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1. RNA结构调控内源性ADAR实现精准高效编辑

RNA structure programs endogenous ADAR for precise and efficient editing

Song D, Liu G, Zhang W, ... , Liu Y, Xiong W, Wei W.; cell; (189, 14)

『Abstract』Leveraging endogenous adenosine deaminase (ADAR) enzymes through engineered ADAR-recruiting RNAs (arRNAs) offers a safe, programmable strategy for RNA editing without exogenous enzyme delivery. Yet an incomplete understanding of ADAR's mechanistic basis has hindered the rational design of arRNAs with improved efficiency and precision. Here, we present LEAPER 3.0 (leveraging endogenous ADAR for programmable editing of RNA), a next-generation RNA-editing platform that integrates AlphaFold 3 structural predictions with systematic biochemical and cellular assays to define the molecular interface between ADAR1 or ADAR2 and double-stranded RNA. These insights enabled the rational optimization of arRNAs to expand the editable sequence range to previously refractory sites, suppress bystander editing within duplex regions, and achieve single-nucleotide discrimination among adjacent adenosines. This work elucidates the structural and mechanistic principles underlying arRNA-mediated editing and establishes a framework for the rational design of highly efficient and precise A-to-I RNA-editing tools.

『摘要』 通过工程化设计的ADAR招募RNA（arRNAs）利用内源性腺苷脱氨酶（ADAR）提供了一种无需外源性酶递送的安全、可编程RNA编辑策略。然而，由于对ADAR作用机制的基础认识尚不充分，阻碍了设计出更高效、更精确的arRNA。在此，我们提出LEAPER 3.0（利用内源性ADAR实现RNA可编程编辑），这是一个新一代RNA编辑平台，它结合了AlphaFold 3结构预测以及系统的生物化学和细胞实验，以确定ADAR1或ADAR2与双链RNA之间的分子界面。这些发现使得对arRNA进行合理优化成为可能，从而将可编辑序列范围扩展至此前难以编辑的位点，抑制双链区域内的旁观者编辑，并实现对相邻腺苷的单核苷酸区分。这项工作阐明了arRNA介导编辑的结构和机制原理，为合理设计高效精确的A-to-I RNA编辑工具奠定了框架。

『总结』 LEAPER 3.0是一个新一代RNA编辑平台，通过结合结构预测和实验分析，阐明了ADAR与双链RNA的分子界面，为设计高效精确的A-to-I RNA编辑工具提供了框架。

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2. 通过环形反义RNA引导外显子跳跃实现对恒河猴和人类杜氏肌营养不良症的长期逆转

Long-term reversal of Duchenne muscular dystrophy via circular arRNA-guided exon skipping in monkeys and humans

Guo W, Tang H, Yi Z, ... , Ji W, Chen Y, Wei W.; cell; (189, 14)

『Abstract』Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of mobility, and premature death. Here, we applied leverage endogenous adenosine deaminase acting on RNA (ADAR) for programmable editing of RNA (LEAPER) 2.0, an RNA editing platform, to achieve exon skipping by harnessing endogenous ADAR through circular ADAR-recruiting RNAs (circ-arRNAs). By engaging key splicing elements, circ-arRNAs bypass out-of-frame DMD mutations and restore dystrophin expression through ADAR-dependent and ADAR-independent mechanisms. In DMD nonhuman primates (NHPs) carrying hotspot mutations, a single administration achieved durable dystrophin restoration and sustained motor improvement for at least 1.5 years without eliciting anti-dystrophin immune responses. In a first-in-human study, a single dose of adeno-associated virus (AAV)-delivered circ-arRNA produced safe, dose-dependent exon skipping in three patients, accompanied by measurable gains in motor and cardiopulmonary function. Together, consistent dystrophin restoration across DMD NHP models, patient-derived cardiomyocytes, and treated patients highlights the translational potential of circ-arRNA-mediated exon skipping as a therapeutic strategy for DMD.

『摘要』 杜氏肌营养不良症（DMD）是一种由DMD基因突变引起的致命性神经肌肉疾病，会导致进行性肌肉退化、行动能力丧失和早亡。本研究采用基于内源性作用于RNA的腺苷脱氨酶（ADAR）的可编程RNA编辑（LEAPER）2.0这一RNA编辑平台，通过环状ADAR招募RNA（circ-arRNAs）利用内源性ADAR实现外显子跳跃。circ-arRNAs通过结合关键剪接元件，绕过DMD无义突变，通过ADAR依赖性和非ADAR依赖性机制恢复抗肌萎缩蛋白表达。在携带热点突变的DMD非人灵长类动物（NHP）模型中，单次给药实现了抗肌萎缩蛋白的持久恢复和至少1.5年的持续运动功能改善，且未引发抗肌萎缩蛋白免疫反应。在首次人体试验中，单剂量腺相关病毒（AAV）递送的circ-arRNA在三名患者中实现了安全且剂量依赖性的外显子跳跃，同时患者的运动和心肺功能得到可测量的改善。综合DMD非人灵长类动物模型、患者来源的心肌细胞和接受治疗患者的抗肌萎缩蛋白恢复情况，circ-arRNA介导的外显子跳跃作为DMD治疗策略具有转化潜力。

『总结』 研究显示circ-arRNA介导的外显子跳跃可恢复DMD模型及患者的抗肌萎缩蛋白表达，改善运动功能，且安全性良好，具有临床转化潜力。

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3. 持续存在和短暂的衰老细胞促进脑屏障的发育

Persistent and transient senescent cells contribute to brain-barrier development

Watson LA, Adelsheim Z, Carter MJ, ... , Palaniappan RH, Augustine JM, Meharena HS.; cell; (189, 14)

『Abstract』Establishment of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier requires precise coordination between diverse cell types to protect and nourish the brain. Here, we identify developmentally programmed p21⁺ senescent cells that exhibit divergent senescence-associated features across these two brain interfaces in mice. In the choroid plexus (ChP), epithelial cells adopt a lifelong, non-inflammatory senescent state associated with CSF production and blood-CSF barrier integrity. In contrast, vascular endothelial cells and brain-resident macrophages transiently exhibit pro-inflammatory senescence profiles during brain vascularization, with reciprocal signaling linked to angiogenic patterning and extracellular matrix assembly. The ablation of p21⁺ cells during mid-gestation disrupts brain vascular patterning and ChP integrity, which results in hemorrhage, impaired CSF production, and ventricular collapse. These findings indicate that embryonic senescent cells adopt divergent transient and long-lived states that support brain-barrier formation and homeostasis, thus reframing the prevailing view of persistent senescence beyond solely a pathological state.

『摘要』 血脑屏障（BBB）和脑脊液（CSF）屏障的建立需要不同细胞类型之间的精确协调，以保护和滋养大脑。本研究在小鼠中发现了发育编程的p21⁺衰老细胞，这些细胞在这两种脑界面上表现出不同的衰老相关特征。在脉络丛（ChP）中，上皮细胞呈现终身、非炎症的衰老状态，与脑脊液生成和血脑脊液屏障的完整性相关。相反，在大脑血管生成期间，血管内皮细胞和脑驻留巨噬细胞短暂表现出促炎衰老特征，且与血管生成模式和细胞外基质组装相关的相互信号传导有关。在妊娠中期清除p21⁺细胞会破坏大脑血管模式和脉络丛的完整性，导致出血、脑脊液生成受损和脑室塌陷。这些发现表明，胚胎衰老细胞呈现出不同的短暂和长期状态，以支持脑屏障的形成和体内平衡，从而重新定义了持久性衰老不仅仅是病理状态的传统观点。

『总结』 研究揭示了胚胎期p21⁺衰老细胞在脑屏障形成中呈现不同状态（脉络丛上皮细胞终身非炎症性衰老、血管内皮细胞和脑驻留巨噬细胞短暂促炎性衰老），清除此类细胞会破坏脑屏障功能，表明持久性衰老不单纯是病理状态。

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4. 破裂细胞（ruptoblasts）的爆发性细胞毒性：连接激素监测与免疫防御

Explosive cytotoxicity of ruptoblasts bridges hormone surveillance and immune defense

Chai C, Sultan E, Sarkar SR, ... , Thiam HR, Rosental B, Wang B.; cell; (189, 14)

『Abstract』Current understanding of cytotoxic immunity is shaped by hematopoietic-derived cells-T cells, natural killer cells, and neutrophils. Here, we identify "ruptoblasts," a previously unknown cytotoxic glandular cell type in regenerative planarian flatworms. Ruptoblasts undergo an explosive cell death, "ruptosis," triggered by activin, a multifunctional hormone acting as an inflammatory cytokine. Excessive activin-induced through protein injection, genetic chimerism, or bacterial infection-initiates ruptosis, discharging potent diffusible cytotoxic agents capable of eliminating nearby cells, bacteria, and even mammalian cells within minutes. Ruptoblast ablation suppresses inflammation but compromises bacterial clearance, highlighting their broad-spectrum immune functions. Mechanistically distinct from known cytotoxic and cell death mechanisms, the explosive nature of ruptosis relies on endoplasmic reticulum (ER)-derived calcium and cytoskeleton-dependent signal amplification. Ruptoblast-like cells appear conserved in diverse basal bilaterians, implying an ancient evolutionary origin. These findings unveil a strategy coupling hormonal regulation with immune defense and expand the landscape of evolutionary immune innovations.

『摘要』 目前对细胞毒性免疫的理解主要基于造血来源的细胞，如T细胞、自然杀伤细胞和中性粒细胞。本研究在再生涡虫中鉴定出一种先前未知的细胞毒性腺细胞类型——“ruptoblasts”。ruptoblasts会经历一种由活化素（一种作为炎症细胞因子的多功能激素）触发的爆炸性细胞死亡，即“ruptosis”。通过蛋白质注射、遗传嵌合或细菌感染诱导的过量活化素会引发ruptosis，释放出强效可扩散的细胞毒性物质，可在数分钟内杀死附近的细胞、细菌甚至哺乳动物细胞。ruptoblasts的缺失会抑制炎症反应，但会削弱细菌清除能力，凸显其广谱免疫功能。ruptosis的爆炸特性在机制上与已知的细胞毒性和细胞死亡机制不同，依赖于内质网（ER）来源的钙和细胞骨架依赖的信号放大。ruptoblast样细胞在多种基部两侧对称动物中似乎保守存在，暗示其具有古老的进化起源。这些发现揭示了一种将激素调控与免疫防御相结合的策略，并拓展了进化免疫创新的图景。

『总结』 本研究发现再生涡虫中存在一种新型细胞毒性腺细胞ruptoblasts，其通过活化素诱导的爆炸性细胞死亡ruptosis释放细胞毒性物质，具有广谱免疫功能，且其机制独特，该细胞在多种基部两侧对称动物中保守，揭示了激素调控与免疫防御结合的新策略及进化免疫创新。

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5. 古基因组揭示了现代狮与洞狮之间的进化关系

Paleogenomes reveal the evolutionary relationship between modern and cave lions

Stanton DWG, Bergstrom A, Heintzman PD, ... , Skoglund P, Frantz L, Dalen L.; cell; (189, 14)

『Abstract』The Eurasian cave lion was abundant across the Northern Hemisphere before the Late Pleistocene megafaunal extinctions. However, the extent of the distinction between cave and modern lions and their adaptive differences have remained unclear. Using 12 cave lion genomes spanning more than 100,000 years, we show that modern and cave lions were distinct evolutionary lineages with separate demographic histories and unique non-synonymous variants. We also identify evidence of ancient gene flow between them, with the best modern lion proxy for this ancestry being an extinct Southwest Asian population. This admixture correlates with global ice extent, with 3.2%-4.4% modern lion ancestry detected in a ∼20,000-year-old cave lion from Central East Asia. These findings provide insight into the evolutionary history of the cave lion, once one of the Northern Hemisphere's most ecologically impactful megafaunal species.

『摘要』 在晚更新世大型动物灭绝之前，欧亚洞狮在北半球分布广泛。然而，洞狮与现代狮子之间的差异程度及其适应性差异仍不明确。我们利用跨越逾10万年的12具洞狮基因组数据，揭示出现代狮子与洞狮分属不同进化谱系，具有独立的人口历史和独特的非同义变异。研究还发现二者存在古老基因交流的证据，其中与洞狮基因最接近的现代狮子群体为已灭绝的西南亚种群。这种基因混合与全球冰川范围相关，在一具距今约2万年的中亚洞狮个体中检测到3.2%至4.4%的现代狮子基因成分。这些发现为洞狮——这一曾对北半球生态产生重大影响的巨型动物——的进化史提供了新的见解。

『总结』 洞狮与现代狮子分属不同进化谱系但存在基因交流，其基因混合程度与冰川范围相关，研究为洞狮进化史提供了新见解。

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6. Wnt信号体胞外复合物组装的结构基础

Structural basis of Wnt signalosome extracellular complex assembly

Yue D, Sun G, Cao Y, ... , Zhang L, Wang Z, Xu W.; cell; (189, 14)

『Abstract』Recognition of Wnt proteins by Frizzled (Fzd) receptors and the low-density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptor is essential for canonical Wnt signaling. It remains enigmatic how Wnt simultaneously interacts with Fzd and LRP5/6 and activates intracellular Wnt/β-catenin signaling. Here, we report cryo-electron microscopy (cryo-EM) structures of Wnt3a/Fzd8/LRP6 extracellular complexes captured in a 2:4:2 stoichiometry, consisting of a Wnt3a-Wnt3a homodimer, whereby each Wnt3a monomer binds to two Fzd8 receptors and one LRP6 co-receptor. This implies that Wnt3a induces Fzd cystine-rich domain (Fzd-CRD) tetramerization, which in turn could promote recruitment of oligomeric Disheveled (Dvl) to Fzd on the cytoplasmic side. Indeed, mutations of key Wnt3a-Wnt3a interface residues abolish Fzd-LRP clustering and downstream signaling, supporting a critical role of Wnt3a-Wnt3a dimerization in Wnt signalosome assembly and signaling. Our structures also show how the Wnt3a N-helical domain recognizes the LRP6 extracellular domain (LRP6-ECD) E3 β-propeller, while the Wnt3a N-C hairpin interacts with the valley between LRP6-E3 and -E4 propellers, underpinning the development of targeted Wnt therapeutics.

『摘要』 卷曲蛋白（Frizzled，Fzd）受体和低密度脂蛋白受体相关蛋白5/6（LRP5/6）辅助受体对Wnt蛋白的识别是经典Wnt信号通路的关键。目前尚不清楚Wnt如何同时与Fzd和LRP5/6相互作用并激活细胞内Wnt/β-连环蛋白信号通路。本研究报告了以2:4:2化学计量比捕获的Wnt3a/Fzd8/LRP6细胞外复合物的冷冻电子显微镜（cryo-EM）结构，该复合物由一个Wnt3a-Wnt3a同源二聚体组成，每个Wnt3a单体与两个Fzd8受体和一个LRP6辅助受体结合。这表明Wnt3a诱导Fzd富含半胱氨酸结构域（Fzd-CRD）四聚化，进而可能在细胞质侧促进寡聚体蓬乱蛋白（Disheveled，Dvl）向Fzd的募集。事实上，Wnt3a-Wnt3a界面关键残基的突变会消除Fzd-LRP聚集和下游信号传导，支持Wnt3a-Wnt3a二聚化在Wnt信号小体组装和信号传导中的关键作用。本研究结构还展示了Wnt3a的N-螺旋结构域如何识别LRP6细胞外结构域（LRP6-ECD）的E3 β螺旋桨，而Wnt3a的N-C发夹结构则与LRP6-E3和-E4螺旋桨之间的谷相互作用，为靶向Wnt疗法的开发提供了基础。

『总结』 研究通过冷冻电镜揭示了Wnt3a/Fzd8/LRP6复合物的2:4:2化学计量结构，阐明了Wnt3a二聚化通过诱导Fzd-CRD四聚化促进信号传导的机制，并解析了Wnt3a与LRP6的特异性结合位点，为靶向Wnt通路的药物开发提供了结构基础。

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7. 法尼基化驱动的KRAS相分离促进结肠肿瘤生长

Farnesylation-driven KRAS phase separation promotes colon tumor growth

Wang X, Zhang Y, Lu M, ... , Ji H, Huang J, Hu Y.; cell; (189, 14)

『Abstract』Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequently activated driver genes across human cancers. We identified a regulatory mechanism where KRAS forms condensates in the cytoplasm through liquid-liquid phase separation (LLPS), driven by farnesylation at the C185 residue within its hypervariable region (HVR). These condensates are associated with advanced stages and poor outcomes in colon cancer. Functionally, KRAS condensates efficiently interact with Ras-converting enzyme 1 (RCE1), promoting RCE1 clustering, enhancing KRAS processing, and facilitating its translocation to the plasma membrane, which amplifies KRAS signaling and promotes tumor growth. Growth factor stimulation further elevates KRAS condensate formation, emphasizing its role in tumor biology. Therapeutically, screening US Food and Drug Administration (FDA)-approved drugs revealed that statins, particularly pitavastatin, disrupt KRAS LLPS by inhibiting farnesylation, effectively suppressing colon cancer growth and enhancing the efficacy of G12Ci treatment. These findings uncover LLPS as a mechanism regulating KRAS activity and provide a promising target for therapeutic intervention.

