《自然》（20251127出版）一周論文導讀
編譯|馮維維
Nature, 27 November 2025, Volume 647 Issue 8091
《自然》2025年11月27日，第647卷，8091期
物理學Physics
Detection of triboelectric discharges during dust events on Mars
火星沙塵事件期間摩擦放電的探測
▲ 作者：Baptiste Chide, Ralph D. Lorenz, Franck Montmessin, Sylvestre Maurice, Yann Parot, Ricardo Hueso, German Martinez, Alvaro Vicente-Retortillo, Xavier Jacob, Mark Lemmon, Bruno Dubois, Pierre-Yves Meslin, Claire Newman, Tanguy Bertrand, Grégoire Deprez, Daniel Toledo, Agustin Sánchez-Lavega, Agnès Cousin & Roger C. Wiens
▲ 鏈接：
https://www.nature.com/articles/s41586-025-09736-y
▲ 摘要：
閃電是行星大氣中能量最強大的電活動表現形式之一，不僅在地球上有記錄，在土星和木星上也有觀測到。在火星上，長期以來一直懷疑存在電活動，但從未得到直接證實。
研究者報告了通過在“毅力號”火星車上的SuperCam載荷設備捕獲的電信號和聲學特征識別出的摩擦放電的原位探測。在兩個火星年期間，共探測到55次此類事件，這些事件通常與塵卷風和沙塵暴對流前鋒有關。這些偶然的觀測結果表明，火星電場可以達到火星近地表大氣的擊穿閾值。
這種電活動可能影響沙塵動力學，并可能加劇反應性電化學環境，從而增強大氣的氧化能力，對有機分子的保存產生影響。這一原位證據可能對表面化學、宜居性和人類探索具有深遠意義。
▲ Abstract：
Lightning is among the most energetic manifestation of electrical activity in planetary atmospheres, with documented observations not only on Earth but also on Saturn and Jupiter. On Mars, the existence of electrical activity has long been suspected but never directly demonstrated.Here we report in situ detections of triboelectric discharges, identified by their electrical and acoustic signatures captured by the SuperCam microphone aboard the Perseverance rover. Fifty-five events have been detected over two Martian years, usually associated with dust devils and dust storm convective fronts. These serendipitous observations demonstrate that Martian electric fields can reach the breakdown threshold of the near-surface atmosphere of Mars, predicted to be on the order of several tens of kV m?1. Such electrical activity could affect dust dynamics and potentially fuel a reactive electrochemical environment enhancing the oxidizing capacity of the atmosphere, with consequences for the preservation of organic molecules. This in situ evidence may have implications for surface chemistry, habitability and human exploration.Entanglement-enhanced nanoscale single-spin sensing
糾纏增強的納米級單自旋傳感
▲ 作者：Xu Zhou, Mengqi Wang, Xiangyu Ye, Haoyu Sun, Yuhang Guo, Shuo Han, Zihua Chai, Wentao Ji, Kangwei Xia, Fazhan Shi, Ya Wang & Jiangfeng Du
▲ 鏈接：
https://www.nature.com/articles/s41586-025-09790-6
▲ 摘要：
探測單個自旋——包括穩態與亞穩態——是量子傳感領域的一項基礎性挑戰，在凝聚態物理、量子化學及單分子磁共振成像等領域具有廣泛應用。盡管金剛石中的氮空位中心（NV）已成為強大的納米級傳感器，但其單自旋探測性能仍受限于顯著的環境噪聲和有限的傳感體積。
研究者提出并演示了一種糾纏增強傳感方案，通過戰略性使用糾纏NV對來突破這些限制。在環境條件下，他們的方法相較于單NV中心實現了3.4倍的靈敏度提升和1.6倍的空間分辨率改進。該方案采用精心設計的糾纏態，通過量子干涉放大目標自旋信號，同時抑制環境噪聲。
關鍵的是，他們將此能力拓展至解析亞穩態單自旋動力學，通過識別狀態依賴的耦合強度直接觀測不同自旋態之間的隨機躍遷。這種雙重功能使得同時探測靜態與動態自旋物種成為可能，為研究復雜量子系統提供了新途徑。所實現的性能確立了糾纏增強傳感作為實現量子材料與界面原子尺度表征的有效路徑。
▲ Abstract：
