal Ca2+ imaging and electrophysiological recordings, we show that astrocyte Ca2+ signalling enables neuronal encoding of fear memory retrieval and extinction, and readout through a BLA–prefrontal circuit. Our findings reveal a key role for astrocytes in the generation and adaptation of fear-state-related neural representations, revising neurocentric models of critical amygdala-mediated adaptive functions.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"156 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152350","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}
Metal halide perovskite light-emitting diodes (PeLEDs) have demonstrated excellent external quantum efficiency (EQE), easy colour tunability and low-cost processability, making them promising next-generation display techniques1,2,3. However, PeLEDs still underperform compared with organic light-emitting diodes (LEDs) with an EQE of about 40% because of insufficient charge confinement and defect-caused non-radiative recombination on the film surface. Here we report a spontaneously formed 3D/2D vertically oriented perovskite heterojunction by means of a simple one-step spin-coating method, which could effectively confine the charge carriers and shift the radiation zone away from the defect-rich surface region. Notably, the 2D perovskite on top exhibits a wrinkled surface morphology, which offers up to 45.4% light extraction efficiency. The resulting PeLEDs achieved an EQE of 42.9% for the green emission (certified 42.3%). Our work sheds light on the strategies for fabricating high-efficiency PeLEDs in the future.
{"title":"Maximizing perovskite electroluminescence with ordered 3D/2D heterojunction","authors":"Jingyu Peng, Xulan Xue, Shihao Liu, Yingguo Yang, Tianqi Yang, Bingyan Zhu, Xin Wang, Hanzhuang Zhang, Wenfa Xie, Gengsheng Chen, Shanglei Feng, Lina Li, Renzhong Tai, Aiwei Tang, Haizhou Lu, Wenyu Ji","doi":"10.1038/s41586-026-10134-1","DOIUrl":"https://doi.org/10.1038/s41586-026-10134-1","url":null,"abstract":"Metal halide perovskite light-emitting diodes (PeLEDs) have demonstrated excellent external quantum efficiency (EQE), easy colour tunability and low-cost processability, making them promising next-generation display techniques1,2,3. However, PeLEDs still underperform compared with organic light-emitting diodes (LEDs) with an EQE of about 40% because of insufficient charge confinement and defect-caused non-radiative recombination on the film surface. Here we report a spontaneously formed 3D/2D vertically oriented perovskite heterojunction by means of a simple one-step spin-coating method, which could effectively confine the charge carriers and shift the radiation zone away from the defect-rich surface region. Notably, the 2D perovskite on top exhibits a wrinkled surface morphology, which offers up to 45.4% light extraction efficiency. The resulting PeLEDs achieved an EQE of 42.9% for the green emission (certified 42.3%). Our work sheds light on the strategies for fabricating high-efficiency PeLEDs in the future.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"1 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-025-10050-w
Bumsik Cho, Diane E. Youngstrom, Samantha Killiany, Camilo Guevara, Caitlin E. Randolph, Connor H. Beveridge, Pooja Saklani, Gaurav Chopra, Amita Sehgal
Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery1,2. Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater—a member of the Nimrod receptor family—reduces sleep. Loss of eater also disrupts haemocyte localization to the brain and lipid uptake, which results in increased brain levels of acetyl-CoA and acetylated proteins, including mitochondrial proteins PGC1α and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD+, is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.
