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TWIST1 drives endothelial-to-mesenchymal-transition to stabilize atherosclerotic plaques TWIST1驱动内皮向间质转化以稳定动脉粥样硬化斑块
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69808-z
Blanca Tardajos Ayllon, Mannekomba Diagbouga, Ankita Das, Siyu Tian, Andreas Edsfeldt, Joanna Kalucka, Jovana Serbanovic-Canic, Emily Chambers, Jiangming Sun, Chrysostomi Gialeli, Mark Dunning, Sheila E. Francis, Xiuying Li, Akiko Mammoto, Michael Simons, Helle F. Jørgensen, Isabel Goncalves, Suowen Xu, Paul C. Evans
Rupture of unstable atherosclerotic plaques is a major cause of mortality. Endothelial-to-mesenchymal transition associates with advanced atherosclerotic plaques and contributes to plaque progression. We examined the role of Twist1 , a transcription factor that drives endothelial-to-mesenchymal transition, in plaque progression by inducible deletion from endothelial cells in hypercholesterolemic mice ( Twist1 ECKO Apo -/- ). Single-cell RNA sequencing coupled to endothelial cell-tracking reveals that Twist1 promotes endothelial-to-mesenchymal transition in advanced atherosclerotic plaques. Histological analyses demonstrate that endothelial Twist1 promotes plaque growth and hallmarks of plaque stability (collagen, ACTA2-positive cells) and reduces features of instability (necrosis, macrophage accumulation). Analysis of cultured human aortic endothelial cells shows that TWIST1 contributes to endothelial-to-mesenchymal transition by promoting migration and proliferation through the transcriptional coactivator PELP1. Additionally, TWIST1 promotes endothelial cell proliferation via AEBP1-dependent upregulation of COL4A1. These findings challenge the prevailing view that endothelial-to-mesenchymal transition uniquely destabilizes plaques, by suggesting that TWIST1-driven endothelial-to-mesenchymal transition can promote plaque stability, offering new insights into atherosclerosis pathophysiology and therapeutic potential.
不稳定动脉粥样硬化斑块破裂是死亡的主要原因。内皮细胞向间质细胞的转变与晚期动脉粥样硬化斑块有关,并有助于斑块的进展。我们研究了Twist1在高胆固醇血症小鼠内皮细胞诱导缺失斑块进展中的作用,Twist1是一种驱动内皮向间质转化的转录因子(Twist1 ECKO载脂蛋白载脂蛋白-/-)。单细胞RNA测序结合内皮细胞跟踪显示,Twist1促进晚期动脉粥样硬化斑块的内皮向间质转化。组织学分析表明,内皮Twist1促进斑块生长和斑块稳定性的标志(胶原、acta2阳性细胞),并减少不稳定性的特征(坏死、巨噬细胞积聚)。对培养的人主动脉内皮细胞的分析表明,TWIST1通过转录辅激活子PELP1促进迁移和增殖,从而促进内皮细胞向间质细胞的转变。此外,TWIST1通过aebp1依赖的COL4A1上调促进内皮细胞增殖。这些发现挑战了主流观点,即内皮到间质转化是斑块不稳定的唯一因素,表明twist1驱动的内皮到间质转化可以促进斑块稳定性,为动脉粥样硬化的病理生理学和治疗潜力提供了新的见解。
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引用次数: 0
A bacterial YopJ-family acetyltransferase suppresses host immune response by Nε-acetylation of JAK1. 细菌yopj家族乙酰转移酶通过JAK1的nε -乙酰化抑制宿主免疫应答。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69623-6
Tao-Tao Chen, Si-Ru Zheng, Binbin Yang, Qiuhua Lu, Xueyan Liu, Wenhong Zhong, Zhengfeng Jiang, Fan Li, Guosheng Hu, Yue Feng, Chunyi Hu, Jingqian Su, Songying Ouyang