Detecting individual spins—including stable and metastable states—represents a fundamental challenge in quantum sensing, with broad applications across condensed matter physics, quantum chemistry and single-molecule magnetic resonance imaging. Although nitrogen–vacancy (NV) centres in diamond have emerged as powerful nanoscale sensors, their performance for single-spin detection remains constrained by substantial environmental noise and restricted sensing volume. Here we propose and demonstrate an entanglement-enhanced sensing protocol that overcomes these limitations through the strategic use of entangled NV pairs. Our approach achieves a 3.4-fold enhancement in sensitivity and a 1.6-fold improvement in spatial resolution relative to single NV centres under ambient conditions. The protocol uses carefully engineered entangled states that amplify target spin signals through quantum interference while suppressing environmental noise. Crucially, we extend these capabilities to resolve metastable single-spin dynamics, directly observing stochastic transitions between different spin states by identifying state-dependent coupling strengths. This dual functionality enables simultaneous detection of static and dynamic spin species for studying complex quantum systems. The achieved performance establishes entanglement-enhanced sensing as a viable pathway towards atomic-scale characterization of quantum materials and interfaces.
化學Chemistry
Photocatalytic oxygen-atom transmutation of oxetanes
氧雜環丁烷的光催化氧原子嬗變
▲ 作者：Ying-Qi Zhang, Shuo-Han Li, Xinglong Zhang & Ming Joo Koh
▲ 鏈接：
https://www.nature.com/articles/s41586-025-09723-3
▲ 摘要：
非芳香雜環和碳環構成了無數生物活性與功能分子的骨架結構。值得注意的是，四元飽和環狀分子如氮雜環丁烷、硫雜環丁烷和環丁烷，在藥物化學領域日益受到關注。這類分子通常具備與藥物研發相關的物理化學特性：高效性、穩定性、代謝穩定性及靶標特異性。通過對易得的氧雜環丁烷進行氧原子替換，將為獲取多種環狀藥效團提供直接途徑，然而此類原子置換反應在非芳香分子體系中鮮有報道。
研究者提出了一種通用光催化策略，能夠選擇性地將氧雜環丁烷中的氧原子替換為含氮、含硫或含碳基團，通過一步操作即可將其轉化為多種飽和環狀結構單元。該原子置換方法展現出優異的官能團兼容性，適用于后期功能化修飾，可大幅簡化藥物及復雜藥物類似物的合成流程——這些分子原本需要通過多步反應才能制備。機理研究揭示了化學選擇性的起源：環內氧原子優先反應生成無環二鹵代物中間體，隨后在親核試劑存在下實現高效環重構。
▲ Abstract：
Non-aromatic heterocycles and carbocycles form the skeleton of countless bioactive and functional molecules. Of note, four-membered saturated cyclic molecules such as azetidines, thietanes and cyclobutanes have garnered increasing attention in medicinal chemistry. These molecules often have physicochemical properties relevant to drug discovery: potency, stability, metabolic stability and target specificity. The replacement of oxygen atoms in readily available oxetanes would offer a direct route to a variety of these cyclic pharmacophores, yet such atom swapping has been rarely reported for non-aromatic molecules. Here we report a general photocatalytic strategy that selectively substitutes the oxygen atom of an oxetane with a nitrogen-based, sulfur-based or carbon-based moiety, transforming it into a diverse range of saturated cyclic building blocks in a single operation. This atom-swapping method exhibits high functional group compatibility and is applicable to late-stage functionalization, substantially simplifying the synthesis of pharmaceuticals and complex drug analogues that would otherwise require multistep routes. Mechanistic investigations unveil insights on the origin of chemoselectivity that allows the endocyclic oxygen atom to react preferentially to generate an acyclic dihalide intermediate, which then undergoes efficient ring reconstruction in the presence of a nucleophilic species.
