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A countercurrent microflow strategy for simultaneous high selectivity and conversion in aromatic nitration. 芳香族硝化同时高选择性和转化的逆流微流策略。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69902-2
Jing Song, Yongqi Pan, Ruobing Xin, Zifei Yan, Tianyao Tang, Kai Wang, Yujun Wang, Jian Deng, Guangsheng Luo

Aromatic nitration, a hazardously complex process, poses serious risks. A major challenge for the reaction is the trade-off effect between spatiotemporal conversion rate and selectivity, particularly the over-nitration side reactions that have plagued the field for nearly 200 years. We propose a countercurrent microflow mode between two microreactors, which boosts spatiotemporal conversion rate by over five times compared to the normal single-stage co-current microflow mode, and two orders of magnitude compared to traditional batch reactors. Meanwhile, we identify an inhibition mechanism of over-nitration. The generated H2O in the main reaction can in situ reduce the dissolution of nitroaromatics in the aqueous phase and effectively prevent over-nitration. Through synergistic control of both kinetics and thermodynamics in the microreaction process, high spatiotemporal conversion and selectivity are achieved simultaneously, overcoming the trade-off effect. Furthermore, we demonstrate the broad applicability of the microflow strategy across various aromatic nitration processes.

芳香硝化是一个危险复杂的过程,具有严重的风险。该反应面临的主要挑战是时空转化率和选择性之间的权衡效应,特别是近200年来困扰该领域的过度硝化副反应。我们提出了两个微反应器之间的逆流微流模式,该模式比普通的单级共流微流模式提高了5倍以上的时空转化率,比传统的间歇式反应器提高了2个数量级。同时,我们确定了过度硝化的抑制机制。主反应生成的H2O能原位减少硝基芳烃在水相的溶解,有效防止过硝化。通过对微反应过程中动力学和热力学的协同控制,同时实现了高时空转化率和选择性,克服了权衡效应。此外,我们证明了微流策略在各种芳香硝化过程中的广泛适用性。
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引用次数: 0
Precision engineering chiral interfaces for efficient spin injection in metal halide heterostructures 金属卤化物异质结构中有效自旋注入的精密工程手性界面
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69455-4
Jin Xiao, Yang Li, Yanan Liu, Jing Li, Li Fang, Haofeng Zheng, Yanlong Wang, Qi Liu, Xuyu Ma, Shuai Pang, Jing Hu, Jianbo Wang, Shaocong Hou
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引用次数: 0
In situ structures of the portal-neck-tail complex of bacteriophage T4 inform a viral genome positioning mechanism T4噬菌体门颈尾复合体的原位结构为病毒基因组定位机制提供了信息
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69106-8
Andrei Fokine, Jingen Zhu, Thomas Klose, Frank Vago, Charles-Adrien Arnaud, Zhiqing Wang, Baldeep Khare, Michael G. Rossmann, Zhenguo Chen, Lei Sun, Qianglin Fang, Richard J. Kuhn, Venigalla B. Rao
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引用次数: 0
Computing-in-memory architecture for Kolmogorov-Arnold networks based on tunable Gaussian-like memory cells 基于可调类高斯记忆单元的Kolmogorov-Arnold网络的内存计算体系结构
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69592-w
Zhixing Wen, Qirui Zhang, Jiangang Chen, Tianhua Yang, Fan Yang, Xuemei Wang, Qing Liu, Xiao Luo, Peng Lin, Liang-Jian Deng, Fucai Liu
Inspired by the Kolmogorov-Arnold representation theorem, the Kolmogorov-Arnold networks serve as promising alternatives to multilayer perceptrons. Kolmogorov-Arnold networks utilize a superposition of finite basis functions to implement variable continuous univariate activation functions, offering greater flexibility and adaptability. However, the hardware implementation of its basis functions remains costly, making it challenging to achieve complex computations with minimal equipment. Here, we designed the device defined as Gaussian-like memory cell, composed of a Gaussian transistor and a memristor, to ensure the tunable Gaussian-like current-voltage responses. Furthermore, we constructed the circuits based on Gaussian-like memory cells to accommodate the parallel inference computation of Kolmogorov-Arnold networks. This study demonstrates that the proposed architecture based on Gaussian-like memory cells can effectively maintain the algorithmic advantages across various tasks including one-dimensional function regression, image recognition, partial differential equation solving, and time-series forecasting. Notably, the proposed architecture achieves significant improvements in energy efficiency. The results provide a promising avenue for computing-in-memory architecture for Kolmogorov-Arnold networks, and expand the flexibility and efficiency of the neuromorphic computing paradigm.