A common host response to pathogen infection involves the production of robust interferons or proinflammatory cytokines to activate the JAK-STAT pathway, thereby limiting pathogen replication. The bacterial pathogen Legionella pneumophila creates an intracellular niche and evades host immunity utilizing a cohort of effectors by diverse biochemical activities, thereby permissive for its intracellular replication. However, roles of the JAK-STAT pathway during bacterial infection remain elusive. Here, we identify for the first time that L. pneumophila acetyltransferase effector Lem17 acts as a negative regulator of the JAK-STAT signaling. Lem17 directly interacts with JAK1 through a JAK1-binding Box1-like motif, preventing its recruitment by cytokine receptors. As a YopJ-family acetyltransferase, Lem17 catalyzes Nε-lysine acetylation of JAK1 and impairs its kinase activity, thereby disrupting JAK1-mediated signaling transduction. Our findings provide insights into the mechanism by which L. pneumophila subverts host immunity through acetylation and underscore the role of the JAK-STAT pathway against bacterial infection.

宿主对病原体感染的常见反应包括产生强大的干扰素或促炎细胞因子来激活JAK-STAT通路,从而限制病原体复制。细菌病原体嗜肺军团菌通过多种生化活动创造细胞内生态位并利用一系列效应物逃避宿主免疫,从而允许其在细胞内复制。然而,JAK-STAT通路在细菌感染中的作用仍然难以捉摸。在这里,我们首次发现嗜肺乳杆菌乙酰转移酶效应Lem17作为JAK-STAT信号的负调节因子。Lem17通过JAK1结合的box1样基序直接与JAK1相互作用,阻止其被细胞因子受体募集。作为yopj家族的乙酰转移酶,Lem17催化JAK1的nε -赖氨酸乙酰化并损害其激酶活性,从而破坏JAK1介导的信号转导。我们的发现为嗜肺杆菌通过乙酰化破坏宿主免疫的机制提供了见解,并强调了JAK-STAT途径对抗细菌感染的作用。
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引用次数: 0
Scalable semitransparent organic solar cells with robust film thickness tolerance for building-integrated photovoltaics. 可伸缩的半透明有机太阳能电池,具有强大的薄膜厚度公差,用于建筑集成光伏发电。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69537-3
Tong Wang, Jin Fang, Hao Zhang, Chenyang Tian, Yuhan Wang, Zhen Fu, Wenjun Zou, Dan Deng, Xiaotao Hao, Chang He, Jianqi Zhang, Zhixiang Wei

Building-integrated photovoltaics (BIPVs) is a promising application for semitransparent organic solar cells (ST-OSCs). However, conventional ultra-thin (<80 nm) active layers for ST-OSCs, while balancing transmittance and efficiency, limit the cell-to-module efficiency remaining ratio (CTM) below 56%. Here, we achieve high semitransparency and efficiency in ST-OSCs with reasonable active layer thickness by manipulating the aggregation of acceptors in various donor-diluted blends processed with non-halogen solvent in ambient air. Using PM6:Qx-p-4Cl as a model system, we elucidate a unique film-formation mechanism and charge generation process, demonstrating that the fiber network and suitable aggregation size are crucial for ensuring higher performance in donor-diluted ST-OSCs. The 1 cm2 donor-diluted ST-OSCs with active layer thicknesses of 119 and 301 nm exhibit high light utilization efficiencies (LUEs) of 4.04% and 3.02%, respectively. Notably, a 100 cm2 module demonstrates a CTM ratio of ~85% and a LUE of 3.32%, owing to its high film thickness tolerance, setting a new benchmark for large-area semitransparent modules. Furthermore, we demonstrate the feasibility of BIPVs in terms of power generation, energy storage, and temperature control through a scale-down model with a 600 cm2 power-generating window. These results reveal promising prospects for ST-OSCs in real-world applications.

