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1. 数字控制硅量子处理单元

A digitally controlled silicon quantum processing unit

['Members of the HRL Quantum Team and Collaborators.']; nature; (655, 8125)

『Abstract』Commercially relevant quantum computers will require large numbers of high-performing qubits that can be manufactured, integrated and controlled at scale. Silicon exchange-only qubits are a strong candidate modality owing to their control-signal simplicity and compatibility with advanced semiconductor manufacturing, but questions remain around the achievability of sufficiently low noise and a scalable control and wiring solution. Here we introduce a quantum processing unit composed of a custom-designed cryogenic complementary metal-oxide-semiconductor (CMOS) controller, a high-density superconducting ribbon cable and a low-noise exchange-only qubit device. The quantum chip features a 3-rail array of 54 exchange-coupled quantum dots, configurable to host up to 18 exchange-only qubits. We integrate and use these components to demonstrate qubit performance for both single-qubit and entangling operations that advances the exchange-only state of the art by an order of magnitude. We further validate this system by implementing a distance-5 repetition code and a distance-2 quantum error-detecting code and then make detailed comparisons with simulations. Our work facilitates the development of future utility-scale quantum computers with manageable operational and capital requirements.

『摘要』 具有商业价值的量子计算机需要大量高性能的量子比特，且这些量子比特能够大规模制造、集成和控制。硅基仅交换量子比特因其控制信号简单且与先进半导体制造工艺兼容，成为极具潜力的候选方案之一，但能否实现足够低的噪声水平以及可扩展的控制和布线解决方案仍存在疑问。本文介绍了一种由定制设计的低温互补金属氧化物半导体（CMOS）控制器、高密度超导带状电缆和低噪声仅交换量子比特器件组成的量子处理单元。该量子芯片具有54个交换耦合量子点的三轨阵列，最多可配置18个仅交换量子比特。我们集成了这些组件并演示了单量子比特和纠缠操作的性能，将仅交换量子比特的现有技术水平提升了一个数量级。我们还通过实施距离为5的重复码和距离为2的量子纠错检测码来验证该系统，并与模拟结果进行了详细比较。我们的工作有助于开发未来满足运营和资本需求的实用规模量子计算机。

『总结』 具有商业价值的量子计算机对量子比特要求高，硅基仅交换量子比特有潜力但面临挑战，本文介绍了相关量子处理单元，集成组件提升了仅交换量子比特水平，还验证系统并作比较，利于开发实用规模量子计算机。

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2. 自旋穿梭架构中的四权重奇偶校验

Weight-four parity checks in a spin-shuttling architecture

Undseth B, Meggiato N, Wu YH, ... Scappucci G, Greplova E, Vandersypen LMK.; nature; (655, 8125)

『Abstract』Recent advances in coherent spin shuttling have made sparse semiconductor spin-qubit arrays an appealing solid-state platform to realize quantum processors. The dynamic and long-range connectivity enabled by shuttling is also essential for many quantum error-correction schemes. Here we demonstrate a silicon spin-qubit device comprising a shuttling bus for coherently transporting qubits that can interact at four isolated locations that we call bus stops. We dynamically populate the array and tune all single- and two-qubit operations using shuttling and quantum non-demolition spin measurements, without access to charge sensing in most of the device. We achieve universal control of the effective five-qubit processor and select the connectivity required to form a surface-code stabilizer plaquette that supports X- and Z-type parity checks up to weight four. We use the parity checks to generate multi-qubit entanglement between all qubit combinations in the array and report the genuine entanglement of a five-qubit Greenberger-Horne-Zeilinger state, constituting one of the largest such states constructed with gate-defined semiconductor spins. The protocols developed here lay the groundwork for modular calibration and operation of sparse spin-qubit arrays, and we highlight the feasibility of near-term quantum error-correction experiments with mobile spin qubits.

『摘要』 相干自旋穿梭技术的最新进展使稀疏半导体自旋量子比特阵列成为实现量子处理器的极具吸引力的固态平台。穿梭技术所实现的动态和长程连接性对于许多量子纠错方案也至关重要。本文展示了一种硅基自旋量子比特器件，该器件包含一个用于相干传输量子比特的穿梭总线，这些量子比特可在四个我们称之为“站点”的独立位置发生相互作用。通过穿梭技术和量子非破坏性自旋测量，我们对阵列进行动态填充并调整所有单量子比特和双量子比特操作，且无需在设备的大部分区域使用电荷传感。我们实现了对有效五量子比特处理器的通用控制，并选择了形成表面码稳定子片所需的连接性，该稳定子片支持最高权重为四的X型和Z型奇偶校验检查。我们利用奇偶校验检查在阵列中的所有量子比特组合之间生成多量子比特纠缠，并报告了五量子比特格林伯格-霍恩-泽林格态的真实纠缠情况，这是用门定义半导体自旋构建的最大此类状态之一。本文开发的协议为稀疏自旋量子比特阵列的模块化校准和操作奠定了基础，同时凸显了近期利用移动自旋量子比特开展量子纠错实验的可行性。

『总结』 相干自旋穿梭技术让稀疏半导体自旋量子比特阵列成实现量子处理器的好选择，研究展示了硅基自旋量子比特器件，能动态操控、实现通用控制等，开发协议为相关操作奠基并凸显近期量子纠错实验可行性。

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3. 相变过程中序参量的非高斯统计

Non-Gaussian statistics of the order parameter across a phase transition

Allemand M, Dupuy G, Paquiez P, ... Roscilde T, Chalopin T, Clement D.; nature; (655, 8125)

『Abstract』Second-order phase transitions are characterized by critical scaling and universality. The singular behaviour of thermodynamic quantities at the transition, in particular, is determined by critical exponents of the universality class of the transition. However, critical properties are also characterized by the probability distribution of the order parameter across the transition, in which non-Gaussian statistics are expected, but remain largely unexplored. Here, making use of single-atom-resolved detection in momentum space, we measure the full probability distribution of the order-parameter amplitude across a continuous phase transition in an interacting lattice Bose gas. We find that fluctuations are captured by an effective potential-reconstructed from the measured probability distribution by analogy with Landau theory-displaying a non-trivial minimum in the superfluid (ordered) phase, which vanishes at the transition point. Moreover, we observe non-Gaussian statistics of the order parameter near the transition, distinguished by non-zero high-order cumulants undergoing abrupt sign changes. We show numerically that these sign changes of the cumulants obey critical scaling in homogeneous systems, and that their experimental behaviour is not reproduced by classical models, whereas it is captured by a low-temperature quantum model. Our results underscore the crucial role of order parameter statistics in probing critical phenomena and universality.

『摘要』 二级相变的特点是临界标度和普适性。特别是，相变时热力学量的奇异行为由该相变所属普适类的临界指数决定。然而，临界特性还体现在相变过程中序参量的概率分布上，其中非高斯统计预期会出现，但目前尚未得到充分研究。本研究利用动量空间中的单原子分辨探测技术，测量了相互作用晶格玻色气体在连续相变过程中序参量幅度的完整概率分布。我们发现，通过与朗道理论类比、从测得的概率分布中重构出的有效势能可以捕捉涨落现象——在超流（有序）相中呈现出一个非平凡的最小值，且该最小值在相变点消失。此外，我们在相变附近观察到序参量的非高斯统计特征，其显著表现为非零的高阶累积量发生突变式符号变化。数值模拟表明，这些累积量的符号变化在均匀系统中遵循临界标度律，经典模型无法重现其实验表现，而低温量子模型则能够与之吻合。我们的研究结果凸显了序参量统计在探究临界现象和普适性方面的关键作用。

『总结』 二级相变具有临界标度和普适性特点，其临界特性体现在序参量概率分布上，本研究用单原子分辨探测技术测量了相关概率分布，发现有效势能可捕捉涨落，观察到序参量非高斯统计特征及高阶累积量突变式符号变化，数值模拟显示其遵循临界标度律，低温量子模型可解释实验表现，凸显了序参量统计对探究临界现象和普适性的重要性。

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4. 具有可控层间距的氧化石墨烯-聚多巴胺膜

Graphene oxide-polydopamine membranes with controlled interlayer spacing

Lu Y, Wei L, Xie ZA, ... Fang WH, Zeng XC, Wang J.; nature; (655, 8125)

『Abstract』Stacked graphene oxide membranes (GOMs) show exceptional capabilities for high-throughput sieving of water, ions and molecules, offering transformative potential in environmental and energy sectors. However, achieving GOMs with subnanometre interlayer spacing and subangstrom tunability while maintaining their structural robustness for rapid and selective ion transport remains a big challenge. Here we present polydopamine-pillared composite GOMs with tunable and stable interlayer spacing, featuring controllable interlayer spacing down to 5.9 Å in the dry state, and capable of sieving hydrated rubidium (Rb⁺) and potassium (K⁺) ions differing in size by less than 0.1 Å in aqueous environments, achieving an Rb⁺/K⁺ separation factor of 5,320. These composite GOMs were fabricated by using the dopamine assembly and reaction timescale separation method. Specifically, the GOM fabrication capitalizes on the fact that nanoconfined water has a lower freezing temperature than that of bulk water, such that the interlayer spacing is regulated by the rapid assembly of dopamines into nanopillars, driven by nanoconfined liquid water while the surrounding is in bulk ice. The assembly process can be halted anytime by further lowering the temperature to tune and fix the interlayer spacing. Thereafter, the GOM is rigidified through the slower chemical reactions, including polymerization of dopamine molecules and covalent bonding at specific oxygen-containing sites on the graphene oxide surface while retaining ample graphene subnanochannels for high-flux transportation. The GOMs deliver continuous freshwater production for 30 days at a water permeance of 67.9 l m^-2 h^-1 bar^-1, 1-2 orders of magnitude higher than conventional membranes.

『摘要』 堆叠的氧化石墨烯膜（GOMs）在高通量筛分水、离子和分子方面展现出卓越能力，在环境和能源领域具有变革性潜力。然而，要制备出层间距小于1纳米且亚埃级可调的GOMs，同时保持其结构稳固以实现快速选择性离子传输，仍是一大挑战。本研究展示了由聚多巴胺支撑的复合GOMs，其层间距可调且稳定，干燥状态下可控至5.9 Å，能在水环境中筛分尺寸差异小于0.1 Å的水合铷（Rb⁺）和水合钾（K⁺）离子，实现了5320的Rb⁺/K⁺分离因子。这些复合GOMs通过多巴胺组装与反应时间尺度分离法制备而成。具体而言，该制备方法利用了纳米限域水的冻结温度低于块体水的特性，使得层间距可通过纳米限域液态水驱动的多巴胺快速组装成纳米柱来调节，而周围环境为块状冰。通过进一步降低温度，可随时停止组装过程，从而调整并固定层间距。随后，GOM通过较慢的化学反应变硬，包括多巴胺分子的聚合以及在氧化石墨烯表面特定含氧位点处的共价键合，同时保留充足的石墨烯亚纳米通道用于高流量传输。这些GOMs在67.9 l m^-2 h^-1 bar^-1的水渗透率下可持续产淡水30天，比传统膜高出1-2个数量级。

『总结』 堆叠氧化石墨烯膜具高通量筛分潜力但面临制备难题，研究展示的聚多巴胺支撑复合GOMs层间距可调且稳定，能高效筛分微小尺寸差异离子，还介绍了其制备方法及性能优势。

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5. 代谢物胶作为嘌呤感应和化疗反应的手段

Metabolite glues as a means of purine sensing and chemotherapeutic response

Witus SR, Kober MM, Roh H, ... Ghate AS, Titov DV, Rape M.; nature; (655, 8125)

『Abstract』Molecular glues stabilize weak interactions to impart new functionalities to complexes. Although molecular glues have been described in plant signalling and as human therapeutics, it is unclear whether this modality provides endogenous regulation in human cells. Here we show that purine nucleotides are molecular glues that tether the rate-limiting enzyme in purine biosynthesis-phosphoribosyl pyrophosphate amidotransferase (PPAT)-to its inhibitor NUDT5. This mechanism allows cells to sense the levels of purines and to establish essential feedback control of their synthesis. We refer to such molecules as metabolite glues. Thiopurine chemotherapeutics, which have been in clinical use since the 1950s, glue the same complex but adopt distinct orientations for enhanced function. Unlike most known glues, the PPAT-NUDT5 metabolite-glue pocket can adjust its conformation to notable compound alterations, enabling increased glue potency and improved on-target activity. We therefore identify endogenous metabolite glues as a mode of nutrient sensing that can be exploited for therapeutic benefit.