{"title":"Sleep-dependent clearance of brain lipids by peripheral blood cells","authors":"Bumsik Cho, Diane E. Youngstrom, Samantha Killiany, Camilo Guevara, Caitlin E. Randolph, Connor H. Beveridge, Pooja Saklani, Gaurav Chopra, Amita Sehgal","doi":"10.1038/s41586-025-10050-w","DOIUrl":"https://doi.org/10.1038/s41586-025-10050-w","url":null,"abstract":"Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery1,2. Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater—a member of the Nimrod receptor family—reduces sleep. Loss of eater also disrupts haemocyte localization to the brain and lipid uptake, which results in increased brain levels of acetyl-CoA and acetylated proteins, including mitochondrial proteins PGC1α and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD+, is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"7 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-026-10106-5
Bin Li, Ming-Chao Zhong, Cristian Camilo Galindo, Jiayu Dou, Jin Qian, Zhenghai Tang, Dominique Davidson, André Veillette
Inhibitory receptors like PD-1 and CTLA-4 contribute to T cell dysfunction in cancer1,2,3. Monoclonal antibodies (mAbs) blocking the interactions in trans of these receptors with their ligands on cancer cells or in the tumour microenvironment lead to clinical responses in some but not all types of cancer. Signalling lymphocytic activation molecule 6 (SLAMF6, also known as Ly108) is a homotypic receptor preferentially expressed on progenitor or stem-like exhausted T (Tpex) cells, but not on terminally exhausted T (Tex) cells, as demonstrated in mouse models4,5,6,7,8,9. In contrast to Tex cells, Tpex cells retain the capacity for functional restoration after immune checkpoint blockade10,11,12. The role of SLAMF6 in T cells remains ambiguous, as it has both activating and inhibitory effects, complicating its evaluation as a therapeutic target. Here we find that SLAMF6 was triggered in cis by homotypic interactions at the T cell surface. These interactions elicited inhibitory effects that suppressed activation of T cells and limited anti-tumour immunity, independently of SLAMF6 expression on tumour cells. mAbs against human SLAMF6 with a robust ability to disrupt the cis interactions strongly augmented T cell activation, reduced the proportions of exhausted T cells and inhibited tumour growth in vivo. Collectively, these findings show that SLAMF6 functions exclusively as a T cell inhibitory receptor, which is triggered by cis homotypic interactions. They also position SLAMF6 as a promising target for therapies aimed at enhancing anti-tumour immunity, regardless of SLAMF6 expression on tumour cells.
{"title":"SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer","authors":"Bin Li, Ming-Chao Zhong, Cristian Camilo Galindo, Jiayu Dou, Jin Qian, Zhenghai Tang, Dominique Davidson, André Veillette","doi":"10.1038/s41586-026-10106-5","DOIUrl":"https://doi.org/10.1038/s41586-026-10106-5","url":null,"abstract":"Inhibitory receptors like PD-1 and CTLA-4 contribute to T cell dysfunction in cancer1,2,3. Monoclonal antibodies (mAbs) blocking the interactions in trans of these receptors with their ligands on cancer cells or in the tumour microenvironment lead to clinical responses in some but not all types of cancer. Signalling lymphocytic activation molecule 6 (SLAMF6, also known as Ly108) is a homotypic receptor preferentially expressed on progenitor or stem-like exhausted T (Tpex) cells, but not on terminally exhausted T (Tex) cells, as demonstrated in mouse models4,5,6,7,8,9. In contrast to Tex cells, Tpex cells retain the capacity for functional restoration after immune checkpoint blockade10,11,12. The role of SLAMF6 in T cells remains ambiguous, as it has both activating and inhibitory effects, complicating its evaluation as a therapeutic target. Here we find that SLAMF6 was triggered in cis by homotypic interactions at the T cell surface. These interactions elicited inhibitory effects that suppressed activation of T cells and limited anti-tumour immunity, independently of SLAMF6 expression on tumour cells. mAbs against human SLAMF6 with a robust ability to disrupt the cis interactions strongly augmented T cell activation, reduced the proportions of exhausted T cells and inhibited tumour growth in vivo. Collectively, these findings show that SLAMF6 functions exclusively as a T cell inhibitory receptor, which is triggered by cis homotypic interactions. They also position SLAMF6 as a promising target for therapies aimed at enhancing anti-tumour immunity, regardless of SLAMF6 expression on tumour cells.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"16 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-026-10114-5
Xukang Wang , Yuanzhu Ma , Yihan Niu (牛一涵), Bo Xiong (熊博), Anke Zhang (张安科), Guoxun Zhang (张国勋), Yifan Chen (陈一帆), Wei Wei (魏威), Lu Fang (方璐), Jiamin Wu (吴嘉敏), Qionghai Dai (戴琼海)
Volumetric additive manufacturing has emerged as a promising technique for the flexible production of complex structures, with diverse applications in engineering, photonics and biology1,2. However, present methods still face a trade-off between resolution and volumetric build rate, restricting efficient and flexible production of high-resolution 3D structures. Here we propose a method, called digital incoherent synthesis of holographic light fields (DISH), to generate high-resolution 3D light distributions through continuous multi-angle projections with a high-speed rotating periscope without the requirement of sample rotation. The iterative optimization of the holograms for different angles in DISH maintains 19-μm printing resolution across the 1-cm range that is far beyond the depth of field of the objective and enables high-resolution in situ 3D printing of millimetre-scale objects within only 0.6 s. Acrylate materials in a range of viscosities are used to demonstrate the general compatibility of DISH. Integrating DISH with a fluid channel, we achieved mass production of complex and diverse 3D structures within low-viscosity materials, demonstrating its potential for broad applications in diverse fields.