建筑集成光伏(bipv)是一种很有前途的半透明有机太阳能电池(ST-OSCs)。而活性层厚度分别为119 nm和301 nm的传统超薄(2供体稀释)ST-OSCs光利用效率(LUEs)分别为4.04%和3.02%。值得注意的是,100 cm2模块的CTM比为~85%,LUE为3.32%,这是由于其高膜厚公差,为大面积半透明模块设定了新的基准。此外,我们通过一个具有600 cm2发电窗口的缩小模型,证明了bipv在发电、储能和温度控制方面的可行性。这些结果揭示了ST-OSCs在实际应用中的良好前景。
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引用次数: 0
Energy-sensing molecule RORγ regulates cholesterol metabolism and immune signaling in diabetic kidney disease and aging 能量传感分子RORγ调节糖尿病肾病和衰老过程中的胆固醇代谢和免疫信号
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69724-2
Zhen Liang, Jiaqing Xiang, Guangyan Yang, Xiaomai Liu, Lixing Li, Yanchun Li, Yan Lu, Lin Kang, Yuanli Chen, Chuanrui Ma, Shu Yang
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引用次数: 0
Conformational biosensors delineate endosomal G protein regulation by GPCRs. 构象生物传感器描绘了gpcr对内体G蛋白的调节。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69329-9
Brian Wysolmerski, Nicole M Fisher, Andrew N Dates, Asuka Inoue, Emily E Blythe, Mark von Zastrow

Many GPCRs trigger a second phase of G protein-coupled signaling from endosomes after signaling from the plasma membrane, necessitating GPCRs to increase the concentration of active-state G proteins on the endosome membrane. How this is achieved remains unclear. Here, we show that three Gs-coupled GPCRs-the β2-adrenergic receptor, VIP-1 receptor, and adenosine 2B receptor-each trigger a net redistribution of Gαs from the plasma membrane to endosomes at native expression levels and without requiring receptor internalization. We then show that active-state Gαs production on endosomes, in contrast, is GPCR internalization-dependent. We further identify location bias in the selectivity of GPCR coupling between Gs and Gq on endosomes relative to the plasma membrane. We propose that endosomal Gs regulation involves discrete GPCR-G protein coupling reactions, one at the plasma membrane controlling Gs concentration and another at endosomes controlling Gs activity, and that GPCR endocytosis can switch signaling selectivity between G protein classes.

许多gpcr在从质膜发出信号后触发来自核内体的G蛋白偶联信号的第二阶段,这就要求gpcr增加核内体膜上活性状态G蛋白的浓度。如何实现这一目标尚不清楚。在这里,我们发现了三种gs偶联的gpcr——β2-肾上腺素能受体、VIP-1受体和腺苷2B受体——每一种都能触发Gαs从质膜到核内体的净再分配,达到天然表达水平,而不需要受体内化。相反,我们发现核内体上活性态Gαs的产生依赖于GPCR的内化。我们进一步确定了相对于质膜,GPCR在核内体上g和Gq之间偶联的选择性的位置偏差。我们提出,内体Gs调控涉及离散的GPCR-G蛋白偶联反应,一个在质膜上控制Gs浓度,另一个在内体上控制Gs活性,并且GPCR内吞作用可以改变G蛋白类别之间的信号选择性。
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引用次数: 0
Electrocatalytic C(sp3)-H bond functionalization using biomass-derived electrodes. 生物质电极电催化C(sp3)-氢键功能化。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69274-7
Lijun Lu, Yan Li, Hao Li, Xueyu Jiang, Xianglin Pei, Dali Yang, Yu-Chung Chang, Jeng-Lung Chen, Fan Liao, Aiwen Lei