『摘要』 分子胶通过稳定弱相互作用，为复合物赋予新的功能。尽管分子胶在植物信号传导和人类药物中已有描述，但尚不清楚这种作用方式是否能在人体细胞内提供内源性调控。本研究表明，嘌呤核苷酸作为分子胶，将嘌呤生物合成中的限速酶——磷酸核糖焦磷酸酰胺转移酶（PPAT）与其抑制剂NUDT5连接在一起。这一机制使细胞能够感知嘌呤水平并建立对其合成的必要反馈控制。我们将此类分子称为代谢物胶。自20世纪50年代以来一直用于临床的硫代嘌呤化疗药物同样能粘附该复合物，但其通过不同的取向增强功能。与大多数已知的分子胶不同，PPAT-NUDT5代谢物胶结合口袋可调整其构象以适应显著的化合物变化，从而增强分子胶效力并改善靶向活性。因此，我们确定内源性代谢物胶是一种可用于治疗益处的营养感应模式。

『总结』 研究发现嘌呤核苷酸是分子胶，可将嘌呤生物合成中的关键酶PPAT与其抑制剂NUDT5连接，实现细胞对嘌呤水平的感知和合成反馈控制；还发现硫代嘌呤化疗药物也能粘附此复合物且方向不同，且PPAT - NUDT5代谢物胶结合口袋构象可变，增强了效力与靶向活性，确定了内源性代谢物胶可作为营养感应模式用于治疗。

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6. 通过弹性失稳实现超材料的抗断裂性能编程

Programming fracture resistance in metamaterials via elastic instabilities

Wang Y, Liu Y, Wu K, ... Wang Y, Li X, Gao H.; nature; (655, 8125)

『Abstract』The design of fracture-resistant materials has long been hindered by the complexity of toughening mechanisms across multiple length scales. Mechanical metamaterials offer a promising platform to address this challenge, yet existing research has largely focused on passively characterizing fracture in conventional lattice architectures. Recent studies have demonstrated the potential of elastic instabilities to enhance functionalities in architected materials; however, their connection to fracture resistance remains unexplored. Here we demonstrate that fracture behaviours in mechanical metamaterials can be actively programmed by exploiting elastic instabilities, thereby bridging the two traditionally disconnected failure modes. Through a combination of experiments and simulations, we show that controlled manipulation of the inelastic zone size in pseudoplastic metamaterials enables a transition from intrinsic to extrinsic fracture behaviour, accompanied by up to a one-order-of-magnitude increase in fracture energy. This work represents a shift from passive observation to active control of fracture mechanics, establishing a new framework for designing metamaterials with tailored fracture resistance. Our findings not only advance the fundamental understanding of instability-fracture interactions in metamaterials but also suggest a broadly applicable route for programming fracture behaviours through instability design.

『摘要』 长期以来，抗断裂材料的设计因多尺度增韧机制的复杂性而受到阻碍。机械超材料为应对这一挑战提供了有前景的平台，但现有研究大多集中于对传统晶格结构中断裂的被动表征。近期研究表明，弹性失稳具有增强结构材料功能的潜力；然而，其与抗断裂性的关联尚未得到探索。本研究表明，通过利用弹性失稳可主动调控机械超材料的断裂行为，从而弥合两种传统上互不关联的失效模式之间的差距。通过实验和模拟相结合的方法，我们发现伪塑性超材料中非弹性区尺寸的可控调节能够引发从本征断裂向非本征断裂行为的转变，同时使断裂能提高一个数量级。这项工作标志着从被动观察到主动控制断裂力学的转变，为设计具有定制化抗断裂性能的超材料建立了新框架。我们的发现不仅推进了对超材料中失稳-断裂相互作用的基本理解，还提出了一种通过失稳设计来编程断裂行为的通用途径。

『总结』 长期以来抗断裂材料设计受阻于多尺度增韧机制复杂，现有研究多被动表征传统晶格结构断裂，近期虽发现弹性失稳可增强功能但未涉及其与抗断裂性关联，本研究利用弹性失稳主动调控机械超材料断裂行为，实现本征与非本征断裂转变并大幅提高断裂能，建立新框架并提出通用途径。

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7. 向均值回归可解释地磁风暴的饱和现象

Regression to the mean can explain saturation of geomagnetic storms

Sivadas N, Sibeck D, Subramanyan V, ... Ozturk DS, Ferdousi B, Michotte de Welle B.; nature; (655, 8125)

『Abstract』Extreme space weather events on Earth occur during intervals of strong solar wind driving. The solar wind drives plasma convection and currents in the near-Earth space environment. For low values of the driver, the Earth's response is linear, estimated by parameters such as the polar cap index based on ground magnetometer activity. Curiously, for extreme solar wind driving, the Earth's response appears not to increase beyond a saturation limit. Theorists have advanced a host of explanations for this saturation effect, but there is no consensus. Here we demonstrate that this saturation is a manifestation of the regression to the mean effect arising from random uncertainty in the timing and magnitude of solar wind measurements. Our results reveal that data analysis underpinning the saturation theories is nonlinearly biased, thereby challenging the validity of the theories. Correcting for the uncertainties reveals that the Earth's response to solar wind driving is linear throughout, and that the impact of extreme geomagnetic storms can be twice as large as previously thought. We show that regression to the mean is a fundamental property of the relationship between measurement and the truth, where the truth corresponding to the measurement is closer to the mean. This effect is particularly pronounced for uncertain measurements of extreme values and is likely to manifest across various fields, from extreme climate studies to chronic medical pain.

『摘要』 地球上的极端空间天气事件发生在太阳风强劲驱动期间。太阳风会驱动近地空间环境中的等离子体对流和电流。当驱动值较低时，地球的反应呈线性，可通过基于地面磁力计活动的极冠指数等参数来估算。奇怪的是，对于极端太阳风驱动情况，地球的反应似乎不会超过一个饱和极限。理论家们为这种饱和效应提出了许多解释，但尚未达成共识。本研究表明，这种饱和现象是回归均值效应的体现，该效应源于太阳风测量时间和幅度上的随机不确定性。研究结果揭示，支撑饱和理论的现有数据分析存在非线性偏差，从而对这些理论的合理性提出质疑。校正这些不确定性后发现，地球对太阳风驱动的反应始终呈线性，且极端地磁风暴的影响可能是此前认为的两倍。研究表明，回归均值是测量与真实值之间关系的基本属性，即与测量对应的真实值更接近平均值。这一效应在极端值的不确定测量中尤为明显，并可能广泛存在于从极端气候研究到慢性医学疼痛等多个领域。

『总结』 地球极端空间天气事件受太阳风驱动，低驱动下地球反应线性，高驱动下有饱和现象，此前对此的解释因分析有偏差而存疑，校正后发现地球反应始终线性，极端地磁风暴影响或翻倍，还指出回归均值是测量与真实值关系基本属性且在多领域可能出现。

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8. 全球变化下的知识森林

The forest of knowledge under global change

['Camara-Leret R', 'Roehrdanz PR', 'Bascompte J.']; nature; (655, 8125)

『Abstract』Amazonia harbours more than 10% of the terrestrial biodiversity of the Earth and more than 400 Indigenous groups. So far, however, no study has assessed how climate change and the loss of Indigenous languages may simultaneously impact its biological and cultural heritage. Here, to bridge this gap, we first assembled a database of 90,536 reports from 700 references to understand the societal benefits that native plants provide across all countries of the Amazon basin. We found that humans utilize 5,796 native plant species, which amounts to one-third of the known Amazon vascular seed plant flora. Next, analysing 8,429 species distribution models across three future climate scenarios (SSP1-2.6, SSP3-7.0 and SSP5-8.5), we show that climate change will produce a greater reduction in the ranges of utilized than of non-utilized species by 2060-2080. Locally, Indigenous cultures may lose an average of 28-34% of their utilized plant species and 18-23% of their associated services from climate change. Regionally, the loss of threatened Indigenous languages may result in a 26% reduction in the Amazonian knowledge pool. Overall, our results point to the strong climate and language vulnerability of Amazonian biocultural heritage. At the same time, these results-together with our publicly available dataset-may serve to guide biocultural restoration and reverse the growing global change effects on ecosystems and cultural traditions.

『摘要』 亚马逊地区拥有地球上10%以上的陆地生物多样性和400多个原住民群体。然而，迄今为止，尚无研究评估气候变化和原住民语言丧失如何同时对其生物和文化遗产产生影响。在此，为填补这一空白，我们首先汇集了来自700篇参考文献的90,536份报告数据，以了解亚马逊流域各国本土植物所提供的社会效益。我们发现人类利用了5,796种本土植物物种，占已知亚马逊维管种子植物群的三分之一。接下来，通过分析三种未来气候情景（SSP1-2.6、SSP3-7.0和SSP5-8.5）下的8,429个物种分布模型，我们发现到2060年至2080年，气候变化将导致被利用物种的分布范围比未被利用物种减少得更多。在地方层面，气候变化可能导致原住民文化平均失去28%-34%的已利用植物物种以及18%-23%的相关服务。在区域层面，濒危原住民语言的消失可能导致亚马逊知识库减少26%。总体而言，我们的研究结果揭示了亚马逊生物文化遗产对气候和语言的脆弱性。与此同时，这些研究结果——连同我们公开的数据集——可能有助于指导生物文化修复工作，并扭转全球变化对生态系统和文化传统日益加剧的影响。

『总结』 亚马逊地区拥有丰富的生物多样性及众多原住民群体，但目前没有研究评估气候变化与原住民语言丧失对其生物和文化遗产的综合影响。本研究通过构建数据库和分析物种分布模型发现，气候变化将使被利用物种的分布范围缩减更甚，且会导致原住民文化失去大量已利用植物物种及相关服务，濒危原住民语言的消失也会使亚马逊知识库大幅减少，不过研究成果可助力生物文化修复及应对全球变化带来的不良影响。

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9. 氨气压力控制熔盐中胶体金属氮化物的合成

Ammonia pressure controls colloidal metal nitride synthesis in molten salts

Lin R, Khokhar V, Jiang N, ... Schaller RD, Jiang DE, Talapin DV.; nature; (655, 8125)

『Abstract』Metal nitrides represent a large class of materials with extensive applications in optoelectronics, energy and healthcare technologies. For example, GaN and related nitride semiconductors are key materials for solid-state lighting and high-power electronics. TiN and other early transition metal nitrides (TMNs) are widely used in wear-resistant alloys, tool coatings, catalysts and medical implants. Strong metal-nitrogen bonds grant nitrides structural rigidity as well as chemical and thermal stability. However, the covalency of metal-nitrogen bonds necessitates high temperatures to synthesize crystalline metal nitrides. Common synthetic routes include high-temperature solid-state nitridation, crystal growth in supercritical ammonia, molecular-beam epitaxy (MBE), reactive sputtering and chemical vapour deposition. The solution synthesis of colloidal nanocrystals (NCs) has been demonstrated for late TMNs with relatively weak chemical bonds, whereas the synthesis of early TMN NCs is challenging because it requires temperatures far above the stability range of commonly used solvents. Here we report a general approach to solution synthesis of refractory metal nitride NCs by reacting metal halides and ammonia dissolved in molten inorganic salts at elevated pressures. Successful syntheses of colloidal TiN, VN, GaN, NbN, Mo₂N, Ta₃N₅, TaN, W₂N and ternary Ti_1-xV_xN NCs are demonstrated. These NCs expand the scope of solution-processable technologically important materials.

『摘要』 金属氮化物是一大类材料，广泛应用于光电子、能源和医疗保健技术领域。例如，氮化镓（GaN）及相关氮化物半导体是固态照明和高功率电子器件的关键材料；氮化钛（TiN）和其他早期过渡金属氮化物（TMNs）则广泛用于耐磨合金、刀具涂层、催化剂及医用植入物中。强金属-氮键赋予了氮化物结构刚性以及化学和热稳定性。然而，金属-氮键的共价性要求合成结晶态金属氮化物时需高温条件。常见的合成方法包括高温固相渗氮法、超临界氨中的晶体生长、分子束外延（MBE）、反应溅射法和化学气相沉积法等。胶体纳米晶（NCs）的溶液合成已成功应用于具有相对较弱化学键的晚期过渡金属氮化物，而早期过渡金属纳米晶的合成则颇具挑战，因为其所需温度远高于常用溶剂的稳定范围。本研究提出了一种在高压下通过熔融无机盐溶解金属卤化物与氨来合成难熔金属氮化物纳米晶的通用方法。成功合成了胶体TiN、VN、GaN、NbN、Mo₂N、Ta₃N₅、TaN、W₂N以及三元Ti_1-xV_xN纳米晶。这些纳米晶拓展了可溶液加工的技术重要材料的范畴。

『总结』 金属氮化物应用广泛，但因金属-氮键共价性强致合成需高温，早期过渡金属氮化物纳米晶溶液合成困难，本文提出一种通用方法实现多种难熔金属氮化物纳米晶的溶液合成并拓展了相关材料范畴。

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10. 甲磺酸在大气颗粒物成核与生长中的作用

Role of methanesulfonic acid in atmospheric particle nucleation and growth

Baalbaki R, Shen J, Simon M, ... Kirkby J, Lehtipalo K, He XC.; nature; (655, 8125)

『Abstract』Dimethyl sulfide (DMS; CH₃SCH₃) from marine phytoplankton is a notable source of atmospheric sulfur. Its oxidation products include sulfuric acid (SA; H₂SO₄) and methanesulfonic acid (MSA; CH₃SO₃H), which has a higher yield than SA below 10 °C (ref. ). Although SA is known to drive the formation of new particles, which may subsequently grow and act as cloud condensation nuclei (CCN), the role of MSA remains unclear. Here, in experiments performed under atmospheric conditions at the CERN CLOUD (Cosmics Leaving OUtdoor Droplets) chamber, we show that MSA nucleates together with ammonia (NH₃) below -10 °C, at rates comparable with SA-NH₃. Moreover, MSA and SA nucleate synergistically below -10 °C, forming multi-acid molecular clusters with NH₃. Even at ultralow NH₃ levels, MSA drives particle growth at or near the kinetic limit below 9 °C and above 40% relative humidity (RH). Because MSA and SA generally coexist at similar concentrations in cool marine regions, our findings indicate that nucleation rates may be accelerated up to tenfold and growth rates up to twofold compared with SA-NH3 alone. Our global model simulations indicate that MSA can enhance CCN concentrations, especially in polar regions. We propose that MSA might be an important driver of biogenic particles in cool, pristine marine regions of both the present-day and pre-industrial atmospheres and yet is unaccounted for in global climate models.

