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Divergent stem cell mechanisms govern the primary body axis and appendage regeneration in the axolotl 不同的干细胞机制支配着美西螈的主体轴和附属物再生

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.adx5697

Liqun Wang, Li Song, Chao Yi, Jing Zhou, Zhouying Yong, Yan Hu, Xiangyu Pan, Na Qiao, Hao Cai, Wandong Zhao, Rui Zhang, Lieke Yang, Lei Liu, Guangdun Peng, Elly M. Tanaka, Hanbo Li, Yanmei Liu, Ji-Feng Fei

Exploring the fundamental mechanisms of organ regeneration is crucial for advancing regenerative medicine. The axolotl tail represents an opportunity to study regeneration of the primary axis including segmented muscle, vertebrae, and skin. During tail development, muscle stem cells (MuSCs) displayed expected specificity to the muscle lineage. Tail amputation, however, induced expansion of MuSC potential yielding clonal contribution to muscle, connective tissue including cartilage, pericytes, and fibroblasts. This expanded potential was not observed during limb regeneration, and cross-transplantation showed that these differences in potential are likely intrinsically determined. Single-cell RNA sequencing profiling revealed that tail MuSCs revert to an embryonic mesoderm–like state. Through genetic manipulation involving the overexpression of constitutively active transforming growth factor–β (TGF-β) receptors or Smad7 (antagonist of TGF-β signaling) in MuSCs, we demonstrated that the levels of TGF-β signal determine the fate outcome of MuSCs to connective tissue lineage or muscle, respectively. Our findings illustrate that variation in MuSCs may represent a fundamental difference between regeneration of primary axis versus appendage.

探索器官再生的基本机制是推动再生医学发展的关键。蝾螈的尾巴代表了一个研究主轴再生的机会，包括分段肌肉、椎骨和皮肤。在尾巴发育过程中，肌肉干细胞（MuSCs）表现出预期的肌肉谱系特异性。然而，尾巴截肢诱导MuSC潜力扩增，产生克隆贡献给肌肉、结缔组织，包括软骨、周细胞和成纤维细胞。在肢体再生过程中没有观察到这种扩大的电位，交叉移植表明这些电位的差异可能是内在决定的。单细胞RNA测序分析显示，尾部musc恢复到胚胎中胚层样状态。通过在musc中过度表达构成型活性转化生长因子-β (TGF-β)受体或Smad7 （TGF-β信号拮抗剂）的遗传操作，我们证明TGF-β信号的水平分别决定了musc向结缔组织系或肌肉的命运结局。我们的研究结果表明，musc的变异可能代表了主轴和附属物再生之间的根本差异。

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引用次数: 0

Resolving emergent transient oscillations in gene circuits with a growth-coupled model 用生长耦合模型求解基因回路中的瞬态振荡

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.adz2310

Hari R. Namboothiri, Ayush Pandey, Chelsea Y. Hu

Synthetic gene circuits often behave unpredictably in batch cultures, where shifting physiological states are rarely accounted for in conventional models. Here, we find that degradation-tagged protein reporters could exhibit transient oscillatory expression, which standard single-scale models do not capture. We resolve this discrepancy by developing Gene Expression Across Growth Stages (GEAGS), a dual-scale modeling framework that explicitly couples intracellular gene expression to logistic population growth. Using a chemical reaction network model with growth phase–dependent rate-modifying functions, GEAGS accurately reproduces the observed transient oscillations and identifies amino acid recycling and growth-phase transition as key drivers. We reduce the model to an effective form for practical use and demonstrate its adaptability by applying it to layered feedback circuits, resolving long-standing mismatches between model predictions and measured dynamics. These results establish GEAGS as a generalizable platform for predicting emergent behaviors in synthetic gene circuits and underscore the importance of multiscale modeling for robust circuit design in dynamic environments.