体积增材制造已经成为复杂结构柔性生产的一种有前途的技术，在工程、光子学和生物学中有着广泛的应用1,2。然而，目前的方法仍然面临着分辨率和体积构建率之间的权衡，限制了高分辨率3D结构的高效和灵活生产。本文提出了一种全息光场数字非相干合成（digital incoherent synthesis of holographic light fields， DISH）方法，利用高速旋转潜望镜，在不需要样品旋转的情况下，通过连续多角度投影生成高分辨率的三维光分布。在DISH中，不同角度全息图的迭代优化在1厘米范围内保持了19 μm的打印分辨率，远远超出了物镜的景深，并在0.6秒内实现了毫米级物体的高分辨率原位3D打印。丙烯酸酯材料在一定的粘度范围内被用来证明DISH的一般相容性。将DISH与流体通道相结合，我们在低粘度材料中实现了复杂多样的3D结构的批量生产，展示了其在不同领域的广泛应用潜力。
{"title":"Sub-second volumetric 3D printing by synthesis of holographic light fields","authors":"Xukang Wang , Yuanzhu Ma , Yihan Niu \u0000 (牛一涵), Bo Xiong \u0000 (熊博), Anke Zhang \u0000 (张安科), Guoxun Zhang \u0000 (张国勋), Yifan Chen \u0000 (陈一帆), Wei Wei \u0000 (魏威), Lu Fang \u0000 (方璐), Jiamin Wu \u0000 (吴嘉敏), Qionghai Dai \u0000 (戴琼海)","doi":"10.1038/s41586-026-10114-5","DOIUrl":"https://doi.org/10.1038/s41586-026-10114-5","url":null,"abstract":"Volumetric additive manufacturing has emerged as a promising technique for the flexible production of complex structures, with diverse applications in engineering, photonics and biology1,2. However, present methods still face a trade-off between resolution and volumetric build rate, restricting efficient and flexible production of high-resolution 3D structures. Here we propose a method, called digital incoherent synthesis of holographic light fields (DISH), to generate high-resolution 3D light distributions through continuous multi-angle projections with a high-speed rotating periscope without the requirement of sample rotation. The iterative optimization of the holograms for different angles in DISH maintains 19-μm printing resolution across the 1-cm range that is far beyond the depth of field of the objective and enables high-resolution in situ 3D printing of millimetre-scale objects within only 0.6 s. Acrylate materials in a range of viscosities are used to demonstrate the general compatibility of DISH. Integrating DISH with a fluid channel, we achieved mass production of complex and diverse 3D structures within low-viscosity materials, demonstrating its potential for broad applications in diverse fields.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"45 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-025-10077-z
Jessica A. Lueders-Dumont, Aaron O’Dea, Erin M. Dillon, Brigida de Gracia, Chien-Hsiang Lin, Sergey Oleynik, Seth Finnegan, Daniel M. Sigman, Xingchen Tony Wang
Caribbean reefs have experienced major human-driven changes to their coral and fish communities1,2,3,4, yet how these changes have affected trophic dynamics remains poorly understood owing to challenges in reconstructing the trophic structure of pre-human-impact reefs. Advances in fossil-bound protein nitrogen isotope (15N/14N) analysis now enable the reconstruction of ancient trophic dynamics5,6, as the 15N to 14N ratio reflects an animal’s trophic position7. Here we apply this method to modern and prehistoric (7,000-year-old) fish otoliths (ear stones) and corals from Caribbean Panama and the Dominican Republic, focusing on fishes occupying low to middle trophic levels. We find that although the trophic level typically declined in high-trophic-level fishes over time, it increased or remained unchanged in low-trophic-level fishes, indicating that modern food chains are 60–70% shorter than on the prehistoric reefs in both Panama and the Dominican Republic. Furthermore, across all trophic groups, we observed a marked reduction in dietary variation, with a 20–70% lower trophic range on the modern reefs compared to the prehistoric reefs. This pattern is best explained by less dietary specialization in modern reefs, consistent with less ecological complexity than in prehistoric reefs. These differences document and quantify the trophic simplification that has occurred on modern Caribbean reefs, a change that may increase their vulnerability to ecosystem collapse.