受Kolmogorov-Arnold表示定理的启发,Kolmogorov-Arnold网络作为多层感知器的有前途的替代品。Kolmogorov-Arnold网络利用有限基函数的叠加来实现可变连续单变量激活函数,提供更大的灵活性和适应性。然而,其基本功能的硬件实现仍然昂贵,使得用最小的设备实现复杂的计算具有挑战性。本文设计的器件定义为类高斯存储单元,由高斯晶体管和忆阻器组成,以确保可调谐的类高斯电流-电压响应。此外,我们构建了基于类高斯记忆单元的电路,以适应Kolmogorov-Arnold网络的并行推理计算。研究表明,基于类高斯记忆单元的结构可以有效地在一维函数回归、图像识别、偏微分方程求解和时间序列预测等任务中保持算法优势。值得注意的是,所提出的架构在能源效率方面取得了显著的改进。研究结果为Kolmogorov-Arnold网络的内存计算架构提供了一条有前途的途径,并扩展了神经形态计算范式的灵活性和效率。
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引用次数: 0
Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy 接受CD19 CAR - T细胞治疗的白血病患者长期反应的免疫代谢决定因素
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69857-4
Lior Goldberg, Eric R. Haas, Jiaqi Wu, Bryan Garcia, Ryan Urak, Vibhuti Vyas, Ruby Espinosa, Tamara Munoz, Shirley Bierkatz, Khyatiben V. Pathak, Nathaniel P. Hansen, Patrick Pirrotte, Jyotsana Singhal, James L. Figarola, Ricardo Zerda Noriega, Zhuo Li, Dasol Wi, Erin Tanaka, Ramon Klein Geltink, Min-Hsuan Chen, Xiwei Wu, Jamie R. Wagner, Jinny Paul, Mary C. Clark, Dat Ngo, Ibrahim Aldoss, Stephen J. Forman, Xiuli Wang
Although most patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cell therapy achieve remission, loss of CAR T cell functionality and subsequent relapse remains an unmet therapeutic need. Herein, we apply an integrative approach to study the immunometabolism of pre- and post-infusion CD19-CAR T cells of patients with relapsed/refractory B-ALL. Pre-infusion CAR T cells of long-term responders (LTR) have increased oxidative phosphorylation, fatty acid oxidation, and pentose phosphate pathway activities, higher mitochondrial mass, tighter cristae, and lower mTOR expression compared to products of short-term responders. Post-infusion CAR T cells in bone marrow (BM) of LTR have high immunometabolic plasticity and mTOR-pS6 expression supported by the BM microenvironment. Transient inhibition of mTOR during manufacture induces metabolic reprogramming and enhances anti-tumor activity of CAR T cells. Our findings provide insight into immunometabolic determinants of long-term response and suggest a therapeutic strategy to improve long-term remission.