Controlling pyramidal nitrogen chirality by asymmetric organocatalysis
通過不對稱有機催化控制錐形氮手性
▲ 作者：San Wu, Pengquan Chen, Meng Duan, Peng-Ying Jiang, Qingyang Zhou, Shao-Hua Xiang, K. N. Houk & Bin Tan
▲ 鏈接：
https://www.nature.com/articles/s41586-025-09607-6
▲ 摘要：
手性是生命現象的核心特征，而控制一對鏡像分子（對映體）中特定構型的生成更是合成化學的基本準則。盡管對手性碳、硅、磷和硫中心的控制已司空見慣，但胺類物質中的氮手性中心通常難以穩定存在。
目前氮手性對映選擇性構建的有限成果主要集中于季銨鹽和橋聯雙環胺類體系——這些結構的錐形構型本身受限。對于非橋聯錐形氮手性化合物的不對稱合成，長期面臨需要超化學計量手性源且立體選擇性低下等難題。
研究者提出了一種通過手性布朗斯特酸催化的氯化反應構建無環氮立體中心的催化對映選擇性策略。他們設計了具有立體專一性的分子內反應，以克服氮氯化羥胺的結構與構型不穩定性。更重要的是，該策略已成功應用于構建具有構型穩定氮手性中心的N-氯氮丙啶對映體。控制實驗為分子內親核取代過程的SN2反應路徑提供了證據。
▲ Abstract：
Chirality is central to life, and controlling the formation of one of a pair of mirror-image molecules (enantiomers) is a central tenet of synthetic chemistry. Although controlling stereogenic carbon, silicon, phosphorus and sulfur centres is commonplace, nitrogen centres in amines are not typically stable. Limited achievements in the enantioselective construction of nitrogen chirality have primarily been established in quaternary ammonium salts and bridged bicyclic amines, which have a restricted pyramidal configuration. The asymmetric synthesis of non-bridged pyramidal nitrogen-chirogenic compounds suffers from a super-stoichiometric chiral source and exhibits poor stereoselectivity. Here we present a catalytic enantioselective strategy for construction of acyclic nitrogen stereocentres via a chiral Br?nsted acid-catalysed chlorination reaction. We designed a stereospecific intramolecular reaction to overcome the structural and configurational instabilities of nitrogen-chlorinated hydroxylamines. Furthermore, this strategy has been applied successfully to synthesize the enantioselective N-chloroaziridines with a configurationally stable nitrogen stereogenic centre. Control experiments provide evidence for an SN2 pathway for the intramolecular nucleophilic substitution event.
生命科學Life Science
Efficient and accurate search in petabase-scale sequence repositories
在拍堿基規模序列庫中實現高效精準搜索
▲ 作者：Mikhail Karasikov, Harun Mustafa, Daniel Danciu, Oleksandr Kulkov, Marc Zimmermann, Christopher Barber, Gunnar R?tsch & André Kahles
▲ 鏈接：
https://www.nature.com/articles/s41586-025-09603-w
▲ 摘要：
公共數據庫中可用的生物測序數據量正在快速增長，已成為生物醫學研究的重要資源。然而，如何高效精準地實現這些數據的全文檢索仍面臨挑戰。
研究者基于表征大規模序列集的高效數據結構和算法，提出MetaGraph方法框架，能夠利用標注德布魯因圖可擴展地索引大型DNA、RNA或蛋白質序列集。通過整合七個公共數據源，他們實現了對1880萬個獨特DNA/RNA序列集及2100億個氨基酸殘基的全文檢索——涵蓋病毒、細菌、真菌、植物、動物和人類等所有生命譜系。
他們還證明了在大型序列庫（原始序列達67拍堿基對）中進行經濟高效全文檢索的可行性：針對不超過1兆堿基對的小型查詢，按需成本約100美元；大型查詢成本可低至每兆堿基對0.74美元。研究表明，所有公共生物序列的高度壓縮表征可容納于少數消費級硬盤（總成本約2,500美元），使其具備經濟實用性并易于傳輸用于深度分析。
研究者通過多個實踐案例探索了挖掘現有檔案中有價值關聯的可能性，展示了該索引在整合分析中的應用，并證明此類能力有望推動生物醫學研究的突破性進展。
▲ Abstract：
The amount of biological sequencing data available in public repositories is growing rapidly, forming a critical resource for biomedicine. However, making these data efficiently and accurately full-text searchable remains challenging. Here we build on efficient data structures and algorithms for representing large sequence sets. We present MetaGraph, a methodological framework that enables us to scalably index large sets of DNA, RNA or protein sequences using annotated de Bruijn graphs. Integrating data from seven public sources, we make 18.8 million unique DNA and RNA sequence sets and 210 billion amino acid residues across all clades of life—including viruses, bacteria, fungi, plants, animals and humans—full-text searchable. We demonstrate the feasibility of a cost-effective full-text search in large sequence repositories (67 petabase pairs (Pbp) of raw sequence) at an on-demand cost of around US$100 for small queries up to 1 megabase pairs (Mbp) and down to US$0.74 per queried Mbp for large queries. We show that the highly compressed representation of all public biological sequences could fit on a few consumer hard drives (total cost of around US$2,500), making it cost-effective to use and readily transportable for further analysis. We explore several practical use cases to mine existing archives for interesting associations, demonstrating the use of our indexes for integrative analyses, and illustrating that such capabilities are poised to catalyse advancements in biomedical research.