『摘要』 海洋浮游植物释放的二甲基硫醚（DMS；CH₃SCH₃）是大气中硫的重要来源。其氧化产物包括硫酸（SA；H₂SO₄）和甲磺酸（MSA；CH₃SO₃H），在10℃以下时，MSA的生成量高于SA（参考文献）。已知SA能够驱动新粒子的形成，这些粒子随后可能生长并充当云凝结核（CCN），但MSA的作用尚不明确。本研究在欧洲核子研究组织（CERN）CLOUD（宇宙射线离开室外液滴）实验舱的大气条件下进行实验，结果表明，在-10℃以下，MSA与氨（NH₃）共同成核，速率可与SA-NH₃体系相媲美。此外，在-10℃以下，MSA和SA协同成核，并与NH₃形成多酸分子团簇。即使在超低NH₃水平下，在9℃及以下且相对湿度（RH）超过40%的条件下，MSA仍能推动粒子在动力学极限或接近动力学极限的情况下增长。由于在凉爽的海洋区域，MSA和SA通常以相近浓度共存，我们的研究结果指出，与仅考虑SA-NH3的情况相比，成核速率可能加快至十倍，生长速率则可能提高至两倍。全球模型模拟表明，MSA可以增加CCN浓度，尤其是在极地地区。我们提出，无论是在当今还是工业化前的大气中，MSA都可能是凉爽、原始海洋区域生物源颗粒的重要驱动因素，然而目前全球气候模型尚未将其纳入考量。

『总结』 研究表明海洋浮游植物的二甲基硫醚氧化产物MSA在低温下能与氨成核，与硫酸协同作用加速成核和粒子生长，对云凝结核浓度有重要影响，但未被全球气候模型考虑。

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11. 通过糖肼自由基交叉偶联反应合成C-糖苷

C-glycoside synthesis through radical cross-coupling of glycohydrazides

Guo Y, Li Y, Buchberger B, ... Kawamata Y, Aggarwal VK, Baran PS.; nature; (655, 8125)

『Abstract』Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition and cell signalling. Within this domain, C-glycosides, in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis. Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin and empagliflozin, which are frontline therapies for type 2 diabetes. However, scalable syntheses of C-aryl glycosides have relied traditionally on protected sugar derivatives, lengthy sequences or conventional cross-couplings that often suffer from poor selectivity, limited scope and extensive protecting-group manipulation. Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. Beyond anomeric functionalization, this platform enables C-C bond formation at several positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases, expanding practical access to carbohydrate-derived therapeutics and chemical tools.

『摘要』 碳水化合物是自然界中含量最丰富、结构最多样的生物分子之一，在能量储存、分子识别和细胞信号传导中发挥着核心作用。在这一领域中，C-糖苷（其中O-糖苷的糖苷键氧原子被碳取代）因其抗酶水解性而成为药物化学中的宝贵基团。其中，C-芳基糖苷尤为重要，例如钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂达格列净、卡格列净和恩格列净，它们是治疗2型糖尿病的一线疗法。然而，传统上可扩展的C-芳基糖苷合成方法依赖于受保护的糖衍生物、冗长的反应序列或常规交叉偶联反应，这些方法往往存在选择性差、适用范围有限以及需要大量保护基操作等问题。在此，我们报道了一种使用糖基磺酰肼作为氧化还原中性自由基前体进行交叉偶联反应来制备C-芳基糖苷的实用方法。这些试剂可直接从未经保护的天然糖制备，在温和条件下生成糖基自由基，并能高效地获得多种C-芳基糖苷，包括所有已获批的SGLT2抑制剂、沙门氏菌素和新岩藻素等天然产物以及具有药用价值的探针。除了异头位功能化外，该平台还能在碳水化合物骨架的多个位置实现碳-碳键的形成，并支持立体保留自由基偶联反应，从而克服了固有的立体化学偏向性，为开发基于碳水化合物的治疗药物和化学工具提供了更便捷的途径。

『总结』 本文报道了利用糖基磺酰肼作为自由基前体，通过交叉偶联反应高效合成C-芳基糖苷的新方法，该方法无需保护基且条件温和，适用于多种天然产物和治疗药物的制备。

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12. 恢复皮层去抑制可改善亨廷顿病表型

Restoring cortical disinhibition improves Huntington's disease phenotypes

Blumenstock S, Arakelyan D, Del Grosso N, ... Klein R, Dudanova I, Komiyama T.; nature; (655, 8125)

『Abstract』Huntington's disease (HD) is a devastating movement disorder without a cure at present. Although the monogenic basis of HD is well defined, the complex downstream effects that underlie behavioural symptoms are poorly understood. These effects include cortical dysfunction, yet the roles of specific cortical neuronal subtypes in HD symptoms remain largely unexplored. Here we used longitudinal in vivo two-photon calcium imaging to examine the activity of three cortical inhibitory neuron (IN) subtypes and excitatory corticostriatal (CStr) projection neurons in the motor cortex of the transgenic R6/2 HD mouse model throughout disease progression. We found that motor deficits in R6/2 mice were accompanied by neuron subtype-specific abnormalities in movement-related activity. This included marked hypoactivity of vasoactive intestinal peptide (VIP)-INs and CStr neurons, which was also observed in the knock-in zQ175DN HD mouse model. Optogenetic activation of VIP-INs in R6/2 mice restored healthy levels of activity in VIP-INs and their downstream CStr neurons and ameliorated motor deficits in R6/2 mice; behavioural improvements persisted for days after stimulation. Our findings highlight cortical INs as a potential therapeutic target for HD.

『摘要』 亨廷顿病（HD）是一种目前尚无治愈方法的毁灭性运动障碍疾病。尽管亨廷顿病的单基因基础已明确界定，但导致行为症状的复杂下游效应仍知之甚少。这些效应包括皮质功能障碍，然而特定皮质神经元亚型在亨廷顿病症状中的作用在很大程度上仍未得到探索。本研究利用纵向体内双光子钙成像技术，对转基因R6/2亨廷顿病小鼠模型运动皮层中三种皮质抑制性神经元（IN）亚型和兴奋性皮质纹状体（CStr）投射神经元在整个病程中的活动进行了研究。研究发现，R6/2小鼠的运动缺陷伴随着与运动相关活动的神经元亚型特异性异常。这包括血管活性肠肽（VIP）-INs和CStr神经元的显著低活性，在敲入zQ175DN亨廷顿病小鼠模型中也观察到了这一现象。对R6/2小鼠VIP-INs进行光遗传激活后，VIP-INs及其下游CStr神经元的活动恢复到健康水平，并改善了R6/2小鼠的运动缺陷；刺激后的行为改善持续数天。我们的发现强调了皮质INs可能是治疗亨廷顿病的潜在靶点。

『总结』 亨廷顿病病因复杂，特定皮质神经元亚型在其症状中的作用未明，本研究用相关技术对转基因小鼠进行研究，发现其运动缺陷伴神经元亚型特异性异常，光遗传激活VIP-INs可改善运动缺陷，表明皮质INs或是潜在治疗靶点。

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13. 立体保留脱羰C(sp)-C(sp)交叉偶联反应

Stereoretentive decarbonylative C(sp)-C(sp) cross-coupling

Huang Z, Wu T, Yuan Z, ... Guzei IA, Wu B, Weix DJ.; nature; (655, 8125)

『Abstract』Although C(sp)-C(sp) bond-forming cross-coupling methods have become more common, stereocontrolled bond formation remains a challenge, despite its importance for drug discovery, where there is a emerging demand for molecules with increased sp character. Enantiospecific cross-coupling approaches would complement advances in enantioselective coupling, but have been limited to specialized substrates with lower availability because stereospecific oxidative addition of more abundant chiral alkyl electrophiles is unknown. Inspired by the classic, stereoretentive Curtius rearrangement, here we disclose a catalytic strategy that proceeds by an analogous stereoretentive decarbonylation step to form a versatile chiral alkylnickel intermediate from easily available chiral amino acid and α-hydroxy-acid derivatives. The chiral alkylnickel intermediates decompose and/or racemize on the order of minutes, but are sufficiently stable to enable stereoretentive cross-electrophile coupling with alkyl radicals (derived from alkyl iodides) at relatively low temperature (22-40 °C). This mechanistic strategy provides a straightforward approach to stereocontrolled C(sp)-C(sp) bond formation, including diastereomers that are inaccessible by stereoselective radical mechanisms. The 'metallo-Curtius' strategy described in this study lays a mechanistic foundation for the development of many stereospecific cross-coupling reactions.

『摘要』 尽管C(sp)-C(sp)键形成的交叉偶联方法已愈发普遍，但立体控制键的形成仍是一大挑战。尽管这对药物发现至关重要（因为对具有更高sp杂化特征的分子需求日益增加），但由于缺乏对更丰富手性烷基亲电试剂的立体专一性氧化加成反应，对映特异性交叉偶联方法仅限于使用供应量较低的特殊底物。受经典、立体保留型Curtius重排反应的启发，我们在此提出一种催化策略，该策略通过类似的立体保留脱羰步骤，从易得的手性氨基酸和α-羟基酸衍生物生成多功能手性烷基镍中间体。这些手性烷基镍中间体在数分钟内分解或外消旋化，但在相对低温（22-40 °C）下足够稳定，可与来自碘代烷烃的烷基自由基发生立体保留交叉亲电偶联反应。这一机理策略为立体控制C(sp)-C(sp)键形成提供了一种直接的方法，包括通过对映选择性自由基机制无法获得的非对映异构体。本研究描述的“金属-Curtius”策略为开发多种立体专一性交叉偶联反应奠定了机理基础。

『总结』 尽管C(sp)-C(sp)键形成的交叉偶联方法增多，但立体控制键形成仍有挑战，受经典反应启发提出新催化策略，能生成多功能手性烷基镍中间体并实现立体保留交叉亲电偶联，为相关反应开发奠定基础。

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14. 预启动复合物的结构解释了CMGE的生物发生

Structure of the pre-initiation complex explains CMGE biogenesis

Puhringer T, Canal B, Palm G, ... Lewis JS, Diffley JFX, Costa A.; nature; (655, 8125)

『Abstract』When cells enter S phase, bidirectional DNA replication is initiated through the kinase-regulated recruitment of three activators (Cdc45, GINS and Pol ε) to a duplex-DNA-loaded double hexamer of minichromosome maintenance (MCM) ATPases. Together, these proteins form two CMGE helicases that establish divergent replication forks as they become separated. Here, to gain an understanding of CMGE biogenesis, we reconstituted the pre-initiation complex with purified yeast proteins. The cryo-electron-microscopy structure shows a set of firing factors caught in the act of assembling two symmetrical CMGEs. We show how stepwise complex formation reshapes MCM in preparation for DNA opening, and we explain how ATP promotes firing-factor ejection and CMGE maturation. We find that although Sld2 facilitates the recruitment of GINS to MCM, as expected, it also aids the efficient separation of the CMGE dimer, and is essential for the ejection of the lagging strand from MCM. These findings have direct implications for our understanding of the metazoan Sld2 orthologue, RECQL4, and point to a replication-fork establishment mechanism that is conserved across eukaryotes.