在批量培养中，合成基因回路的行为通常是不可预测的，而在常规模型中，生理状态的变化很少被考虑在内。在这里，我们发现降解标记的蛋白质报告可以表现出短暂的振荡表达，这是标准的单尺度模型所不能捕捉到的。我们通过开发跨生长阶段基因表达（GEAGS）来解决这一差异，这是一个双尺度建模框架，明确地将细胞内基因表达与逻辑种群增长相结合。利用具有生长相依赖的速率修正函数的化学反应网络模型，GEAGS准确地再现了观察到的瞬态振荡，并确定了氨基酸循环和生长相转变是关键驱动因素。我们将模型简化为实际使用的有效形式，并通过将其应用于分层反馈电路来证明其适应性，解决了模型预测与测量动态之间长期存在的不匹配。这些结果建立了GEAGS作为预测合成基因电路紧急行为的通用平台，并强调了动态环境下多尺度建模对鲁棒电路设计的重要性。

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引用次数: 0

Climate, ecological dynamics, and the seasonal distribution of birds in mountains 山区气候、生态动态与鸟类季节分布

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.adz5547

Marius Somveille, Benjamin G. Freeman, Frank A. La Sorte, Mao-Ning Tuanmu

Biodiversity is unevenly distributed along elevational gradients. The predominant hypothesis is that macroevolutionary dynamics and climatic niche conservatism explain today’s elevational patterns of biodiversity, but the alternative energy efficiency hypothesis emphasizes modern ecological interactions related to energy budgets. We test these competing hypotheses by examining seasonal elevational ranges for 10,998 bird populations in 34 mountain regions. Multiple lines of evidence support the energy efficiency hypothesis, including that many mountain birds do not seasonally track their thermal niche with high fidelity while simulation models based on optimal energy balancing under current environmental conditions yield predictions that tightly match empirical data. Our results reveal that altitudinal migration, which is widespread yet considerably understudied, is a behavioral mechanism fulfilling the same ecological function as long-distance latitudinal migration. Overall, this work provides a better understanding and predictive capacity for mountain birds under global change.

生物多样性沿海拔梯度分布不均匀。主流假说认为宏观进化动力学和气候生态位保守性解释了当今生物多样性的海拔格局，但替代能源效率假说强调与能源预算相关的现代生态相互作用。我们通过研究34个山区10,998个鸟类种群的季节性海拔范围来检验这些相互矛盾的假设。多种证据支持能量效率假说，包括许多山鸟不能高保真地跟踪它们的热生态位，而基于当前环境条件下最佳能量平衡的模拟模型产生的预测与经验数据紧密匹配。研究结果表明，海拔迁移是一种与长距离纬度迁移具有相同生态功能的行为机制，尽管海拔迁移是一种广泛存在但尚未得到充分研究的行为机制。总体而言，本研究为全球变化下的山地鸟类提供了更好的认识和预测能力。

引用次数: 0

Expansive spatial pattern of Aβ deposition in patients with cerebral amyloid angiopathy: A three-dimensional surface-to-depth analysis 脑淀粉样血管病患者Aβ沉积的扩张空间模式：三维表面-深度分析

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.aea7539

Hideki Hayashi, Rie Saito, Akinori Miyashita, Takeshi Ikeuchi, Mari Tada, Kohei Akazawa, Osamu Onodera, Kazuki Tainaka, Akiyoshi Kakita

Cerebral amyloid angiopathy (CAA) is a neurodegenerative condition characterized by amyloid-β (Aβ) deposition in small vessel walls, often coexisting with Alzheimer’s disease due to impaired Aβ clearance. However, the spatial distribution of Aβ within the human brain remains unclear as the vascular network’s complexity and scale hinder visualization by conventional thin-slice analysis. To address this, we performed three-dimensional (3D) volumetric imaging of the cerebrovascular network and Aβ deposition in autopsied brains with CAA using advanced tissue clearing and light-sheet fluorescence microscopy, labeling for smooth muscle actin (SMA) and Aβ. We found prominent Aβ deposition and SMA loss in leptomeningeal and superficial cortical segments, which were anatomically contiguous with deeper Aβ-positive segments, indicating a surface-to-deep progression pattern of Aβ extension. The perivascular plaque density was significantly lower around Aβ-positive vessels. This technology may provide further insights into CAA pathology and is recommended for research on the 3D pathology of neurological disorders.