Hijacking a bacterial ABC transporter for genetic code expansion
劫持細菌ABC轉運體實現遺傳密碼擴展
▲ 作者：Tarun Iype, Maximilian Fottner, Paul B?hm, Carlos Piedrafita, Yannis M?ller, Michael Groll & Kathrin Lang
▲ 鏈接：
https://www.nature.com/articles/s41586-025-09576-w
▲ 摘要：
通過位點特異性編碼非天然氨基酸（ncAAs），為擴展蛋白質功能庫提供了強大工具。然而，當前ncAA摻入策略效率低下，制約了其在基礎研究和生物技術領域的廣泛應用。研究者揭示了細胞對ncAA攝取不足是高效遺傳密碼擴展的主要障礙，并通過劫持細菌ATP結合盒（ABC）轉運體突破此瓶頸——該工程化轉運體可主動攝入易合成的異肽鍵連接三肽，后者在細胞內被加工釋放為ncAAs。
利用該策略，他們成功實現了多種此前難以獲得的ncAAs的高效編碼，為蛋白質裝備了生物正交與交聯基團、翻譯后修飾以及化學酶促偶聯功能基團。他們還進一步開發了高通量定向進化平臺，針對歷史上難以高效攝取的非天然氨基酸，定制了專屬轉運系統。表達這些進化轉運體的定制大腸桿菌菌株，可實現單位點與多位點ncAA摻入，且效率達到野生型水平。
此外，研究者改造了三肽支架使其能共轉運兩種不同ncAAs，實現了二者的高效雙摻入。本研究整體表明，通過工程化改造攝取系統，是實現化學多樣性構建單元程序化導入的有效策略。
▲ Abstract：
The site-specific encoding of non-canonical amino acids (ncAAs) provides a powerful tool for expanding the functional repertoire of proteins. Its widespread use for basic research and biotechnological applications is, however, hampered by the low efficiencies of current ncAA incorporation strategies. Here we reveal poor cellular ncAA uptake as a main obstacle to efficient genetic code expansion and overcome this bottleneck by hijacking a bacterial ATP-binding cassette (ABC) transporter5 to actively import easily synthesizable isopeptide-linked tripeptides that are processed into ncAAs within the cell. Using this approach, we enable efficient encoding of a variety of previously inaccessible ncAAs, decorating proteins with bioorthogonal6 and crosslinker moieties, post-translational modifications and functionalities for chemoenzymatic conjugation. We then devise a high-throughput directed evolution platform to engineer tailored transporter systems for the import of ncAAs that were historically refractory to efficient uptake. Customized Escherichia coli strains expressing these evolved transporters facilitate single and multi-site ncAA incorporation with wild-type efficiencies. Additionally, we adapt the tripeptide scaffolds for the co-transport of two different ncAAs, enabling their efficient dual incorporation. Collectively, our study demonstrates that engineering of uptake systems is a powerful strategy for programmable import of chemically diverse building blocks.
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