{"title":"Fossil isotope evidence for trophic simplification on modern Caribbean reefs","authors":"Jessica A. Lueders-Dumont, Aaron O’Dea, Erin M. Dillon, Brigida de Gracia, Chien-Hsiang Lin, Sergey Oleynik, Seth Finnegan, Daniel M. Sigman, Xingchen Tony Wang","doi":"10.1038/s41586-025-10077-z","DOIUrl":"https://doi.org/10.1038/s41586-025-10077-z","url":null,"abstract":"Caribbean reefs have experienced major human-driven changes to their coral and fish communities1,2,3,4, yet how these changes have affected trophic dynamics remains poorly understood owing to challenges in reconstructing the trophic structure of pre-human-impact reefs. Advances in fossil-bound protein nitrogen isotope (15N/14N) analysis now enable the reconstruction of ancient trophic dynamics5,6, as the 15N to 14N ratio reflects an animal’s trophic position7. Here we apply this method to modern and prehistoric (7,000-year-old) fish otoliths (ear stones) and corals from Caribbean Panama and the Dominican Republic, focusing on fishes occupying low to middle trophic levels. We find that although the trophic level typically declined in high-trophic-level fishes over time, it increased or remained unchanged in low-trophic-level fishes, indicating that modern food chains are 60–70% shorter than on the prehistoric reefs in both Panama and the Dominican Republic. Furthermore, across all trophic groups, we observed a marked reduction in dietary variation, with a 20–70% lower trophic range on the modern reefs compared to the prehistoric reefs. This pattern is best explained by less dietary specialization in modern reefs, consistent with less ecological complexity than in prehistoric reefs. These differences document and quantify the trophic simplification that has occurred on modern Caribbean reefs, a change that may increase their vulnerability to ecosystem collapse.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"1 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-026-10111-8
Iñigo Olalde, Eveline Altena, Quentin Bourgeois, Harry Fokkens, Luc Amkreutz, Steffen Baetsen, Marie-France Deguilloux, Alessandro Fichera, Damien Flas, Francesca Gandini, Jan F. Kegler, Lisette M. Kootker, Judith van der Leije, Kirsten Leijnse, Constance van der Linde, Leendert Louwe Kooijmans, Roel Lauwerier, Rebecca Miller, Helle Molthof, Pierre Noiret, Daan C. M. Raemaekers, Maïté Rivollat, Liesbeth Smits, John R. Stewart, Theo ten Anscher, Michel Toussaint, Kim Callan, Olivia Cheronet, Trudi Frost, Lora Iliev, Matthew Mah, Adam Micco, Jonas Oppenheimer, Iris Patterson, Lijun Qiu, Gregory Soos, J. Noah Workman, Ceiridwen J. Edwards, Iosif Lazaridis, Swapan Mallick, Nick Patterson, Nadin Rohland, Martin B. Richards, Ron Pinhasi, Wolfgang Haak, Maria Pala, David Reich
Ancient DNA studies revealed that, in Europe from 6500 to 4000 BCE, descendants of western Anatolian farmers mixed with local hunter-gatherers resulting in 70–100% ancestry turnover1, then steppe ancestry spread with the Corded Ware complex 3000–2500 BCE2. Here we document an exception in the wetland, riverine and coastal areas of the Netherlands, Belgium and western Germany, using genome-wide data from 112 people 8500–1700 BCE. A distinctive population with high (approximately 50%) hunter-gatherer ancestry persisted 3,000 years later than in most European regions, reflecting incorporation of female individuals of Early European Farmer ancestry into local communities. In the western Netherlands, the arrival of the Corded Ware complex was also exceptional: lowland individuals from settlements adopting Corded Ware pottery had hardly any steppe ancestry, despite a Y-chromosome characteristic of people associated with the early Corded Ware complex. These distinctive patterns may reflect the specific ecology that they inhabited, which was not amenable to full adoption of the early Neolithic type of farming introduced with Linearbandkeramik3, and resulted in distinct communities where transfer of ideas was accompanied by little gene flow. This changed with the formation of Lower Rhine–Meuse Bell Beaker users by fusion of local people (13–18%) and Corded Ware associated migrants of both sexes. Their subsequent expansion then had a disruptive impact across a much wider part of northwestern Europe, especially in Great Britain where they were the main source of a 90–100% replacement of local Neolithic ancestry.