『摘要』 当细胞进入S期时，双向DNA复制通过激酶调控招募三种激活因子（Cdc45、GINS和Pol ε）至微小染色体维持蛋白（MCM）ATP酶的双链DNA加载双六聚体上启动。这些蛋白质共同形成两个CMGE解旋酶，随着它们分离建立发散的复制叉。本研究为理解CMGE生物发生机制，用纯化酵母蛋白重建了预引发复合物。冷冻电镜结构显示一组引发因子正在组装两个对称的CMGE。我们展示了逐步形成的复合物如何重塑MCM以准备打开DNA，并解释了ATP如何促进引发因子的释放和CMGE成熟。我们发现尽管Sld2如预期那样促进GINS向MCM的募集，但它也有助于CMGE二聚体的有效分离，并且对于从MCM中弹出滞后链至关重要。这些发现对我们理解后生动物Sld2同源物RECQL4具有直接意义，并指出了一种在真核生物中保守的复制叉建立机制。

『总结』 研究通过重构预引发复合物揭示了CMGE解旋酶的生成机制，阐明了ATP驱动的分子重塑过程及Sld2在复制叉建立中的关键作用，为理解真核生物DNA复制调控提供了新视角。

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15. STING诱导免疫的突变图谱

The mutational landscape of STING-induced immunity

Zhang B, Xu P, Meng Y, ... Fremond ML, Correia BE, Ablasser A.; nature; (655, 8125)

『Abstract』Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein-protein interactions and coordinated intracellular trafficking. Despite its central role in immunity and relevance as therapeutic target, the sequence elements that govern STING (in)activation in cells remain incompletely understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2'3'-cGAMP or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts.

『摘要』 干扰素基因刺激因子（STING）是一种进化保守的免疫信号蛋白，在宿主防御、癌症、衰老和炎症中发挥关键作用。STING下游的一型干扰素、炎性细胞因子信号传导和非典型自噬受多层机制调控，该机制整合了配体诱导的结构转变、蛋白质-蛋白质相互作用以及协调的细胞内运输过程。尽管STING在免疫系统中处于核心地位且是重要的治疗靶点，但控制其在细胞中激活或失活的序列元件仍未完全明确。本研究开发了一种大规模并行检测方法，以系统性地绘制STING的序列-功能图谱。通过对数千个单氨基酸变体的分析，我们确定了影响STING免疫刺激能力及其将配体识别转化为不同信号输出的能力的结构和功能决定因素。对部分STING高活性变体的冷冻电镜结构解析揭示了新的调控原则，这些原则决定了STING从非活化状态向具有信号传导能力状态的构象转变。突变效应广泛存在于功能图谱中，可使STING对天然配体2'3'-cGAMP更敏感，或将干扰素诱导与非典型自噬解耦，表明通过单个位点替换可产生多种可能的反应。最后，我们的数据展示了天然存在的STING蛋白变体的临床和进化意义。总之，这些发现定义了调节STING活性的分子原理，并描绘了其在不同免疫背景下功能潜力的图景。

『总结』 研究开发大规模并行检测法绘制STING序列 - 功能图谱，确定其结构和功能决定因素，揭示新调控原则及突变效应，还展示天然变体临床和进化意义，为理解STING提供依据。

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16. 面向疾病管理的会话式人工智能

Towards conversational artificial intelligence for disease management

Lievin V, Palepu A, Weng WH, ... Tu T, Karthikesalingam A, Schaekermann M.; nature; (655, 8125)

『Abstract』Although large language models have shown promise in diagnostic dialogue, their capabilities for effective management reasoning, including disease progression, therapeutic response and safe medication prescription, have remained underexplored. We have advanced the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE) using a new large-language-model-based agentic system optimized for multivisit clinical management and dialogue. To ground the reasoning of AMIE in authoritative clinical knowledge, we leveraged the long-context capabilities of Gemini, combining in-context retrieval with structured reasoning to align its output with up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multivisit case scenarios designed to reflect the guidance of the UK National Institute for Health and Care Excellence and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning, as assessed by specialists, and scored better both with respect to preciseness of treatment and investigation, and in terms of its alignment with and grounding in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark that was derived from two national drug formularies (from the USA and UK) and validated by board-certified pharmacists. Although AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher-difficulty questions. Although further research will be needed before real-world translation of AMIE, its strong performance across evaluations marks a significant step towards use of conversational artificial intelligence as a tool in disease management.

『摘要』 尽管大型语言模型在诊断对话中展现出潜力，但其在有效管理推理（包括疾病进展、治疗反应和安全用药处方）方面的能力仍未得到充分探索。我们利用一种基于新型大语言模型的智能系统改进了此前展示的“清晰医疗智能探索者”（Articulate Medical Intelligence Explorer, AMIE）的诊断能力，该系统针对多次就诊的临床管理和对话进行了优化。为使AMIE的推理过程基于权威临床知识，我们借助Gemini的长上下文处理能力，将情境检索与结构化推理相结合，使其输出结果符合最新的临床实践指南和药品目录。在一项随机双盲虚拟客观结构化临床考试研究中，AMIE与21名初级保健医生（PCPs）在100个反映英国国家卫生与保健卓越研究所及《英国医学杂志》最佳实践指南指导的多就诊案例场景中进行了比较。经专家评估，AMIE在管理推理方面不逊于初级保健医生，且在治疗和检查精确性以及与临床指南的一致性和依据方面得分更高。为评估药物推理能力，我们开发了RxQA——一个从美国和英国两个国家级药品目录衍生并由认证药师验证的多选题基准测试。尽管AMIE和初级保健医生均受益于获取外部药物信息的能力，但AMIE在高难度问题上的表现优于初级保健医生。虽然AMIE在实际应用前仍需进一步研究，但其各项评估中的优异表现为使用会话式人工智能作为疾病管理工具迈出了重要一步。

『总结』 大型语言模型虽在诊断对话中有潜力，但在管理推理上未充分探索。研究用新系统改进AMIE，结合长上下文处理能力使其推理符合临床指南。在对比实验中，AMIE在管理推理等方面不逊于甚至优于初级保健医生，开发的RxQA基准测试也显示其药物推理优势，虽实际应用尚待研究，但为会话式AI用于疾病管理迈出重要一步。

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17. 迈向自主型医疗人工智能主体

Towards autonomous medical artificial intelligence agents

Ferber D, Hilgers L, Hoper C, ... Truhn D, Jager D, Kather JN.; nature; (655, 8125)

『Abstract』Large language models (LLMs) show great potential for clinical decision-making, yet most applications remain narrow, task-specific chat tools rather than systems integrated into clinical workflows. However, building physician copilots will require models that operate within the electronic health record (EHR), with governed access to patient data and the ability to initiate permitted EHR actions within defined safety constraints. Yet it remains unproven whether such a system can manage patient cases with physician-level performance. Here we show that MIRA (Medical Intelligence for Reasoning and Action), an autonomous artificial intelligence agent operating in a sandboxed EHR environment, can navigate a large clinical action space to obtain patient histories; order and interpret laboratory, imaging and microbiology tests; generate differential diagnoses; and formulate treatment plans such as prescribing medications, scheduling surgical procedures and planning admissions. In simulations on real patient cases spanning multiple diagnoses, MIRA outperformed physicians in diagnostic accuracy and made guideline-concordant, medication-safe and appropriate admission decisions. Compared with previous LLM applications that addressed isolated subtasks or provided free-text advice, these results suggest that an EHR-integrated artificial intelligence agent can turn clinical intent into structured, actionable EHR operations, possibly making it a more effective decision-support partner for physicians. Further work is needed to establish generalization, safety and governance through prospective, real-world studies.

『摘要』 大型语言模型（LLMs）在临床决策中展现出巨大潜力，但多数应用仍局限于特定任务的聊天工具，而非融入临床工作流程的系统。然而，构建医生辅助系统需要模型能在电子健康档案（EHR）内运行，具备受控访问患者数据的能力，并能在既定安全约束下启动允许的EHR操作。不过，此类系统能否以医生水平处理患者病例仍有待验证。本研究表明，MIRA（用于推理和行动的医学智能），一个在沙盒化EHR环境中运行的自主人工智能代理，能够在大规模的临床操作空间中进行导航，获取患者病史；开具并解读实验室、影像学及微生物学检查；生成鉴别诊断；制定治疗方案，如开药、安排手术及规划住院等。在对涵盖多种疾病的真实患者病例模拟测试中，MIRA的诊断准确率高于医生，且其做出的用药、住院决定符合指南要求、用药安全且合理。与以往仅解决孤立子任务或提供自由文本建议的大型语言模型应用相比，这些结果表明，集成于EHR的人工智能代理能够将临床意图转化为结构化的可执行EHR操作，可能成为更有效的医生决策支持伙伴。未来需通过前瞻性真实世界研究来确立其泛化能力、安全性及治理机制。

『总结』 大型语言模型虽具临床决策潜力，但多局限于特定任务，而MIRA作为集成于EHR的自主AI代理，能完成多项临床操作，在真实病例模拟中表现优于医生，有望成有效决策支持伙伴，但仍需进一步研究。

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18. 克隆性造血中与突变相关的对睡眠和运动的反应

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Gerhardt T, Jacob W, Gaebel L, ... Goedeke L, Honigberg MC, McAlpine CS.; nature; (655, 8125)

『Abstract』Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle. In two human datasets, moderate-to-vigorous physical activity was associated with lower prevalence of non-DNMT3A-driven CH. In atherogenic mice with Jak2^V617F or Tet2 loss of function (LOF), but not Trp53 LOF or Dnmt3a^R878H CH, uninterrupted sleep or exercise curtails clone expansion. In CH with the Jak2^V617F mutation, sleep and exercise reduces clone expansion by selectively reprogramming mutant, but not cohabitant wild type, haematopoietic progenitor cells towards antiproliferative and metabolically healthy phenotypes by tempering bone marrow macrophage-haematopoietic progenitor cell IL-1β signalling. Sleep or exercise also lessens Jak2^V617F-driven, Tet2 LOF-driven and Trp53 LOF-driven, but not Dnmt3a^R878H-driven, atherosclerosis by locally reprogramming mutant vascular macrophages, independent of peripheral clone dynamics. In Jak2^V617F, but not adjacent wild type, aortic macrophages, uninterrupted sleep blunts CLEC4E-dependent inflammasome activation, consequently diminishing lesions. Exercise, meanwhile, activates PAC1⁺ neurons in the locus coeruleus, raising the levels of peripheral noradrenaline, which signals through adrenergic receptor β2 (ADRβ2) whose expression is preserved by exercise in Jak2^V617F, but not cohabitant wild type, aortic macrophages, selectively repressing their inflammatory programming and atherosclerosis. Our findings establish that healthy lifestyles gene-specifically diminish CH and selectively reprogram mutant haematopoietic progenitor cells and macrophages to maintain cardiovascular health.

『摘要』 克隆性造血（clonal haematopoiesis，CH）会激活炎症反应并增加动脉粥样硬化的风险。然而，生活方式是否会影响CH克隆的扩张或CH突变细胞的表型编程，进而影响动脉粥样硬化，目前尚不清楚。本研究在人类和小鼠中，针对Jak2、Tet2、Trp53和Dnmt3a基因的突变进行了研究，发现CH对睡眠和运动的反应具有突变依赖性，且突变细胞对生活方式的改变尤为敏感。在两个人类数据集中，中等至高强度的身体活动与非DNMT3A驱动的CH患病率较低相关。在携带Jak2^V617F或Tet2功能缺失（loss of function，LOF）突变（而非Trp53 LOF或Dnmt3a^R878H CH）的致动脉粥样硬化小鼠中，不间断的睡眠或运动可抑制克隆扩张。对于携带Jak2^V617F突变的CH，睡眠和运动通过调节骨髓巨噬细胞-造血祖细胞IL-1β信号传导，选择性地使突变（而非共存的野生型）造血祖细胞重新编程为抗增殖和代谢健康的表型，从而减少克隆扩张。此外，睡眠或运动还可通过局部重新编程突变血管巨噬细胞，降低Jak2^V617F驱动、Tet2 LOF驱动和Trp53 LOF驱动（但非Dnmt3a^R878H驱动）的动脉粥样硬化，且这一过程独立于外周克隆动态。在Jak2^V617F（而非相邻野生型）主动脉巨噬细胞中，不间断的睡眠可减弱CLEC4E依赖性的炎症小体激活，从而减轻病变。同时，运动可激活蓝斑中的PAC1⁺神经元，提高外周去甲肾上腺素水平，该激素通过肾上腺素能受体β2（adrenergic receptor β2，ADRβ2）发出信号，而Jak2^V617F（而非共存野生型）主动脉巨噬细胞中ADRβ2的表达因运动得以保留，从而选择性抑制其炎症编程和动脉粥样硬化。我们的研究结果表明，健康的生活方式能够特异性地减少特定基因相关的CH，并通过选择性地对突变造血祖细胞和巨噬细胞进行重编程来维持心血管健康。

『总结』 研究发现健康生活方式（如睡眠与运动）可通过基因特异性机制减少特定基因相关的克隆性造血，并通过选择性重编程突变造血祖细胞及巨噬细胞，抑制其促炎表型以维护心血管健康。

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19. 伴侣蛋白引导RNA诱导沉默复合体组装的结构基础

Structural basis for chaperone-guided assembly of RNA-induced silencing complex

Lee YY, Jeong M, Lee H, ... Park J, Kim VN, Roh SH.; nature; (655, 8125)

『Abstract』The RNA-induced silencing complex (RISC), comprising an Argonaute (AGO) protein and a small RNA, is the central effector in RNA silencing. Small RNAs are loaded onto AGO as bulky duplexes in an HSP70- and HSP90-dependent process, but the molecular mechanism remains poorly understood. Here we identify the human AGO-HSP90-p23 complex, which captures AGO in an RNA-free state, termed the AGO maturation complex (AMC). The purified AMC enables RNA loading and AGO folding, faithfully recapitulating de novo RISC assembly. Using cryogenic electron microscopy, we determined the structure of AMC bound to a microRNA duplex. In contrast to its conformation in the RISC, AGO adopts a highly open conformation in the AMC: the N domain and the RNA-binding module (PAZ-MID-PIWI) are fully detached and anchored to opposite sides of the HSP90 dimer, connected solely by the unfolded L1 linker. This arrangement exposes a positively charged cleft that accommodates an RNA duplex. AGO folding is facilitated by a small RNA duplex containing a 5'-terminal phosphate-but not by single-stranded RNAs-revealing a role for the RNA duplex as a chaperone-like cofactor that directs AGO domain assembly. These findings elucidate the RISC assembly mechanism and establish the AMC as a molecular tool for probing optimal RNA features and chemical modifications for the rational design of small interfering RNA therapeutics. Our study also sheds light on how chaperones, together with ligands, can guide the folding of client proteins.