Organic electrosynthesis is a versatile and evergreen tool for constructing chemical compounds. However, the study of highly active electrodes has not received enough attention, which limits the further development of organic electrosynthesis. This work introduces a bottom-up route to prepare chitin-derived composite carbon aerogel electrodes (CCAEs), which can be directly used as electrodes in organic electrosynthesis systems. Various metal nanoparticles, such as Pt, Pd, RuO2, Cu and Ni, are well confined in these free-standing and porous CCAEs (M-CCAEs). The linear sweep voltammetry and in-situ Raman tests under electrochemical conditions show that RuO2-CCAEs possess good electrochemical oxidation ability for chlorine anions and good stabilizing effect on the generated chlorine radicals, which can serve as a mediator for the electrochemical C(sp3)-H activation. The combination of M-CCAEs with mediators achieves a series of electrochemical oxidative C(sp3)-H chlorination, bromination, nitration and etherification. Moreover, M-CCAEs promote the electrochemical hydrogen isotope exchange reaction of some important drug molecule structures, such as Ibuprofen, Diclofenac and Zolpidem.

有机电合成是一种用途广泛、常绿的合成化合物的方法。然而,对高活性电极的研究还没有得到足够的重视,这限制了有机电合成的进一步发展。本工作介绍了一种自下而上制备几丁质衍生的复合碳气凝胶电极(CCAEs)的方法,该电极可直接用作有机电合成系统的电极。各种金属纳米颗粒,如Pt, Pd, RuO2, Cu和Ni,都被很好地限制在这些独立的多孔ccae (m - ccae)中。电化学条件下的线性扫描伏安和原位拉曼测试表明,RuO2-CCAEs对氯离子具有良好的电化学氧化能力,对生成的氯自由基具有良好的稳定作用,可以作为C(sp3)-H的电化学活化介质。m - ccae与介质结合可实现C(sp3)-H的氯化、溴化、硝化和醚化等一系列电化学氧化反应。此外,m - ccae促进了一些重要药物分子结构的电化学氢同位素交换反应,如布洛芬、双氯芬酸和唑吡坦。
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引用次数: 0
Poly(vinyl alcohol) induced chirality inversion and amplification of circularly polarized room-temperature phosphorescence in homopolypeptide aggregates. 聚乙烯醇诱导均多肽聚集体室温圆极化磷光的手性反转和放大。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69707-3
Jinhui Jiang, Yiwen Pan, Jingyi Zhao, Siwei Zhang, Fulong Ma, Zicong Zhang, Mengli Liu, Zijie Qiu, Zheng Zhao, Jianwei Sun, Ryan T K Kwok, Yu Xiong, Jacky W Y Lam, Wei Han, Ben Zhong Tang

Organic circularly polarized room-temperature phosphorescence (CPRTP) materials represent an emerging research frontier with broad application prospects. However, achieving efficient and controllable CPRTP remains challenging due to inefficient chirality transfer and the limited ability to regulate chiral environments. Here, we develop a strategy involving self-assembled chiral homopolypeptides to realize manipulable CPRTP. Chiral homopolypeptides functionalized with achiral phosphorescent terminals are first designed, which self-assemble into vesicles exhibiting weak CPRTP. Remarkably, dispersing these vesicles into a poly(vinyl alcohol) matrix induces structural reorganization, leading to inversion and significant amplification of CPRTP. Experimental and computational studies reveal the critical role of matrix-assistance in chirality propagation, inversion, and amplification. Moreover, multicolor afterglow films with tunable emissions are readily achieved by varying the terminal phosphor. This work not only establishes a universal platform for constructing tunable CPRTP materials through homopolypeptide self-assembly but also provides deep mechanistic insights into supramolecular chirality manipulation.