『摘要』 KRAS（Kirsten鼠肉瘤病毒癌基因同源物）是人类癌症中最常见的激活驱动基因之一。我们发现了一种调控机制，即KRAS通过其高变区（HVR）内C185残基的法尼基化驱动的液-液相分离（LLPS）在细胞质中形成凝聚物。这些凝聚物与结肠癌晚期和不良预后相关。功能上，KRAS凝聚物可与Ras转化酶1（RCE1）高效相互作用，促进RCE1聚集，增强KRAS加工并促进其向质膜的转位，从而放大KRAS信号并促进肿瘤生长。生长因子刺激可进一步促进KRAS凝聚物的形成，凸显了其在肿瘤生物学中的作用。在治疗方面，对美国食品药品监督管理局（FDA）批准的药物进行筛选发现，他汀类药物尤其是匹伐他汀可通过抑制法尼基化破坏KRAS的LLPS，有效抑制结肠癌生长并增强G12Ci治疗的疗效。这些发现揭示了LLPS是调控KRAS活性的机制，并为治疗干预提供了有前景的靶点。

『总结』 KRAS通过液-液相分离形成细胞质凝聚物，该机制与结肠癌进展和不良预后相关，且可被他汀类药物破坏，为治疗提供新靶点。

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8. 伤害性感觉神经支配限制三级淋巴结构以促进肺癌发展

Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer

Ho YH, Bregni G, Stazi M, ... , Swanton C, Chen JS, Li L.; cell; (189, 14)

『Abstract』Sensory innervation regulates lung physiology and pathology, but its role in lung cancer is poorly understood. We show that lung adenocarcinoma (LUAD) progression locally amplifies nociceptive sensory innervation and activation, which drives the release of a major sensory neuropeptide, calcitonin gene-related peptide (CGRP). CGRP acts on a subset of macrophages, thereby impairing the recruitment of CXCL13⁺ fibroblasts and blocking tertiary lymphoid structure (TLS) assembly, a key predictor of LUAD prognosis. Local sensory denervation restores TLS formation, enhances B and T cell-dependent immunity, and suppresses tumor growth. Cigarette smoke extract (CSE) further activates this neural circuit to accelerate LUAD progression. In CSE-exposed animals, pharmacologic CGRP blockade sensitizes tumors to immunotherapy and prolongs survival. Together, our findings uncover a neuroimmune axis linking nociceptive neurons, TLS, and LUAD and identify neurogenic inflammation as a mechanism by which smoking promotes lung tumorigenesis independent of somatic mutagenesis.

『摘要』 感觉神经支配调控肺的生理和病理过程，但其在肺癌中的作用尚不清楚。我们发现，肺腺癌（LUAD）进展过程中局部会增强伤害性感觉神经支配和激活，从而促使主要感觉神经肽——降钙素基因相关肽（CGRP）释放。CGRP作用于部分巨噬细胞，进而损害CXCL13⁺成纤维细胞的募集，并阻断三级淋巴结构（TLS）的组装，而TLS是LUAD预后的重要预测指标。局部感觉神经去支配可恢复TLS的形成，增强B和T细胞依赖性免疫，并抑制肿瘤生长。香烟烟雾提取物（CSE）会进一步激活这一神经回路，加速LUAD进展。在接触CSE的动物中，药物性CGRP阻断可使肿瘤对免疫治疗更敏感，并延长生存期。总之，我们的发现揭示了连接伤害性神经元、TLS和LUAD的神经免疫轴，并确定神经源性炎症是吸烟促进肺癌发生的一种机制，且该机制独立于体细胞突变。

『总结』 研究揭示了感觉神经支配在肺腺癌进展中的作用，发现肺腺癌进展会增强局部伤害性感觉神经支配，促使CGRP释放，损害TLS组装，局部感觉神经去支配可抑制肿瘤生长，CSE会加速肺腺癌进展，药物性CGRP阻断可延长生存期，揭示了神经免疫轴及神经源性炎症是吸烟促进肺癌发生的机制。

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9. 清道夫受体F类成员2是乙型肝炎病毒的细胞内受体

Scavenger receptor class F member 2 is an intracellular receptor for hepatitis B virus

Li C, Wang Y, Xiong R, ... , Choe H, Sui J, Li W.; cell; (189, 14)

『Abstract』Hepatitis B virus (HBV) infects hepatocytes by specific binding to the cell-surface receptor-sodium taurocholate cotransporting polypeptide (NTCP)-through the preS1 region of its large envelope protein, followed by a less well-understood transport process across the cytoplasm to the nucleus. Here, we report that scavenger receptor class F member 2 (SCARF2), a single-pass transmembrane protein, functions as an intracellular receptor for HBV. SCARF2 binds to a preS1 region downstream of the NTCP binding site through its N-terminal epidermal growth factor (EGF)-like domains 4-6, and its proline-rich C-terminal domain also plays an indispensable role in the infection. The internalized HBV virions are transported to the cytoplasmic side of nuclear pore complexes within the SCARF2-containing endosomes. HBV nucleocapsid release from the endosomal vesicles is impaired by knockdown of SCARF2. These results suggest a model in which SCARF2 conveys HBV to the periphery of nuclear pore complexes (NPCs) and ultimately leads to viral nucleocapsid release for nuclear entry.

『摘要』 乙型肝炎病毒（HBV）通过其大包膜蛋白的preS1区与细胞表面受体牛磺胆酸钠共转运多肽（NTCP）特异性结合，感染肝细胞，随后经一个尚未完全明了的转运过程穿过细胞质到达细胞核。本研究发现，单次跨膜蛋白清道夫受体F类成员2（SCARF2）可作为HBV的细胞内受体。SCARF2通过其N端表皮生长因子（EGF）样结构域4-6与NTCP结合位点下游的preS1区结合，其富含脯氨酸的C端结构域在感染过程中也发挥不可或缺的作用。内化的HBV病毒颗粒被转运至含SCARF2的内涵体中的核孔复合体（NPC）细胞质侧。敲低SCARF2会损害HBV核衣壳从内涵体囊泡中的释放。这些结果表明，SCARF2将HBV转运至核孔复合体周围，最终促进病毒核衣壳释放进入细胞核。

『总结』 研究揭示SCARF2是HBV的细胞内受体，通过与preS1区结合及内涵体转运机制，介导病毒核衣壳释放至核孔复合体周围以实现核入侵。

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10. 移植依赖光反应以实现哺乳动物眼睛的光合作用

Transplanting light-dependent reactions for mammalian eye photosynthesis

Xing K, Yan Y, Zhu Z, ... , Sun X, Ye J, Leong DT.; cell; (189, 14)

『Abstract』Mammalian eyes are exposed to visible light but cannot perform photosynthesis. Here, we show that introducing a nanoscale, structurally and functionally preserved thylakoid system, LEAF (light-reaction enriched thylakoid NADPH-foundry), into corneal cells enables light-driven bona fide photosynthetic production of NADPH and ATP, similar to plant leaves, which alleviates oxidative stress and inflammation. LEAF acts in two domains. Intracellularly, it integrates with host cells to supply NADPH and ATP via intact photosynthetic electron transport, restoring redox balance. Extracellularly, photosynthesized NADPH enhances endogeneous antioxidant enzyme activity and reduces reactive oxygen species in the local environment. These results establish a strategy for using light as an energy input in mammalian metabolic systems and suggest a possible cross-kingdom, endosymbiosis-like interaction in which animal cells derive functional benefits from plant-derived photosynthetic neo-organelles.

『摘要』 哺乳动物的眼睛暴露在可见光下，但无法进行光合作用。在此，我们表明，将一种纳米级、结构和功能均保持完整的类囊体系统——LEAF（光反应富集类囊体NADPH合成装置）引入角膜细胞，能够像植物叶片一样实现由光驱动的真正光合作用，产生NADPH和三磷酸腺苷（ATP），从而缓解氧化应激和炎症。LEAF在两个领域发挥作用。在细胞内，它与宿主细胞整合，通过完整的光合电子传递提供NADPH和ATP，恢复氧化还原平衡。在细胞外，光合作用产生的NADPH增强内源性抗氧化酶活性，并减少局部环境中的活性氧。这些结果确立了一种在哺乳动物代谢系统中利用光作为能量输入的策略，并暗示了一种可能的跨界、类似内共生的相互作用，即动物细胞从植物衍生的光合作用新生器官中获取功能益处。

『总结』 引入LEAF系统至角膜细胞可实现光驱动的光合作用，产生NADPH和ATP，缓解氧化应激和炎症，为哺乳动物代谢系统利用光能提供了新策略，并暗示了跨界类似内共生的相互作用。

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11. 植物非典型拟昼夜节律基因调控网络的发现及异源重建

Discovery and heterologous reconstitution of a plant noncanonical quasi-circadian gene regulatory network

Wang S, Su Y, Xu Y, ... , Zhou M, He H, Wang W.; cell; (189, 14)

『Abstract』Circadian rhythms are mainly generated by a gene regulatory network (GRN) constituted by transcription factors (TFs). Comparisons between plant and mammalian circadian clock GRNs suggest conservation of the network architecture rather than its components. Therefore, a rhythm-generating capacity is not restricted to canonical circadian clock GRNs. Here, we showed that although the circadian clock GRN was arrhythmic, circadian rhythms were maintained in refrigerated postharvest strawberries. Through systematic dual-luciferase assays and network analysis, we discovered a noncanonical GRN pillared by five uncharacterized TFs. We developed a heterologous reconstitution system and demonstrated the rhythm-generating ability of this GRN. Subsequent systematic evolution of ligands by exponential enrichment followed by high-throughput sequencing (SELEX-seq), electrophoretic mobility shift assay (EMSA), and DNA affinity purification (DAP)-qPCR analyses suggested that this GRN was responsible for the circadian rhythms of downstream genes. Fruit-specific perturbation of this GRN led to enhanced susceptibility to Botrytis cinerea. Collectively, our study identified a noncanonical quasi-circadian GRN, realized the heterologous reconstitution of eukaryotic circadian GRNs, and demonstrated its function in immune regulation.

『摘要』 昼夜节律主要由转录因子（TFs）构成的基因调控网络（GRN）产生。植物和哺乳动物昼夜节律基因调控网络的比较表明，网络架构而非其组成部分具有保守性。因此，节律生成能力并非仅限于经典昼夜节律基因调控网络。本研究表明，尽管昼夜节律基因调控网络无节律性，但冷藏后的收获期草莓仍保持昼夜节律。通过系统的双荧光素酶检测和网络分析，发现了一个由五个未知转录因子支撑的非经典基因调控网络。构建异源重组系统，并证实该基因调控网络具有节律生成能力。随后通过指数富集配体的系统进化技术结合高通量测序（SELEX-seq）、电泳迁移率变动分析（EMSA）和DNA亲和纯化（DAP）-qPCR分析表明，该基因调控网络是下游基因昼夜节律的成因。对该基因调控网络进行果实特异性干扰后，草莓对灰葡萄孢的易感性增强。综上所述，本研究发现了一个非经典准昼夜基因调控网络，实现了真核生物昼夜基因调控网络的异源重组，并证实了其在免疫调节中的作用。

『总结』 研究发现非经典准昼夜基因调控网络可维持冷藏草莓昼夜节律，并通过异源重组证实其节律生成能力及免疫调节功能。

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12. 人工智能预测的空间转录组学从病理学中解锁乳腺癌生物标志物

AI-predicted spatial transcriptomics unlocks breast cancer biomarkers from pathology

Shulman ED, Campagnolo EM, Lodha R, ... , Lee JS, Hoang DT, Ruppin E.; cell; (189, 14)

『Abstract』Spatial transcriptomics (ST) assays are transforming our understanding of tumor heterogeneity, but their high cost limits their application in large-scale biomarker discovery. Here, we present "Path2Space," a deep-learning model that predicts spatial gene expression directly from histopathology slides. Trained on extensive breast cancer ST data, Path2Space robustly predicts the spatial expression of thousands of genes, outperforming 21 established methods. Charting the tumor microenvironment (TME) of 976 breast cancer TCGA (The Cancer Genome Atlas) tumors, it accurately infers cell-type abundances and identifies three spatially defined breast cancer subgroups with distinct survival outcomes. Notably, the derived low-cost spatial TME landscapes enable more accurate predictions of patient response to chemotherapy and trastuzumab compared with costly conventional bulk-sequencing-based biomarkers. Path2Space thus offers a scalable, fast, and cost-effective alternative to molecular assays. It opens avenues for large cohort treatment biomarker discovery and translationally relevant insights into tumor biology, with potential applicability across many cancer indications.

『摘要』 空间转录组学（ST）检测正在改变我们对肿瘤异质性的认知，但其高昂成本限制了在大规模生物标志物发现中的应用。本研究提出“Path2Space”深度学习模型，可基于组织病理学切片直接预测空间基因表达。该模型通过大量乳腺癌ST数据训练，能稳健预测数千个基因的空间表达，性能优于21种现有方法。通过对976例TCGA（癌症基因组图谱）乳腺癌肿瘤的肿瘤微环境（TME）进行绘制，该模型可准确推断细胞类型丰度，并识别出三个具有不同生存结局的空间定义乳腺癌亚组。值得注意的是，与基于传统昂贵的大规模测序生物标志物相比，这种低成本的空间TME图谱能更准确地预测患者对化疗和曲妥珠单抗的反应。因此，Path2Space为分子检测提供了一种可扩展、快速且经济高效的替代方案，为大规模队列治疗生物标志物的发现和肿瘤生物学的转化研究开辟了新途径，具有应用于多种癌症类型的潜力。

『总结』 Path2Space深度学习模型通过组织病理学切片预测空间基因表达，成本低且性能优越，可准确推断细胞类型丰度、识别乳腺癌亚组，为分子检测提供替代方案，在癌症研究中有广泛应用潜力。

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13. 人类衰老的多模态时钟

Multimodal clocks of human aging

Li J, Jiang B, Zhang W, ... , Zhao G, Zhang W, Liu GH.; cell; (189, 14)

『Abstract』Human aging is characterized by complex structural and functional decline, but quantifying its heterogeneity and assessing biological age remain challenges. We present the mCAS (multicentric Chinese aging standardized cohort) developed from 2,019 Chinese individuals aged 18-91 years. Integrating high-dimensional clinical, physiological, and molecular-level data, we constructed a three-tiered aging framework: the core capacity clock (CC-clock) to quantify clinical physiological decline, the multimodal clock (MM-clock) with extensive parameter coverage and enhanced predictive precision, and organ-associated aging clocks. Cross-layer analysis demonstrates that plasma protein clocks not only capture chronological age but also serve as efficient proxies for systemic physiological capacity. Leveraging this framework for discovery, we identified the age-dependent accumulation of coagulation factors as a driver of multi-organ senescence and systemic inflammatory activation. This study provides a foundational framework that bridges molecular signatures with functional decline, identifies new biomarkers for aging assessment, and reveals a novel translational driver of aging.

『摘要』 人体衰老表现为复杂结构和功能衰退，但量化其异质性及评估生物学年龄仍是挑战。我们基于2019名18-91岁中国人群数据开发了多中心中国衰老标准化队列（mCAS），通过整合高维临床、生理及分子数据构建了三级衰老评估框架：核心能力时钟（CC-clock）量化临床生理衰退，多模态时钟（MM-clock）通过广泛参数提升预测精度，以及器官特异性衰老时钟。跨层级分析显示血浆蛋白时钟不仅能反映实际年龄，还可作为系统生理能力的有效替代指标。基于该框架的探索性研究发现，凝血因子随年龄增长的积累是多器官衰老和全身性炎症激活的关键驱动因素。该研究建立了连接分子特征与功能衰退的基础框架，发现了衰老评估的新生物标志物，并揭示了衰老的全新转化驱动机制。

『总结』 该研究通过构建多层级衰老评估框架，整合多维度数据揭示了凝血因子积累驱动多器官衰老和炎症激活的机制，为衰老评估提供了新标志物和转化医学新方向。

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14. LARES-2卫星测量地球周围的参考系拖拽效应

LARES-2 satellite measures frame-dragging effect around the Earth

Ciufolini I, Paolozzi A, Pavlis EC, ... , Ni WT, Penrose R, Gurzadyan V.; nature; (655, 8122)

『Abstract』Laser-ranging provides some of the most precise tests of gravity in the weak-field regime, enabling experimental probes of Einstein's general theory of relativity using the Earth as a laboratory. A central test of general relativity is the amplitude of frame-dragging, that is, the dragging of spacetime by a rotating mass. Owing to its optimized orbit, a very low surface-to-mass ratio and a highly uniform retroreflector distribution, we show that the recently launched Laser Relativity Satellite 2 (LARES-2)-together with its predecessor LAGEOS and the GRACE satellites-enables a measurement of terrestrial frame-dragging with a relative uncertainty at the one-part-in-a-thousand level, representing an order-of-magnitude improvement over previous Solar System determinations. This result provides a stringent confirmation of general relativity in the near-Earth environment and places strong constraints on alternative gravitational models that predict deviations specifically in frame-dragging, including scalar-tensor extensions such as Chern-Simons gravity. Beyond tests of fundamental physics, the combined analysis of LARES-2 and LAGEOS also improves the determination of Earth's lunisolar tides, illustrating the broader geophysical impact of high-precision relativistic satellite experiments.

『摘要』 激光测距为弱场条件下的引力测试提供了最精确的方法之一，使得利用地球作为实验室对爱因斯坦的广义相对论进行实验探测成为可能。广义相对论的一个核心检验是参考系拖拽的幅度，即旋转质量对时空的拖拽。由于LARES-2卫星轨道优化、表面质量比极低且角反射器分布高度均匀，研究表明，最近发射的激光相对论卫星2号（LARES-2）与其前身LAGEOS卫星以及重力恢复和气候实验（GRACE）卫星共同协作，能够以千分之一的相对不确定性测量地球的参考系拖拽效应，比此前太阳系内的测定精度提高了一个数量级。这一结果在近地环境中为广义相对论提供了严格验证，并对预测特别是参考系拖拽方面存在偏差的替代引力模型（包括标量-张量扩展模型，如切恩-西蒙斯引力）施加了严格限制。除基础物理检验外，LARES-2与LAGEOS的联合分析还改进了地球日月潮汐的测定精度，体现了高精度相对论卫星实验对地球物理学的更广泛影响。

『总结』 激光测距卫星LARES-2与LAGEOS及GRACE卫星联合，将地球参考系拖拽效应的测量精度提升至千分之一，验证了广义相对论并限制了替代引力模型，同时改进了地球潮汐测定。

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15. 一个巨大链霉菌巨型基因簇编码协同作用的生物素靶向抗生素

A Streptomyces megacluster encodes synergistic biotin-targeting antibiotics

Gordzevich R, Xu M, Wang W, ... , Wei A, Wright GD, Brown ED.; nature; (655, 8122)

『Abstract』Natural products remain a major source of antibiotics, but discovery efforts have traditionally treated biosynthetic gene clusters as sources of individual bioactive molecules. Increasing evidence has suggested that microorganisms can instead encode coordinated multi-metabolite systems, yet the genetic architectures and biological logic of such systems remain poorly understood. Here we show that Streptomyces spp. encode a highly conserved biosynthetic megacluster that produces four structurally distinct natural product families-stravidins, acidomycin, dapamycins, and 2-methyl-7-keto-8-aminopelargonic acid (α-Me-KAPA)-alongside the biotin-binding protein streptavidin. These components converge on bacterial biotin metabolism through complementary mechanisms, including enzyme inhibition, prodrug activation, cofactor mimicry and biotin sequestration. The encoded metabolites are co-produced and act synergistically across Gram-negative and mycobacterial species, with stravidin S2 and α-Me-KAPA showing enhanced efficacy in combination in a mouse model of multidrug-resistant Escherichia coli infection. This megacluster reveals a genetically encoded chemical arsenal that functions as a naturally evolved combination therapy against a conserved metabolic pathway. More broadly, our findings suggest that higher-order biosynthetic architectures may represent an overlooked reservoir of antibiotic mechanisms and support a shift from discovering isolated natural products to reconstructing native synergistic systems.

