61. In vivo haemopoietic stem cell gene therapy enabled by postnatal trafficking.
作者: Michela Milani.;Anna Fabiano.;Marta Perez-Rodriguez.;Raisa Jofra Hernandez.;Alessandra Zecchillo.;Erika Zonari.;Sofia Ottonello.;Luca Basso-Ricci.;Cesare Canepari.;Monica Volpin.;Valeria Iannello.;Valentina Capo.;Pamela Quaranta.;Luca Seffin.;Fabio Russo.;Mauro Biffi.;Leonardo Ormoli.;Chiara Brombin.;Filippo Carlucci.;Antonella Forlino.;Marta Filibian.;Eugenio Montini.;Serena Scala.;Anna Villa.;Juan Antonio Bueren.;Paula Rio.;Alessandro Aiuti.;Alessio Cantore.;Luigi Naldini.
来源: Nature. 2025年
Lentiviral vector (LV)-mediated ex vivo gene therapy for haematopoietic stem and progenitor cells (HSPCs) has delivered on the promise of a 'one-and-done' treatment for several genetic diseases1. However, ex vivo manipulation and patient conditioning before transplantation are major hurdles that could be overcome by an in vivo approach. Here we demonstrate that in vivo gene delivery to HSPCs after systemic LV administration is enabled by the substantial trafficking of these cells from the liver to the bone marrow in newborn mice. We improved gene-transfer efficiency using a phagocytosis-shielded LV, successfully reaching bona fide HSPCs capable of long-term multilineage output and engraftment after serial transplantation, as confirmed by clonal tracking. HSPC mobilization further increased gene transfer, extending the window of intervention, although permissiveness to LV transduction declined with age. We successfully tested this in vivo strategy in mouse models of adenosine deaminase deficiency, autosomal recessive osteopetrosis and Fanconi anaemia. Interestingly, in vivo gene transfer provided a selective advantage to corrected HSPCs in Fanconi anaemia, leading to near-complete haematopoietic reconstitution and prevention of bone marrow failure. Given that circulating HSPCs in humans are also most abundant shortly after birth, in vivo HSPC gene transfer holds strong translational potential across multiple diseases.
62. Global dominance of seasonality in shaping lake-surface-extent dynamics.
Lakes are crucial for ecosystems1, greenhouse gas emissions2 and water resources3, yet their surface-extent dynamics, particularly seasonality, remain poorly understood at continental to global scales owing to limitations in satellite observations4,5. Although previous studies have focused on long-term changes6-8, comprehensive assessments of seasonality have been constrained by trade-offs between spatial resolution and temporal resolution in single-source satellite data. Here we show that seasonality is the dominant driver of lake-surface-extent variations globally. By leveraging a deep-learning-based spatiotemporal fusion of MODIS and Landsat-based datasets, combined with high-performance computing, we achieved monthly mapping of 1.4 million lakes (2001-2023). Our approach yielded basin-level median user's and producer's accuracies of 93% and 96%, respectively, when validated against the Global Surface Water dataset7. Seasonality-dominated lakes constitute 66% of the global lake area and approximately 60% of total lake counts, with over 90% of the world's population residing in regions where such lakes prevail. During seasonality-induced extreme events, the impacts can exceed the combined magnitude of 23-year long-term changes and regular seasonal variations, doubling the contraction of 42% of shrinking lakes and fully offsetting the expansion of 45% of growing lakes. These results uncover previously hidden seasonal dynamics that are crucial for understanding hydrospheric responses to environmental changes9, protecting lacustrine systems10-12 and improving global climate models13,14. Our findings underscore the importance of incorporating seasonality into future research and suggest that advancements in the fusion of multisource remote-sensing data offer a promising path forward.
63. Dating the evolution of oxygenic photosynthesis using La-Ce geochronology.
作者: Laureline A Patry.;Pierre Bonnand.;Maud Boyet.;Munira Afroz.;Dylan T Wilmeth.;Brittany Ramsay.;Philippe Nonnotte.;Martin Homann.;Pierre Sansjofre.;Philip W Fralick.;Stefan V Lalonde.
来源: Nature. 2025年
There is ongoing debate as to when oxygenic photosynthesis evolved on Earth1,2. Geochemical data from ancient sediments indicate localized or ephemeral photosynthetic O2 production before the Great Oxidation Event (GOE) approximately 2.5-2.3 billion years ago (Ga), and currently suggest Archaean origins, approximately 3 Ga or earlier3-9. However, sedimentary records of the early Earth often suffer from preservation issues, and poor control on the timing of oxidation leaves geochemical proxy data for the ancient presence of O2 open to critique10-13. Here, we report rare Earth element data from three different Archaean carbonate platforms preserved in greenstone belts of the northwest Superior Craton (Canada), which were deposited by the activity of marine photosynthetic bacteria 2.87 Ga, 2.85 Ga and 2.78 Ga. All three indicate O2 production before the GOE in the form of significant depletions in cerium (Ce), reflecting oxidative Ce removal from ancient seawater, as occurs today14. Using 138La-138Ce geochronology, we show that La/Ce fractionation, and thus Ce oxidation, occurred at the time of deposition, making these the oldest directly dated Ce anomalies. These results place the origin of oxygenic photosynthesis in the Mesoarchaean or earlier and bring an important new perspective on a long-standing debate regarding Earth's biological and geochemical evolution.