{"title":"Lasting Lower Rhine–Meuse forager ancestry shaped Bell Beaker expansion","authors":"Iñigo Olalde, Eveline Altena, Quentin Bourgeois, Harry Fokkens, Luc Amkreutz, Steffen Baetsen, Marie-France Deguilloux, Alessandro Fichera, Damien Flas, Francesca Gandini, Jan F. Kegler, Lisette M. Kootker, Judith van der Leije, Kirsten Leijnse, Constance van der Linde, Leendert Louwe Kooijmans, Roel Lauwerier, Rebecca Miller, Helle Molthof, Pierre Noiret, Daan C. M. Raemaekers, Maïté Rivollat, Liesbeth Smits, John R. Stewart, Theo ten Anscher, Michel Toussaint, Kim Callan, Olivia Cheronet, Trudi Frost, Lora Iliev, Matthew Mah, Adam Micco, Jonas Oppenheimer, Iris Patterson, Lijun Qiu, Gregory Soos, J. Noah Workman, Ceiridwen J. Edwards, Iosif Lazaridis, Swapan Mallick, Nick Patterson, Nadin Rohland, Martin B. Richards, Ron Pinhasi, Wolfgang Haak, Maria Pala, David Reich","doi":"10.1038/s41586-026-10111-8","DOIUrl":"https://doi.org/10.1038/s41586-026-10111-8","url":null,"abstract":"Ancient DNA studies revealed that, in Europe from 6500 to 4000 BCE, descendants of western Anatolian farmers mixed with local hunter-gatherers resulting in 70–100% ancestry turnover1, then steppe ancestry spread with the Corded Ware complex 3000–2500 BCE2. Here we document an exception in the wetland, riverine and coastal areas of the Netherlands, Belgium and western Germany, using genome-wide data from 112 people 8500–1700 BCE. A distinctive population with high (approximately 50%) hunter-gatherer ancestry persisted 3,000 years later than in most European regions, reflecting incorporation of female individuals of Early European Farmer ancestry into local communities. In the western Netherlands, the arrival of the Corded Ware complex was also exceptional: lowland individuals from settlements adopting Corded Ware pottery had hardly any steppe ancestry, despite a Y-chromosome characteristic of people associated with the early Corded Ware complex. These distinctive patterns may reflect the specific ecology that they inhabited, which was not amenable to full adoption of the early Neolithic type of farming introduced with Linearbandkeramik3, and resulted in distinct communities where transfer of ideas was accompanied by little gene flow. This changed with the formation of Lower Rhine–Meuse Bell Beaker users by fusion of local people (13–18%) and Corded Ware associated migrants of both sexes. Their subsequent expansion then had a disruptive impact across a much wider part of northwestern Europe, especially in Great Britain where they were the main source of a 90–100% replacement of local Neolithic ancestry.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"9 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-026-10152-z
Yun Zheng, Hanyu Wang, Xinyu Jia, Jiahui Huang, Huihong Yuan, Chonghao Zhai, Junhao Dai, Jingbo Shi, Lei Zhang, Xuguang Zhang, Minxue Zhuang, Jinchang Liu, Jun Mao, Tianxiang Dai, Zhaorong Fu, Yuqing Jiao, Yaocheng Shi, Daoxin Dai, Xingjun Wang, Yan Li, Qihuang Gong, Zhiliang Yuan, Lin Chang, Jianwei Wang