『摘要』 天然产物仍是抗生素的主要来源，但传统上发现抗生素的努力是将生物合成基因簇视为单个生物活性分子的来源。越来越多的证据表明，微生物可以编码协调的多代谢物系统，但此类系统的遗传结构和生物学逻辑仍知之甚少。本研究表明，链霉菌属编码了一个高度保守的生物合成超基因簇，该超基因簇可产生四种结构不同的天然产物家族——stravidins、acidomycin、dapamycins和2-甲基-7-酮-8-氨基辛酸（α-Me-KAPA），以及生物素结合蛋白链霉亲和素。这些成分通过包括酶抑制、前药激活、辅因子模拟和生物素隔离在内的互补机制，共同作用于细菌生物素代谢。编码的代谢物共同产生，并在革兰氏阴性菌和分枝杆菌中协同作用，其中stravidin S2和α-Me-KAPA在多药耐药大肠杆菌感染的小鼠模型中联合使用时显示出增强的疗效。这个超基因簇揭示了一种遗传编码的化学武器库，可作为针对保守代谢途径的自然进化联合疗法。更广泛地说，本研究结果表明，高阶生物合成结构可能代表了一个被忽视的抗生素机制储备库，并支持从发现孤立天然产物向重建天然协同系统的转变。

『总结』 研究揭示链霉菌属编码的生物合成超基因簇可产生多种天然产物协同作用于细菌生物素代谢，为抗生素发现提供新思路，即从发现孤立天然产物转向重建天然协同系统。

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16. 光学模拟中受激霍金辐射的反作用

Backreaction of stimulated Hawking radiation in an optical analogue

Procopio LM, Aguero-Santacruz R, Bermudez D, Leonhardt U.; nature; (655, 8122)

『Abstract』Hawking radiation-the emission of quantum particles at the event horizon of a black hole-connects gravity with quantum mechanics and thermodynamics. But Hawking radiation has never been observed in astronomy, only in laboratory analogues, and the chances of ever observing it in space are astronomically small. The energy of Hawking radiation must come from the gravitational field around the black hole, but how field quanta generate Hawking quanta has been unknown. Here we report on experimental and theoretical evidence for the process that generates Hawking radiation in a fibre-optical analogue of the event horizon. There, as in gravity, it has been believed that Hawking radiation comes from a complicated, cascaded process; here we have identified theoretically a simple, direct process and observed experimentally how this process reacts back onto the field. Our findings suggest an equally direct process for other laboratory analogues and perhaps also for gravitational fields, shedding light on how black holes might radiate.

『摘要』 黑洞事件视界处量子粒子的发射——霍金辐射，将引力与量子力学和热力学联系在一起。然而，霍金辐射从未在天文观测中被发现，只在实验室模拟中被观测到，且在太空中观测到它的可能性极小。霍金辐射的能量必定来自黑洞周围的引力场，但场量子如何产生霍金量子一直未知。本文报告了在光纤模拟事件视界中产生霍金辐射的过程的实验和理论证据。在那里，就像在引力场中一样，人们一直认为霍金辐射来自一个复杂的、级联的过程；本文在理论上确定了一个简单、直接的过程，并通过实验观察到了该过程如何反馈到场中。这些发现表明，其他实验室模拟以及或许引力场也存在同样直接的过程，为黑洞如何辐射提供了线索。

『总结』 本文报告了光纤模拟事件视界中产生霍金辐射的实验和理论证据，确定了简单直接的产生过程，该发现或为其他模拟及引力场中霍金辐射的产生提供线索。

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17. 二维材料晶体管中载流子传输长度的直接探测

Directly probing the carrier transfer length in 2D-material transistors

Yang ZL, Huang BC, Lin YK, ... , Lan YW, Li LJ, Chiu YP.; nature; (655, 8122)

『Abstract』Transistors based on two-dimensional (2D) materials are on the roadmap for the beyond 1 nm logic technology node. This stems from their ultrathin thickness and defect-free surfaces, granting remarkable electrostatic gate control. The physical channel length of 2D transistors may eventually reach <10 nm for advanced node devices. However, the equally important scaling limit for metal contacts remains unknown because of the lack of technology to directly probe the carrier injection region in contact areas. Here we use cross-sectional scanning tunnelling microscopy to directly measure the carrier transfer length as approximately 2.0 nm at the contact region of a bismuth-contacted monolayer MoS₂ transistor. This approach allows contact scaling constraints to be determined, providing information for the development of future ultra-scaled electronic devices.

『摘要』 基于二维（2D）材料的晶体管已被纳入超越1纳米逻辑技术节点的路线图。这得益于其超薄厚度和无缺陷表面，使其具备出色的静电栅控能力。先进节点器件中二维晶体管的物理沟道长度最终可能达到小于10纳米。然而，由于缺乏直接探测接触区域载流子注入区的技术，金属接触的同等重要缩放极限仍然未知。本研究采用横截面扫描隧道显微镜直接测量铋接触单层二硫化钼（MoS₂）晶体管接触区域的载流子传输长度约为2.0纳米。该方法可确定接触缩放的限制条件，为未来超小型电子器件的开发提供信息。

『总结』 本研究利用横截面扫描隧道显微镜首次测得铋接触单层MoS₂晶体管接触区域的载流子传输长度约2.0纳米，突破了金属接触缩放极限的研究瓶颈，为超小型电子器件开发提供关键数据支撑。

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18. 通过挥发性配位实现稳定的锡钙钛矿晶体管

Tin perovskite transistors stabilized through volatile coordination

Park G, Lee DH, Reo Y, ... , Park JS, Zhu H, Noh YY.; nature; (655, 8122)

『Abstract』Tin (Sn²⁺) halide perovskites are promising lead-free semiconductors for optoelectronic and electronic devices, owing to their tunable bandgaps and favourable charge transport. However, their practical implementation is fundamentally limited by an intrinsic redox instability at undercoordinated Sn²⁺ sites, which drives uncontrolled self-p-doping and rapid oxidative degradation. Here we introduce a volatile-assisted coordination strategy that reconstructs the perovskite surface through transient acetate coordination and volatilization, which transforms reactive SnI₂-terminated surfaces into chemically equilibrated and defect-mitigated interfaces. This surface reconstruction suppresses undercoordinated Sn-related trap states and stabilizes the local stoichiometry, thus enabling p-type transistors with robust transport characteristics, a near-zero threshold voltage and high on/off ratios exceeding 10⁸. More importantly, the reconstructed interface acts as a self-passivating and thermally resilient barrier, resulting in markedly enhanced environmental stability, with devices maintaining stable operation for over 1 month at 100 °C. These results establish volatile-assisted surface reconstruction as an effective method for defect equilibration in metastable semiconductors, and they provide a general strategy for enabling durable, device-grade functionality in Sn²⁺-based materials.

『摘要』 由于具有可调节的带隙和有利的电荷传输特性，锡（Sn²⁺）卤化物钙钛矿是有前途的无铅光电和电子器件半导体。然而，欠配位Sn²⁺位点的固有氧化还原不稳定性从根本上限制了其实际应用，这种不稳定性会导致不受控制的自p型掺杂和快速氧化降解。在此，我们引入了一种挥发物辅助配位策略，通过瞬态乙酸配位和挥发来重建钙钛矿表面，将反应性SnI₂终止表面转变为化学平衡且缺陷缓解的界面。这种表面重建抑制了与欠配位锡相关的陷阱态，稳定了局部化学计量比，从而实现了具有强大传输特性、近零阈值电压和高开关比（超过10⁸）的p型晶体管。更重要的是，重建的界面充当自钝化和热稳定的屏障，从而显著提高了环境稳定性，器件在100℃下仍能稳定运行超过1个月。这些结果确立了挥发物辅助表面重建作为亚稳态半导体中缺陷平衡的有效方法，并为在Sn²⁺基材料中实现持久、器件级功能提供了一般策略。

『总结』 本文提出挥发物辅助配位策略重建钙钛矿表面，抑制了陷阱态，稳定了局部化学计量比，提高了环境稳定性，为Sn²⁺基材料实现持久、器件级功能提供了一般策略。

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19. 二维异质结构中界面电荷转移实现的光学冷却

Optical cooling by interfacial charge transfer in 2D heterostructures

Lin J, Xiang B, Liu R, ... , Gao H, Xiong Q, Xu W.; nature; (655, 8122)

『Abstract』Optical refrigeration, or laser cooling of solids, offers a cryogen-free route to temperature control for quantum and electronic systems. Existing progress relies on a phonon-assisted up-conversion photoluminescence approach, which remains constrained by stringent material and excitation requirements. Here we demonstrate a distinct route, interfacial-charge-transfer-driven optical cooling, in two-dimensional semiconductor heterostructures. Photo-excited carriers in WSe₂ cross a type-II junction into MoSe₂ or WS₂, extracting lattice energy nonradiatively-through a phonon-assisted interfacial charge transfer process. Raman and photoluminescence measurements show prominent low-temperature signatures in the WSe₂ layer, with transient absorption spectroscopy identifying a phonon-assisted, barrier-activated interlayer charge transfer. Molecular dynamics simulations show a prominent interfacial thermal resistance sustaining the temperature gradient. This barrier-mediated phonon extraction bypasses the need for near-unity quantum efficiency or resonant excitation, offering a promising strategy for cryogen-free refrigeration and thermal management in quantum, optoelectronic and nanoscale systems.

『摘要』 光学制冷，即固体的激光制冷，为量子系统和电子系统的温度控制提供了一种无需使用低温制冷剂的途径。现有进展依赖于声子辅助的上转换光致发光方法，但该方法仍受限于严格的材料和激发条件。本文展示了在二维半导体异质结构中通过界面电荷转移驱动的光学制冷这一独特途径。光激发的载流子在二硒化钨（WSe₂）中穿过II型结进入二硒化钼（MoSe₂）或二硫化钨（WS₂），通过声子辅助的界面电荷转移过程非辐射性地提取晶格能量。拉曼和光致发光测量结果显示，二硒化钨层中存在明显的低温特征，瞬态吸收光谱则识别出声子辅助、势垒激活的层间电荷转移。分子动力学模拟表明，显著的界面热阻维持了温度梯度。这种势垒介导的声子提取无需接近100%的量子效率或共振激发，为量子、光电和纳米尺度系统的无低温制冷剂制冷和热管理提供了一种有前景的策略。

『总结』 本文提出了一种通过界面电荷转移驱动的光学制冷方法，在二维半导体异质结构中实现了非辐射性晶格能量提取，为量子和纳米尺度系统的无低温制冷剂制冷和热管理提供了新策略。

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20. 通过气凝胶粘弹性相分离制备的透气水凝胶

Air-permeable hydrogels through viscoelastic phase separation of aerogels

Yan XY, Li S, Song WJ, ... , Smith ZP, Kumar A, Zhao X.; nature; (655, 8122)

『Abstract』Hydrogels are widely used in biomedical interfaces, in which effective gas exchange (for example, O₂, CO₂) within a water-rich environment is essential. However, hydrogels show intrinsically limited air exchange efficiency, owing to the low solubility (C) and diffusivity (D) of non-polar gases in the polar water medium. This limitation poses a substantial bottleneck in long-term applications, such as wearable health monitors and tissue engineering. Existing methods to enhance air permeability suffer from poor robustness and/or an inherent trade-off between permeability and water content (for example, <50 vol%). Here we introduce a viscoelastic phase separation (VPS)-enabled strategy to create a non-collapsible, air-rich network in high-water-content hydrogels, achieving a record-high oxygen permeability of 185 barrer with 70 vol% water-a tenfold increase compared with pristine hydrogels. VPS, a ubiquitous phenomenon in soft matter, is used to drive hydrophobic, dry gas particles within a hydrophilic, wet medium into a thin, stable three-dimensional network. This approach allows the facile and scalable fabrication of air-permeable hydrogels across diverse chemistries and form factors. Physiological tests over a 10-day continuous wear condition confirmed their effectiveness in preventing fluid accumulation and maintaining skin health. This strategy paves the way for hydrogels in long-term biomedical applications in which efficient and sustained air exchange becomes critical.

『摘要』 水凝胶广泛应用于生物医学界面，其中在富水环境中进行有效的气体交换（如氧气、二氧化碳）至关重要。然而，由于非极性气体在极性水介质中的低溶解度（C）和低扩散性（D），水凝胶的空气交换效率存在固有局限。这一局限在可穿戴健康监测器和组织工程等长期应用中构成了重大瓶颈。现有提高透气性的方法存在稳健性差和/或透气性与含水量（如<50%）之间存在固有权衡的问题。本研究介绍了一种利用粘弹性相分离（VPS）在高含水量水凝胶中构建不可坍塌、富空气网络的策略，在含水量70%的条件下实现了185 barrer的创纪录高氧渗透率，较原始水凝胶提高了十倍。VPS是软物质中普遍存在的现象，可将亲水性湿介质中的疏水性干气体颗粒驱动形成薄而稳定的三维网络。该方法可轻松且可扩展地制备适用于不同化学体系和形状的透气水凝胶。连续10天佩戴的生理测试证实了其在防止体液积聚和维持皮肤健康方面的有效性。该策略为水凝胶在需要高效持续气体交换的长期生物医学应用中开辟了道路。

『总结』 研究提出利用粘弹性相分离策略制备高含水量透气水凝胶，突破了传统水凝胶空气交换效率的局限，在生理测试中表现出良好性能，为长期生物医学应用提供了新途径。

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21. 欧洲西北部晚期尼安德特人的遗传多样性

Genetic diversity of late Neanderthals in northwestern Europe

Bossoms Mesa A, Essel E, Peyregne S, ... , Kelso J, Peter BM, Hajdinjak M.; nature; (655, 8122)

『Abstract』Archaeological, osteological and genetic evidence suggests that Neanderthals lived in small groups; however, less is known about whether these groups were part of isolated communities or belonged to larger, well-connected populations. The dense concentration of broadly contemporaneous Neanderthal sites in the Meuse Basin, Belgium, provides a rare opportunity to study regional populations at high resolution. Here we generated genetic data from 27 Neanderthals who lived less than approximately 52,500 years ago from ten archaeological sites in Belgium and France, including a high-coverage genome from a 45,000-year-old individual from Goyet, Belgium. We show that most of these individuals are more closely related to one another than to other contemporaneous late Neanderthals in Europe. Further, some of these individuals carry DNA from a Neanderthal lineage predating the split of late Neanderthals. Although these Neanderthals overlapped temporally with early modern humans in northwestern Europe from around 47,000 years ago, we find no evidence of recent gene flow from modern humans. They also do not show the genetic signatures of mating among close relatives found in Altai Neanderthals, suggesting that they lived in larger or better-connected groups. Moreover, genetic load did not accumulate over time, arguing against progressive genetic deterioration as a driver of Neanderthal extinction.

『摘要』 考古学、骨骼学和遗传学证据表明，尼安德特人以小群体方式生活；然而，对于这些群体是孤立社区的一部分还是属于更大且联系紧密的种群，我们知之甚少。比利时默兹河流域大量同时期的尼安德特人遗址密集分布，为高分辨率研究区域种群提供了难得的机会。本研究从来自比利时和法国10个考古遗址的27个尼安德特人（均生活在约52500年前）身上获取了遗传数据，其中包括来自比利时戈耶特一个45000年个体的高覆盖率基因组。研究发现，这些个体中的大多数彼此间的亲缘关系比与欧洲其他同时期晚期尼安德特人的亲缘关系更近。此外，其中一些个体携带的尼安德特人血统DNA早于晚期尼安德特人的分化时间。尽管这些尼安德特人在约47000年前与欧洲西北部的早期现代人类存在时间重叠，但并未发现近期现代人类基因流动的证据。他们也没有表现出阿尔泰地区尼安德特人中近亲交配的遗传特征，这表明他们生活在规模更大或联系更紧密的群体中。此外，遗传负荷并未随时间积累，这反驳了遗传逐渐恶化是导致尼安德特人灭绝原因的观点。

『总结』 研究表明比利时和法国的尼安德特人彼此间亲缘关系更近，未发现与现代人类近期基因流动及近亲交配的遗传特征，且遗传负荷未随时间积累，表明其可能生活在规模更大或联系更紧密的群体中，反驳了遗传逐渐恶化是导致其灭绝原因的观点。

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22. 吉咖秒差距尺度上各向异性宇宙结构的探测

Detection of anisotropic cosmic structures on a gigaparsec scale

Sylos Labini F, Galoppo M.; nature; (655, 8122)

『Abstract』Galaxy redshift surveys map the cosmic web and provide a key observational test of whether the Universe becomes statistically homogeneous and isotropic on sufficiently large scales, as assumed by the cosmological principle underpinning the standard cosmological model. In this framework, beyond the nonlinear regime of structure formation, inhomogeneous and anisotropic features are expected to fade rapidly, reflecting the near-isotropic primordial density field and its subsequent gravitational evolution. Although supported by the small amplitude of cosmic microwave background anisotropies, this view is increasingly challenged by the complex network of large-scale structures and voids in the galaxy distribution, as well as by independent probes reporting possible large-scale deviations from statistical homogeneity and isotropy. Here we show that the galaxy distribution exhibits persistent anisotropic structures extending to scales on the order of one gigaparsec. Using the Angular Distribution of Pairwise Distances (ADPD), a parameter-free statistic that measures directional correlations, we detect anisotropy signals exceeding those in isotropic controls and geometry-matched ΛCDM mock catalogues with conservative significance greater than 3σ. These results provide direct evidence that directional coherence persists to larger scales than predicted in the standard framework, challenging the assumption of large-scale isotropy. They call for a reassessment of how homogeneity and isotropy are realized in the observed Universe and motivate new tests of cosmological models based on directional statistics.