虽然大多数复发/难治性b细胞急性淋巴细胞白血病(B-ALL)患者接受cd19靶向嵌合抗原受体(CAR) T细胞治疗后获得缓解,但CAR - T细胞功能丧失和随后的复发仍然是一个未满足的治疗需求。在此,我们采用一种综合方法来研究复发/难治性B-ALL患者输注前和输注后CD19-CAR - T细胞的免疫代谢。与短期应答者相比,长期应答者(LTR)的预输注CAR - T细胞具有更高的氧化磷酸化、脂肪酸氧化和戊糖磷酸途径活性、更高的线粒体质量、更紧密的嵴和更低的mTOR表达。LTR骨髓(BM)输注后CAR - T细胞具有较高的免疫代谢可塑性和BM微环境支持的mTOR-pS6表达。在制造过程中短暂抑制mTOR诱导代谢重编程并增强CAR - T细胞的抗肿瘤活性。我们的研究结果为长期反应的免疫代谢决定因素提供了见解,并提出了改善长期缓解的治疗策略。
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引用次数: 0
Plant traits explain variation in symbiotic nitrogen fixation responses to global nitrogen enrichment: a meta-analysis 植物性状解释了共生固氮对全球氮富集反应的变化:一项荟萃分析
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69876-1
Yanzhong Yao, Bingbing Han, Peter M. van Bodegom, Xunzhuo Dong, Yunyao Zhong, Shuli Niu, Xinping Chen, Zhaolei Li
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引用次数: 0
A spatially resolved human glioblastoma atlas reveals distinct cellular and molecular patterns of anatomical niches 空间分辨的人类胶质母细胞瘤图谱揭示了解剖壁龛的不同细胞和分子模式
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69716-2
Pranali Sonpatki, Hyun Jung Park, Yao Lulu Xing, Kyung Yeon Han, Brett A. Schroeder, Hyeon Jong Yu, Hye Jin Kim, Tamrin Chowdhury, Jong Ha Hwang, Sun Mo Nam, Yoon Hwan Byun, Ho Kang, Joo Ho Lee, Soon-Tae Lee, Jae-Kyung Won, Tae Min Kim, Seung Hong Choi, Ja-Lok Ku, Sungyoung Lee, Hongseok Yun, Sung-Hye Park, Claudia K. Petritsch, Chul-Kee Park, Woong-Yang Park, Nameeta Shah
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引用次数: 0
Genetic modifiers of APOE-ε4-associated cognitive decline. APOE-ε4相关认知衰退的遗传修饰因子。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-68933-z
Alex G Contreras, Skylar Walters, Jaclyn M Eissman, Derek B Archer, Alexandra N Regelson, Alaina Durant, Michelle Clifton, Subhabrata Mukherjee, Michael L Lee, Seo-Eun Choi, Phoebe Scollard, Emily H Trittschuh, Jesse Mez, William S Bush, Brian W Kunkle, Carlos Cruchaga, Adam C Naj, Katherine A Gifford, Murat Bilgel, Amanda B Kuzma, Michael L Cuccaro, Margaret A Pericak-Vance, Lindsay A Farrer, Li-San Wang, Gerard D Schellenberg, Jonathan L Haines, Angela L Jefferson, Walter A Kukull, C Dirk Keene, Andrew J Saykin, Paul M Thompson, Eden R Martin, Marilyn S Albert, Sterling C Johnson, Corinne D Engelman, Luigi Ferrucci, David A Bennett, Lisa L Barnes, Julie A Schneider, Reisa A Sperling, Susan M Resnick, Paul K Crane, Logan Dumitrescu, Timothy J Hohman

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers.