Quantum key distribution (QKD) makes use of the principles of quantum mechanics to enable provably secure communication1,2. One substantial challenge persists in building large-scale QKD networks with many clients over long communication distances3. Although quantum relays continue to pose practical difficulties4, existing trusted-node networks5,6,7,8,9, point-to-multipoint networks10,11 and wavelength-multiplexed entanglement networks12,13 encounter issues such as reliance on trusted intermediaries or limited distances. Twin-field quantum key distribution (TF-QKD) provides a compelling architecture that can overcome those issues while enhancing communication distance14. Although long-distance point-to-point TF-QKD has been achieved15,16,17,18,19,20,21, realizing large-scale networks requires scalable quantum devices. Here we report a proof-of-principle demonstration of an integrated-photonics TF-QKD network with exceptional scalability and reliability. This network includes 20 independent client-side QKD transmitter chips with one server-side optical microcomb chip. The microcomb generates a broad range of ultralow-noise coherent frequency combs with Hz-level linewidths, which serve as seeds and references for all client chips. Each client chip regenerates ultralow-noise light phase-locked to microcombs and prepares quantum keys. We sequentially implement pairwise QKD across 20 client chips through ten wavelength-multiplexed channels, with each surpassing the repeaterless bound at 370 km in spooled fibre, achieving a networking capability (client pairs × communication distance) of 3,700 km. We further demonstrate the wafer-scale reproducibility of both server-side microcomb chips and client-side QKD transmitter chips, together establishing system-level scalability. Combining mass-manufacturability, cost-effectiveness and high scalability of integrated photonics with long-distance quantum communication represents a viable path to large-scale quantum networks.
{"title":"Large-scale quantum communication networks with integrated photonics","authors":"Yun Zheng, Hanyu Wang, Xinyu Jia, Jiahui Huang, Huihong Yuan, Chonghao Zhai, Junhao Dai, Jingbo Shi, Lei Zhang, Xuguang Zhang, Minxue Zhuang, Jinchang Liu, Jun Mao, Tianxiang Dai, Zhaorong Fu, Yuqing Jiao, Yaocheng Shi, Daoxin Dai, Xingjun Wang, Yan Li, Qihuang Gong, Zhiliang Yuan, Lin Chang, Jianwei Wang","doi":"10.1038/s41586-026-10152-z","DOIUrl":"https://doi.org/10.1038/s41586-026-10152-z","url":null,"abstract":"Quantum key distribution (QKD) makes use of the principles of quantum mechanics to enable provably secure communication1,2. One substantial challenge persists in building large-scale QKD networks with many clients over long communication distances3. Although quantum relays continue to pose practical difficulties4, existing trusted-node networks5,6,7,8,9, point-to-multipoint networks10,11 and wavelength-multiplexed entanglement networks12,13 encounter issues such as reliance on trusted intermediaries or limited distances. Twin-field quantum key distribution (TF-QKD) provides a compelling architecture that can overcome those issues while enhancing communication distance14. Although long-distance point-to-point TF-QKD has been achieved15,16,17,18,19,20,21, realizing large-scale networks requires scalable quantum devices. Here we report a proof-of-principle demonstration of an integrated-photonics TF-QKD network with exceptional scalability and reliability. This network includes 20 independent client-side QKD transmitter chips with one server-side optical microcomb chip. The microcomb generates a broad range of ultralow-noise coherent frequency combs with Hz-level linewidths, which serve as seeds and references for all client chips. Each client chip regenerates ultralow-noise light phase-locked to microcombs and prepares quantum keys. We sequentially implement pairwise QKD across 20 client chips through ten wavelength-multiplexed channels, with each surpassing the repeaterless bound at 370 km in spooled fibre, achieving a networking capability (client pairs × communication distance) of 3,700 km. We further demonstrate the wafer-scale reproducibility of both server-side microcomb chips and client-side QKD transmitter chips, together establishing system-level scalability. Combining mass-manufacturability, cost-effectiveness and high scalability of integrated photonics with long-distance quantum communication represents a viable path to large-scale quantum networks.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"15 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-11DOI: 10.1038/s41586-025-09941-9