『摘要』 星系红移巡天绘制宇宙网图，为检验宇宙在足够大的尺度上是否如标准宇宙学模型所依赖的宇宙学原理所假设的那样，在统计上呈现均匀性和各向同性，提供了关键的观测检验。在此框架下，超出结构形成的非线性区域后，非均匀和各向异性特征预计会迅速消失，反映出近乎各向同性的原始密度场及其随后的引力演化。尽管宇宙微波背景各向异性的幅度较小支持了这一观点，但星系分布中复杂的大尺度结构网络和空洞，以及报告可能存在大尺度偏离统计均匀性和各向异性的独立探测，正日益对此观点构成挑战。本研究表明，星系分布展现出持续存在的各向异性结构，其延伸尺度可达十亿秒差距量级。利用测量方向相关性的无参数统计量——成对距离角分布（ADPD），我们检测到各向异性信号，其强度超过了各向同性对照和几何匹配的ΛCDM模拟星表，保守估计显著性大于3σ。这些结果为方向一致性持续存在的尺度大于标准框架预测值提供了直接证据，对大尺度各向同性的假设提出了挑战。它们要求重新评估均匀性和各向同性在观测宇宙中的实现方式，并推动基于方向统计量的宇宙学模型新检验。

『总结』 星系红移巡天研究显示星系分布存在延伸至十亿秒差距量级的各向异性结构，挑战了宇宙大尺度各向同性的假设，要求重新评估均匀性和各向同性在观测宇宙中的实现方式，并推动宇宙学模型新检验。

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23. 现今海洋岛屿源区中的哈迪恩期布里奇曼石

Hadean bridgmanite in the source of a present-day ocean island

Israel C, Chauvel C, Inglis E, Chen H, Hebert C, Badro J.; nature; (655, 8122)

『Abstract』Constraining the complex dynamics of the inner Earth unites research efforts across several scientific disciplines, including geochemistry, geophysics and geodynamics. Seismological and geodynamic studies offer insights into the present state of the mantle structure, whereas geochemical approaches characterize its chemical and isotopic heterogeneities, shedding light on the complexity of its evolution. One key challenge is determining the age and origin of its chemical heterogeneities. Here we present new high-precision Nd isotopic measurements in present-day volcanism that identify heterogeneities dating back to the Earth's earliest history. We report significantly positive Nd anomalies in lavas from the submarine Fani Maore volcano in the Comoros archipelago. These anomalies require the preservation, in the mantle, of material depleted in light rare-earth elements (REE) and formed within the first 100 million years (Myr) of Earth's history. We suggest that this material is mainly composed of bridgmanite that crystallized from an early Earth magma ocean. This Hadean bridgmanite may be more widespread in the present-day mantle than previously expected, raising new questions about its survival over billions of years of plate tectonics and vigorous mantle convection.

『摘要』 约束地球内部复杂动力学的研究工作跨越了多个科学学科，包括地球化学、地球物理学和地球动力学。地震学和地球动力学研究提供了对地幔结构现状的洞察，而地球化学方法则描述了其化学和同位素不均一性，揭示了其演化过程的复杂性。其中一个关键挑战是确定其化学不均一性的年代和起源。本文展示了在现今火山活动中进行的高精度钕同位素测量，确定了可追溯至地球早期历史的异质性。我们报告了科摩罗群岛海底Fani Maore火山岩浆中显著的正钕异常。这些异常表明，地幔中保存了贫轻稀土元素（REE）的物质，且这些物质形成于地球历史的前1亿年（Myr）内。我们认为，这种物质主要由早期地球岩浆海洋结晶形成的布里奇曼石组成。这种太古宙布里奇曼石在现今地幔中的分布可能比之前预期的更为广泛，这引发了关于其在数十亿年板块构造和强烈地幔对流中如何存续的新问题。

『总结』 本文通过高精度钕同位素测量揭示了地球早期历史中形成的化学不均一性，并指出这些不均一性可能主要由早期岩浆海洋结晶形成的布里奇曼石组成，其广泛分布引发了关于其长期存续的新问题。

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24. 人类造血干细胞能记住炎症应激

Human haematopoietic stem cells remember inflammatory stress

Zeng AGX, Nagree MS, Jakobsen NA, ... , Vyas P, Dick JE, Xie SZ.; nature; (655, 8122)

『Abstract』Inflammation activates blood cells, contributing to ageing and malignancy. Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis, but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation-recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were identified with one, termed HSC inflammatory memory (HSC-iM), retaining a molecular memory of previous inflammatory treatments. The HSC-iM subset exhibited quiescence and restrained haematopoietic output. Molecularly, the HSC-iM program was enriched in HSCs from adult and paediatric samples across conditions ranging from COVID-19 recovery, sickle cell disease, ageing and clonal haematopoiesis, establishing both the validity of our xenograft models and the physiological relevance of HSC-iM. Clonal haematopoiesis mutations in HSC-iM attenuated the effects of inflammatory stress by promoting HSC activation and differentiation. Moreover, transmission of the pro-inflammatory HSC-iM transcriptional program to differentiated immune progeny was demonstrated in xenograft and physiological settings. Finally, HSC-iM program enrichment in circulating blood cells was associated with a heightened risk score for all-cause mortality in population cohort analyses, underscoring the clinical relevance of this newly identified HSC subset in characterizing heterogeneous health outcomes across a lifetime.

『摘要』 炎症会激活血细胞，促进衰老和恶性肿瘤的发生。造血干细胞（HSCs）在一生中历经无数次感染，维持终生造血功能，但人类造血干细胞如何应对和适应炎症应激在很大程度上仍属未知。本研究中，为实证性地了解这种适应性变化，我们开发了异种移植炎症恢复模型，并对异种移植的人类造血干细胞进行了单细胞多组学分析。我们鉴定出两个在转录和表观遗传层面存在差异的造血干细胞亚群，其中一个亚群被称为造血干细胞炎症记忆（HSC-iM），保留了先前炎症处理的分子记忆。HSC-iM亚群表现出静息状态，造血输出受到抑制。从分子层面看，HSC-iM程序在从新冠肺炎康复、镰状细胞病、衰老到克隆性造血等多种情况下的成人和儿童样本的造血干细胞中均富集，这既验证了我们异种移植模型的有效性，也证明了HSC-iM的生理相关性。HSC-iM中的克隆性造血突变通过促进造血干细胞激活和分化，减轻了炎症应激的影响。此外，在异种移植和生理环境中，促炎的HSC-iM转录程序被传递至分化后的免疫子代细胞。最后，在人群队列分析中，循环血细胞中HSC-iM程序的富集与全因死亡风险评分升高相关，这凸显了新发现的这一造血干细胞亚群在表征一生中健康结局异质性方面的临床重要性。

『总结』 本研究发现人类造血干细胞存在炎症记忆亚群（HSC-iM），其分子特征与多种病理生理状态相关，且克隆性造血突变可调节其炎症应激反应，该亚群特征与全因死亡风险升高相关，具有重要临床意义。

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25. 通过非共价催化剂组装实现的手性选择性氢原子接力

Enantioselective hydrogen atom relay via non-covalent catalyst assembly

Yalamanchili N, Alexandre JH, Anderson RL, Zuccarello G.; nature; (655, 8122)

『Abstract』Most biological functions are regulated by chiral molecules that contain at least one tertiary stereogenic carbon, that is, a carbon with one C(sp)-H bond. Hydrogen atom transfer (HAT) is a straightforward strategy that can be used to either edit or introduce tertiary stereocentres in multiple synthetically useful transformations, especially when coupled with photoredox catalysis. However, traditional de novo design of chiral HAT catalysts that provide sufficient enantiocontrol over short-lived open-shell intermediates has represented a major hurdle in the development of enantioselective HAT reactions. Here we describe a distinct approach in which chiral HAT catalysts are obtained in situ by non-covalent self-assembly of privileged chiral phosphoric acids and commercial 2-mercaptopyridines. The phosphoric acid serves as a modular interchangeable chiral element that renders the achiral thiol effectively chiral, thereby allowing access to a previously inaccessible combinatorial space of chiral HAT catalysts. This platform enabled the photochemical deracemization of 2-aryl pyrrolidines, which are prevalent scaffolds in active pharmaceutical ingredients. Optical enrichment occurs by means of enantioselective hydrogen atom relay, in which a single chiral assembly orchestrates hydrogen atom abstraction and delivery. This conceptual approach of relaying chiral information through non-covalent assembly paves the way for discovery of numerous asymmetric radical transformations.

『摘要』 大多数生物功能由至少含有一个三级立体碳（即含有一个C(sp)-H键的碳）的手性分子调控。氢原子转移（HAT）是一种简单策略，可用于在多种合成有用的转化中编辑或引入三级立体中心，尤其是与光氧化还原催化相结合时。然而，传统从头设计的手性HAT催化剂，在针对短寿命开壳中间体提供足够的对映选择性控制方面，一直是开发对映选择性HAT反应的主要障碍。本文介绍了一种独特的方法，通过将优势手性磷酸与市售的2-巯基吡啶进行非共价自组装，现场获得手性HAT催化剂。磷酸作为模块化的可互换手性元件，使非手性硫醇具有手性，从而进入以前无法获得的组合空间，获得手性HAT催化剂。该平台实现了2-芳基吡咯烷的光化学去消旋化，2-芳基吡咯烷是活性药物成分中常见的结构单元。光学富集通过手性氢原子接力实现，其中单一手性组装体协调氢原子的夺取和传递。这种通过非共价组装传递手性信息的概念性方法为发现众多不对称自由基转化铺平了道路。

『总结』 本文介绍了一种新方法，即通过非共价自组装优势手性磷酸与市售2-巯基吡啶现场获得手性HAT催化剂，实现了2-芳基吡咯烷的光化学去消旋化，为发现不对称自由基转化提供了新途径。

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26. 揭示高能量锂硫电池中的竞争性界面反应

Revealing competitive interfacial reactions in high-energy Li-S batteries

Zhou S, Pei F, Zheng Q, ... , Huang Y, Sun SG, Liao HG.; nature; (655, 8122)

『Abstract』Charge transfer at solid-liquid interfaces plays a critical role in various energy-storage systems, particularly under dynamically varying reactant concentrations. Deciphering these intricate reaction pathways remains a substantial challenge, notably in lithium-sulfur (Li-S) batteries, in which achieving high energy density requires efficient conversion of highly concentrated lithium polysulfides (LiPSs). However, the mechanisms governing lithium sulfide (Li₂S) deposition and dissolution under lean electrolyte conditions remain poorly understood. Here, using in situ liquid-cell electron microscopy, we directly visualize concentration-driven phase segregation at the electrode-electrolyte interface. Within these high-concentration interfacial layers (HCILs), competitive surface and solution dictate the charge-transfer dynamics and ultimately govern Li₂S deposition at different phase boundaries. Density functional theory (DFT) calculations reveal that the aggregation of LiPSs alters molecular geometry, electronic properties and orbital hybridization, collectively facilitating charge transfer through highly concentrated LiPSs clusters. Guided by these insights, we design optimized electrodes that balance interfacial reaction pathways, enabling fast charging (4 C, 26.8 mA cm^-2) and achieving high energy densities exceeding 400 Wh kg^-1. These findings provide mechanistic understanding of interfacial reactions under practical working conditions and offer a design strategy to advance Li-S batteries.

『摘要』 在各种储能系统中，固液界面处的电荷转移起着至关重要的作用，尤其是在反应物浓度动态变化的情况下。解析这些复杂的反应路径仍然是一项重大挑战，特别是在锂硫（Li-S）电池中，要实现高能量密度需要高效转化高浓度的多硫化锂（LiPSs）。然而，在贫电解液条件下，控制硫化锂（Li₂S）沉积和溶解的机制仍知之甚少。本研究利用原位液体池电子显微镜，直接观察了电极-电解质界面处浓度驱动的相分离现象。在这些高浓度界面层（HCILs）中，表面和溶液的竞争作用决定了电荷转移动力学，并最终控制了不同相边界处的Li₂S沉积。密度泛函理论（DFT）计算表明，多硫化锂的聚集改变了分子几何结构、电子性质和轨道杂化，共同促进了电荷通过高浓度多硫化锂簇的转移。基于这些见解，我们设计了优化电极，平衡了界面反应路径，实现了快速充电（4 C，26.8 mA cm^-2）并达到了超过400 Wh kg^-1的高能量密度。这些发现为实际工作条件下的界面反应提供了机制性理解，并为推进锂硫电池的设计提供了策略。

『总结』 本研究通过原位显微镜观察和理论计算揭示了锂硫电池在贫电解液条件下界面反应的机制，并据此设计了优化电极，实现了快速充电与高能量密度。

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27. β-抑制蛋白凝聚体调节G蛋白偶联受体功能

β-Arrestin condensates regulate G-protein-coupled receptor function

Anderson PJ, Xiao P, Zhong YN, ... , Snyder JC, Sun JP, Rajagopal S.; nature; (655, 8122)

『Abstract』β-Arrestins 1 and 2 are multifunctional adaptor proteins that regulate the signalling of G-protein-coupled receptors (GPCRs), the largest class of receptors, which impact nearly all aspects of physiology and are one of the most common drug targets. Although β-arrestins interact with a wide array of signalling effectors at many GPCRs, it is unclear how β-arrestins promote such varied functions. Here we show that β-arrestins undergo liquid-liquid phase separation, forming condensates that regulate GPCR function. We show that condensation is specific to visual arrestins and β-arrestins, and demonstrate that β-arrestin oligomerization occurs in proximity to the GPCR to regulate GPCR functions such as internalization and signalling. Our work provides a paradigm for β-arrestin condensates as regulators of GPCR function, with liquid-liquid phase separation serving as an important promoter of signalling compartmentalization at GPCRs.

『摘要』 β-阻遏蛋白1和2是多功能适配蛋白，可调控G蛋白偶联受体（GPCRs）的信号传导。GPCRs是最大的一类受体，几乎影响生理学的所有方面，是最常见的药物靶点之一。尽管β-阻遏蛋白在许多GPCRs处与多种信号效应物相互作用，但β-阻遏蛋白如何促进如此多样的功能尚不清楚。本研究表明，β-阻遏蛋白可发生液-液相分离，形成凝聚物以调控GPCR功能。研究显示，凝聚作用是视觉阻遏蛋白和β-阻遏蛋白所特有的，且β-阻遏蛋白寡聚化发生在GPCR附近，以调控GPCR的内吞和信号传导等功能。本研究为β-阻遏蛋白凝聚物作为GPCR功能调控因子提供了范例，其中液-液相分离是促进GPCR信号传导区室化的重要因素。

『总结』 β-阻遏蛋白通过液-液相分离形成凝聚物调控GPCR功能，揭示了信号传导区室化的新机制。

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28. 分泌到水稻中的病原长链非编码RNA通过隔离宿主miRNA以增强致病性

A pathogen lncRNA secreted into rice sequesters a host miRNA for virulence

He M, Su J, Zhou X, ... , Li W, Wang J, Chen X.; nature; (655, 8122)

『Abstract』Plants and animals respond to pathogens through pattern recognition receptor and Nod-like receptor proteins. Pathogens commonly use protein effectors to suppress host immunity for successful infection. However, the existence of non-protein effector classes remains comparatively understudied. Here we report an RNA-RNA recognition mechanism governing pathogen-host interaction, mediated by a regulatory RNA-encoding DNA sequence that separately generates two complementary regulatory RNAs. Specifically, a long non-coding RNA transcribed from this DNA region in the fungal pathogen Magnaporthe oryzae translocates into host rice cells and sequesters a complementary microRNA (miRNA), derived from a distinct host DNA region, thereby subverting host immunity. In turn, this rice-derived miRNA promotes disease resistance by repressing the expression of PKR1, a gene that encodes a negative regulator of host immunity. Sequestration of the host miRNA by the fungal long non-coding RNA releases PKR1 expression to facilitate fungal infection. We discovered that this regulatory RNA-encoding DNA sequence is probably widely present across diverse life species, mediating interactions between pathogens and their plant hosts. Collectively, our findings provide an approach for effective disease control using miRNAs derived from this important DNA region.