『摘要』 RNA诱导的沉默复合体（RISC）由Argonaute（AGO）蛋白和小RNA组成，是RNA沉默的核心效应因子。小RNA以庞大的双链体形式在依赖HSP70和HSP90的过程中加载到AGO上，但其分子机制仍知之甚少。本研究鉴定了人类AGO-HSP90-p23复合物，该复合物捕获无RNA状态的AGO，称为AGO成熟复合物（AMC）。纯化的AMC可实现RNA加载和AGO折叠，真实再现从头开始的RISC组装过程。利用冷冻电子显微镜技术，我们确定了与微小RNA双链结合的AMC结构。与在RISC中的构象不同，AGO在AMC中呈高度开放构象：N结构域和RNA结合模块（PAZ-MID-PIWI）完全分离并锚定于HSP90二聚体的两侧，仅通过未折叠的L1连接子相连。这种排列暴露出一个带正电荷的裂隙，可容纳RNA双链。AGO折叠需要含有5'末端磷酸基团的小RNA双链——而非单链RNA——这揭示了RNA双链作为伴侣样辅助因子的作用，指导AGO结构域的组装。这些发现阐明了RISC的组装机制，并将AMC确立为一种分子工具，可用于探究优化RNA特征及化学修饰，从而合理设计小干扰RNA疗法。本研究还揭示了伴侣蛋白如何与配体共同引导客户蛋白折叠。

『总结』 研究发现了人类AGO-HSP90-p23复合物即AGO成熟复合物（AMC），确定其结构，阐述了其对RISC组装、AGO折叠的作用，为相关研究和治疗提供依据并揭示伴侣蛋白引导客户蛋白折叠的方式。

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20. 分配公共物品时，合作与平等相冲突

Cooperation conflicts with equality when allocating public goods

['Sheng A', 'Su Q', 'McAvoy A', 'Wang L', 'Plotkin JB.']; nature; (655, 8125)

『Abstract』Cooperation is typically seen as the ideal outcome in a social dilemma. Because cooperators are vulnerable to exploitation, much of the literature has focused on mechanisms, such as spatial structure, that support prosocial behaviour and the production of public goods. Yet the rules for distributing these goods also shape behaviour and long-term prosperity. Here we study policies for allocating public goods, comparing equitable allocation, in which returns are proportional to potential contributions, with uniform allocation, in which all individuals receive equal shares. For most social networks, we find that uniform allocation facilitates the spread of cooperation compared with equitable allocation. But this success comes with a cost. Uniform allocation concentrates resources in a small number of highly connected individuals, whereas peripheral individuals receive fewer benefits and may even be worse off than in a non-cooperative society. We develop a theoretical analysis of the tension between cooperation and equality, and we identify this conflict across diverse empirical social networks. Our results show that inequality may be an unavoidable consequence of allocation policies designed to foster cooperation in spatially heterogeneous populations. The question of how to promote cooperation is therefore incomplete: because policies that facilitate cooperation can also generate social stratification, we must weigh the benefits of cooperation against the inequality that accompanies it.

『摘要』 合作通常被视为社会困境中的理想结果。由于合作者容易受到剥削，许多文献都聚焦于支持亲社会行为和公共物品生产的机制，如空间结构等。然而，这些公共物品的分配规则也会影响人们的行为和长期繁荣。本研究探讨了公共物品的分配政策，比较了公平分配（回报与潜在贡献成正比）和统一分配（所有人获得均等份额）。在大多数社交网络中，我们发现相较于公平分配，统一分配更有利于合作的传播。但这种成功是有代价的。统一分配会使资源集中在少数高度连接的个体手中，而边缘个体获得的利益较少，甚至可能比非合作社会的状况还要差。我们对合作与平等之间的紧张关系进行了理论分析，并在各种实证社交网络中发现了这一冲突。研究结果表明，在空间异质性群体中，旨在促进合作的分配政策可能会不可避免地导致不平等。因此，如何促进合作的问题并不完整：因为促进合作的政策也可能产生社会分层，所以我们必须权衡合作带来的益处与其伴随的不平等。

『总结』 合作常被视作社会困境的理想结果，多数文献关注支持亲社会行为的机制，研究发现公共物品统一分配利于合作传播却有代价，会致资源集中、边缘个体获益少，对合作与平等的紧张关系进行理论分析后发现促进合作的政策或致不平等，需权衡二者。

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21. 海马体CA3区与CA1区之间的稀疏到密集编码转换

Sparse-to-dense coding transformation between hippocampal areas CA3 and CA1

Maimon SR, Eliav T, Aljadeff J, ... Moss CF, Las L, Ulanovsky N.; nature; (655, 8125)

『Abstract』The hippocampus is crucial for spatial memory and navigation. It contains place cells: spatially selective neurons found in areas CA1 and CA3-two distinct hippocampal subregions with substantially different anatomical connectivity. Previous studies have found highly similar spatial coding between CA1 and CA3 place cells. This raises the question of why two subregions that form consecutive processing stages would exhibit identical neural coding. Here we hypothesized that the lack of differences between CA1 and CA3 spatial coding is due to the experimental paradigm: using small arenas. We tested this hypothesis by simultaneously recording from CA1 and CA3 neurons in bats flying in flight tunnels up to 200 m in length. We identified highly distinct neural coding in CA1 and CA3: whereas CA1 neurons exhibited dense spatial coding, consisting of multiple place fields, CA3 neurons exhibited ultrasparse spatial coding, consisting predominantly of single place fields. Despite this marked difference, the sizes of place fields were very similar between the two subregions, across 5 different environment sizes ranging from 6 m to 200 m. Using a neural-network model, we show that such a sparse-to-dense transformation can facilitate fast learning of new spatial maps. We also found that in a large multicompartment environment, place cells were strongly modulated by trajectory history-a contextual effect (retrospective coding) that could last for over 100 m. Together, by using large naturalistic environments, we identified a CA3-to-CA1 coding transformation that serves to reformat spatial information into a more efficient, compressed neural code.

『摘要』 海马体对空间记忆和导航至关重要。它包含位置细胞，这些具有空间选择性的神经元存在于CA1和CA3区域——这两个海马体亚区具有截然不同的解剖学连接性。先前研究发现，CA1和CA3的位置细胞在空间编码方面高度相似。这引发了一个问题：为何形成连续处理阶段的两个亚区会表现出相同的神经编码？在此，我们假设CA1和CA3空间编码之间缺乏差异是由于实验范式所致，即使用小场地。为验证这一假设，我们在蝙蝠于长达200米的飞行隧道中飞行时，同时记录其CA1和CA3神经元活动。我们发现CA1和CA3的神经编码存在显著差异：CA1神经元呈现出密集的空间编码，由多个位置场组成；而CA3神经元则表现为超稀疏的空间编码，主要由单个位置场构成。尽管存在这种明显差异，但在从6米到200米的5种不同环境规模下，两个亚区的位置场大小却非常相似。利用神经网络模型，我们表明这种从稀疏到密集的转换有助于快速学习新的空间地图。我们还发现，在一个大型多隔间环境中，位置细胞受到轨迹历史的强烈调节——这是一种上下文效应（回顾性编码），可持续超过100米。总之，通过使用大型自然环境，我们确定了CA3到CA1的编码转换，该转换可将空间信息重新格式化为更高效、压缩的神经编码。

『总结』 研究揭示了海马体CA1与CA3亚区在不同规模环境下的空间编码差异，发现CA3呈现超稀疏编码而CA1呈现密集编码，但两者位置场大小一致，且这种转换机制可提升空间信息的学习效率。

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22. 转录因子编码大脑神经元基本布局模式

Transcription factor codes patterning neuronal groundplans of the cerebrum

['Elkahlah NA', 'Lin Y', 'Pan Y', 'Carter JA', 'Shirangi TR', 'Josephine Clowney E.']; nature; (655, 8125)

『Abstract』Brain regions that regulate motivated behaviours, including the vertebrate hypothalamus and arthropod cerebrum, house bespoke neural circuits dedicated to perceptual and internal regulation of many behavioural states. These circuits are built to purpose from complex sets of cell types whose patterning has been challenging to elucidate. Here we developed methods in Drosophila melanogaster to embed well-studied neurons that regulate mating in the transcriptional contexts of the neuronal lineages that generate them. By comparing transcription within and between lineages, we identified a large set of transcription factors expressed in complex combinations that delineate cerebral hemilineages-classes of postmitotic neurons born from the same stem cell and sharing Notch status. Hemilineages comprise the major anatomic classes in the cerebrum and these transcription factors are required to generate their gross features. We show that subtypes of the same hemilineage can provide a common computational module to circuits regulating different drives, and identify an orthogonal set of transcription factors that stratify hemilineage subtypes of differing birth order. Our findings suggest that distinct sets of transcription factors operate in a hierarchical system to build, diversify and sexually differentiate lineally related neurons that compose motivated behaviour circuits. By linking developmental patterning to separable transcriptional axes that produce gross versus fine aspects of information flow, we provide a logical framework for cerebral control of diverse drives.

『摘要』 包括脊椎动物下丘脑和节肢动物大脑在内的调节动机行为的脑区，拥有专门用于感知和内部调控多种行为状态的定制神经回路。这些回路由复杂的细胞类型集合构建而成，其模式化一直难以阐明。本研究在黑腹果蝇中开发了方法，将调控交配的、研究充分的神经元嵌入到产生它们的神经元谱系的转录背景中。通过比较谱系内外的转录情况，我们确定了一组以复杂组合方式表达的大量转录因子，这些转录因子界定了大脑半谱系（即由同一干细胞产生且具有相同Notch状态的后有丝分裂神经元的类别）。半谱系构成了大脑的主要解剖学类别，生成这些主要特征需要这些转录因子。我们发现，同一半谱系的亚型可以为调控不同驱动力的回路提供通用的计算模块，并确定了另一组正交的转录因子，它们对出生顺序不同的半谱系亚型进行分层。我们的研究结果表明，不同的转录因子组在一个层次系统中发挥作用，以构建、多样化和性别分化组成动机行为回路的谱系相关神经元。通过将发育模式与可分离的产生信息流粗细方面的转录轴联系起来，我们为大脑对各种驱动力的控制提供了一个逻辑框架。

『总结』 研究发现不同转录因子组在层次系统中构建、多样化及性别分化谱系相关神经元，为大脑控制各种驱动力提供了逻辑框架。

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23. SAUR基因通过促进花丝伸长增强玉米抗旱性

A SAUR gene enhances maize drought resilience by promoting silk elongation

Zhu C, Yang Z, Yang S, ... Wang X, Liu S, Qin F.; nature; (655, 8125)

『Abstract』Drought poses a substantial threat to world food security. Maize (Zea mays) is a major crop for food and forage, and is particularly susceptible to drought during flowering. As a monoecious plant species, drought induces asynchronous maturation of male and female inflorescences in maize plants, leading to an increased interval between pollen shedding (anthesis) and silk (elongated stigma and style) exposure (silking). This drought-induced anthesis-silking interval (ASI) fundamentally undermines maize yield stability, but the genetic control of the ASI remains largely unknown. Here we report cloning of a quantitative trait locus, Drought Resistance 9 (qDR9), that shortens the drought-increased ASI and enhances the yield stability under drought conditions. The causal gene underlying qDR9 encodes a Small Auxin Up RNA (SAUR) protein (ZmSAUR72) that is highly expressed in maize silks but downregulated under drought. ZmSAUR72 inhibits a plasma membrane-localized protein phosphatase, thereby increasing H⁺-ATPase activity and promoting silk growth. The favourable ZmSAUR72 allele-which lacks a transposon-like insertion in its promoter-drives higher expression, shortens ASI under drought, stabilizes yield and imposes no yield penalty under normal conditions. Thus, our findings offer new insights into maize ASI under drought and provide strong candidate genes to breed maize cultivars with enhanced yield stability under water-deficit conditions.

