| 《科学》（20260430出版）一周论文导读 |
编译|李言
Science,科学 30 April 2026, Volume 392 Issue 6797
《科学》2026年4月30日 ，第392卷 ，出版6797期
化学Chemistry
Precision indole skeletal editing for single-carbon replacement
精准编辑吲哚骨架完成单碳置换
▲ 作者 ：Ling Zhang,周论 Yatao Lang, Zhen Luo, Xinlong Han et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.aec3587
▲摘要 ：
吲哚普及存在于药物和天然产品中。研究者展示了色胺衍生物的文导一种分子内骨架编辑回响 。该回响经由过程侧链酰胺的读旧光回响完成 ，同时完成了吲哚C2位区域选择性的事科单碳置换与庖代 。该计策不单可以在吲哚C2位完成氘代 、学网烷基化 、科学芳基化和酰基化 ，出版还可以将13C标识表记标帜的周论碳原子引进骨架中 。
经由过程对宏壮单萜吲哚生物碱quebrachamine的文导精练四步全分化 ，研究者验证了该编制的读旧合用价值 。考验考验研究与密度泛函幻想筹算揭穿了一条触及级联[2+2]环加成 、事科retro-[2+2]开环 、学网脱羰基及环化的科学回响路途 ，从原子层面阐了然回响过程。功用晃荡 ，且得益于电缆聚合物护套的防潮呵护 ，仍能保管80%的导电性 。
▲ Abstract：
Indole is widely present in pharmaceuticals and natural products. In this work, we report an intramolecular skeletal editing reaction of tryptamine derivatives enabled by photoreaction of a pendant amide that simultaneously achieves regioselective single-carbon replacement and substitution at the C2 position of indoles. This strategy facilitates deuteration, alkylation, arylation, and acylation at the indole C2 position while also enabling the incorporation of 13C-labeled carbon into the scaffold. We highlighted the practical applicability of this method through a concise four-step total synthesis of quebrachamine, a complex monoterpene indole alkaloid. Experimental studies and density functional theory (DFT) calculations revealed a reaction pathway involving cascade [2+2] cycloaddition, retro-[2+2] ring opening, decarbonylation, and cyclization, elucidating the sequence at an atomic level.
人工智能Artificial Intelligence
Toward life with a 19–amino acid alphabet through generative artificial intelligence design
经由过程生成式人工智能筹划迈向含19种氨基酸字母表的生命琐细
▲ 作者 ：Liyuan Liu, Charlotte Rochereau et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.aeb5171
▲摘要 ：
因为全数已知生物体均由起码20种经典氨基酸构成，独霸更简化的氨基酸“字母表”的可行性尚不了了 。研究者连络筹算筹划与分化生物学 ，试探从含19种氨基酸字母表构建细胞的大年夜大年夜约性 。
末尾分化注解 ，异亮氨酸多是可被剔除的 ，研究者经由过程直代更调除夜肠杆菌必须蛋白中的全数异亮氨酸残基证了然这一点 。关头的是 ，在除夜除夜都气候下 ，需求独霸蛋白质言语模型和基于筹划的模型来从头筹划无异亮氨酸的下场性蛋白 。
研究者琐细性地更调了核糖体中全数382个异亮氨酸残基 ，并在原生基因组位点上组合了21个从头筹划的亚基，成功掉落踪掉落踪了可存活且退步晃荡的细胞 。这项工作为自初期退步以来首个含19种氨基酸生物体的构建供给了线路图 。
▲ Abstract：
Because all known living organisms are made from at least 20 canonical amino acids, the feasibility of life using a more simplified alphabet remains unclear. In this work, we leveraged computational design and synthetic biology to explore building a cell from a 19–amino acid alphabet. Initial analyses suggested that isoleucine (Ile) may be dispensable, which we confirmed by directly replacing Ile residues in essential proteins in Escherichia coli. Critically, protein language models and structure-based models were necessary to redesign functional Ile-less proteins in most cases. We systematically replaced all 382 Ile residues from the ribosome and combined 21 redesigned subunits at a native genomic locus to produce a viable, evolutionarily stable cell. This work provides a roadmap to create the first 19–amino acid organism since early evolution.
