《科学》（20260226出版）一周论文导读

 

编译｜李言

Science, 26 Feb 2026, VOL 391, ISSUE 6788

《科学》2026年2月26日，第391卷，6788期

生物学Biology

Sensitive CAR T cells redefine targetable CD70 expression in solid tumors

高敏性CAR-T细胞重新定义实体瘤中可靶向的CD70表达

▲ 作者：Sophie A. Hanina, Tyler Park et al.

▲链接：

https://www.science.org/doi/10.1126/science.adv7378

▲摘要：

实体瘤抗原异质性对包括嵌合抗原受体T细胞在内的癌症免疫疗法构成重大挑战。

与B细胞恶性肿瘤中的CD19不同，目前尚未在实体瘤中发现具有全细胞表达且在正常关键细胞中缺失的理想靶点。CD70是一个颇具前景的候选分子，其在生理状态下仅限于免疫细胞亚群表达，但在多种癌症中异常表达。

研究者发现，肿瘤中CD70的异质性表达受表观遗传调控，单个细胞表达水平从高到低跨度极大，以致常规检测方法显示为阴性。

通过使用共表达共刺激分子CD80和4-1BBL的高敏非HLA依赖型T细胞受体，研究者有效清除了原型CAR-T细胞无法识别的CD70异质性肿瘤。这些发现为治疗多种实体瘤提供了潜在新策略。

▲ Abstract：

Solid tumor antigen heterogeneity is a major challenge for cancer immunotherapies, including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a promising candidate, physiologically confined to immune cell subsets and aberrantly expressed in many cancers. We show that heterogeneous CD70 expression in tumors is epigenetically regulated, ranging from high to very low in individual cells, appearing negative by conventional detection methods. Using a highly sensitive CD70 receptor, HLA-independent T cell (HIT) receptor coexpressing CD80 and 4-1BBL for costimulation, we efficiently eliminated CD70-heterogeneous tumors that evade prototypic CAR T cells. These findings provide a potential strategy to treat a broad range of solid tumors.

天文学Astronomy

A precessing jet from an active galactic nucleus drives gas outflow from a disk galaxy

活动星系核的进动喷流驱动盘状星系中的气体外流

▲ 作者：Justin A. Kader, Vivian U et al.

▲链接：

https://www.science.org/doi/10.1126/science.adp8989

▲摘要：

为复现观测到的星系特性，宇宙学模拟要求大质量星系必须经历活动星系核的反馈过程，以调控其内部的恒星形成。

然而，对这些反馈过程的能量学与时间尺度认知仍十分有限。研究者整合了对活动星系VV 340a的光学、红外、亚毫米波和射电多波段观测。

该星系中心超大质量黑洞驱动着低功率喷流。研究者发现该喷流存在进动现象，周期为（8.2±5.5）×10⁵年，并以每年19.4±7.9个太阳质量的速率驱动气体外流。

喷流对气体产生激波，形成从星系核延伸数千秒差距的高电离等离子体。该外流从星系中排出的气体量足以影响其恒星形成速率。

▲ Abstract：

To reproduce observed galaxy properties, cosmological simulations require that massive galaxies experience feedback from active galactic nuclei, which regulates star formation within those galaxies. However, the energetics and timescales of these feedback processes are poorly constrained. We combined optical, infrared, submillimeter, and radio observations of the active galaxy VV 340a, which is hosting a low-power jet launched from a supermassive black hole at its center. We found that the jet undergoes precession, with a period of (8.2 ± 5.5) × 10⁵ years, and drives an outflow of gas at a rate of 19.4 ± 7.9 solar masses per year. The jet shocks the gas, producing highly ionized plasma that extends several kiloparsecs from the nucleus. The outflow ejects sufficient gas from the galaxy to influence its star-formation rate.

生态学Ecology

Acceleration hotspots of North American birds’ decline are associated with agriculture

北美鸟类数量加速下降的热点地区与农业活动相关

▲ 作者：Fran?ois Leroy, Marta A. Jarzyna, and Petr Keil

▲链接：

https://www.science.org/doi/10.1126/science.ads0871

▲摘要：

人类活动可能加速了物种种群数量的下降，但这一加速过程尚未得到充分研究。

研究者利用1987年至2021年间1033条北美繁殖鸟类调查路线数据，分析了261种鸟类、54个科及10种栖息地的种群数量变化及其加速趋势。

结果显示，全美范围内每条路线观测到的鸟类平均数量呈下降趋势，下降热点集中于北美南部及温暖地区，而下降加速热点则位于中大西洋地区、中西部及加利福尼亚州，与农业活动密集区空间分布高度吻合。

总体而言，122种鸟类（占比47%）呈现显著下降，其中63种的下降趋势仍在加速，67种的平均增长率持续走低，这引发了人们对北美大部分鸟类种群状况的担忧。

研究表明，鸟类数量下降总体呈加速态势，其空间分布特征提示农业活动强度可能是这一趋势的关键驱动因素。

▲ Abstract：

Human activities might have accelerated declines of population abundance, but this acceleration remains underexplored. Using 1033 North American Breeding Bird Survey routes, we analyze abundance change and its acceleration for 261 bird species, 54 avian families, and 10 habitats from 1987 to 2021. We show an average continent-wide decline of abundance of all birds per local route, with hotspots of decline in southern and warm parts of North America and hotspots of accelerating decline in the Mid-Atlantic, Midwest, and California, matching patterns of agricultural intensity. Overall, 122 species (47%) exhibit significant declines, of which 63 also show acceleration of this decline, and 67 show declining per-capita growth rate, raising concerns for a large part of North American bird populations. These findings suggest that bird abundance decline is mostly accelerating, with spatial patterns of this acceleration indicating that agricultural intensity may be a driver of this trend.