脑淀粉样血管病（CAA）是一种以淀粉样蛋白β (a β)沉积在小血管壁为特征的神经退行性疾病，由于a β清除受损，常与阿尔茨海默病共存。然而，由于血管网络的复杂性和规模阻碍了传统薄层分析的可视化，Aβ在人脑中的空间分布仍然不清楚。为了解决这一问题，我们使用先进的组织清除和光片荧光显微镜对尸检大脑中的脑血管网络和Aβ沉积进行了三维（3D）体积成像，并标记了平滑肌肌动蛋白（SMA）和Aβ。我们发现，在与更深的a β阳性节段解剖学上相邻的轻脑膜和皮层浅表节段中，a β沉积和SMA丢失明显，表明a β延伸的表面到深度的进展模式。a β阳性血管周围斑块密度明显降低。该技术可以为CAA病理学提供进一步的见解，并推荐用于神经疾病的3D病理学研究。

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引用次数: 0

Electrically pumped single-mode microlasers with omnidirectional radiation for optical broadcasting communication 光广播通信用全向辐射电泵单模微激光器

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.aeb1682

Feifan Xu, Jushi Liu, Yimeng Sang, Tao Tao, Junlong Kou, Jianping Liu, Ting Zhi, Zhe Zhuang, Rong Zhang, Bin Liu

Semiconductor whispering gallery mode (WGM)–visible microlasers are promising compact, on-chip light sources for high-speed visible-light communication due to their small footprints, high Q factors, and in-plane emission. However, achieving fabrication robustness, precise mode selection, narrow linewidths, and low thresholds for WGM-visible microlasers remains challenging. Here, we report a scalable strategy to fabricate continuous-wave, electrically pumped WGM blue microlasers based on III-nitride semiconductors with low threshold current densities and high slope efficiencies across diverse diameters from 10 to 160 micrometers. This high performance was achieved through effective vertical optical confinement by the waveguide structures and minimal sidewall scattering from atomically smooth surfaces. We further converted the laser cavity from a microdisk to a microring, which suppresses high-order WGMs and allows for single-mode operation with a high Q factor of 17,066. The omnidirectional in-plane radiation of WGM microlasers demonstrates angle-independent, high-modulation bandwidths, enabling synchronous broadcasting communication with high data transmission rates.

半导体窃窃廊模式(WGM) -可见微激光器由于其占地面积小、Q因子高、面内发射等优点，是一种很有前途的紧凑片上光源，可用于高速可见光通信。然而，实现wgm -可见微激光器的制造鲁棒性、精确的模式选择、窄线宽和低阈值仍然具有挑战性。在这里，我们报告了一种可扩展的策略来制造基于iii -氮化物半导体的连续波，电泵浦WGM蓝色微激光器，具有低阈值电流密度和高斜率效率，直径从10到160微米不等。这种高性能是通过波导结构的有效垂直光约束和原子光滑表面的最小侧壁散射来实现的。我们进一步将激光腔从微盘转换为微环，这抑制了高阶wgm，并允许单模工作，高Q因子为17066。WGM微激光器的全向面内辐射具有与角度无关的高调制带宽，可实现具有高数据传输速率的同步广播通信。

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引用次数: 0

Bacterial metabolic remodeling by convergent evolution unlocks nutrient availability after a host switch 通过趋同进化的细菌代谢重塑打开了宿主转换后的营养可利用性

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.adw9419

Amy C. Pickering, Jamie Gorzynski, Grace Taylor-Joyce, Rhodri Evans, Willow Fox, Pedro Melo, Joana Alves, Hannah Schlauch, Fiona Sargison, Gonzalo Yebra, Natalie Ring, J. Ross Fitzgerald

New pathogens typically arise from host jump events between species. Staphylococcus aureus is a multihost pathogen responsible for a global burden of human disease and a leading cause of intramammary infection in dairy cattle. Here, we demonstrate that following historical human-to-bovine host switch events, S. aureus has undergone adaptive metabolic remodeling in response to distinct nutrient availability in the dairy niche. In particular, we found that bovine S. aureus has evolved the capacity for protease-mediated degradation of casein, a protein abundant in bovine milk, to access nutrients for proliferation. This phenotype has evolved convergently in different S. aureus lineages via mutations in distinct gene loci driving overexpression of the protease aureolysin. Together, we have dissected a key host-adaptive trait, which facilitates the enzymatic release of nutrients from a substrate specific to the new host milieu. These findings highlight the remarkable evolutionary plasticity of a major bacterial pathogen underpinning its multihost species tropism.