64. Electrical switching of a p-wave magnet.
作者: Qian Song.;Srdjan Stavrić.;Paolo Barone.;Andrea Droghetti.;Daniil S Antonenko.;Jörn W F Venderbos.;Connor A Occhialini.;Batyr Ilyas.;Emre Ergeçen.;Nuh Gedik.;Sang-Wook Cheong.;Rafael M Fernandes.;Silvia Picozzi.;Riccardo Comin.
来源: Nature. 2025年
Magnetic states with zero magnetization but non-relativistic spin splitting are outstanding candidates for the next generation of spintronic devices. Their electronvolt (eV)-scale spin splitting, ultrafast spin dynamics and nearly vanishing stray fields make them particularly promising for several applications1,2. A variety of such magnetic states with non-trivial spin textures have been identified recently, including even-parity d-wave, g-wave or i-wave altermagnets and odd-parity p-wave magnets3-7. Achieving voltage-based control of the non-uniform spin polarization of these magnetic states is of great interest for realizing energy-efficient and compact devices for information storage and processing8,9. Spin-spiral type II multiferroics are optimal candidates for such voltage-based control, as they exhibit an inversion-symmetry-breaking magnetic order that directly induces ferroelectric polarization, allowing for symmetry-protected cross-control between spin chirality and polar order10-14. Here we combine photocurrent measurements, first-principles calculations and group-theory analysis to provide direct evidence that the spin polarization of the spin-spiral type II multiferroic NiI2 exhibits odd-parity character connected to the spiral chirality. The symmetry-protected coupling between chirality and polar order enables electrical control of a primarily non-relativistic spin polarization. Our findings represent an observation of p-wave magnetism in a spin-spiral type II multiferroic, which may lead to the development of voltage-based switching of non-relativistic spin polarization in compensated magnets.
65. Air pollution modulates trends and variability of the global methane budget.
作者: Yuanhong Zhao.;Bo Zheng.;Marielle Saunois.;Philippe Ciais.;Michaela I Hegglin.;Shengmin Lu.;Yifan Li.;Philippe Bousquet.
来源: Nature. 2025年
Air pollution affects climate through various complex interactions1. It perturbs the Earth's radiative energy balance and alters the atmospheric oxidation capacity, which determines the lifetimes of short-lived climate forcers, such as methane1. A key mechanism in this dynamic is the impact of air pollutants on the hydroxyl radical (OH), the most important oxidant in the troposphere, which accounts for approximately 90% of the methane chemical sink2. However, a comprehensive quantification of the interactions between air pollutants, OH and methane over decadal timescales remains incomplete2. Here we develop an integrated observation-driven and model-driven approach to quantify how variations in key air pollutants influence the methane chemical sink and alter the methane budget. Our results indicate that, from 2005 to 2021, enhanced tropospheric ozone, increased water vapour and decreased carbon monoxide levels collectively contributed to a 1.3-2.0 Tg year-1 increase per year in the global methane sink, thereby buffering atmospheric methane growth rates. This increase in the methane sink was primarily concentrated in tropical regions and exhibited a north-south asymmetry. Periods of high methane growth were typically linked to abrupt OH level declines driven by fluctuations in air pollutants, especially during extreme events such as mega wildfires and the COVID-19 pandemic. Our study suggests a trade-off between O3 pollution control and methane removal mediated by OH and highlights the risk of increasing carbon monoxide emissions from widespread wildfires.
66. Protein-primed homopolymer synthesis by an antiviral reverse transcriptase.
作者: Stephen Tang.;Rimantė Žedaveinytė.;Nathaniel Burman.;Shishir Pandey.;Josephine L Ramirez.;Louie M Kulber.;Tanner Wiegand.;Royce A Wilkinson.;Yanzhe Ma.;Dennis J Zhang.;George D Lampe.;Mirela Berisa.;Marko Jovanovic.;Blake Wiedenheft.;Samuel H Sternberg.
来源: Nature. 2025年
Bacteria defend themselves from viral predation using diverse immune systems, many of which target foreign DNA for degradation1. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this strategy by leveraging DNA synthesis instead2,3. We and others recently showed that DRT2 systems use an RNA template to assemble a de novo gene that encodes an antiviral effector protein, Neo4,5. It remains unknown whether similar mechanisms of defense are employed by other related DRT families. Focusing on DRT9, here we uncover an unprecedented mechanism of DNA homopolymer synthesis. Viral infection triggers polydeoxyadenylate (poly-dA) accumulation in the cell, driving abortive infection and population-level immunity. Cryo-EM structures reveal how a noncoding RNA serves as both a structural scaffold and reverse transcription template to direct hexameric complex assembly and poly-dA synthesis. Remarkably, biochemical and functional experiments identify tyrosine residues within the reverse transcriptase itself that likely prime DNA synthesis, leading to the formation of high-molecular weight protein-DNA covalent adducts. Synthesis of poly-dA by DRT9 in vivo is regulated by the competing activities of phage-encoded triggers and host-encoded silencers. Collectively, our work unveils a novel nucleic acid-driven defense system that expands the paradigm of bacterial immunity and broadens the known functions of reverse transcriptases.