Performance of a large language model on the reasoning tasks of a physician
除夜言语模型在医疗诊断使射中的默示
▲ 作者 ：Peter G. Brodeur, Thomas A. Buckley et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.adz4433
▲摘要：
起码65年之前 ，宏壮的临床诊断推理案例就已被引进作为评价专家医学筹算琐细的金标准 ，这一标准沿袭至今 。研究者经由过程五项考验考验，以数百名医师为基线，陈述了对除夜型言语模型在具有挑衅性的临床案例上的医师评价下场 。
随后 ，研究者陈述了一项真实全国研究 ，在某除夜型***学术医学中心的急诊科，随机拔取患者 ，斗劲人类专家与人工智能第二定见的诊断默示 。在全数考验考验中 ，除夜言语模型均超出医师基线程度 ，并揭显露相较于前几代AI临床决意狡计支撑琐细的延续改进 。
研究注解 ，除夜言语模型已超出除夜除夜都临床推理基准，亟需鞭挞前瞻性临床履行 。
▲ Abstract ：
More than 65 years ago, complex clinical diagnostic reasoning cases were introduced as the gold standard for the evaluation of expert medical computing systems, a standard that has held ever since. In this study, we report the results of a physician evaluation of a large language model (LLM) on challenging clinical cases across five experiments with a baseline of hundreds of physicians. We then report a real-world study comparing human expert and artificial intelligence (AI) second opinions in randomly selected patients in the emergency room of a major tertiary academic medical center. In all experiments, the LLM outperformed physician baselines and displayed continued improvement from prior generations of AI clinical decision support. Our study suggests that LLMs have eclipsed most benchmarks of clinical reasoning, motivating the urgent need for prospective trials.
地舆学Astronomy
Deeper detection limits in astronomical imaging using self-supervised spatiotemporal denoising
自拒守时空降噪汲引地舆成像探测极限
▲ 作者 ：Yuduo Guo, Hao Zhang et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.ady9404
▲摘要 ：
地舆成像不美不美不雅察的探测极限受多种噪声源制约 。个中部分噪声在相邻像素与暴光序列间存在相干性，是以幻想上可以经由过程进修举办校订。研究者提出了基于自拒守Transformer的地舆往噪算法，该算法整合了多幅暴光图象中的时空信息 。
对模仿数据的基准测试注解 ，ASTERIS在贯穿连接点扩大年夜大年夜大年夜大年夜函数和测光精度的前提下 ，在90%无缺性和纯真度前提下将探测极限汲引了1.0星等 。独霸詹姆斯·韦伯空间看远镜和斯巴鲁看远镜数据的不美不雅不雅不雅不雅不雅不雅考验证 ，辨认出此前没法探测的特点 ，包含低外不雅亮度星系筹划和引力透镜弧。
将ASTERIS独霸于韦伯看远镜的深场图象后 ，红移?9的星系候选体数量较传统编制添加了三倍，其活动帧紫外光度暗至1.0星等 。
▲ Abstract ：
The detection limit of astronomical imaging observations is limited by several noise sources. Some of that noise is correlated between neighboring pixels and exposures, so in principle it could be learned and corrected. We present the Astronomical Self-supervised Transformer-based Denoising (ASTERIS) algorithm, which integrates spatiotemporal information across multiple exposures. Benchmarking on mock data indicated that ASTERIS improves detection limits by 1.0 magnitude at 90% completeness and purity while preserving the point spread function and photometric accuracy. Observational validation using data from the James Webb Space Telescope (JWST) and the Subaru Telescope identified previously undetectable features, including low-su***ce-brightness galaxy structures and gravitationally lensed arcs. Applied to deep JWST images, ASTERIS identified three times more redshift ?9 galaxy candidates than previous methods, with rest-frame ultraviolet luminosity 1.0 magnitude fainter.