新的病原体通常是由物种之间的宿主跳跃事件引起的。金黄色葡萄球菌是一种多宿主病原体，造成全球人类疾病负担，也是奶牛乳腺内感染的主要原因。在这里，我们证明了在人类到牛宿主的历史转换事件之后，金黄色葡萄球菌经历了适应性代谢重塑，以响应奶牛生态位中不同的营养可用性。特别是，我们发现牛金黄色葡萄球菌已经进化出蛋白酶介导的酪蛋白降解能力，酪蛋白是牛乳中丰富的蛋白质，可以获得增殖所需的营养物质。这种表型在不同的金黄色葡萄球菌谱系中通过不同基因位点的突变驱动蛋白酶金溶素的过度表达而趋同进化。我们共同剖析了一个关键的宿主适应特性，该特性促进了新宿主环境特异性底物中营养物质的酶促释放。这些发现突出了一种主要细菌病原体的显著进化可塑性，支撑了它的多宿主物种趋向性。

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引用次数: 0

A near-complete map of human cytosolic degrons and their relevance for disease 近乎完整的人类细胞质退化图及其与疾病的相关性

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.adz3483

Vasileios Voutsinos, Kristoffer E. Johansson, Fia B. Larsen, Martin Grønbæk-Thygesen, Nicolas Jonsson, Emma Holm-Olesen, Giulio Tesei, Amelie Stein, Douglas M. Fowler, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen

Degrons are short protein segments that direct proteins for degradation via the ubiquitin-proteasome system, ensuring the removal of signaling proteins and clearance of misfolded proteins. We have performed a large-scale screen of more than 200,000 30-residue peptides from more than 5000 human cytosolic proteins, achieving 99.7% coverage. We find that 19% of peptides act as strong degrons, 30% as intermediate, and 51% as non-degrons. We identify both known and previously unidentified degradation signals and show that most depend on the E1 ubiquitin-activating enzyme and the proteasome. Structural mapping shows that many degrons are buried and likely become active upon protein unfolding. Training of a machine learning model allowed us to describe the degron properties and predict the cellular abundance of missense variants that operate by forming degrons in exposed and disordered protein regions, thus providing a mechanism of pathogenicity for germline coding variants at such positions.

Degrons是一种短的蛋白质片段，通过泛素-蛋白酶体系统指导蛋白质降解，确保信号蛋白的去除和错误折叠蛋白的清除。我们已经从5000多种人类细胞质蛋白中对超过20万个30残基肽进行了大规模筛选，覆盖率达到99.7%。我们发现19%的肽作为强肽，30%作为中间肽，51%作为非肽。我们鉴定了已知的和以前未鉴定的降解信号，并表明大多数依赖于E1泛素激活酶和蛋白酶体。结构图显示许多退化被掩埋，并可能在蛋白质展开时变得活跃。机器学习模型的训练使我们能够描述度子特性，并预测通过在暴露和无序的蛋白质区域形成度子而起作用的错义变异的细胞丰度，从而为这些位置的种系编码变异提供了一种致病性机制。

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引用次数: 0

Critical quantum metrology robust against dissipation and nonadiabaticity 抗耗散和非绝热的临界量子计量学

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.ady2358

Jia-Hao Lü, Wen Ning, Fan Wu, Ri-Hua Zheng, Ken Chen, Xin Zhu, Zhen-Biao Yang, Huai-Zhi Wu, Shi-Biao Zheng

Critical systems near quantum phase transitions were predicted to be useful for improvement of metrological precision, thanks to their ultrasensitive response to tiny variations of the control Hamiltonian. However, realizing criticality enhanced quantum metrology is experimentally challenging, mainly owing to decoherence and critical slowing down associated with the corresponding quantum state preparation. We circumvent these problems by making use of the critical behaviors in the Jaynes-Cummings model, to which the signal field is coupled. The information is encoded in the qubit’s excitation number, which displays a divergent changing rate at the critical point, and is extremely robust against decoherence and nonadiabatic effects. We demonstrate such a metrological protocol in a superconducting circuit, where an Xmon qubit, interacting with a resonator, is used as a probe for estimating the amplitude of a microwave field. The measured quantum Fisher information exhibits a critical quantum enhancement, confirming the potential for quantum metrology.