古人类学Paleoanthropology

Interbreeding between Neanderthals and modern humans was strongly sex biased

尼安德特人与现代人类的杂交呈现显著性别偏向性

▲ 作者：Alexander Platt, Daniel N. Harris, and Sarah A. Tishkoff

▲链接：

https://www.science.org/doi/10.1126/science.aea6774

▲摘要：

性别偏向性在混血及其他人口统计学过程中是人类演化的常见特征。针对尼安德特人与解剖学现代人（AMHs）之间的混血现象，性别偏向性假说被用于解释为何现代人X染色体中的尼安德特人血统比例显著低于常染色体。

研究者通过观测到尼安德特人X染色体中AMHs血统相对富集62%，揭示了两者杂交的主要模式为尼安德特男性与现代女性之间的结合。

分析模型与数值模拟表明，与纯粹的性别差异化迁徙模式相比，择偶偏好是解释该性别偏向性更直白的成因。

▲ Abstract：

Sex biases in admixture and other demographic processes are recurrent features throughout human evolution. For admixture between Neanderthals and anatomically modern humans (AMHs), sex bias has been proposed as an explanation for the relative lack of Neanderthal ancestry in modern human X chromosomes compared with that in modern human autosomes. By observing a 62% relative excess of AMH ancestry in Neanderthal X chromosomes, we characterized the interbreeding between the two groups as predominantly male Neanderthals with female AMHs. Analytic and numerical modeling presents mate preference as a more parsimonious cause of the sex bias than purely demographic processes with differential patterns of male and female migration.

动物学Zoology

Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds

趋同与谱系特异性基因组变化共同塑造食蜜鸟类的适应性进化

▲ 作者：Ekaterina Osipova, Meng-Ching Ko et al.

▲链接：

https://www.science.org/doi/10.1126/science.adt1522

▲摘要：

高糖饮食可导致人类代谢性疾病，然而多个鸟类谱系却趋同适应了以富含糖分的花蜜或果实为食。研究者通过生成9个新基因组和90个组织特异性转录组，探究了蜂鸟、鹦鹉、吸蜜鸟和太阳鸟的分子适应机制。

比较筛选发现，食蜜鸟类蛋白质编码序列与调控区域均存在过量重复选择信号，提示遗传元件的重复利用。

食蜜鸟类基因序列或表达变化涉及血压调控、脂质代谢、氨基酸代谢及碳水化合物代谢相关基因，实验证实吸蜜鸟己糖激酶3存在功能改变。

MLXIPL作为糖脂代谢稳态的关键调控因子，在所有食蜜鸟类谱系中均表现出趋同的序列与调控变化；实验表明蜂鸟MLXIPL具有增强的糖诱导转录活性，凸显其在高糖饮食适应性中的关键作用。

▲ Abstract：

High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation and lipid, amino acid, and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL, a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL, highlighting its adaptive role in high-sugar diets.

A cellular basis for the mammalian nocturnal-diurnal switch

哺乳动物昼夜行动转换的细胞基础

▲ 作者：Andrew D. Beale, Matthew J. Christmas et al.

▲链接：

https://www.science.org/doi/10.1126/science.ady2822

▲摘要：

在恐龙主导白昼的时期，早期哺乳动物是夜行性的。白垩纪—古近纪灭绝事件后，哺乳动物向昼行性活动的转变加速，但其潜在机制尚不明确。

研究者发现了一种保守的细胞内热力学机制，可能促进了这一转变。与夜行性哺乳动物细胞相比，昼行性哺乳动物细胞内的蛋白质合成、磷酸化过程及昼夜节律计时对温度变化的敏感性较低。

比较基因组学揭示，包括雷帕霉素靶蛋白复合体（mTOR）在内的核心信号通路经历了加速进化，增强了昼行性动物细胞时钟对热扰动和渗透压扰动的鲁棒性。

在夜行性小鼠中，抑制mTOR信号可使细胞、组织及行为向昼行性活动模式转变。这些发现揭示了昼夜转换的遗传与生化基础，强调了细胞信号网络如何编码时间生态位选择等复杂表型。

▲ Abstract：

Early mammals were nocturnal while dinosaurs dominated the daytime. Mammalian transition to daytime activity accelerated after the Cretaceous-Paleogene extinction, but the underlying mechanisms remain unclear. We identified a conserved cell-intrinsic, thermodynamic mechanism that likely facilitated this shift. In cells from diurnal mammals, protein synthesis, phosphorylation, and circadian timing were less sensitive to temperature changes than were cells from nocturnal mammals. Comparative genomics revealed accelerated evolution within essential signaling pathways, including mechanistic target of rapamycin (mTOR), that increase the robustness of diurnal cellular clocks to thermal and osmotic perturbation. In nocturnal mice, mTOR inhibition shifted cells, tissues, and behavior toward diurnal activity. These findings uncover a genetic and biochemical basis for nocturnal-diurnal switching, emphasizing how cellular signaling networks can encode complex phenotypes such as temporal niche selection.