『摘要』 植物和动物通过模式识别受体和Nod样受体蛋白对病原体作出反应。病原体通常利用蛋白效应子抑制宿主免疫，以实现成功感染。然而，非蛋白效应子类别的存在却鲜有研究。本研究报告了一种调控病原体与宿主相互作用的RNA-RNA识别机制，该机制由一个编码调控RNA的DNA序列介导，该序列可分别生成两种互补的调控RNA。具体而言，稻瘟病菌（Magnaporthe oryzae）中该DNA区域转录的长链非编码RNA可转移至宿主水稻细胞中，并捕获来自宿主不同DNA区域的互补微小RNA（miRNA），从而破坏宿主免疫。相应地，这种源自水稻的miRNA通过抑制编码宿主免疫负调控因子PKR1的基因表达来增强抗病性。稻瘟病菌的长链非编码RNA捕获宿主miRNA后，PKR1表达得到释放，进而促进真菌感染。研究发现，这种编码调控RNA的DNA序列可能广泛存在于多种生物物种中，介导病原体与植物宿主之间的相互作用。总之，本研究结果为利用这一重要DNA区域产生的miRNA实现有效疾病防控提供了方法。

『总结』 本研究发现了一种由编码调控RNA的DNA序列介导的RNA-RNA识别机制，该机制通过长链非编码RNA与微小RNA相互作用调控病原体与宿主免疫，为疾病防控提供了新方法。

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29. 歌唱小鼠运动皮层投射的特异性扩展

Specific expansion of motor cortical projections in a singing mouse

Isko EC, Harpole CE, Zheng XM, ... , Davis MB, Zador AM, Banerjee A.; nature; (655, 8122)

『Abstract』Elucidating how modifications in neural circuit architecture drive behavioural innovation remains a key challenge in neuroscience and evolutionary biology. In mammals, the neocortex is posited to play a crucial part in facilitating rapid behavioural innovations. Although changes in long-range connectivity have been proposed to underlie such innovations, these hypotheses remain largely untested quantitatively, which is partly due to the lack of high-throughput neuronal projection data at single-neuron resolution across species. Here we studied the Alston's singing mouse (Scotinomys teguina), which exhibits a striking vocal behaviour absent in the laboratory mouse (Mus musculus), to quantitatively determine species-specific changes in motor cortical projections throughout the brain. We used bulk tracing, serial two-photon tomography and high-throughput DNA sequencing of more than 76,000 barcoded neurons to discover a specific and substantial expansion of orofacial motor cortical projections to an auditory cortical region and the midbrain periaqueductal grey, regions that are implicated in vocal behaviours. Moreover, analyses of projection motifs of individual orofacial motor cortical neurons revealed preferential expansion of exclusive projections to the auditory cortical region in the singing mouse. Our results suggest that selective expansion of ancestral motor cortical projections may lead to behavioural divergence over short timescales. Furthermore, the results facilitate mechanistic investigations of enhanced cortical control over vocalizations-a crucial preadaptation for human language. This approach of comparing recently diverged species with substantial behavioural divergences can be readily generalized across other model clades to discover quantitative rules of neural circuit evolution.

『摘要』 阐明神经回路结构改变如何推动行为创新仍是神经科学和进化生物学领域的关键挑战。在哺乳动物中，新皮质被认为在促进快速行为创新方面发挥着至关重要的作用。尽管已有假设提出长程连接性的改变是此类创新的基础，但这些假设在很大程度上尚未得到定量验证，部分原因是缺乏跨物种单神经元分辨率的高通量神经元投射数据。本研究以表现出显著发声行为（实验室小鼠无此行为）的阿尔斯通歌唱鼠（Scotinomys teguina）为对象，定量确定了其运动皮层投射在整个大脑中的物种特异性变化。我们利用批量示踪、连续双光子断层扫描技术以及对超过76,000个带条形码的神经元进行高通量DNA测序，发现口面部运动皮层投射向听觉皮层区域和中脑导水管周围灰质区域（均与发声行为相关）发生了特定且显著的扩张。此外，对单个口面部运动皮层神经元投射模式的分析显示，歌唱鼠对听觉皮层区域的专属投射发生了优先扩张。我们的研究结果表明，祖先运动皮层投射的选择性扩张可能导致短时间尺度上的行为分化。此外，该结果有助于从机制上探究增强皮层对发声的控制——这是人类语言的关键前适应。将近期分化的、行为差异较大的物种进行比较的方法，可轻松推广至其他模型类群，以发现神经回路进化的定量规律。

『总结』 本研究以阿尔斯通歌唱鼠为对象，发现其口面部运动皮层投射发生特定扩张，表明祖先运动皮层投射的选择性扩张可致短时间尺度行为分化，且该研究方法有助于探究神经回路进化定量规律。

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30. SNOR促进休眠后翻译重新启动

SNOR promotes translation restart after dormancy

Gluc M, Rosa H, Bozko M, ... , Gould KL, Mattei S, Jomaa A.; nature; (655, 8122)

『Abstract』Cellular dormancy enables survival during prolonged nutrient limitation by reversibly suppressing protein synthesis. How inactive eukaryotic ribosomes are reactivated when nutrients return remains unclear. Here, using high-resolution in situ cryo-electron tomography in Schizosaccharomyces pombe, we identify SNOR, an SBDS domain-containing ribosome-associated factor that binds at the peptidyl transferase centre and contacts the hypusinated loop of eIF5A during glucose depletion-induced dormancy. Rather than acting as a canonical hibernation factor, SNOR licenses dormant ribosomes for rapid translational restart. Upon glucose repletion, SNOR and eIF5A act together to promote efficient recovery of polysomes and exit from dormancy. These findings define a stress-responsive ribosome restart module that couples carbon-source limitation to surveillance of the ribosomal active site and reactivation of protein synthesis.

『摘要』 细胞休眠通过可逆地抑制蛋白质合成，使细胞能够在长时间的营养限制下存活。当营养恢复时，休眠的真核核糖体如何被重新激活仍不清楚。在此，利用裂殖酵母中的高分辨率原位冷冻电子断层扫描技术，我们确定了SNOR是一种含有SBDS结构域的核糖体相关因子，在葡萄糖耗尽诱导的休眠期间，该因子会结合在肽基转移酶中心，并与eIF5A的胍基化环接触。SNOR并非作为一种典型的休眠因子发挥作用，而是使休眠核糖体能够快速重新启动翻译。葡萄糖恢复后，SNOR和eIF5A共同作用，促进多聚核糖体有效恢复并使细胞退出休眠状态。这些发现定义了一个应激响应核糖体重启模块，该模块将碳源限制与核糖体活性位点的监测以及蛋白质合成的重新激活联系起来。

『总结』 研究利用冷冻电子断层扫描技术发现了一种名为SNOR的核糖体相关因子，该因子在营养缺乏诱导的细胞休眠期间结合在核糖体上，并在营养恢复时与eIF5A共同作用，促进核糖体快速重启蛋白质合成，使细胞退出休眠状态。

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31. 用于科学发现自动化的多智能体系统

A multi-agent system for automating scientific discovery

Ghareeb AE, Chang B, Mitchener L, ... , Finnemann SC, Hinks MM, Rodriques SG.; nature; (655, 8122)

『Abstract』Scientific discovery is driven by the iterative process of observation, hypothesis generation, experimentation and data analysis. Despite recent advancements in applying artificial intelligence (AI) to biology, no system has yet automated all these stages. Here we introduce Robin, a multi-agent system capable of fully automating both hypothesis generation and data analysis for experimental biology. By integrating literature search agents with data analysis agents, Robin can generate hypotheses, propose experiments, interpret experimental results and generate updated hypotheses, achieving a semi-autonomous approach to scientific discovery. By applying this system, we were able to identify promising therapeutic candidates for dry age-related macular degeneration, the major cause of blindness in the developed world. Robin proposed enhancing retinal pigment epithelium phagocytosis as a therapeutic strategy, and identified and confirmed in vitro efficacy for ripasudil and KL001. Ripasudil is a clinically used Rho kinase inhibitor that, to our knowledge, has never previously been proposed for the treatment of dry age-related macular degeneration. To elucidate the mechanism of ripasudil-induced upregulation of phagocytosis, Robin then proposed and analysed a follow-up RNA sequencing experiment, which revealed upregulation of ABCA1, which encodes a lipid efflux pump and represents a possible novel target. All hypotheses, experimental directions, data analyses and data figures in the main text of this report were produced by Robin. As one of the first AI systems to autonomously discover and validate novel therapeutic candidates within an iterative lab-in-the-loop framework, Robin establishes a new paradigm for AI-driven scientific discovery.

『摘要』 科学发现是由观察、假设生成、实验和数据分析的迭代过程推动的。尽管最近人工智能（AI）在生物学领域的应用取得了进展，但还没有系统能自动化所有这些阶段。在此，我们介绍了一种名为Robin的多智能体系统，它能够为实验生物学完全自动化生成假设和进行数据分析。通过将文献检索智能体与数据分析智能体相结合，Robin可以生成假设、提出实验、解释实验结果并生成更新后的假设，从而实现科学发现的半自主方法。通过应用这一系统，我们能够确定治疗干性年龄相关性黄斑变性（发达国家失明的主要原因）的有前景的治疗候选药物。Robin提出增强视网膜色素上皮细胞吞噬作用作为一种治疗策略，并确定并证实了ripasudil和KL001的体外疗效。据我们所知，ripasudil是一种临床使用的Rho激酶抑制剂，此前从未被提出用于治疗干性年龄相关性黄斑变性。为了阐明ripasudil诱导吞噬作用上调的机制，Robin随后提出并分析了一项后续RNA测序实验，该实验揭示了ABCA1的上调，ABCA1编码一种脂质外排泵，代表一个可能的新靶点。本报告正文中的所有假设、实验方向、数据分析和数据图表均由Robin生成。作为首个在迭代实验室循环框架内自主发现和验证新型治疗候选药物的AI系统之一，Robin为AI驱动的科学发现建立了新范式。

『总结』 Robin是一个多智能体系统，通过自动化生成假设和数据分析，实现了科学发现的半自主方法，并成功确定了治疗干性年龄相关性黄斑变性的有前景的药物候选，为AI驱动的科学发现建立新范式。

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32. 维持小胶质细胞修复功能可促进中风后康复

Sustaining microglial reparative function enhances stroke recovery

Tsuyama J, Sakai S, Kurabayashi K, ... , Prinz M, Kawaji H, Shichita T.; nature; (655, 8122)

『Abstract』Neurological symptoms after brain injury can remain as lifelong detrimental sequelae because most of the spontaneous recovery response disappears within a few months after the injury. Microglia have an essential role in this process; however, the cellular and molecular mechanisms that diminish spontaneous functional recovery in the brain remain unclear. Here using cellular fate analysis, we show that reparative microglia persist in the brain after a stroke even after losing their beneficial functions. In these cells, ZFP384 is identified as a pivotal transcriptional regulator that diminishes the expression of genes associated with the recovery phase, turning them into dysfunctional microglia that lose their reparative functions. Mechanistically, ZFP384 diminishes the YY1-mediated chromatin interaction necessary to induce the expression of these genes in microglia. The use of antisense oligonucleotides that target Zfp384 can sustain the broad range of neural repair effects of microglia and enhance recovery after stroke, even in the chronic phase of ischaemic stroke. Thus, therapeutics that prevent the loss of reparative immunity-the beneficial restorative functions of immune cells-can prolong functional recovery in the brain.

『摘要』 脑损伤后的神经症状可能成为终身有害的后遗症，因为大多数自发恢复反应在损伤后几个月内便会消失。小胶质细胞在这一过程中发挥关键作用，但大脑中抑制自发功能恢复的细胞和分子机制尚不明确。本研究通过细胞命运分析发现，即使失去有益功能，修复性小胶质细胞仍会持续存在于中风后的脑组织中。在这些细胞中，ZFP384被鉴定为关键转录调控因子，其通过降低与恢复期相关基因的表达，使小胶质细胞转变为失去修复功能的失能状态。从机制上看，ZFP384会削弱YY1介导的染色质相互作用，而该作用对于诱导小胶质细胞中这些基因的表达至关重要。使用靶向Zfp384的反义寡核苷酸可维持小胶质细胞广泛的神经修复作用，即使在缺血性中风慢性期也能促进功能恢复。因此，防止修复性免疫功能丧失（即免疫细胞的有益修复功能）的治疗方法可延长大脑功能恢复时间。

『总结』 研究发现小胶质细胞中ZFP384通过抑制恢复相关基因表达导致神经修复功能丧失，靶向抑制ZFP384可延长中风后大脑功能恢复期。

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33. 谱系与器官信号依次构建器官内在神经系统

Lineage and organ signals sequentially build organ intrinsic nervous systems

Hsu IY, Zhao J, Lin Y, ... , Zhao H, Zhang L, Chang RB.; nature; (655, 8122)

『Abstract』Organ intrinsic nervous systems (OINSs) are critical components of the body-brain axis and coordinate visceral organ function with systemic physiological control. Despite their importance, how these distinct neural architectures arise from a common neural crest cell origin has remained unclear. Here we present a systems-level, cross-organ analysis of OINS development, integrating lineage tracing, 3D imaging, single-cell transcriptomics and genetic perturbations across the heart, pancreas, intestine and lungs. We show that differences in neural crest cell migratory trajectories prefigure the spatial architecture of OINSs, laying the foundation for organ-specific patterning. By contrast, molecular identity emerges largely in response to local environments, indicating that extrinsic cues have a major instructive role. Using in vitro co-cultures, we demonstrate that organ-derived cues reprogramme intrinsic neurons towards organ-specific transcriptional profiles and direct neuronal differentiation, with extracellular matrix (ECM) contact as a central mediator. In vivo, ECM-integrin signalling supports neurogenesis of intrinsic cardiac neurons, and ECM crosslinking stabilizes their stereotyped ganglionic organization. Together, these findings reveal that OINS diversity arises through a dual logic: lineage programmes prefigure spatial frameworks, whereas organ-specific cues instruct final molecular identities and architectural precision. This work establishes a conceptual paradigm for how organs actively build their nervous systems, illuminating principles that underlie body-brain integration.

『摘要』 器官内在神经系统（OINSs）是体脑轴的关键组成部分，负责协调内脏器官功能与全身生理控制。尽管其重要性不言而喻，但这些独特的神经结构如何从共同的神经嵴细胞起源中形成尚不清楚。本研究通过整合谱系追踪、三维成像、单细胞转录组学和基因扰动等技术，对心脏、胰腺、肠道和肺部的OINS发育进行了系统层面的跨器官分析。结果显示，神经嵴细胞迁移轨迹的差异预先决定了OINSs的空间结构，为器官特异性模式形成奠定了基础；相比之下，分子特性主要受局部环境影响，表明外在信号具有重要指导作用。通过体外共培养实验，研究发现器官来源的信号可重编程内在神经元，使其呈现器官特异性转录谱并指导神经元分化，其中细胞外基质（ECM）接触是核心介质。在体内，ECM-整合素信号支持心脏内在神经元的神经发生，ECM交联则稳定其典型的神经节组织结构。总之，这些发现揭示了OINS多样性的双重形成机制：谱系程序预先构建空间框架，而器官特异性信号则指导最终分子特性和结构精确性。本研究为器官如何主动构建自身神经系统提供了概念性范式，阐明了体脑整合的基本原理。

『总结』 器官内在神经系统的多样性通过谱系程序构建空间框架与器官特异性信号指导分子特性及结构精确性双重机制形成，为体脑整合原理提供了新范式。

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34. 从抵抗力与恢复力预测时间稳定性和恢复力

Predicting temporal stability and resilience from resistance and recovery

Isbell F, Mori AS, Loreau M, ... , Xu Q, Zheng L, Zirbel CR.; nature; (655, 8122)

『Abstract』Stability can be desirable for many natural and social systems. Temporal stability, the invariability of a system over time, can be enhanced by resisting displacement during perturbations, accelerating recovery after them, or both. Likewise, resilience (sensu proximity to unperturbed levels after a perturbation) also has components of withstanding (resistance) and recovering after perturbations. Here we develop and test new predictions for how temporal stability and resilience depend on their resistance and recovery components. We find that temporal stability could often be predicted from resistance, even without information about how quickly the system recovers. By contrast, resilience is predicted to depend at least as much on recovery as on resistance, as in earlier theory. Using plant productivity data from the world's longest-running biodiversity experiment, we find that long-term temporal stability, quantified over a quarter century at the ecosystem or species level, is predicted with moderate accuracy from single-year estimates of resistance alone, with only slight improvement by also considering recovery. Resilience was predicted with moderate accuracy by a combination of resistance and recovery at the ecosystem level. We also find that ecosystem drought resistance can be forecasted by monitoring temporal stability before the drought. Our results reveal that long-term temporal stability and short-term resistance may often be predicted from one another and clarify how resistance and recovery can be leveraged to enhance the stability of both natural and managed systems.

『摘要』 许多自然和社会系统都追求稳定性。时间稳定性，即系统随时间推移保持不变的能力，可以通过在受到干扰时抵抗位移、在干扰后加速恢复或两者兼而有之来增强。同样，恢复力（指干扰后恢复到未受干扰水平的能力）也包含抵抗干扰（抗性）和干扰后恢复的成分。本文提出并检验了关于时间稳定性和恢复力如何依赖于其抗性和恢复成分的新预测。研究发现，即使不了解系统恢复的速度，时间稳定性通常也可通过抗性来预测。相比之下，正如早期理论所预测的那样，恢复力至少在同等程度上依赖于恢复和抗性。通过利用全球持续时间最长的生物多样性实验的植物生产力数据，研究发现，在生态系统或物种层面，通过25年的时间尺度量化得出的长期时间稳定性，仅通过单年的抗性估算就能达到中等预测精度，若同时考虑恢复情况，预测精度仅略有提升。在生态系统层面，通过结合抗性和恢复情况，可中等准确地预测恢复力。研究还发现，通过监测干旱前的时间稳定性可以预测生态系统的抗旱性。研究结果表明，长期时间稳定性和短期抗性往往可以相互预测，并阐明了如何利用抗性和恢复来增强自然和管理系统的稳定性。

『总结』 研究提出并检验了时间稳定性和恢复力如何依赖于抗性和恢复的新预测，发现时间稳定性常可通过抗性预测，恢复力则至少同等依赖于恢复和抗性，且长期时间稳定性和短期抗性常可相互预测，阐明了如何利用抗性和恢复增强系统稳定性。

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35. 借助Co-Scientist加速科学发现

Accelerating scientific discovery with Co-Scientist

Gottweis J, Weng WH, Daryin A, ... , Pawlosky A, Karthikesalingam A, Natarajan V.; nature; (655, 8122)

『Abstract』Scientific discovery is driven by scientists generating hypotheses for complex problems that undergo rigorous experimental validation. To augment this process, we introduce Co-Scientist, a multi-agent artificial intelligence (AI) system built on Gemini for structured scientific thinking and hypothesis generation. Co-Scientist aims to help scientists discover new original knowledge. Conditioned on their research objectives and previous scientific evidence, it formulates demonstrably novel research hypotheses for experimental verification. The system's design involves agents continuously generating, critiquing and refining hypotheses accelerated by scaling test-time compute. Key contributions include (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling, and (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute scaling, improving hypothesis quality over time. Although this is a general-purpose system, we focus the validation in three biomedical applications: drug repurposing; novel-target discovery; and explaining mechanisms of antimicrobial resistance. Specifically, Co-Scientist helped to identify new drug-repurposing candidates and synergistic combination therapies for acute myeloid leukaemia that were validated through in vitro experiments. These real-world validations demonstrate the potential of Co-Scientist to accelerate scientific discovery and usher in an era of AI-empowered scientists.