Xin Zhang (张新), Liu Leo Liu (刘柳)
Aluminium comprises over 8% of Earth’s crust and is the most abundant metallic constituent1. Historically, aluminium catalysis has predominantly exploited the inherent Lewis acidity associated with its stable +III oxidation state2. Owing to its uniquely low electronegativity (1.61)—the lowest among p-block elements—and the absence of an inert-pair effect, aluminium presents formidable intrinsic challenges for engaging in catalytic redox transformations. Here we report the redox catalytic capability of a low-valent aluminium species, carbazolylaluminylene3, which carries out a complete Al(I)/Al(III) catalytic cycle encompassing oxidative addition, double insertion, intramolecular isomerization and reductive elimination—fundamental mechanistic steps conventionally exclusive to transition-metal catalysis. Leveraging this Al(I)/Al(III) redox cycle, we achieve highly efficient and regioselective Reppe cyclotrimerization of alkynes4,5, producing diverse benzene derivatives with a turnover number of up to 2,290. Through X-ray crystallographic and quantum chemical analyses, we elucidate how the dynamic nitrogen geometry within the carbazolyl ligand framework precisely modulates the aluminium coordination environment, thereby facilitating the catalytic cycle. This work fundamentally advances the conceptual understanding of main-group redox catalysis. It further sets a compelling precedent for future catalyst design and sustainable synthetic methodologies centred on aluminium redox transformations.
{"title":"Aluminium redox catalysis enables cyclotrimerization of alkynes","authors":"Xin Zhang \u0000 (张新), Liu Leo Liu \u0000 (刘柳)","doi":"10.1038/s41586-025-09941-9","DOIUrl":"https://doi.org/10.1038/s41586-025-09941-9","url":null,"abstract":"Aluminium comprises over 8% of Earth’s crust and is the most abundant metallic constituent1. Historically, aluminium catalysis has predominantly exploited the inherent Lewis acidity associated with its stable +III oxidation state2. Owing to its uniquely low electronegativity (1.61)—the lowest among p-block elements—and the absence of an inert-pair effect, aluminium presents formidable intrinsic challenges for engaging in catalytic redox transformations. Here we report the redox catalytic capability of a low-valent aluminium species, carbazolylaluminylene3, which carries out a complete Al(I)/Al(III) catalytic cycle encompassing oxidative addition, double insertion, intramolecular isomerization and reductive elimination—fundamental mechanistic steps conventionally exclusive to transition-metal catalysis. Leveraging this Al(I)/Al(III) redox cycle, we achieve highly efficient and regioselective Reppe cyclotrimerization of alkynes4,5, producing diverse benzene derivatives with a turnover number of up to 2,290. Through X-ray crystallographic and quantum chemical analyses, we elucidate how the dynamic nitrogen geometry within the carbazolyl ligand framework precisely modulates the aluminium coordination environment, thereby facilitating the catalytic cycle. This work fundamentally advances the conceptual understanding of main-group redox catalysis. It further sets a compelling precedent for future catalyst design and sustainable synthetic methodologies centred on aluminium redox transformations.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"315 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152343","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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