APOE-ε4等位基因是迟发性阿尔茨海默病最强的遗传危险因素。然而,APOE-ε4不是决定性的,强调需要确定其他遗传和环境因素。APOE-ε4与认知能力加速下降有关,因此我们试图研究改变APOE-ε4相关认知能力下降的遗传因素。我们使用来自32,778名参与者的统一认知数据进行跨祖先APOE-ε4分层和交互GWAS,其中包括29,354名非西班牙裔白人和3,424名非西班牙裔黑人。我们的主要结果是晚年认知,使用记忆、执行功能和语言的统一综合评分来测量,建模为反映规范认知衰老和疾病相关衰退的连续特征。我们在APOE-ε4携带者中发现了两个全基因组显著位点,从而在全基因组范围内对执行功能具有重要意义。这些基因座也显示了在其他领域的名义关联,表明对认知的广泛影响。在非携带者中,我们发现ITGB8在全基因组范围内的显著关联仅限于执行功能,另一个位点与语言相关。我们进一步通过表达和甲基化数据库将这些位点与SEMA6D、GRIN3A和ITGB8联系起来。gwas后分析还发现了其他基因,包括SLCO1A2和DNAH11。遗传相关分析显示APOE-ε4在免疫相关性状上存在差异,提示APOE-ε4携带者的免疫相关倾向可能会加剧认知风险。
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引用次数: 0
Author Correction: Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype. 作者更正:核AURKA获得不依赖激酶的反激活功能以增强乳腺癌干细胞表型。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69300-8
Feimeng Zheng, Caifeng Yue, Guohui Li, Bin He, Wei Cheng, Xi Wang, Min Yan, Zijie Long, Wanshou Qiu, Zhongyu Yuan, Jie Xu, Bing Liu, Qian Shi, Eric W-F Lam, Mien-Chie Hung, Quentin Liu
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引用次数: 0
Substorm expansion embedded in a global cycle of field-aligned currents and auroral electrojets 亚暴扩张嵌入在场向电流和极光电喷流的全球循环中
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-20 DOI: 10.1038/s41467-026-69753-x
Tonghui Wang, Lei Dai, C. Philippe Escoubet, Walter Gonzalez, Yong Ren, Minghui Zhu, Shan Wang, Chi Wang, Xu Wang, Kailai Wang, Jinjuan Liu
Geomagnetic substorms transfer solar wind energy into the planetary magnetosphere and ionosphere, producing auroral displays and ground magnetic disturbances, particularly intense during the expansion phase. Despite decades of study, the mechanisms governing the expansion phase remain unresolved. Based on coordinated observations of storm-time intense substorms, we reveal that substorm expansion is temporally embedded within a global cycle of field-aligned currents and auroral electrojets, coupled to large-scale plasma convection. The cycle manifests as a coherent movement of current peaks across magnetic longitude and latitude—first antisunward and equatorward, then sunward and poleward—and coincides with enhanced sunward ionospheric convection. This cycle involves two components of the auroral electrojets: the convection-driven DP-2 current and the expansion-phase DP-1 substorm current. The antisunward-equatorward phase, corresponding to intervals of dominant dayside reconnection, begins with DP-2 and can stepwise transition into DP-1. During the subsequent sunward-poleward phase, reflecting intervals of dominant nightside reconnection, DP-1 either persists from the earlier interval or develops within this phase. These observations show that expansion onset can occur under dominance of either dayside or nightside reconnection, while the full development of DP-1 generally involves nightside reconnection, providing insight into substorm evolution.
地磁亚暴将太阳风能量转移到行星磁层和电离层,产生极光和地面磁扰动,在膨胀阶段尤其强烈。尽管经过几十年的研究,控制膨胀阶段的机制仍未得到解决。基于对风暴时强亚暴的协调观测,我们揭示了亚暴的扩展是暂时嵌入在场向电流和极光电喷流的全球周期中,并与大规模等离子体对流相耦合。这个周期表现为电流峰值在磁经纬度上的一致运动——首先是反太阳方向和赤道方向,然后是向太阳方向和极地方向——与向太阳的电离层对流增强相吻合。这个周期涉及极光电喷流的两个组成部分:对流驱动的DP-2电流和膨胀阶段的DP-1亚暴电流。逆日向赤道阶段,对应于优势日面重联的间隔,从DP-2开始,逐步过渡到DP-1。在随后的向阳向极阶段,反映了占优势的夜侧重新连接的时间间隔,DP-1要么从早期的时间间隔持续存在,要么在这一阶段发展。这些观测结果表明,扩张的开始可能发生在昼侧或夜侧重新连接的主导下,而DP-1的全面发展通常涉及夜侧重新连接,这为亚暴演变提供了深入的见解。
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引用次数: 0
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