『摘要』 干旱对世界粮食安全构成重大威胁。玉米（Zea mays）是重要的粮食和饲料作物，在开花期尤其易受干旱影响。作为一种雌雄同株的植物，干旱会导致玉米植株雄性和雌性花序成熟不同步，使花粉散落（抽雄）与花丝（伸长的柱头和花柱）露出（吐丝）之间的间隔延长。这种由干旱引起的抽雄-吐丝间隔（ASI）从根本上破坏了玉米产量的稳定性，但目前对ASI的遗传调控机制仍知之甚少。本研究报告了一个数量性状基因座Drought Resistance 9（qDR9）的克隆，该基因座可缩短干旱导致的ASI延长并增强干旱条件下的产量稳定性。qDR9的因果基因编码一种生长素上调小RNA（SAUR）蛋白（ZmSAUR72），该蛋白在玉米花丝中高表达但在干旱条件下下调。ZmSAUR72抑制质膜定位的蛋白磷酸酶，从而提高H⁺-ATPase活性并促进花丝生长。有利的ZmSAUR72等位基因——其启动子区域缺少类转座子插入——驱动更高水平的表达，可在干旱条件下缩短ASI、稳定产量且在正常条件下不会降低产量。因此，我们的研究结果为理解干旱下玉米的ASI提供了新见解，并为培育缺水条件下具有更强产量稳定性的玉米品种提供了强有力的候选基因。

『总结』 干旱严重影响玉米产量稳定性，因其会延长抽雄-吐丝间隔（ASI）。研究发现qDR9基因座通过编码ZmSAUR72蛋白缩短ASI，该蛋白在干旱时下调表达，能促进花丝生长，有利等位基因可在干旱时稳定产量且不影响正常产量，为抗旱玉米育种提供依据。

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24. 通过生物分子凝聚进行细胞水势感知

Cellular water-potential sensing through biomolecular condensation

['Wang Y', 'Zhu L', 'Yang Y', 'Li X', 'Zhang X', 'Fang X.']; nature; (655, 8125)

『Abstract』Water molecules, as solvents for biomolecules, are essential to cells. The water potential of the cell decreases under water-deficient conditions, yet how cells sense changes in water potential remains unknown. Here we identify a sterile alpha motif (SAM)-containing protein, SAM8, that undergoes water-potential-dependent condensation both in vivo and in vitro and is crucial for hyperosmotic stress tolerance and seed germination. We use biophysical techniques, in vitro reconstitution and bioimaging to demonstrate that SAM8 is strongly hydrated under normal water conditions, preventing its macroscopic condensation. A negatively charged patch determines SAM8 hydration by creating an electric field and micropolar environment. Water-deficient conditions weaken this hydration, thereby activating SAM8 condensation by reprogramming hydrogen bond, electrostatic and hydrophobic interactions. Furthermore, we demonstrate that SAM8 condensates selectively sequester RNA export factors, leading to nuclear retention of mRNAs and translational reprogramming under hyperosmotic stress. Our findings show a mechanism by which plant cells directly sense and respond to water status, shedding light on how they adapt to water deficit conditions.

『摘要』 水分子作为生物分子的溶剂，对细胞至关重要。在缺水条件下，细胞的水势会降低，但细胞如何感知水势变化仍不得而知。本研究发现了一种含有无菌α基序（sterile alpha motif, SAM）的蛋白质——SAM8，它在体内和体外均能发生依赖于水势的凝聚现象，且对于高渗胁迫耐受性和种子萌发至关重要。我们利用生物物理技术、体外重建和生物成像方法证明，在正常水分条件下，SAM8高度水合，从而阻止其宏观凝聚。一个带负电荷的区域通过产生电场和微极性环境来决定SAM8的水合状态。缺水条件会削弱这种水合作用，进而通过重编程氢键、静电和疏水相互作用激活SAM8的凝聚。此外，我们还证明，在高渗胁迫下，SAM8凝聚物选择性地隔离RNA输出因子，导致信使核糖核酸（mRNA）滞留于细胞核内并引发翻译重编程。我们的研究揭示了植物细胞直接感知并响应水分状态的机制，为理解它们如何适应缺水条件提供了新见解。

『总结』 研究发现含无菌α基序的蛋白质SAM8能在体内外依水势凝聚，正常水分时因高度水合不宏观凝聚，缺水时水合减弱致其凝聚，且其凝聚物在高渗胁迫下有特定作用，揭示了植物细胞感知和响应水分状态的机制。

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25. 星形胶质细胞糖皮质激素受体信号传导限制神经元可塑性

Astrocyte glucocorticoid receptor signalling restricts neuronal plasticity

Gegenhuber B, Sonoda T, Traunmuller L, ... Griffith EC, Chen C, Greenberg ME.; nature; (655, 8125)

『Abstract』Sensory experience refines neural circuits during critical periods of postnatal development. Although neuronal activity is known to orchestrate the circuit wiring that underlies this process, the environmental cues that restrain developmental plasticity as animals mature are less clear. Here we examine the experience-dependent maturation of the mouse primary visual cortex across postnatal development using paired single-cell transcriptomic and chromatin accessibility sequencing. In addition to identifying the activity-dependent gene programs that emerge within each cortical cell type, we find that light exposure drives astrocyte maturation through cell-type-specific recruitment of the glucocorticoid receptor (encoded by Nr3c1) to chromatin. Astrocyte glucocorticoid receptor signalling activates an extensive gene regulatory program that is partially conserved in human brain development and promotes maturation processes that may regulate critical period closure. Collectively, these findings reveal that astrocyte glucocorticoid receptor signalling restricts neuronal plasticity. Glucocorticoid regulation of astrocyte maturation may also contribute to the effects of early-life stress across the brain, and the disruption of this process may increase susceptibility to neuropsychiatric disease.

『摘要』 在出生后发育的关键时期，感官体验会优化神经回路。尽管已知神经元活动可协调支撑这一过程的回路连接，但动物成熟过程中限制发育可塑性的环境线索尚不明确。本研究利用配对单细胞转录组和染色质可及性测序技术，研究了小鼠出生后初级视觉皮层依赖经验的成熟过程。除了确定每种皮质细胞类型中出现的依赖于活动的基因程序外，我们还发现光照通过将糖皮质激素受体（由Nr3c1编码）特异性招募至染色质来驱动星形胶质细胞的成熟。星形胶质细胞糖皮质激素受体信号激活了一个广泛的基因调控程序，该程序在人类大脑发育中得到部分保留，并促进可能调节关键期关闭的成熟过程。总之，这些研究结果表明，星形胶质细胞糖皮质激素受体信号可限制神经元可塑性。星形胶质细胞成熟的糖皮质激素调控也可能影响早期生活压力对全脑的影响，而这一过程的破坏可能会增加患神经精神疾病的风险。

『总结』 研究发现光照通过招募糖皮质激素受体驱动星形胶质细胞成熟，进而限制神经元可塑性，且该机制与人类大脑发育相关，或影响早期压力反应及神经精神疾病风险。

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26. 磁性杂质中近藤关联的精确量子多体处理方法探讨

Toward an exact quantum many-body treatment of Kondo correlation in magnetic impurities

['Zhu T', 'Peng L', 'Zhai H', 'Cui ZH', 'Chi R', 'Chan GK.']; science; (393, 6810)

『Abstract』The Kondo effect is a prototypical quantum phenomenon arising from the interaction between localized electrons in a magnetic impurity and itinerant electrons in a metallic host. Although this phenomenon has served as the testing ground for quantum many-body methods for decades, the precise description of Kondo physics with material specificity remains challenging. Here, we present a systematic ab initio approach to converge toward an exact zero-temperature electronic treatment of Kondo correlations. Across a series of 3d transition metals, we extracted Kondo temperatures matching subtle experimental trends, with accuracy exceeding that of standard models. We further obtained microscopic insight into the origin of these trends. More broadly, we demonstrate the possibility to start from fully ab initio many-body simulations and push toward the realm of converged predictions.

『摘要』 近藤效应是一种典型的量子现象，源于磁性杂质中的局域电子与金属宿主中的巡游电子之间的相互作用。尽管几十年来这一现象一直是量子多体方法的试验场，但精确描述具有材料特异性的近藤物理仍颇具挑战。本研究提出了一种系统的从头算方法，旨在实现对近藤关联的精确零温电子处理。通过对一系列3d过渡金属的研究，我们提取出与微妙实验趋势相符的近藤温度，其精度超越了标准模型。我们还进一步从微观层面揭示了这些趋势的起源。更广泛地说，我们展示了从完全从头算的多体模拟出发并迈向收敛预测领域的可能性。

『总结』 研究提出了系统从头算方法实现近藤关联的精确零温电子处理，对3d过渡金属提取的近藤温度精度超标准模型且揭示了实验趋势起源，还展示向收敛预测领域迈进的可能性。

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27. 镜像花朵手性发育的超基因控制

Supergene control of chiral development in mirror-image flowers

Xue H, Saltini M, Illing N, ... Deinum EE, Ingle RA, Lenhard M.; science; (393, 6810)

『Abstract』How genes determine the development of chiral structures is a fascinating question. The reciprocal placement of female and male organs on opposite sides of mirror-image flowers promotes efficient cross-pollination. Here, we identified that in butterfly lilies, female and male organs deflect by a combination of genetically controlled chirality and gravitropism, orienting left and right with respect to an external rather than internal reference axis. We found coordinated organ placement to be controlled by a hemizygous supergene containing two candidate causal loci, MIR156-R and YUCCA-R, that are responsible for opposite female and male organ orientation, respectively. The resulting differential placement of pollen carrying the two supergene alleles on pollinators' bodies leads to their transfer to the stigmas of flowers with opposite handedness and maintenance of the reproductive polymorphism.

『摘要』 基因如何决定手性结构的发育是一个引人入胜的问题。雌雄器官在镜像花朵相对两侧的对称分布，可促进高效的异花授粉。本研究发现，蝴蝶百合中雌雄器官的偏转由遗传控制的手性和向重力性的共同作用决定，其左右取向是相对于外部而非内部参考轴而言的。研究发现，协调的器官定位受一个半合子超基因控制，该超基因包含两个候选因果位点MIR156-R和YUCCA-R，分别负责雌性和雄性器官相反方向的定位。由此产生的携带两种超基因等位基因的花粉在传粉者身体上的差异分布，导致它们被转移到具有相反手性花朵的柱头上，从而维持了生殖多态性。

『总结』 研究揭示了蝴蝶百合中雌雄器官手性定位的遗传机制，发现半合子超基因通过调控手性与向重力性实现高效异花授粉并维持生殖多态性。

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28. 钙同位素将海洋酸化与阿普第期-阿尔布期有孔虫灭绝事件联系起来

Calcium isotopes link ocean acidification to Aptian-Albian foraminiferal extinctions

Chen J, Jacobson AD, Huber BT, ... Waldeck AR, Balestra B, Sageman BB.; science; (393, 6810)

『Abstract』The second-largest extinction event in the evolutionary history of planktic foraminifera occurred at the Aptian-Albian boundary. This extinction may reflect ocean acidification (OA) associated with Oceanic Anoxic Event 1b. As calcium isotope ratios (δ^44/40Ca) can track how biocalcification rates respond to OA, we measured δ^44/40Ca records for planktic and benthic foraminifera, bulk carbonates, and authigenic calcite across the Aptian-Albian boundary in the South Atlantic. Benthic and bulk δ^44/40Ca data display a distinct sequence of negative and positive excursions, similar to δ^44/40Ca variations across other OA events. Planktic δ^44/40Ca values increase markedly, tracking a reduction in calcification rates coincident with decreases in the size, diversity, and shell thickness of planktic foraminifera. These results suggest that OA drove extinctions of planktic foraminifera at the Aptian-Albian boundary.

