| 《科学》（20260226出版）一周论文导读 |
编译｜李言
Science,科学 26 Feb 2026, VOL 391, ISSUE 6788
《科学》2026年2月26日 ，第391卷 ，出版6788期
生物学Biology
Sensitive CAR T cells redefine targetable CD70 expression in solid tumors
高敏性CAR-T细胞从头定义实体瘤中可靶向的周论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含嵌合抗原受体T细胞在内的癌症免疫疗法构成重除夜挑衅 。
与B细胞恶性肿瘤中的文导CD19不合，如今还没有在实体瘤中创作创造具有全细胞表达且在正常关头细胞中缺损掉落踪落的读旧志向靶点 。CD70是事科一个颇具前景的候选分子，其在心思外形下仅限于免疫细胞亚群表达，学网但在多种癌症中特别很是科学表达。
研究者创作创造，出版肿瘤中CD70的周论异质性表达受表不美不雅不雅不雅不雅不雅不雅遗传调控，单个细胞表达程度从高到低跨度极除夜，文导甚至常例检测编制展示为阴性 。读旧
经由过程独霸共表达共安慰分子CD80和4-1BBL的事科高敏非HLA依托型T细胞受体 ，研究者有效断根了原型CAR-T细胞没法识其他CD70异质性肿瘤 。学网这些创作创造为医治多种实体瘤供给了埋伏新计策。科学
▲ 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.
地舆学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 ：
为复现不美不美不雅察到的星系特点 ，宇宙学模仿请求除夜质量星系必须经验活动星系核的回响过程，以调控其内部的恒星构成 。
可是，对这些回响过程的能量学与时分标准认知仍特别很是无穷 。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不美不美不雅察 。
该星系中心超除夜质量黑洞驱动着低功率喷流 。研究者创作创造该喷流存在进动气候 ，周期为（8.2±5.5）×105年 ，并以每年19.4±7.9个太阳质量的速度驱动气体外流。
喷流对气体产生发火激波 ，构成从星系核延长数千秒差距的高电离等离子体。该外流从星系中排斥的气体量足以影响其恒星构成速度 。
▲ 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) × 105years, 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
北美鸟类数量加快降低的抢手区域与农业活动相干
▲ 作者：Fran?ois Leroy, Marta A. Jarzyna, and Petr Keil
▲链接：
https://www.science.org/doi/10.1126/science.ads0871
▲摘要 ：
人类活动大年夜大年夜约加快了物各类群数方针降低 ，但这一加快过程还没有掉落踪掉落踪充分研究 。
研究者独霸1987年至2021年间1033条北美繁衍鸟类查询访谒线路数据 ，分化了261种鸟类、54个科及10种栖息地的种群数量改削及其加快趋势 。
下场展示 ，全美局限内每条线路不美不美不雅察到的鸟类平均数量呈降低趋势 ，降低抢手集结于北美南部及次要区域，而降低加快抢手则位于中除夜西洋区域 、中西部及加利福尼亚州 ，与农业活动鳞集区空间分布高度契合 。
集团而言 ，122种鸟类（占比47%）展示较着降低 ，个中63种的降低趋势仍在加快 ，67种的平均添加率延续走低，这激起了人们对北美除夜部分鸟类种群外形的忧虑 。
研究注解，鸟类数面前降集团呈加快态势 ，其空间分布特点提示农业活动强度多是这一趋势的关头驱解缆分 。
▲ 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.
祖先类学Paleoanthropology
Interbreeding between Neanderthals and modern humans was strongly *** biased
尼安德特人与现代人类的杂交展示较着性别偏向性
▲ 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别人丁统计学过程中是人类演变的罕有特点 。针对尼安德特人与解剖学现代人（AMHs）之间的混血气候，性别偏向性假说被用于诠释为何现代人X染色体中的尼安德特人血缘比例较着低于常染色体 。
研究者经由过程不美不美不雅察到尼安德特人X染色体中AMHs血缘绝对富集62%，揭穿了二者杂交的次要编制为尼安德特男性与现代女性之间的连络。
分化模型与数值模仿注解，与地道的性别不合化迁徙编制比照 ，择偶偏好是诠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), *** 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 *** bias than purely demographic processes with differential patterns of male and female migration.
植物学Zoology
Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds
趋同与谱系特异性基因组改削合营塑造食蜜鸟类的适应性退步
▲ 作者 ：Ekaterina Osipova, Meng-Ching Ko et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.adt1522
▲摘要 ：
高糖饮食可致令人类代谢性疾病 ，可是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 。研究者经由过程生成9个新基因组和90个构造特异性转录组 ，根究了蜂鸟 、鹦鹉、吸蜜鸟和太阳鸟的分子适应机制 。
斗劲遴选创作创造 ，食蜜鸟类蛋白质编码序列与调控区域均存在过量几回选择旗子记号 ，提示遗传元件的几回独霸。
食蜜鸟类基因序列或表达改削触及血压调控 、脂质代谢、氨基酸代谢及碳水化合物代谢相干基因，考验考验证实吸蜜鸟己糖激酶3存不才场改削 。
MLXIPL作为糖脂代谢稳态的关头调控因子 ，在全数食蜜鸟类谱系中均默示出趋同的序列与调控改削；考验考验注解蜂鸟MLXIPL具有加强的糖困惑转录活性 ，凸显其在高糖饮食适应性中的关头感染。
▲ 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
哺乳植物日夜行动转换的细胞根本
▲ 作者 ：Andrew D. Beale, Matthew J. Christmas et al.
▲链接 ：
https://www.science.org/doi/10.1126/science.ady2822
▲摘要 ：
在恐龙主导日间的时代 ，初期哺乳植物是夜行性的 。白垩纪—古近纪灭尽义务后 ，哺乳植物向昼行性活动的改削加快 ，但其埋伏机制尚不了了 。
研究者创作创造了一种保守的细胞内热力学机制 ，大年夜大年夜约促进了这一改削 。与夜行性哺乳植物细胞比照 ，昼行性哺乳植物细胞内的蛋白质分化 、磷酸化过程及日夜节律计时对温度改削的敏感性较低 。
斗劲基因组学揭穿 ，包含雷帕霉素靶蛋白复合体（mTOR）在内的中心旗子记号通路经验了加快退步 ，加强了昼行性植物细胞时钟对热扰动和渗入压扰动的鲁棒性 。
在夜行性小鼠中 ，阻拦mTOR旗子记号可使细胞 、构造及举意向昼行性活动编制改削。这些创作创造揭穿了日夜转换的遗传与生化根本，朴实了细胞旗子记号群集若何编码时分生态位选择等宏壮表型 。
▲ 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.
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