67. Pt migration-lockup in zeolite for stable propane dehydrogenation catalyst.
作者: Zhikang Xu.;Mingbin Gao.;Yao Wei.;Yuanyuan Yue.;Zhengshuai Bai.;Pei Yuan.;Paolo Fornasiero.;Jean-Marie Basset.;Bingbao Mei.;Zhongmin Liu.;Haibo Zhu.;Mao Ye.;Xiaojun Bao.
来源: Nature. 2025年
The shale gas revolution has shifted propylene production from naphtha cracking to on-purpose production with propane dehydrogenation (PDH) as the dominant technology1-9. Because PDH is endothermic and requires high temperatures that favour sintering and coking, the challenge is to develop active and stable catalysts1-3 that are sufficiently stable10,11. Zeolite-supported Pt-Sn catalysts have been developed to balance activity, selectivity and stability12,13, and more recent work documented a PDH catalyst based on zeolite-anchored single rhodium atoms with exceptional performance and stability14. Here we show for silicalite-1 (S-1) that migration of encapsulated Pt-Sn2 clusters and hence agglomeration and anchoring within the zeolite versus agglomeration on the external surface can be controlled by adjusting the length of the S-1 crystals' b-axis. We find that when this axis is longer than 2.00 μm, migration of Pt-Sn2 monomers during PDH results in intra-crystalline formation of (Pt-Sn2)2 dimers that are securely locked in the channels of S-1 and capable of converting pure propane feed to propylene at 550 °C for more than 6 months with 98.3% selectivity at 91% equilibrium conversion. This performance exceeds that of other Pt-based PDH catalysts and approaches that of the Rh-based catalyst. While synthesis requirements and cost are currently prohibitive for industrial use, we anticipate that our approach to controlling the migration and lockup of metals in zeolites may enable to development of other noble metal catalysts that offer extended service lifetimes in industrial applications15-17.
68. Electricity-driven enzymatic dynamic kinetic oxidation.
作者: Beibei Zhao.;Yuanyuan Xu.;Qin Zhu.;Aokun Liu.;Xichao Peng.;Tianying Zhang.;Lu Yu.;Yan Zhang.;Xiaoqiang Huang.
来源: Nature. 2025年
Electrochemistry is undergoing a resurgence in synthetic chemistry and boasts compelling advantages1. Repurposing natural enzymes through synthetic chemical strategies holds significant promise for exploring new chemical space2-6. Elegant strategies, including directed evolution7-10, artificial enzymes11, and photoenzymatic catalysis12,13 have demonstrated their capacities for expanding the applications of enzymes in both academia and industry. However, the integration of electrochemistry with enzymes has primarily been limited to replicating previously established enzyme functions14-16. Key challenges in achieving new enzyme reactivity with electricity include compatibility issues and difficulties in heterogeneous electron transfer. Here we report the reshaping of thiamine-dependent enzymes with ferrocene-mediated electrocatalysis to unlock an unnatural dynamic kinetic oxidation of α-branched aldehydes. This robust electroenzymatic approach yields various bioactive (S)-profens with up to 99% enantiomeric excess, is applicable with whole cells overexpressing the enzyme and using down to 0.05 mol% enzyme loadings. Mechanistic investigations reveal multiple functions of the electroenzyme in the precise substrate discrimination, accelerating racemization, and facilitating kinetically matched electron transfer events.
73. Observing anyonization of bosons in a quantum gas.
作者: Sudipta Dhar.;Botao Wang.;Milena Horvath.;Amit Vashisht.;Yi Zeng.;Mikhail B Zvonarev.;Nathan Goldman.;Yanliang Guo.;Manuele Landini.;Hanns-Christoph Nägerl.
来源: Nature. 2025年
Anyons1,2 are low-dimensional quasiparticles that obey fractional statistics, hence interpolating between bosons and fermions. In two dimensions, they exist as elementary excitations of fractional quantum Hall states3-5 and are believed to enable topological quantum computing6,7. One-dimensional anyons have been theoretically proposed, but their experimental realization has proven to be difficult. Here we observed emergent anyonic correlations in a one-dimensional strongly interacting quantum gas, resulting from the phenomenon of spin-charge separation8-10. A mobile impurity provides the necessary spin degree of freedom to engineer anyonic correlations in the charge sector and simultaneously acts as a probe to reveal these correlations. Starting with bosons, we tune the statistical phase to transmute bosons through anyons to fermions and observe an asymmetric momentum distribution11-14, a hallmark of anyonic correlations. Going beyond equilibrium conditions, we observed dynamical fermionization of the anyons15. This study opens the door to the exploration of non-equilibrium anyonic phenomena in a highly controllable setting15-17.
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