『摘要』 浮游有孔虫进化史上第二大规模的灭绝事件发生在阿普第期-阿尔布期界线。此次灭绝可能反映了与海洋缺氧事件1b相关的海洋酸化（OA）。由于钙同位素比值（δ^44/40Ca）可以追踪生物钙化速率对海洋酸化的响应，我们测量了南大西洋阿普第期-阿尔布期界线处浮游和底栖有孔虫、块状碳酸盐以及自生方解石的δ^44/40Ca记录。底栖和块状δ^44/40Ca数据呈现出明显的负偏移和正偏移序列，与其他海洋酸化事件的δ^44/40Ca变化类似。浮游δ^44/40Ca值显著增加，表明钙化速率降低，同时浮游有孔虫的大小、多样性和壳体厚度也相应减少。这些结果表明，海洋酸化导致了阿普第期-阿尔布期界线处浮游有孔虫的灭绝。

『总结』 研究表明阿普第期-阿尔布期界线处浮游有孔虫的第二大规模灭绝由海洋酸化导致，通过测量多种物质的钙同位素比值发现其变化能反映生物钙化速率等改变。

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29. DNA聚合作用激活类似逆转录酶的抗病毒酶对RNA的切割

DNA polymerization activates RNA cleavage of a reverse transcriptase-like antiviral enzyme

Rong X, Xiao J, Zhao X, ... Wang X, Wang L, Zhu B.; science; (393, 6810)

『Abstract』Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated deoxynucleotide triphosphate levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising guanosine 3'-monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

『摘要』 与防御相关的逆转录酶（DRTs）可转录非编码RNA（ncRNAs）以进行抗病毒防御，但非编码RNA非依赖型DRTs的作用机制尚不清楚。本研究表明，单一的DRT4通过整合DNA聚合酶、核酸外切酶和RNA内切酶活性介导针对RNA的抗噬菌体防御。首先，DRT4通过其DNA聚合酶活性和核酸外切酶活性之间的平衡来感知噬菌体感染，因为脱氧核苷三磷酸水平升高会使平衡向聚合酶活性方向移动，从而促进蛋白质引发的单链DNA（ssDNA）合成。其次，足够长度的单链DNA、噬菌体DNA结合蛋白和脱氧鸟苷三磷酸共同激活DRT4一种不寻常的RNA内切酶活性，从噬菌体和宿主RNA中切除鸟苷3'-单磷酸以终止感染。这些发现揭示了一种独特的免疫策略，该策略结合了核酸合成与降解过程，拓展了DRTs的功能范围，为新的DNA和RNA处理技术提供了可能。

『总结』 研究发现单一DRT4通过整合多种酶活性介导RNA靶向抗噬菌体防御，揭示了结合核酸合成与降解的独特免疫策略并拓展了DRTs功能应用。

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30. 南美洲早期天花的基因组特征

The genomic identity of early smallpox in South America

Romero Gonzalez B, Reyes-Madrid M, Arriaza B, ... Moraga M, la Fuente Castro C, Nakagome S.; science; (393, 6810)

『Abstract』Smallpox was a major driver of population collapse in the Americas after European contact, yet the genetic identity of the causal strains remains unknown. Here, we report the first ancient smallpox genomes in the Americas, dating to approximately 1492-1631 common era (CE), recovered from two Inca-Colonial individuals in northern Chile. These genomes form a now-extinct lineage that diverged around 1296 CE, after the splitting of early medieval European strains but before the emergence of modern variola lineages, providing direct molecular evidence for smallpox introduction through European colonization. We further identify a constant tempo of gene inactivation until the late 16th century, followed by a phase of constraint and a subsequent rebound in substitution rates, linking variola virus evolution to major shifts in human demography and epidemiology.

『摘要』 在与欧洲人接触后，天花成为美洲人口锐减的主要推动因素之一，然而引发疾病的毒株的遗传特征至今仍不明确。本研究报告了美洲首个古代天花基因组，这些基因组可追溯至大约公元1492年至1631年，是从智利北部的两名印加殖民时期个体中提取出来的。这些基因组构成了一个现已灭绝的谱系，该谱系于公元1296年左右分化而来，晚于欧洲早期中世纪毒株的分裂时间，但早于现代天花病毒谱系的出现时间，为天花通过欧洲殖民引入美洲提供了直接的分子证据。我们还发现，在16世纪晚期之前，基因失活一直以恒定的速度进行，随后进入一个限制阶段，之后替换率又出现反弹，这表明天花病毒的进化与人类人口统计学和流行病学的重大转变有关。

『总结』 研究发现了美洲首个约公元1492 - 1631年的古代天花基因组，其构成已灭绝谱系，为天花经欧洲殖民引入提供直接分子证据，还揭示了天花病毒进化与人类相关转变的联系。

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31. 线粒体蛋白酶对血红素生物合成进行反馈调控的适配器

An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease

Cottle T, Joh L, Posner C, ... Fleming MD, Ducamp S, Kardon JR.; science; (393, 6810)

『Abstract』Heme biosynthesis is tightly coordinated to support essential functions without accumulating toxic porphyrins and depleting cellular iron. Heme induces degradation of the heme biosynthetic enzyme, 5-aminolevulinate synthase (ALAS), by the mitochondrial caseinolytic protease complex CLPX-CLPP (CLPXP), but the mechanism for heme-triggered degradation had not been elucidated. We found that polymerase delta-interacting protein 2 (POLDIP2) is a heme-sensing adaptor protein sufficient to reconstitute negative feedback degradation of ALAS by CLPXP. POLDIP2 was necessary to support ALAS turnover in cells and regulate heme production during erythropoiesis. POLDIP2 directly recognized and recruited heme-bound ALAS to CLPXP. Degradation initiation required a carboxyl-terminal element of ALAS, truncations of which cause an erythropoietic protoporphyria. Our findings establish a mechanism for conditional degradation by CLPXP that underlies erythropoietic protoporphyrias linked to CLPX and ALAS.

『摘要』 血红素生物合成受到严格调控，以支持基本功能，同时避免有毒卟啉的积累和细胞铁的耗竭。血红素通过线粒体酪蛋白溶解性蛋白酶复合物CLPX-CLPP（CLPXP）诱导血红素生物合成酶5-氨基乙酰丙酸合酶（ALAS）的降解，但血红素触发降解的机制尚未阐明。我们发现聚合酶δ相互作用蛋白2（POLDIP2）是一种血红素感应适配蛋白，足以重建CLPXP对ALAS的负反馈降解。在细胞中，POLDIP2是维持ALAS周转和支持红细胞生成过程中调节血红素产生所必需的。POLDIP2可直接识别并结合血红素的ALAS，并将其招募至CLPXP。降解起始需要ALAS的羧基末端元件，其截短会导致红细胞生成性原卟啉症。我们的研究结果建立了一种由CLPXP介导的条件性降解机制，该机制与CLPX和ALAS相关的红细胞生成性原卟啉症有关。

『总结』 研究发现POLDIP2作为血红素感应适配蛋白，可重建CLPXP对ALAS的负反馈降解，且在细胞中对于维持ALAS周转和红细胞生成时调节血红素产生必不可少，还揭示了与相关疾病有关的条件性降解机制。

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32. 时空多组学揭示转移定植过程中肿瘤生态系统动态变化

Spatiotemporal multiomics uncover tumor ecosystem dynamics during metastatic colonization

Sun Y, Zhong Y, Liu S, ... Zhou J, Wu L, Fan J.; science; (393, 6810)

『Abstract』The mechanisms underlying the interactions between disseminated tumor cells (DTCs) and their tissue microenvironment during metastatic colonization are currently poorly understood. We integrated multimodal single-cell and spatial profiling from liver cancer mouse models and human metastases to track the spatiotemporal dynamics of DTCs and their microenvironments from single-cell seeding to overt lung metastasis. We identified a residual population of quiescent Phgdh^high DTCs that survived initial innate immune clearance and became transiently enriched in micrometastases. These cells shaped an immune-scarce microenvironment through PHGDH-dependent, H3K27me3-mediated epigenetic silencing of chemokine transcription, thereby promoting metastatic expansion. Cx3cr1^high interstitial macrophages were also transiently enriched before DTC expansion, creating an immune-privileged niche for metastatic outgrowth by recruiting immunosuppressive cells. Inactivating the PHGDH-H3K27me3 axis in DTCs or depleting interstitial macrophages restored immune surveillance and inhibited metastatic colonization. These findings provide insights into the development of micrometastasis-targeting regimens.

『摘要』 目前，对于转移性定植过程中播散性肿瘤细胞（DTCs）与其组织微环境之间相互作用的潜在机制，我们尚知之甚少。本研究整合了肝癌小鼠模型和人类转移灶的多模态单细胞及空间分析数据，追踪了从单个细胞着床到明显肺转移期间，DTCs及其微环境的时空动态变化。研究发现，存在一群残留的静止型Phgdh^high DTCs，它们在初始先天免疫清除中存活下来，并在微转移灶中短暂富集。这些细胞通过PHGDH依赖、H3K27me3介导的趋化因子转录表观遗传沉默，塑造了一个缺乏免疫细胞的微环境，从而促进了转移性增殖。此外，在DTCs扩增之前，Cx3cr1^high间质巨噬细胞也短暂富集，它们通过招募免疫抑制细胞为转移性生长创造了一个免疫特权生态位。在DTCs中使PHGDH-H3K27me3轴失活或耗尽间质巨噬细胞可恢复免疫监视并抑制转移性定植。这些发现为开发针对微转移的治疗方案提供了见解。

『总结』 研究揭示了播散性肿瘤细胞与组织微环境相互作用促进转移性定植的机制，发现特定DTCs和间质巨噬细胞的作用，以及相关干预手段对抑制转移的效果，为治疗提供新思路。

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33. 氟化钾催化下的醇的Appel氟化反应

Catalytic Appel fluorination of alcohols with potassium fluoride

Mondal A, Struijs JJC, Doyle CJN, ... Paton RS, Aldridge S, Gouverneur V.; science; (393, 6810)

『Abstract』Appel halogenation reactions are widely used to convert alcohols to alkyl halides but are not suitable to prepare alkyl fluorides because fluoride is sequestered as a difluorophosphorane. In this work, we introduce bench-stable neopentoxyphosphonium salts to solve this enduring challenge. With these reagents, various alcohols undergo fluorination with potassium fluoride under hydrogen bonding phase-transfer catalysis, a manifold offering a pathway to enantioselective fluorination of alcohols. Mechanistically, a neopentoxyfluorophosphorane is formed, which undergoes reversible exchange with the alcohol substrate in preference to difluorophosphorane formation. The catalyst assists with potassium fluoride solubilization and with phosphorus-fluorine bond dissociation, leading to the alkoxyphosphonium fluoride ion pair undergoing stereoinvertive fluorination. Turnover results from stronger binding of the catalyst to fluoride than phosphine oxide, the by-product of the reaction, which is recyclable as starting material for the synthesis of the phosphonium reagents.

『摘要』 卤代阿佩尔反应（Appel halogenation）广泛用于将醇转化为烷基卤化物，但不适用于制备烷基氟化物，因为氟离子会以二氟代膦烷的形式被捕获。本研究引入了实验室稳定的新戊氧基磷鎓盐来解决这一长期存在的难题。使用这些试剂时，多种醇可在氢键相转移催化下与氟化钾发生氟化反应，为醇的对映选择性氟化提供了一条途径。从机理上看，反应过程中会形成新戊氧基氟代膦烷，该物质优先与醇底物进行可逆交换，而非生成二氟代膦烷。催化剂有助于氟化钾的溶解以及磷-氟键的断裂，使烷氧基磷鎓氟化物离子对经历立体反转氟化。由于催化剂与氟离子的结合力强于副产物氧化膦（可作为合成磷鎓试剂的起始原料回收利用），因此实现了反应循环。

『总结』 研究通过引入新戊氧基磷鎓盐和氢键相转移催化体系，解决了传统阿佩尔反应无法直接合成烷基氟化物的难题，并揭示了其通过可逆中间体实现立体反转氟化的机制及催化剂再生原理。

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34. n型聚合物层可实现高效、可扩展且热稳定的钙钛矿太阳能组件

n-Type polymer layers enable efficient, scalable, and thermally stable perovskite solar modules

Gao D, Gong J, Yang L, ... Li S, Gong J, Zhu Z.; science; (393, 6810)

『Abstract』Fullerene-based electron transport layers (ETLs) used in inverted (p-i-n) perovskite solar cells face issues regarding cost, scalability, and instability, whereas highly stable inorganic oxides feature unfavorable energy alignment and enhance hysteresis, which reduce power conversion efficiency (PCE). We report a nonfullerene conjugated polymer, 2PB-T, that incorporates coplanar and electron-withdrawing perylene bisimide (PBI) units into its backbone. The PBI polymeric backbone and side-chain engineering address the instability of small-molecule ETLs by optimizing electron transport properties, film uniformity, and interfacial binding. Small-area devices achieved a champion PCE of 27.8%, with a certified maximum power point tracking (MPPT) efficiency of 27.3%. Perovskite modules with areas of 20.6 and 625 square centimeters reached PCEs of 24.4 and 22.5%, respectively. Small-area devices retained more than 98.6% of their initial PCE after 1752 hours of continuous MPPT at 85°C in air, and the 625-square-centimeter module maintained 96.9% of its initial PCE after 5900 hours of outdoor operation.