『摘要』 科学发现依赖于科学家针对复杂问题提出假设，并通过严格的实验验证。为助力这一过程，我们推出了基于Gemini构建的协同科学家（Co-Scientist）多智能体人工智能系统，该系统支持结构化科学思维与假设生成，旨在帮助科学家发现全新的原创知识。根据研究目标和先前的科学证据，该系统可生成具有可验证性的新颖研究假设供实验验证。系统设计通过多智能体连续生成、批判和改进假设，并借助扩展测试时计算加速这一过程。其核心贡献包括：（1）采用异步任务执行框架的多智能体架构，实现灵活的计算扩展；（2）通过锦标赛进化过程实现假设生成能力的自我提升。自动化评估表明，测试时计算的扩展可持续提升假设质量。尽管该系统为通用型设计，但我们重点在三个生物医学领域进行了验证：药物重定位、新靶点发现以及抗菌药物耐药机制阐释。具体而言，协同科学家系统帮助确定了急性髓系白血病的新药物重定位候选药物和协同联合疗法，并通过体外实验验证了其有效性。这些实际应用验证表明，协同科学家系统具备加速科学发现的潜力，将引领人工智能赋能科学家的新时代。

『总结』 协同科学家系统作为多智能体人工智能工具，通过结构化科学思维与假设生成能力，在生物医学领域验证了其加速科学发现、生成可验证假设并推动人工智能与科学深度融合的潜力。

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36. 高多样性慈鲷鱼肠道内的适应性细胞进化

Adaptive cellular evolution in the intestine of hyperdiverse cichlid fishes

Fages A, Luxey M, Ronco F, ... , Indermaur A, Salzburger W, Tschopp P.; nature; (655, 8122)

『Abstract』The ability of animals to efficiently track down and digest food is crucial for their survival, and the specialization to different diets is a major driver of diversification in this group. Although the evolution of feeding structures has been studied extensively in this context, the nature and extent of adaptations in the digestive tract remain poorly understood. Here, we examine dietary adaptations in the intestines of one of the largest adaptive radiations in vertebrates, the cichlid fishes of Lake Tanganyika. By generating comprehensive single-cell transcriptomic data for 24 Tanganyikan cichlid species with divergent feeding habits, and integrating this with eco-morphological and genomic information, we uncover that, at the cellular level, dietary adaptations primarily involve anterior enterocytes. In particular, we show that the relative abundances of anterior enterocytes as well as the gene expression profiles in this cell population evolved in response to rapid trophic specializations, and that these diet-related adaptations are driven by fast-evolving, cell-population-specific genes. Overall, our findings show that alterations in intestinal epithelium cell composition and in the cell-type-specific molecular makeup provided the substrate for trophic specializations, demonstrating that ecological adaptations target multiple layers of biological organization.

『摘要』 动物高效追踪并消化食物的能力对其生存至关重要，而针对不同食物的特化是该类群多样性的主要驱动力。尽管在此背景下，对摄食结构的进化已有广泛研究，但对消化道适应的性质和范围仍知之甚少。本研究以脊椎动物中最大的适应性辐射类群之一——坦噶尼喀湖慈鲷为研究对象，探究其肠道的饮食适应性。通过对24种具有不同摄食习性的坦噶尼喀湖慈鲷进行全面的单细胞转录组测序，并结合生态形态学和基因组信息，发现细胞层面的饮食适应性主要涉及前肠吸收细胞。特别是，前肠吸收细胞的相对丰度以及该细胞群的基因表达谱随着快速营养特化而进化，且这些与饮食相关的适应性由快速进化的、特定细胞群的基因驱动。总体而言，研究结果表明，肠道上皮细胞组成和细胞类型特异性分子构成的改变为营养特化提供了基础，证明了生态适应针对生物组织的多个层次。

『总结』 研究发现坦噶尼喀湖慈鲷肠道的饮食适应性主要涉及前肠吸收细胞，其相对丰度及基因表达谱随营养特化而进化，且由快速进化的特定细胞群基因驱动，表明生态适应针对生物组织多个层次。

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37. X连锁长链非编码RNA PTCHD1-AS与自闭症的核心特征

An X-linked long non-coding RNA, PTCHD1-AS, and the core features of autism

Bradley CA, Ko SY, Tian M, ... , Frankland PW, Collingridge GL, Scherer SW.; nature; (655, 8122)

『Abstract』There are around 100 genes or copy-number variations used in genetic testing for autism spectrum disorder (ASD). The established genes are protein coding, and the associated phenotypes usually extend beyond sociobehavioural traits seen in autism, including cognitive/medical complexities and attention deficit hyperactivity disorder (ADHD). We examined whole-genome sequencing data in cases of ASD (9,349) and controls (8,332) and identify 27 male individuals with ASD with X-chromosome microdeletions that implicate the long non-coding RNA PTCHD1-AS as an ASD-susceptibility gene (odds ratio = 2.56, P = 0.01). Two Ptchd1-as-knockout mouse models, which were created by disrupting/deleting the evolutionarily conserved exon 3, show ASD-like features in male mice, including increased repetitive behaviours and impaired social behaviour and communication without cognitive comorbidities or ADHD-like behaviours. Hippocampus-dependent synaptic function, complex learning and locomotor activity are unaffected in knockout mice. Native nuclear-enriched mouse Ptchd1-as showed sustained expression from postnatal day 7 onwards in the dorsal striatum, a predominantly GABAergic brain region that is implicated in ASD. Multi-omics analysis revealed transcriptomic alterations in striatal oligodendrocytes, astrocytes and neurons impacting myelination and synaptic plasticity. Disrupting Ptchd1-as led to reductions in conventional protein kinase C (cPKC) isoforms, altered SRC and GSK-3α/β phosphorylation and enhanced striatal synaptic plasticity (long-term potentiation and long-term depression). Together, these findings implicate striatal molecular and circuit-level dysregulation through PTCHD1-AS in ASD aetiology.

『摘要』 在自闭症谱系障碍（ASD）的基因检测中，大约会用到100个基因或拷贝数变异。已确定的基因可编码蛋白质，且相关表型通常超出自闭症中观察到的社会行为特征，涵盖认知/医学复杂性及注意力缺陷多动障碍（ADHD）。本研究对9349例自闭症病例和8332例对照进行全基因组测序数据分析，发现27例男性自闭症患者存在X染色体微缺失，提示长链非编码RNA PTCHD1-AS为自闭症易感基因（比值比=2.56，P=0.01）。通过破坏/删除进化保守的外显子3构建的两种Ptchd1-as敲除小鼠模型，在雄性小鼠中表现出类似自闭症的特征，包括重复行为增加、社交行为和交流受损，但无认知共病或类似ADHD的行为。敲除小鼠的海马体依赖性突触功能、复杂学习和运动活动未受影响。小鼠原生核富集的Ptchd1-as从出生后第7天起在背侧纹状体（一个主要含GABA能神经元且与自闭症相关的脑区）持续表达。多组学分析显示，纹状体少突胶质细胞、星形胶质细胞和神经元的转录组发生改变，影响髓鞘形成和突触可塑性。破坏Ptchd1-as导致常规蛋白激酶C（cPKC）亚型减少，SRC和GSK-3α/β磷酸化改变，并增强纹状体突触可塑性（长时程增强和长时程抑制）。这些发现共同表明，PTCHD1-AS通过纹状体分子和回路水平失调参与自闭症病因。

『总结』 研究通过基因组测序发现PTCHD1-AS为自闭症易感基因，敲除小鼠模型显示其缺失导致自闭症相关行为及纹状体分子和回路失调，揭示其通过影响髓鞘形成、突触可塑性和信号通路参与自闭症发病机制。

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38. 细胞和组织中糖原及其代谢物的泛素化

Ubiquitination of glycogen and metabolites in cells and tissues

Jochem M, Cobbold SA, Goodman CA, ... , Hofmann K, Gregorevic P, Komander D.; nature; (655, 8122)

『Abstract』Ubiquitin signalling covers a wide range of protein modifications, but its scope may still be underestimated, owing to the ubiquitination of non-proteinaceous substrates, such as sugars, lipids and nucleotides. The breadth of ubiquitinated non-protein substrates, their abundance and their cellular roles are currently unclear, as current ubiquitinomic and proteomic techniques do not detect non-proteinaceous modifications. Here we report non-protein ubiquitin clipping (NoPro-clipping) as a mass spectrometry-based technique that combines ubiquitin clippases with sortase labelling. Targeted and untargeted workflows unveil a wide range of ubiquitinated substrates in mammalian cells and in mouse and human tissues. We find ubiquitinated glycogen in glycogen-containing tissues in mice, with the highest abundance in liver and skeletal muscle. Ubiquitination can deliver glycogen to lysosomes and leads to decreased glycogen levels. Glycogen ubiquitination is modulated in glycogen storage diseases and is regulated by the Met1-polyubiquitin machinery. Notably, glycogen depletion in the liver during fasting coincides with increased glycogen ubiquitination, suggesting that ubiquitin is a previously unknown component of physiological glycogen catabolism. We also reveal ubiquitination of endogenous glycerol and spermine in cells and tissues. NoPro-clipping thus reveals unexpected endogenous non-proteinaceous targets of ubiquitination, broadening the role of ubiquitin from a protein modifier to a general modifier of biomolecules.

『摘要』 泛素信号涵盖广泛的蛋白质修饰，但鉴于糖类、脂质和核苷酸等非蛋白质底物也会发生泛素化，其作用范围可能仍被低估。目前，泛素化非蛋白质底物的范围、丰度及其在细胞中的作用尚不明确，因为现有的泛素组学和蛋白质组学技术无法检测非蛋白质修饰。本研究报告了非蛋白质泛素剪切（NoPro-clipping）技术，这是一种基于质谱的方法，将泛素剪切酶与分选酶标记相结合。靶向和非靶向工作流程揭示了哺乳动物细胞以及小鼠和人类组织中存在广泛的泛素化底物。研究发现，小鼠含糖原组织中存在泛素化糖原，其中肝脏和骨骼肌中的含量最高。泛素化可将糖原转运至溶酶体，导致糖原水平下降。糖原贮积病中糖原的泛素化受到调节，且受Met1-多聚泛素机制调控。值得注意的是，禁食期间肝脏糖原的消耗与糖原泛素化增加同时发生，这表明泛素是生理性糖原分解代谢中此前未知的组成部分。研究还揭示了细胞和组织中内源性甘油和精胺的泛素化。因此，NoPro-clipping技术揭示了意想不到的内源性非蛋白质泛素化靶点，将泛素的作用从蛋白质修饰因子扩展到生物分子的一般修饰因子。

『总结』 研究开发了非蛋白质泛素剪切技术，揭示了哺乳动物细胞及组织中存在广泛的非蛋白质泛素化底物，包括糖原、甘油和精胺，扩展了泛素作为生物分子修饰因子的作用范围。

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39. 跃出水面：利用扑翼实现的空水两栖运动

Leaping out of the water: Aerial-aquatic locomotion with flapping wings

Zufferey R, Jeger SL, Husser M, ... , Lapsansky A, Ijspeert A, Floreano D.; science; (393, 6807)

『Abstract』Wing-propelled diving birds flap their wings to move through air and water, yet the wing morphology and kinematics that enable this behavior remain poorly understood because of the difficulty of collecting in situ data. The impact of flapping frequency, wing size, and stiffness on locomotion in-and transition between-the two media are still unknown. We compared data from diving birds against experiments using a flapping-wing robot capable of flying, swimming, plunge diving, and exiting the water. We show that frequency adaptation, flexible wings, and powerful actuation enable seamless transitions without folding wings or legs, that large wings enhance flight without substantially reducing underwater efficiency, and that tail-body distance and egress angle affect water exit. These results clarify how birds (and robots) balance multifluid locomotion constraints.

『摘要』 扑翼潜水鸟类通过拍打翅膀在空气和水中移动，但由于难以收集现场数据，实现这种行为的翅膀形态和运动学原理仍未得到充分理解。拍打频率、翅膀大小和刚度对两种介质中运动及介质间转换的影响仍未知。我们将潜水鸟类的数据与使用一种能够飞行、游泳、俯冲潜水和出水的新型扑翼机器人进行的实验进行了对比。我们发现，频率适应、灵活的翅膀和强大的驱动装置使鸟类（和机器人）无需折叠翅膀或腿部就能实现无缝转换，大翅膀增强了飞行能力且不会显著降低水下效率，尾体距离和出水角度影响出水过程。这些结果阐明了鸟类（和机器人）如何平衡多种流体中的运动限制。

『总结』 通过对比潜水鸟类数据与扑翼机器人实验，揭示了频率适应、翅膀特性等因素对鸟类（及机器人）在空气和水介质中运动及转换的影响，阐明了其平衡多种流体运动限制的机制。

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40. 非洲一种入侵性城市疟蚊的起源、历史及抗性结构

The origin, history, and resistance architecture of an invasive urban malaria mosquito in Africa

Dennis TPW, Sulieman JE, Nouredayem M, ... , Kafy HT, Donnelly MJ, Weetman D.; science; (393, 6807)

『Abstract』The invasive urban malaria vector Anopheles stephensi threatens 126 million city dwellers in Africa. Controlling An. stephensi requires greater understanding of its origin, invasion dynamics, and insecticide resistance mechanisms. Analysis of 645 whole genomes sampled across Africa, the Middle East, and Asia supports an invasion scenario in which an initial South Asian introduction established a bridgehead population in Djibouti, which seeded distinct invasion fronts in Sudan, Ethiopia/Kenya, and Yemen. These incursions show contrasting rates and routes of spread shaped by landscape topology. Insecticide resistance is predominantly mediated by metabolic detoxification genes, with resistance haplotypes and copy-number amplifications introduced from South Asia. These findings, alongside a companion genomic resource, enable genomic surveillance of An. stephensi spread and resistance to aid control strategies.

『摘要』 入侵性城市疟疾媒介斯氏按蚊威胁着非洲1.26亿城市居民。要控制斯氏按蚊，需要更深入地了解其起源、入侵动态以及杀虫剂抗性机制。对来自非洲、中东和亚洲的645个全基因组样本的分析支持这样一种入侵情景：最初由南亚引入，在吉布提建立了桥头堡种群，并在苏丹、埃塞俄比亚/肯尼亚和也门形成了不同的入侵前沿。这些入侵显示出因景观拓扑结构不同而形成的传播速率和途径的差异。杀虫剂抗性主要由代谢解毒基因介导，抗性单倍型和拷贝数扩增来自南亚。这些发现，连同配套的基因组资源，使得能够对斯氏按蚊的传播和抗性进行基因组监测，以辅助制定控制策略。

『总结』 对来自非洲、中东和亚洲的645个斯氏按蚊全基因组样本分析，揭示了其入侵非洲的情景，指出其传播速率和途径受景观拓扑结构影响，抗性由代谢解毒基因介导且抗性单倍型和拷贝数扩增来自南亚，相关发现及配套资源有助于基因组监测和制定控制策略。

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41. 个性化干预益处的统计检验

A statistical test for the benefits of personalizing interventions

Li Z, Brunskill E.; science; (393, 6807)

『Abstract』From medicine to marketing to social sciences, the promise of tailoring interventions to individuals is undeniable. However, practical applications force weighing personalization's potential benefits with its possible increased cost and fragility. We introduce a statistical hypothesis test that evaluates, given historical data, evidence that a personalized intervention policy's performance will surpass deploying the best single intervention. The test maintains strict Type I error control while achieving asymptotic normality with the minimal possible variance under specified conditions. Results on diverse datasets from job training, depression treatment, education, and recommendation systems demonstrate the test's versatility and its superior performance over alternatives. This test can support decision-makers throughout the intervention sciences by providing a simple and powerful quantification of the potential benefits of personalization.

『摘要』 从医学到市场营销再到社会科学，针对个体定制干预措施的潜力不可否认。然而，实际应用中需要权衡个性化干预的潜在益处与可能增加的成本和脆弱性。我们引入了一种统计假设检验方法，该方法基于历史数据评估个性化干预策略的表现是否会优于采用最佳单一干预策略。该检验在严格控制第一类错误的同时，在指定条件下实现了渐近正态性且方差最小化。来自职业培训、抑郁症治疗、教育和推荐系统等多个领域的数据集结果证明了该检验方法的通用性及其优于其他方法的性能。这一检验方法能够为干预科学领域的决策者提供简单而有力的量化依据，以评估个性化的潜在益处。

『总结』 介绍了一种统计假设检验方法，可评估个性化干预策略是否优于单一干预策略，且在控制错误的同时实现渐近正态性，在多个领域证明了其通用性和优越性，可为决策者提供量化依据。

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42. C1q和免疫球蛋白介导成年大脑中与活动相关的突触丢失

C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain

Crowley G, Kim M, O'Neill N, ... , Lignani G, Clatworthy MR, Hong S.; science; (393, 6807)

『Abstract』Complement component 1q (C1q), the initiator of the classical complement cascade, mediates synaptic elimination in development and disease, yet the triggers for its deposition on synapses remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity induces region-specific, C1q-dependent synapse loss in the adult hippocampus. Suppressing perforant pathway hyperactivity in a mouse model of Alzheimer's disease reduced local amyloid-β amounts and C1q deposition and partially rescued synapse loss. Combining spatial transcriptomics, live cell tracking, and super-resolution microscopy, we identified association of antibody-secreting B-lineage cells in the adult hippocampus with activity-dependent, C1q-mediated synapse loss under physiological conditions. Together, these findings link neuronal hyperactivity to C1q-mediated synapse loss in the adult brain and implicate immunoglobulins as players in this process.