由于临界系统对控制哈密顿量的微小变化具有超灵敏的响应，预测其在量子相变附近的临界系统有助于提高计量精度。然而，实现临界增强量子计量在实验上具有挑战性，主要是由于与相应量子态制备相关的退相干和临界慢化。我们利用信号场耦合的Jaynes-Cummings模型中的关键行为来规避这些问题。该信息编码在量子比特的激发数中，在临界点处表现出发散的变化率，并且对退相干和非绝热效应具有极强的鲁棒性。我们在超导电路中演示了这样的计量协议，其中Xmon量子比特与谐振器相互作用，用作估计微波场振幅的探头。被测量的量子费雪信息显示出一个关键的量子增强，证实了量子计量学的潜力。

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引用次数: 0

Three-dimensional printing of nanomaterials-based electronics with a metamaterial-inspired near-field electromagnetic structure 基于纳米材料的电子学三维打印与超材料启发的近场电磁结构

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.adz7415

Jian Teng, Samuel H. Hales, Xin Yang, Jared Anklam, Saebom Lee, Yu Liu, Dwipak Prasad Sahu, Leibin Li, Cordelia Latham, Xi Tian, Derrick Wong, Taylor E. Greenwood, John S. Ho, Yong Lin Kong

Three-dimensional (3D) printing can create freeform architectures and electronics with unprecedented versatility. However, the full potential of electronic 3D printing has so far been limited by the inability to selectively anneal the printed materials, especially on temperature-sensitive substrates. Here, we achieve highly selective and rapid volumetric heating of 3D-printed nanomaterials and polymers in situ by focusing microwaves using a metamaterial-inspired near-field electromagnetic structure (Meta-NFS). In contrast to previous work, the Meta-NFS achieves the spatial resolution and power density needed to 3D print freeform microstructures where the electronic and mechanical properties can be locally programmed even within optically opaque materials. By broadening the material palettes compatible with 3D printing, near-field microwave 3D printing with Meta-NFS enables classes of electronics that are otherwise challenging to create.

三维（3D）打印可以创建具有前所未有的多功能性的自由结构和电子产品。然而，到目前为止，电子3D打印的全部潜力受到无法选择性退火打印材料的限制，特别是在温度敏感的基材上。在这里，我们通过使用超材料启发的近场电磁结构（Meta-NFS）聚焦微波，实现了3d打印纳米材料和聚合物的高选择性和快速体积加热。与之前的工作相比，Meta-NFS实现了3D打印自由微结构所需的空间分辨率和功率密度，即使在光学不透明的材料中，电子和机械性能也可以局部编程。通过扩大与3D打印兼容的材料调色板，使用Meta-NFS的近场微波3D打印使其他具有挑战性的电子产品类别成为可能。

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引用次数: 0

Electrochemically deuterated silane synthesis with D2O 用d2o电化学合成氘化硅烷

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances

Pub Date : 2026-02-06 DOI: 10.1126/sciadv.aeb7677

Chao Gao, Min Liu, Youai Qiu

Deuterium-labeled silanes are of great significance in organic synthesis and drug discoveries, yet obtaining versatile deuterated silanes efficiently and selectively under electrochemical conditions using green deuterium sources remains enormously challenging. Herein, facile and general electrochemical deuteration of silanes using D₂O as the economical deuterium source was reported. A variety of alkyl- and aryl-substituted silanes can be smoothly converted into the corresponding products with excellent levels of deuterium incorporation and yields. Furthermore, this protocol enables 10-gram-scale preparation under high current conditions, underscoring the potential in industry applications. Mechanistic studies have revealed that a catalytic amount of nickel may form a pivotal silicon-nickel intermediate, reversing the polarity of silicon and thereby facilitating the subsequent reactions.

氘标记硅烷在有机合成和药物发现中具有重要意义，但在电化学条件下，利用绿色氘源高效、选择性地获得多功能氘化硅烷仍然是一个巨大的挑战。本文报道了用d2o作为经济的氘源对硅烷进行简单、通用的电化学脱氢。各种烷基和芳基取代的硅烷可以顺利转化为相应的产品，具有优异的氘掺入率和产率。此外，该协议能够在高电流条件下进行10克规模的制备，强调了工业应用的潜力。机理研究表明，催化量的镍可以形成关键的硅-镍中间体，逆转硅的极性，从而促进后续反应。

引用次数: 0

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