『摘要』 基于富勒烯的电子传输层（ETL）用于倒置（p-i-n）钙钛矿太阳能电池时，面临成本、可扩展性和稳定性问题；而高度稳定的无机氧化物则存在能量排列不利和加剧迟滞现象的问题，这降低了光电转换效率（PCE）。本文报道了一种非富勒烯共轭聚合物2PB-T，它将共平面且吸电子的花二酰亚胺（PBI）单元引入主链。通过优化PBI聚合物主链和侧链工程，改善了电子传输特性、薄膜均匀性和界面结合性，解决了小分子ETL的不稳定问题。小面积器件实现了高达27.8%的冠军光电转换效率，认证的最大功率点跟踪（MPPT）效率为27.3%。面积为20.6平方厘米和625平方厘米的钙钛矿组件分别达到了24.4%和22.5%的光电转换效率。在空气中85℃下连续进行1752小时最大功率点跟踪后，小面积器件仍能保持初始光电转换效率的98.6%以上，而625平方厘米的组件在户外运行5900小时后仍能保持初始光电转换效率的96.9%。

『总结』 基于富勒烯的电子传输层用于倒置钙钛矿太阳能电池有诸多不足，研究报道的非富勒烯共轭聚合物2PB-T解决了相关问题，不同面积的器件和组件均取得较高光电转换效率且有良好稳定性。

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35. X染色体失活将L1诱变吸引至人类X染色体

X-chromosome inactivation draws L1 mutagenesis to the human X chromosome

de Los Rios Barreda J, Ferreiro ME, Jansz N, ... Lister R, Moran JV, Faulkner GJ.; science; (393, 6810)

『Abstract』X-chromosome inactivation (XCI) enables gene dosage compensation in XX eutherians. Long interspersed element-1 (LINE-1 or L1) retrotransposons are unusually abundant on the human X chromosome and are hypothesized to facilitate XCI. Here, we used long-read DNA sequencing to conduct a haplotype-aware analysis of engineered L1 integration preferences in the PA-1 human embryonic carcinoma cell line. Crucially, clonal XCI in PA-1 cells enabled derivation of active (Xa) and inactive (Xi) X-chromosome haplotypes. L1 integration strongly favored the Xi and other genomic regions that undergo DNA replication late in S-phase. These results suggest that the X chromosome is L1 rich because of XCI and imply that L1 integration preference for the Xi in XX individuals could potentially double the frequency of X-linked pathogenic L1 mutations in their XY descendants.

『摘要』 X染色体失活（XCI）使XX真兽类动物实现基因剂量补偿。长散在元件-1（LINE-1或L1）逆转录转座子在人类X染色体上异常丰富，据推测可促进X染色体失活。本研究利用长读长DNA测序技术，对PA-1人胚胎癌细胞系中工程化L1整合偏好性进行了单倍型分析。关键在于，PA-1细胞的克隆性X染色体失活使得能够推导出活性（Xa）和非活性（Xi）的X染色体单倍型。L1整合强烈倾向于Xi以及S期晚期进行DNA复制的其他基因组区域。这些结果表明，由于X染色体失活，X染色体富含L1，并且暗示在XX个体中L1对Xi的整合偏好可能会使其XY后代的X连锁致病性L1突变的频率加倍。

『总结』 研究发现人类X染色体因XCI机制而富含L1元件，且L1优先整合于非活性X染色体及S期晚期复制区，这可能使XY后代X连锁致病突变风险翻倍。

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36. 溶酶体衰老图谱揭示了与溶酶体贮积症共有的代谢物特征

Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders

Puszynska AM, Nguyen TP, Cangelosi AL, ... Bell GW, Sabatini DM, Weissman JS.; science; (393, 6810)

『Abstract』Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age, preceding organismal decline. Caloric restriction, a lifespan-extending intervention, mitigated these changes in the heart and muscle but not the brain. Our findings link lysosomal storage disorders to aging-related dysfunction and open avenues for the mechanistic investigation of how lysosomal functions deteriorate during aging and in age-associated diseases.

『摘要』 溶酶体功能障碍是衰老的一个公认特征。在此，我们使用一套快速溶酶体分离工具构建了大脑、心脏、肌肉和白色脂肪组织等不同组织在衰老过程中溶酶体内代谢物变化的多组织图谱。脑、心、肌和白脂中的老化溶酶体积累了甘油磷二酯和胱氨酸，这些代谢物与幼年型溶酶体贮积症、巴顿病和胱氨酸病存在因果关系。这些代谢物的水平随年龄增长呈线性上升，早于机体衰退出现。热量限制作为一种延长寿命的干预措施，可缓解心脏和肌肉中的这些变化，但对大脑无效。我们的研究结果将溶酶体贮积症与衰老相关功能障碍联系起来，并为探究溶酶体功能在衰老及老年相关疾病中如何退化的机制研究开辟了新途径。

『总结』 研究发现溶酶体功能障碍是衰老特征，用工具构建多组织图谱发现老化溶酶体积累特定代谢物且其水平随年龄上升早于机体衰退，热量限制对部分组织有缓解作用，该研究为相关机制研究开辟新途径。

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37. 哺乳动物玻璃体胶原纤维的分子结构

The molecular architecture of mammalian vitreous body collagen fibrils

['Lou X', 'Cong Y', 'Xu Y', 'Liu Y', 'Li Y', 'Yan C.']; science; (393, 6810)

『Abstract』Collagen, a fundamental constituent of the extracellular matrix, has long remained elusive to high-resolution structural characterization. Using a tailored system and optimized cryo-electron microscopy processing for long-period filaments, we determined the structure of native collagen fibrils from the porcine vitreous body, with local resolutions extending from 2.6 to 7 angstroms. Each 67-nanometer periodic unit contains type II, V/XI, and IX collagen triple helices together with opticin, at a stoichiometry of 8:4:4:4, which reveals their detailed higher-order molecular packing. Abundant galactose-glucose disaccharides modify hydroxylysine residues in conserved -glycine-X-hydroxylysine- motifs, mediating fibril packing and structural stability. Our structure uncovers the glycan-mediated assembly principle of collagen fibrils and clarifies the structure-function basis of collagens in the vitreous body.

『摘要』 作为细胞外基质的基本成分，胶原蛋白的高分辨率结构表征长期以来一直难以实现。我们利用定制的系统和针对长周期丝状体优化的冷冻电子显微镜处理技术，确定了猪玻璃体内天然胶原纤维的结构，局部分辨率可达2.6至7埃。每个67纳米周期单元包含II型、V/XI型和IX型胶原蛋白三螺旋以及opticin蛋白，其化学计量比为8:4:4:4，揭示了它们详细的高阶分子堆积方式。丰富的半乳糖-葡萄糖二糖修饰保守的-甘氨酸-X-羟赖氨酸-基序中的羟赖氨酸残基，介导纤维堆积并维持结构稳定性。我们的研究结果揭示了糖基介导的胶原纤维组装原理，阐明了玻璃体内胶原蛋白的结构功能基础。

『总结』 通过定制系统和优化冷冻电镜技术，确定了猪玻璃体内天然胶原纤维结构，揭示高阶分子堆积方式及糖基介导的组装原理与结构功能基础。

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38. 用于高效稳定钙钛矿太阳能电池及组件的等离子体表面工程

Plasma surface engineering for efficient and stable perovskite solar cells and modules

Fan R, Ma Y, Xu S, ... Zhao X, Chen Q, Zhou H.; science; (393, 6810)

『Abstract』The instability of perovskite solar cells (PSCs) stems largely from the formation and evolution of interfacial defects associated with the soft, multicomponent perovskite lattice. We report a scalable, plasma-based passivation strategy that forms conformal, uniform, and strong-bonded heterostructure through in situ chemical reactions on large-area perovskite films. This approach also mitigates defect accumulation within the laser-scribed interconnection regions, where localized damage often dominates module-level performance losses. We achieved a power conversion efficiency (PCE) of 27.2% in small-area devices (active area 8.313 square millimeters) and 24.0% (certified efficiency of 23.5%) in 100-square-centimeter (cm) modules (aperture area 65.05 cm). The small-area device retained 98.1% of its initial PCE after 2000 hours of maximum power point tracking at 85°C under 1-sun illumination, and the 100-cm module retained 99.3% of its initial PCE after 1600 hours at 65°C under 1-sun illumination.

『摘要』 钙钛矿太阳能电池（PSCs）的不稳定性在很大程度上源于与柔软的多组分钙钛矿晶格相关的界面缺陷的形成和演变。我们报告了一种可扩展的、基于等离子体的钝化策略，该策略通过在大面积钙钛矿薄膜上进行原位化学反应，形成共形、均匀且强键合的异质结构。这种方法还减轻了激光划线互连区域内的缺陷积累，而局部损伤往往是导致组件级性能损失的主要因素。我们在小面积器件（有效面积为8.313平方毫米）中实现了27.2%的光电转换效率（PCE），在100平方厘米模块（孔径面积为65.05平方厘米）中实现了24.0%（认证效率为23.5%）的光电转换效率。小面积器件在85℃下经1个太阳光照强度下最大功率点跟踪2000小时后，仍能保持初始PCE的98.1%；100平方厘米模块在65℃下经1个太阳光照强度下1600小时后，仍能保持初始PCE的99.3%。

『总结』 研究提出一种可扩展的基于等离子体钝化策略，改善钙钛矿太阳能电池界面缺陷问题，减轻激光划线互连区域内缺陷积累，提升了小面积器件和大面积模块的光电转换效率及稳定性。

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39. 利用酵母实现基本抗癌药物依托泊苷和替尼泊苷的可持续供应

Enabling sustainable supply of the essential cancer medicines etoposide and teniposide in yeast

Shen S, Hu X, Li D, ... Nielsen J, Huang L, Hu Y.; science; (393, 6810)

『Abstract』Lignans constitute a diverse family of plant metabolites with therapeutic potential. Among them, podophyllotoxin-type aryltetralin lignans serve as precursors for etoposide and teniposide. Etoposide is an essential anticancer medicine approved for first-line treatment of small cell lung cancer, whereas teniposide is used for treatment of leukemia and some brain tumors. Currently, these drugs depend on extraction of precursors from the endangered plant Sinopodophyllum hexandrum, followed by chemical transformations. By identifying key glycosyltransferases and executing more than 60 genetic edits involving 45 heterologous enzymes, the complex biosynthetic pathway of podophyllotoxin-type lignans was reconstructed in yeast. In this study, we established a chemoenzymatic route that streamlines the synthesis of etoposide and teniposide through a single chemical step from biosynthetic precursor 4'-demethyl-epipodophyllotoxin-4-O-glucoside, which enables a secure supply chain of these essential medicines.

『摘要』 木脂素是一类具有治疗潜力的植物代谢产物，种类繁多。其中，鬼臼毒素型芳基四氢萘木脂素是依托泊苷和替尼泊苷的前体物质。依托泊苷是一种获批用于小细胞肺癌一线治疗的抗癌基本药物，而替尼泊苷则用于白血病及部分脑肿瘤的治疗。目前，这些药物的制备依赖于从濒危植物八角莲中提取前体物质，随后进行化学转化。通过鉴定关键糖基转移酶并进行涉及45种异源酶的60多次基因编辑，研究人员在酵母中重建了鬼臼毒素型木脂素的复杂生物合成途径。本研究建立了一条化学酶法路线，通过从生物合成前体4'-去甲基表鬼臼毒素-4-O-葡萄糖苷经单一化学反应步骤即可简化依托泊苷和替尼泊苷的合成过程，从而确保这两种重要药物的稳定供应。

『总结』 研究者在酵母中重建了鬼臼毒素型木脂素的生物合成途径，并建立了化学酶法路线，可简化依托泊苷和替尼泊苷的合成，保障其稳定供应。

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40. 持续1000万年的生物地理“蓄水池”为大美洲生物大迁徙埋下伏笔

A 10-million-year biogeographic holding pen primed the Great American Biotic Interchange

Tseng ZJ, Kahn LX, Pacheco-Castro A, ... Hannold C, McDonald HG, Wang X.; science; (393, 6810)

『Abstract』The movement of taxa between North and South America across the Panamanian land bridge, known as the Great American Biotic Interchange (GABI), established modern-day mammal assemblages in the Americas, heralding the decisive end of what has been called the "splendid isolation" of the South American fauna. Lacking substantive low-latitude records, previous work on this pattern relied on South American and temperate North American fossils to conclude that pulsed interchanges began about 2.8 million years ago (mya). Based on new low-latitude fossil data from Mexico, we found evidence for a prolonged, triphasic interchange. Phase 1 consisted of the initial accumulation of northern higher-latitude mammals in a Mexican "holding pen" beginning 10 mya. Dispersal began in phase 2, with a strong north-south gradient and increasing biogeographic connections (7 to 3 mya). The final phase consisted of the already well-described taxonomic pulses (from ~2.8 mya).

『摘要』 北美洲和南美洲的分类单元通过巴拿马地峡进行迁移，这一过程被称为“大美洲生物交换”（Great American Biotic Interchange, GABI），它确立了现代美洲哺乳动物群落，标志着南美动物区系所谓“辉煌孤立”状态的决定性终结。由于缺乏低纬度记录，此前针对该模式的研究主要依据南美和北温带地区的化石得出结论，认为脉冲式生物交换始于约280万年前（mya）。基于来自墨西哥的新低纬度化石数据，我们发现存在一个持续较长时间的三阶段生物交换过程：第一阶段始于1000万年前，表现为北方高纬度哺乳动物在墨西哥“中转站”的初步聚集；第二阶段始于700万至300万年前，南北向扩散梯度显著增强且生物地理联系日益紧密；第三阶段即已充分描述的分类单元脉冲式交换（约从280万年前开始）。

『总结』 新发现的墨西哥低纬度化石证据表明，大美洲生物交换经历了一个持续数百万年的三阶段过程，而非此前认为的单一脉冲事件。

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