『摘要』 补体成分1q（C1q）是经典补体级联反应的启动因子，在发育和疾病过程中介导突触消除，但其在突触上沉积的触发因素尚不清楚。我们利用体内化学遗传学方法证明，神经元过度活跃会诱导成年海马体特定区域发生C1q依赖性突触丢失。在阿尔茨海默病小鼠模型中，抑制穿通通路过度活跃可减少局部β-淀粉样蛋白含量和C1q沉积，并部分恢复突触丢失。结合空间转录组学、活细胞追踪和超分辨率显微技术，我们发现成年海马体中分泌抗体的B谱系细胞与生理条件下由神经元活动依赖、C1q介导的突触丢失相关。这些发现将神经元过度活跃与成年大脑中C1q介导的突触丢失联系起来，并表明免疫球蛋白在这一过程中发挥作用。

『总结』 研究揭示了神经元过度活跃通过C1q介导成年海马体突触丢失，并发现B谱系细胞和免疫球蛋白参与这一过程。

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43. 用于量子气体的相位显微镜

A phase microscope for quantum gases

Bruggenjurgen JC, Fischer MS, Weitenberg C.; science; (393, 6807)

『Abstract』Coherence properties are central to quantum systems and are at the heart of phenomena such as superconductivity. In this work, we studied coherence properties of an ultracold Bose gas in a two-dimensional optical lattice across the thermal phase transition. To infer the phase coherence and phase fluctuation profiles, we used direct matter-wave imaging of higher Talbot revivals and introduced a phase microscope based on a site-resolved mapping of phase fluctuations to density fluctuations during matter-wave imaging. We observed the algebraic decay of the phase correlations in the superfluid phase and a linear temperature increase of the exponent. These techniques may enable studying coherence properties in strongly correlated quantum systems with full spatial resolution.

『摘要』 相干性是量子系统的核心特性，也是超导等现象的核心所在。本研究中，我们研究了二维光学晶格中超冷玻色气体在热相变过程中的相干特性。为了推断相相干性和相涨落分布，我们利用更高塔尔博特（Talbot）复苏的直接物质波成像，并引入了一种基于物质波成像期间将相涨落映射到密度涨落的位点分辨映射的相位显微镜。我们观察到超流体相中相位关联的代数衰减以及指数的线性温度增加。这些技术或许能够以完全的空间分辨率研究强关联量子系统中的相干特性。

『总结』 本研究通过物质波成像与相位显微镜技术，研究了二维光学晶格中超冷玻色气体的相干特性，并观察到超流体相中相位关联的代数衰减及指数的线性温度增加，为研究强关联量子系统的相干特性提供了新方法。

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44. 根系通过感知局部pH梯度绕过腐烂区域

Roots navigate around decay regions by sensing local pH gradients

Bao Z, Wang H, Zhang A, ... , Fan N, Friml J, Zhang Y.; science; (393, 6807)

『Abstract』Plant tropisms enable roots to navigate complex soils by responding to directional environmental cues. Biological decay, although central to nutrient cycling, also creates microbially active and potentially hostile niches. In this work, we identified "saprotropism," a previously unrecognized growth response that enables roots to actively bend away from decaying plant-derived matter. Fungal-driven microbial decomposition released organic acids and formed stable pH gradients in surrounding soil, allowing roots to pinpoint decay without direct contact. Root epidermal cells sensed this acidic gradient through the root meristem growth factor peptide-receptor module, converting external pH asymmetry into asymmetric abscisic acid (ABA) distribution. ABA asymmetry drove microtubule reorganization, which was decoded into decay-avoidant root bending. Together, these findings establish microbial decay-derived chemical gradients as an instructive signal for root navigation and expand the framework of microbe-soil-plant communication.

『摘要』 植物向性使根系能够通过响应方向性环境信号在复杂土壤中生长。尽管生物降解是养分循环的核心环节，但它也会产生微生物活跃且可能存在敌意的生态位。本研究发现了一种此前未被识别的生长反应——“腐生向性”，它使根系能够主动弯曲避开正在腐烂的植物源物质。真菌驱动的微生物分解会释放有机酸，并在周围土壤中形成稳定的pH梯度，使根系无需直接接触即可定位腐烂区域。根表皮细胞通过根分生组织生长因子肽受体模块感知这种酸性梯度，将外部pH不对称性转化为不对称的脱落酸（ABA）分布。ABA的不对称分布驱动微管重排，进而解码为避开腐烂的根弯曲。这些发现共同表明，微生物降解产生的化学梯度是指导根系导航的信号，并拓展了微生物-土壤-植物通讯的框架。

『总结』 研究揭示了植物根系通过“腐生向性”响应微生物降解产生的化学梯度，实现避开腐烂物质的生长机制，拓展了微生物-土壤-植物通讯的认知。

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45. 社会记忆中效价更新的神经回路

Neural circuits for valence updating in social memory

Suto N, Wang MY, Morikawa S, ... , Takeuchi H, Kira S, Okuyama T.; science; (393, 6807)

『Abstract』Social animals recognize familiar conspecifics and selectively avoid harmful ones. As social relationships shift, continuous updating of social valence is essential, yet the underlying neural mechanisms remain unclear. Here, by artificially transforming a previously neutral conspecific into an aggressive one, we show that valence updating depends on enhanced synaptic connectivity and physiological changes within the hippocampal ventral CA1 (vCA1)-basolateral amygdala (BLA)-nucleus accumbens (NAc) circuit. Following defeat, social memory engram neurons in the vCA1 strengthened their connections with BLA neurons carrying negative valence. The vCA1-BLA-NAc neural circuit flexibly regulates adaptive social behaviors.

『摘要』 群居动物能够识别熟悉的同类，并有选择性地避开有害的同类。随着社会关系的变化，持续更新社会价值判断至关重要，但其背后的神经机制尚不清楚。在此，我们通过将先前中性的同类人为转变为攻击性个体，发现价值判断的更新依赖于海马腹侧CA1区（vCA1）-基底外侧杏仁核（BLA）-伏隔核（NAc）回路内突触连接增强和生理变化。在遭受挫败后，vCA1中的社会记忆印迹神经元增强了与携带负向价值判断的BLA神经元的连接。vCA1-BLA-NAc神经回路灵活调节适应性社会行为。

『总结』 群居动物社会价值判断更新机制尚不明确，通过实验发现其依赖于特定神经回路内突触连接和生理变化，且该神经回路可灵活调节适应性社会行为。

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46. CBi&lt;sup&gt;-&lt;/sup&gt;分子离子中经典三键的相对论坍缩

Relativistic collapse of the classical triple bond in the CBi&lt;sup&gt;-&lt;/sup&gt; molecular ion

Kahraman D, Hui J, Zhang XY, ... , Choi HW, Peterson KA, Wang LS.; science; (393, 6807)

『Abstract』The conventional framework for chemical bonding between main-group elements involves separate σ and π orbitals to describe multiple bonds. However, relativistic effects mix these orbitals in molecules containing heavy elements through spin-orbit coupling, leaving the total angular-momentum projection (ω) as the only good quantum number. Direct experimental evidence that relativistic effects change the σ-π bonding framework has remained elusive. Here, we probe the carbon-bismuth triple bond in the CBi^- anion using high-resolution cryogenic photoelectron spectroscopy, coupled with relativistic four-component Dirac-Coulomb coupled-cluster calculations. Even though the CBi^- anion is isovalent to the well-known CN^- species, we demonstrate that the traditional σ + 2π triple-bond picture collapses into a pure π-like |ω| = 3/2 and two |ω| = 1/2 Kramers pairs containing substantial σ/π mixing.

『摘要』 主族元素间化学键的传统框架涉及独立的σ和π轨道来描述多重键。然而，相对论效应通过自旋轨道耦合使含重元素分子中的这些轨道发生混合，仅保留总角动量投影（ω）作为唯一守恒量子数。目前，相对论效应改变σ-π成键框架的直接实验证据仍难以获得。本研究采用高分辨率低温光电子能谱结合相对论四分量狄拉克-库仑耦合簇计算，探究了CBi^-阴离子中的碳-铋三键。尽管CBi^-阴离子与已知的CN^-物种等价，但结果表明传统σ + 2π三键模型已瓦解，形成纯π型|ω| = 3/2态和两个含显著σ/π混合的|ω| = 1/2克拉默斯对。

『总结』 研究首次通过实验和理论计算证实，相对论效应导致含重元素分子中传统σ-π成键框架瓦解，形成以总角动量投影为特征的混合态。

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47. 安第斯叶耳鼠（世界上栖息海拔最高的哺乳动物）在极端海拔梯度上的适应性

Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world's highest-dwelling mammal

Liphardt S, Bautista NM, Quiroga-Carmona M, ... , D'Elia G, Good JM, Storz JF.; science; (393, 6807)

『Abstract』Andean leaf-eared mice (Phyllotis vaccarum) live at the highest elevations of any mammal, and they also have the broadest elevational range, from sea level to mountain summits of >6700 meters. Highland populations have evolved an enhanced thermogenic capacity in hypoxia relative to lowland conspecifics, and this improved physiological performance is associated with an increased mitochondrial respiratory capacity in skeletal muscle. Population genomic analyses identified mechanisms of hypoxia adaptation and revealed an unanticipated dimension of environmental adaptation in P. vaccarum because selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world's highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology.

『摘要』 安第斯叶耳鼠（Phyllotis vaccarum）生活在所有哺乳动物中海拔最高的地方，其海拔跨度也是最广的，从海平面到海拔超过6700米的山峰都有分布。与低海拔的同类相比，高海拔种群在缺氧环境下进化出了更强的生热能力，这种改善的生理表现与骨骼肌线粒体呼吸能力的增强有关。群体基因组分析确定了缺氧适应的机制，并揭示了P. vaccarum环境适应的一个意想不到的维度，因为对生物转化途径的选择表明其进化出了代谢植物源性膳食毒素的能力。这种世界上栖息海拔最高的哺乳动物已适应了其分布范围内低海拔和高海拔极限的栖息地，且许多与海拔相关的选择都与先前未被重视的觅食生态方面有关。

『总结』 安第斯叶耳鼠适应了广泛海拔的栖息地，其高海拔适应涉及生理和基因层面的改变，且与觅食生态有关。

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48. 用于燃料电池的精准调谐铂包覆金属间化合物催化剂的瞬态组装

Transient assembly of precision-tuned platinum-skin intermetallic catalysts for fuel cells

Ding J, Zhang T, Song W, ... , Zhou J, Liu B, Hu W.; science; (393, 6807)

『Abstract』Highly efficient catalysts require precisely engineered intricate structures, yet conventional thermodynamically controlled syntheses often involve cumbersome procedures and limited structural precision. We report a nonequilibrium transient assembly strategy for the ultrafast synthesis of intricately structured nanocatalysts, including core-shell platinum (Pt)-skinned intermetallic nanocrystals exemplified by Pt@PtFe-i. By using a periodic thermal-pulse protocol to drive the continuous evolution of high-energy transient PtFe configurations, we achieved the synchronous assembly of a high-order PtFe intermetallic core and an atomic-layer-precise Pt skin. The Pt@PtFe-i catalyst exhibits coordination-dependent compressive strain within the Pt skin, creating a high density of highly active sites for the oxygen reduction reaction. The H₂-air fuel cell with Pt@PtFe-i delivers a peak power of 1.25 watts per square centimeter at a cathode Pt loading of 0.1 milligrams per square centimeter, with a small peak power loss of 3.2% after 30,000 accelerated durability testing cycles.

『摘要』 高效催化剂需要精确设计的复杂结构，然而传统的热力学控制合成方法通常涉及繁琐的程序且结构精度有限。我们报告了一种非平衡瞬态组装策略，可用于超快速合成结构复杂的纳米催化剂，包括以Pt@PtFe-i为例的核壳铂（Pt）包覆金属间化合物纳米晶。通过采用周期性热脉冲方案驱动高能瞬态PtFe构型的持续演变，我们实现了高阶PtFe金属间化合物核与原子层级精确的Pt壳的同步组装。Pt@PtFe-i催化剂在Pt壳内表现出配位依赖的压缩应变，为氧还原反应产生了大量高活性位点。使用Pt@PtFe-i的氢-空气燃料电池在阴极铂负载量为每平方厘米0.1毫克时，峰值功率可达每平方厘米1.25瓦，且在30,000次加速耐久性测试循环后，峰值功率损失仅为3.2%。

『总结』 本文报告了一种非平衡瞬态组装策略，可超快速合成复杂结构纳米催化剂，以Pt@PtFe-i为例，实现了高阶金属间化合物核与精确Pt壳的同步组装，该催化剂在氧还原反应中有大量高活性位点，使用其的氢-空气燃料电池性能良好且耐久性佳。

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49. 不依赖降解子（Degron）的KAT2A招募扩大了CRBN分子胶的作用靶点范围

Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues

Ojeda S, Wang M, Baek K, ... , Donovan KA, Armstrong SA, Fischer ES.; science; (393, 6807)

『Abstract』Lysine acetyltransferases (KATs) cooperate with oncogenes such as c-Myc, estrogen receptor, and lysine methyltransferase 2A (KMT2A) fusions to sustain malignant programs. Targeting of KAT proteins has shown clinical efficacy; however, achieving homolog selectivity for most KATs remains a major challenge. By extending cereblon (CRBN)-based molecular glues beyond the canonical degron space, we developed an exquisitely selective degrader of KAT2A. Cryo-electron microscopy revealed that CRBN recruits KAT2A independently of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Selective KAT2A degradation leads to potent ablation of histone H3 lysine 9 acetylation (H3K9Ac), antiproliferative effects in acute myeloid leukemia cell lines, and in vivo efficacy in a patient-derived xenograft model, establishing KAT2A as a targetable vulnerability to treat a wide range of malignancies. More generally, degron-independent recruitment extends the CRBN-targetable proteome.

『摘要』 赖氨酸乙酰转移酶（KATs）与c-Myc、雌激素受体和赖氨酸甲基转移酶2A（KMT2A）融合等癌基因协同作用，维持恶性程序。针对KAT蛋白的治疗已显示出临床疗效；然而，对于大多数KATs实现同源选择性仍是一个主要挑战。通过将基于cereblon（CRBN）的分子胶扩展到经典降解子空间之外，我们开发了一种高度选择性的KAT2A降解剂。冷冻电子显微镜显示，CRBN无需降解子即可招募KAT2A；相反，该分子胶通过与表面暴露的酪氨酸结合，模拟抗体样分子识别。选择性降解KAT2A可有效消除组蛋白H3赖氨酸9乙酰化（H3K9Ac），抑制急性髓系白血病细胞系的增殖，并在患者来源的异种移植模型中显示出体内疗效，证实KAT2A是治疗多种恶性肿瘤的可靶向弱点。更广泛地说，不依赖降解子的招募扩展了CRBN可靶向的蛋白质组。

『总结』 通过扩展基于CRBN的分子胶作用机制，开发出选择性KAT2A降解剂，可有效抑制白血病细胞增殖并验证其体内疗效，同时拓展了CRBN可靶向的蛋白质组范围。

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50. 单个冷冻循环可改变铁矿物的转化过程

A single freeze cycle redirects iron mineral transformation

Luo T, Chen T, Bui Thi TM, ... , Hetherington C, Hanna K, Boily JF.; science; (393, 6807)

『Abstract』Polycrystalline ice formation concentrates mineral nanoparticles into liquid boundaries between growing ice crystals. Here we show that minutes of freezing dictate iron mineral fate over subsequent months of aqueous aging. A single freeze-thaw cycle irreversibly aggregates ferrihydrite through converging physical and chemical mechanisms. Freeze concentration collapses electrostatic barriers while cryosuction strips hydration layers and compresses nanoparticles into micrometer-scale planar aggregates. Chemical evidence points to interfacial (hydr)oxo bridging, alongside hydrogen bonding, that resists disaggregation. These mechanisms lock nanoparticles into mesocrystal-like assemblages that retain their nanoscale identity but inhibit dissolution-reprecipitation to goethite, instead favoring solid-state transformation to hematite. Ice formation thus acts as a geochemical reactor, driving aggregation and interfacial bonding that redirect iron speciation, with broad implications for nutrient cycling and carbon preservation across the cryosphere.

『摘要』 多晶冰的形成会将矿物纳米颗粒集中到正在生长的冰晶之间的液态边界中。在此，我们表明，几分钟的冻结决定了铁矿物在随后数月的水相老化过程中的命运。单个冻融循环通过融合的物理和化学机制使水铁矿发生不可逆的聚集。冻结浓缩会破坏静电屏障，而冷冻抽吸会剥离水化层，并将纳米颗粒压缩成微米级的平面聚集体。化学证据表明，存在界面（羟基）氧桥键以及氢键，可抵抗解聚。这些机制将纳米颗粒锁定在类介晶的集合体中，这些集合体保留了纳米级的特性，但抑制了向针铁矿的溶解 - 再沉淀过程，反而有利于向赤铁矿的固态转化。因此，冰的形成就像一个地球化学反应器，驱动聚集和界面键合，改变铁的物种分布，这对整个冰冻圈的营养物质循环和碳保存具有广泛影响。

『总结』 多晶冰形成使矿物纳米颗粒聚集，几分钟冻结决定铁矿物后续命运，单个冻融循环使水铁矿不可逆聚集，多种机制将纳米颗粒锁定为类介晶集合体，冰形成改变铁物种分布且影响冰冻圈物质循环和碳保存。

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51. CARM1表观遗传酶抑制癌症免疫中交叉呈递树突状细胞的功能

The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity

Zhang X, Xirenayi S, Zhao Y, ... , Van Allen EM, Mooney DJ, Wucherpfennig KW.; science; (393, 6807)

『Abstract』The cancer-immunity cycle requires cross-presenting type I conventional dendritic cells (cDC1s) that induce T cell-mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are currently inadequate. We found the epigenetic enzyme CARM1 (coactivator-associated arginine methyltransferase 1) to be a selective negative regulator of cancer antigen presentation by cDC1s but not cDC2s. Inactivation of the Carm1 gene promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors, and a CARM1 inhibitor enhanced cDC1-mediated priming of T cells by means of a cancer neoantigen vaccine. CARM1 inhibition increased chromatin accessibility at BATF3-Jun and RelA sites that are critical for cDC1 function and activation. Transforming growth factor-β regulated Carm1 expression, which suggests that CARM1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify CARM1 as a potential therapeutic target for enhancing the antitumor function of mouse and human cDC1s.