地球科学Earth Science
Apparent Hack’s law in river deltas
河道三角洲中显见的哈克定律
▲ 作者 ：Tian Y. Dong, Lawrence Vulis et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.ady6805
▲摘要 ：
河道三角洲是人丁鳞集 、生态相当次要的地貌琐细 ，正面对海立体上升的威胁 。分流河道群集经由过程保送聚积物构建三角洲海洋 ，但群集构造与海洋构建之间的相干仍不了然 。
受哈克定律（该定律注解流域汇水面积与主流汇集结的河道长度呈标度相干）启发 ，研究者分化了一套全球分流群集数据集，创作创造分流河道长度与其对应的海洋构建面积（相当于汇水区中的汇水面积）之间展示近乎不异的标度相干。
当然存在这类全球性标度规律 ，研究者进一步辨认出两种不合的局地造陆编制：平均三角洲群集不竭屈就哈克定律 ，而复合三角洲群集则展示标度断裂 ，即从三角洲顶点邻近的充填式展开过渡到海岸邻近的准线性展开 。这些出乎料想的添加编制注解 ，河道三角洲的展开与构造过程中 ，全球规律性与局地多样性是共存的 。
▲ Abstract ：
River deltas are densely populated, ecologically vital landscapes threatened by rising sea levels. Distributary channel networks disperse sediment to build deltaic land, yet the relationship between the network organization and land building remains elusive. Inspired by Hack’s law, which shows that watershed drainage area scales with channel length in tributary networks, we analyzed a global dataset of distributary networks and found a nearly identical scaling relationship between distributary channel length and nourishment area, the land-building counterpart to drainage area. Despite this apparent global scaling, we further identified two distinct local land-building patterns: uniform delta networks consistently follow Hack’s law, whereas composite delta networks exhibit a scale break, transitioning from space-filling growth around the delta apex to quasi-linear growth near the coast. The unexpected growth patterns suggest that global simplicity and local variability coexist in how river deltas grow and organize.
群集科学Network Science
Peer influence decay and behavioral diffusion in adolescent networks: A simulation approach
青少年汇集结火伴影响力弱减与行动分散 ：一项模仿研究
▲ 作者 ：Cheng Wang, Carter T. Butts et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.aea9297
▲摘要 ：
火伴影响力在敷衍汇集结撒播多远后会磨灭踪 ？研究者独霸美国国度青少年至成人安康纵向研究中两所黉舍（共3154名师长教师）的纵向数据，参议了青少年友情汇集结抽烟行动的分散机制 。
研究者采取随机面向行动者模型 ，模仿了针对重度抽烟者的干与干与编制 ，触及不算计策（随机选择 、进度中心性 、特点向量中心性）与袒护比例（10%至100%） 。经由过程一个新的指数衰减模型量化了影响力弱减 ，初度揭穿了方针浅近三阶以内的直接火伴影响力（即溢出效应） 。对10%至30%的中心浅近履行干与干与可使抽烟行动降幅最除夜化 ，但因为群集饱和效应，当袒护比例超出40%—50%后增益趋于高大陡峭 。
研究分化注解 ，相较于更除夜局限但更稀少的群集，较鳞集的群集默示出更普及的分散局限与更迟缓的衰加快度 。该衰减方针可为不合筹划汇集结的干与干与筹划优化供给按照。
▲ Abstract ：
How far does peer influence spread through social networks before dissipating? This study investigates the diffusion of smoking behavior in adolescent friendship networks using longitudinal data from two schools (n = 3154 students) in the National Longitudinal Study of Adolescent to Adult Health. Using Stochastic Actor–Oriented Models, we simulate interventions targeting heavy smokers using various strategies (random, in-degree, eigenvector centrality) and coverage (10 to 100%). A new exponential decay model quantifies influence attenuation, revealing indirect peer influences, or spillover effects, up to three steps from targets. Targeting 10 to 30% of central individuals maximizes smoking reductions, but gains plateau beyond 40 to 50% owing to network saturation. In our analyses, the denser network exhibits broader diffusion and slower decay than the larger, sparser network. This decay metric optimizes intervention design across diverse network structures.
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