『摘要』 癌症免疫循环需要交叉呈递的I型经典树突状细胞（cDC1s）诱导T细胞介导的免疫反应，但目前增强肿瘤内cDC1功能的治疗策略尚不充分。我们发现表观遗传酶CARM1（共激活因子相关精氨酸甲基转移酶1）是cDC1（而非cDC2）呈递癌症抗原的选择性负调控因子。Carm1基因失活可促进cDC1的抗原交叉呈递、激活及肿瘤内聚集，而CARM1抑制剂通过癌症新抗原疫苗增强了cDC1介导的T细胞激活。CARM1抑制增加了BATF3-Jun和RelA位点的染色质可及性，这些位点对cDC1的功能和激活至关重要。转化生长因子-β调控Carm1的表达，这表明CARM1失活可在不改变cDC1稳态的情况下增强肿瘤内cDC1的功能。这些研究将CARM1确定为增强小鼠和人类cDC1抗肿瘤功能的潜在治疗靶点。

『总结』 CARM1是cDC1呈递癌症抗原的负调控因子，抑制CARM1可增强cDC1功能，是潜在的抗肿瘤治疗靶点。

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52. 不含铟的、具有氧化锡复合层和电极的钙钛矿/硅叠层太阳能电池

Indium-free perovskite/silicon tandem solar cells with tin oxide recombination layer and electrodes

Shi W, Wang S, Wang S, ... , Cheng Y, Yang X, Zhang X.; science; (393, 6807)

『Abstract』Indium-based transparent conductive oxides are widely used as electrodes and recombination layers in perovskite/silicon tandem solar cells, yet their scalability is constrained by indium scarcity and sputtering-induced damage. We report high-efficiency and stable indium-free perovskite/silicon tandem solar cells enabled by reactive plasma deposited tin oxide (RPD-SnO_x). For RPD-SnO_x as the recombination layer, we achieved a certified efficiency of 33.6%. Fully indium-free tandems that used RPD-SnO_x as both recombination layer and electrodes delivered a champion power conversion efficiency of 33.2% (1 square centimeter) and a minimodule with a certified efficiency of 31.0% (207.9 square centimeters). Dense and uniform self-assembled monolayer anchoring enabled by RPD-SnO_x suppressed nonradiative recombination and reduced halide migration. Indium-free minimodules exhibited high thermal, damp-heat, and outdoor operational stability and retained 65% of their maximum initial efficiency after 105 days of outdoor operation.

『摘要』 在钙钛矿/硅叠层太阳能电池中，铟基透明导电氧化物被广泛用作电极和复合层，但铟的稀缺性以及溅射造成的损伤限制了其可扩展性。我们报道了通过反应等离子体沉积氧化锡（RPD-SnO_x）制备的高效且稳定的无铟钙钛矿/硅叠层太阳能电池。当RPD-SnO_x用作复合层时，认证效率达到了33.6%。采用RPD-SnO_x同时作为复合层和电极的全无铟叠层电池，冠军功率转换效率为33.2%（1平方厘米），且一个微型组件的认证效率为31.0%（207.9平方厘米）。由RPD-SnO_x实现的致密均匀自组装单层锚定抑制了非辐射复合，减少了卤化物迁移。无铟微型组件展现出较高的热稳定性、湿热稳定性和户外运行稳定性，在户外运行105天后仍保持其初始最大效率的65%。

『总结』 通过反应等离子体沉积氧化锡（RPD-SnO_x）制备的无铟钙钛矿/硅叠层太阳能电池高效且稳定，全无铟叠层电池和微型组件均取得较高效率，无铟微型组件还展现出良好的稳定性。

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53. 激光相位板通过冷冻电镜技术改善小蛋白质的结构测定

Laser phase plate improves structure determination of small proteins by cryo-EM

Petrov PN, Zhang JT, Remis J, ... , Schnurr C, Glaeser RM, Muller H.; science; (393, 6807)

『Abstract』Phase plates can, in principle, overcome the poor image contrast in cryo-electron microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal and have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a modern, custom Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction and recovery of information from the early frames, as well as particle visualization, three-dimensional classification, and alignment. These advances use standard defocus ranges and reconstruction procedures but open the door to LPP-tailored protocols, offering further improvements by leveraging the LPP demonstrated here.

『摘要』 相位板原则上可以克服冷冻电子显微镜（cryo-EM）成像对比度低的问题，以及由此导致的小蛋白质结构重建的限制。然而，以往的设计并不稳定，影响了高分辨率信号，因此无法超越标准冷冻电镜所取得的成果。本研究中，我们在一台定制的现代Titan Krios显微镜上安装了激光相位板（LPP），通过改进样品运动校正、早期帧信息恢复以及颗粒可视化、三维分类和配准，提高了小蛋白质单颗粒重建的分辨率。这些进步采用了标准的离焦范围和重建程序，但为LPP定制方案开辟了道路，利用本文展示的LPP可实现进一步改进。

『总结』 激光相位板可克服冷冻电镜成像对比度低的问题，本研究将其安装于定制显微镜上提高了小蛋白质单颗粒重建分辨率，且为定制方案开辟道路。

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54. 由聚合驱动的自发组装产生的长程延伸链

Long-range extended chains arising from polymerization-driven spontaneous assembly

Chen M, Wang D, Zou Y, ... , Zhu Y, Di CA, Mei J.; science; (393, 6807)

『Abstract』A central challenge for conjugated polymers is to achieve long-range order while remaining solution processable, which is essential for matching the electrical performance of their counterparts of crystalline inorganic semiconductors. In this work, we show that n-doped poly(benzodifurandione) (n-PBDF) can undergo polymerization-driven spontaneous assembly (PSA), in which chain growth, chemical doping, and structural ordering are intrinsically coupled, yielding long-range chain extension over hundreds of nanometers. We reveal that the spontaneously formed n-PBDF nanoribbons arise from a self-initiated, convergent growth mechanism driven by cooperative monomer-polymer interactions and stabilized by proton-coupled duplex chains and the polymer's intrinsic polyelectrolyte character. With long-range extended chains in the nanoribbons, the aligned n-PBDF thin films demonstrate metallic-level conductivity (>10⁴ siemens per centimeter).

『摘要』 共轭聚合物面临的一个核心挑战是，在保持溶液可加工性的同时实现长程有序，这对于达到晶体无机半导体同类材料的电学性能至关重要。在本研究中，我们展示了n型掺杂聚苯并二呋喃二酮（n-PBDF）能够发生聚合驱动自发组装（PSA），其中链增长、化学掺杂和结构有序化是内在耦合的，可形成数百纳米级的长程链延伸。我们发现，自发形成的n-PBDF纳米带源于单体-聚合物协同作用驱动的自引发、收敛生长机制，并由质子耦合双链和聚合物固有的聚电解质特性稳定。纳米带中具有长程延伸链，对齐的n-PBDF薄膜表现出金属级电导率（>10⁴ 西门子/厘米）。

『总结』 本研究展示了n-PBDF的聚合驱动自发组装过程，实现了长程有序和溶液可加工性，其纳米带薄膜表现出金属级电导率。

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55. LEF1和微环境因子共同决定慢性疾病中T细胞的干性

LEF1 and niche factors determine T cell stemness across chronic diseases

Miakicheva S, Hawley KM, Zumbo P, ... , Maillard I, Betel D, Schietinger A.; cell; (189, 14)

『Abstract』In settings of persistent (self or foreign) antigen, such as autoimmunity and chronic infection, immune responses are sustained by stem-like T cells. Although TCF1 has emerged as a key transcription factor (TF) associated with stemness, the TCF1^hi population is heterogeneous, raising the question of whether TCF1 exclusively defines the stem T cell (T_SC) pool. Using preclinical models of autoimmune type 1 diabetes and chronic infection, we discover that a small subset of TCF1^hi T cells express the TF LEF1. LEF1⁺ TCF1^hi T cells define a true self-renewing T_SC pool. T_SC give rise to LEF1^- TCF1^hi progenitor T cells (T_PRO), which lack stem functions and generate terminally differentiated TCF1^lo T cells (T_DIFF) (T_SC→T_PRO→T_DIFF). We show that LEF1 is essential for T cell stemness. Autoimmune and exhausted LEF1⁺ T_SC share a unique epigenetically encoded core program enriched for genes and pathways characteristic of embryonic and adult stem cells, including WNT/β-catenin and Notch signaling. Spatial positioning, niche signals, and migration regulate stem-cell fate; accordingly, targeting integrins or Notch signaling impairs T cell stemness and prevents disease. Our studies identify LEF1 and niche-derived factors as fundamental regulators of T cell stemness across chronic diseases.

『摘要』 在自身免疫性疾病和慢性感染等存在持续（自身或外来）抗原的环境中，免疫反应由干细胞样T细胞维持。尽管TCF1已成为与干细胞特性相关的关键转录因子，但TCF1^hi细胞群具有异质性，这就引发了一个问题，即TCF1是否唯一定义了干细胞样T细胞（T_SC）池。利用自身免疫性1型糖尿病和慢性感染的临床前模型，我们发现一小部分TCF1^hi T细胞表达转录因子LEF1。LEF1⁺ TCF1^hi T细胞定义了真正的自我更新T_SC池。T_SC会产生缺乏干细胞功能的LEF1^- TCF1^hi祖代T细胞（T_PRO），并进一步产生终末分化的TCF1^lo T细胞（T_DIFF）（T_SC→T_PRO→T_DIFF）。研究表明，LEF1对T细胞干细胞特性至关重要。自身免疫性和耗竭的LEF1⁺ T_SC共享一个独特的表观遗传编码核心程序，该程序富含胚胎和成体干细胞特征性的基因和通路，包括WNT/β-连环蛋白和Notch信号通路。空间定位、微环境信号和迁移调控干细胞命运；相应地，靶向整合素或Notch信号通路会损害T细胞干细胞特性并预防疾病。本研究发现LEF1和微环境衍生因子是慢性疾病中T细胞干细胞特性的基本调控因子。

『总结』 在自身免疫和慢性感染中，LEF1⁺ TCF1^hi T细胞定义了真正的自我更新T_SC池，LEF1是T细胞干细胞特性的关键调控因子，且LEF1⁺ T_SC共享独特的表观遗传编码核心程序，靶向整合素或Notch信号通路可调控T细胞干细胞特性并预防疾病。

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56. 对20个纳莱迪人（Homo naledi）牙齿珐琅质的蛋白质组分析未发现男性标志物

Proteomic analysis of dental enamel from 20 Homo naledi individuals shows no male markers

Madupe PP, Taurozzi AJ, Koenig C, ... , Hawks J, Berger L, Cappellini E.; cell; (189, 14)

『Abstract』The Rising Star cave system excavations resulted in a high number of well-preserved skeletal specimens from multiple individuals of Homo naledi, showing a high degree of morphological homogeneity, including dental variation possibly consistent with a single-sex sample. Here, we report the paleoproteomic analysis of dental enamel proteins extracted via micro-destructive acid etching from 23 H. naledi specimens belonging to a minimum of 20 individuals. After excluding the possibility of technical bias, no convincing evidence supporting the confident identification of male individuals was detected in any of the investigated samples. We also detect no variability in the recovered proteome, and we observe two amino acid substitutions: a derived one in amelogenin X compared with Homo, and an ancestral one in COL17A1, also present in Paranthropus robustus. Our results further support the homogeneity of H. naledi fossils and show how to sustainably investigate extinct hominins.

『摘要』 对“新星洞穴系统”的挖掘发现了大量保存完好的纳莱迪人骨骼标本，这些标本来自多个个体，显示出高度的形态同质性，包括牙齿变异可能与单性别样本一致。本研究报告了从属于至少20个个体的23个纳莱迪人标本中，通过微破坏性酸蚀法提取的牙釉质蛋白质的古蛋白质组学分析结果。在排除了技术偏差的可能性后，在所有研究的样本中均未发现支持可靠鉴定男性个体的确凿证据。我们还发现，所回收的蛋白质组没有变异性，并观察到两种氨基酸替换：与智人相比，釉原蛋白X中的一种衍生替换，以及COL17A1中的一种祖先替换，后者也存在于粗壮傍人中。我们的研究结果进一步支持了纳莱迪人化石的同质性，并展示了如何可持续地研究已灭绝的人族。

『总结』 对纳莱迪人化石牙釉质蛋白质的古蛋白质组学分析未发现确凿证据支持男性个体的存在，且蛋白质组无变异性，研究结果进一步支持了其化石的同质性，并展示了可持续研究已灭绝人族的方法。

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57. 用于流感研究功能基因组学的CRISPR基因敲除小鼠库

A CRISPR knockout mouse library for functional genomics in influenza research

Ueki H, Tomita Y, Duong C, ... , Yoshida N, Watanabe T, Kawaoka Y.; cell; (189, 14)

『Abstract』Functional validation of host factors in whole-animal models is a major bottleneck in virology; it hinders the translation of data from in vitro studies into a deeper understanding of the viral life cycle and pathogenesis. To address this challenge, we developed a systematic in vivo screening platform for influenza A virus. This platform comprises a library of 84 CRISPR-Cas9-generated gene-modified mouse lines targeting host factors prioritized from the literature and in vitro small interfering RNA (siRNA) screening studies. Using this resource, we identified 17 host factors whose genetic ablation conferred resistance to influenza A virus infection. Further studies of two of these factors, Arhgef28 and Lasp1, revealed distinct protective mechanisms against influenza A virus. We offer this mouse library to the research community as a powerful platform for studying virus-host interactions in a physiologically relevant context.

『摘要』 在全动物模型中对宿主因子进行功能验证是病毒学研究中的一个主要瓶颈；它阻碍了将体外研究数据转化为对病毒生命周期和发病机制的更深入理解。为应对这一挑战，我们开发了甲型流感病毒的体内系统性筛选平台。该平台包括一个由84个CRISPR-Cas9基因编辑小鼠品系组成的文库，这些品系针对的是从文献和体外小干扰RNA（siRNA）筛选研究中筛选出的宿主因子。利用这一资源，我们确定了17个基因敲除后能赋予对甲型流感病毒感染抵抗力的宿主因子。对其中两个因子Arhgef28和Lasp1的进一步研究揭示了它们对抗甲型流感病毒的不同保护机制。我们将这个小鼠文库提供给研究界，作为在生理相关背景下研究病毒与宿主相互作用的有力平台。

『总结』 为应对全动物模型中宿主因子功能验证的挑战，研究团队开发了甲型流感病毒体内系统性筛选平台，确定了17个可赋予对甲型流感病毒感染抵抗力的宿主因子，并揭示了其中两个因子的不同保护机制，该小鼠文库可作为研究病毒与宿主相互作用的有力平台。

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58. 基于组织病理学的细胞结构与邻域信息虚拟空间肿瘤图谱分析

Cellular architecture and neighborhood-informed virtual spatial tumor profiling from histopathology

Li Y, Li Z, Quinton R, ... , Neal J, Diehn M, Li R.; cell; (189, 14)

『Abstract』The tumor microenvironment (TME) critically shapes disease progression and therapeutic resistance. However, a comprehensive understanding of its spatial architecture remains elusive, and clinical translation is challenging. Here, we present cellular architecture and neighborhood-informed virtual AI-driven spatial profiling (CANVAS), an artificial intelligence platform that infers tumor ecological habitats from hematoxylin and eosin (H&E) histopathology. Built on an atlas of over 18 million cells profiled by 41-plex spatial proteomics across 457 patients with non-small cell lung cancer, CANVAS establishes 10 reproducible cellular neighborhoods (CNs) capturing conserved spatial organization of the TME. Through multimodal alignment and foundation-model-based morphological encoding, CANVAS predicts CN-anchored habitat structures from H&E slides and enables clinical evaluation in over 5,000 patients spanning 9 cancer types. Across patient cohorts, CANVAS supports prognostic modeling, spatial ecotype stratification, and immunotherapy outcome prediction. These results establish CANVAS as a clinically scalable platform for spatial profiling, bridging single-cell analysis to population-level insight and enabling precision oncology.

『摘要』 肿瘤微环境（TME）对疾病进展和治疗抵抗具有关键作用。然而，目前对其空间结构的全面理解仍难以实现，临床转化也颇具挑战性。在此，我们提出细胞结构与邻域信息驱动的虚拟人工智能空间分析（CANVAS），这是一个利用苏木精-伊红（H&E）组织病理学推断肿瘤生态栖息地的人工智能平台。CANVAS基于由41重空间蛋白质组学对457例非小细胞肺癌患者进行剖析、包含超过1800万个细胞的图谱，确立了10种可重复的细胞邻域（CNs），这些邻域捕捉到了TME中保守的空间结构。通过多模态对齐和基于基础模型的形态编码，CANVAS可从H&E切片预测以CN为中心的栖息地结构，并在涵盖9种癌症类型、超过5000名患者的群体中进行临床评估。在不同患者队列中，CANVAS支持预后建模、空间生态型分层和免疫治疗结果预测。这些结果证实了CANVAS作为一个可临床扩展的空间分析平台，将单细胞分析与群体层面的洞察相结合，助力精准肿瘤学发展。

『总结』 CANVAS是一个人工智能平台，可基于H&E切片推断肿瘤生态栖息地，支持预后建模、空间生态型分层和免疫治疗结果预测，助力精准肿瘤学发展。

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