有机圆极化室温磷光(CPRTP)材料是一个新兴的研究前沿,具有广阔的应用前景。然而,由于低效率的手性转移和有限的调节手性环境的能力,实现高效和可控的CPRTP仍然具有挑战性。在这里,我们开发了一种涉及自组装手性均多肽的策略来实现可操纵的CPRTP。首先设计了具有非手性磷光末端功能化的手性均多肽,其自组装成具有弱CPRTP的囊泡。值得注意的是,将这些囊泡分散到聚乙烯醇基质中可诱导结构重组,导致CPRTP的倒置和显著扩增。实验和计算研究揭示了矩阵辅助在手性传播、反转和放大中的关键作用。此外,通过改变终端荧光粉,可以很容易地获得具有可调谐发射的多色余辉薄膜。这项工作不仅建立了一个通过均多肽自组装构建可调CPRTP材料的通用平台,而且为超分子手性操纵提供了深入的机制见解。
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引用次数: 0
Interface-driven energy-independent charge extraction in GaN photocatalysts. 氮化镓光催化剂界面驱动的能量无关电荷提取。
IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69683-8
Yuying Gao, Yuxin Xie, Christian Höhn, Markus Wollgarten, Holger Kropf, Fengtao Fan, Can Li, Roel van de Krol, Dennis Friedrich

Ultrafast charge transfer dynamics are key to photocatalytic efficiency, governing energy relaxation and surface reactivity. However, the temporal evolution of carrier energy landscapes following photoexcitation, particularly at complex metal/semiconductor interfaces, remains poorly understood. Here, we present a surface- and energy-resolved investigation of ultrafast electron dynamics across bare and Pt-modified gallium nitride (GaN) surfaces using time-resolved two-photon photoemission spectroscopy. We show that photogenerated electrons rapidly thermalize to the conduction band minimum and undergo sub-picosecond trapping in nitrogen-vacancy-related surface states. Surface modification with Pt suppresses these trapping channels and introduces an energy-independent ultrafast electron transfer pathway (~50 fs) from GaN into Pt. By disentangling interfacial charge transfer from intrinsic relaxation mechanisms through tailored pump-probe configurations, we demonstrate that Pt facilitates picosecond-scale electron transport from the bulk to the surface by photoinduced dynamic band flattening. Modulating these ultrafast dynamics through interfacial engineering significantly enhances charge separation and photoelectrochemical performance. This study deepens the understanding of interface-dependent relaxation and transfer processes of photocarriers and provides valuable guidance for rational design of advanced photocatalytic systems.

超快电荷转移动力学是光催化效率、控制能量松弛和表面反应性的关键。然而,光激发后载流子能量景观的时间演变,特别是在复杂的金属/半导体界面,仍然知之甚少。在这里,我们提出了一个表面和能量分辨的研究在裸露和pt修饰的氮化镓(GaN)表面上的超快电子动力学使用时间分辨双光子光电发射光谱。我们发现,光产生的电子迅速热化到导带的最小值,并经历亚皮秒捕获在氮空位相关的表面状态。用Pt修饰表面抑制了这些捕获通道,并引入了从GaN到Pt的能量无关的超快电子转移途径(~50 fs)。通过定制的泵浦-探针配置解除了从本然弛豫机制的界面电荷转移,我们证明了Pt通过光诱导动态能带平坦化促进了皮秒级电子从体到表面的传输。通过界面工程调节这些超快动力学可以显著提高电荷分离和光电化学性能。该研究加深了对光载体界面依赖性松弛和转移过程的理解,为合理设计先进的光催化体系提供了有价值的指导。
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引用次数: 0
Mitochondrial heteroplasmy is a risk factor for the development of chronic lymphocytic leukemia 线粒体异质性是慢性淋巴细胞白血病发生的危险因素
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69861-8
Sergiu Pasca, Yun Soo Hong, Wen Shi, Daniela Puiu, Nicole J. Lake, Monkol Lek, Eliseo Guallar, Dan E. Arking, Lukasz P. Gondek
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引用次数: 0
Phase diagram and spectroscopic signatures of a supersolid in the quantum ising magnet K2Co(SeO3)2 量子磁体K2Co(SeO3)2中超固体的相图和光谱特征
IF 16.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-18 DOI: 10.1038/s41467-026-69661-0
Tong Chen, Alireza Ghasemi, Junyi Zhang, Liyu Shi, Zhenisbek Tagay, Youzhe Chen, Lei Chen, Eun Sang Choi, Marcelo Jaime, Minseong Lee, Yiqing Hao, Huibo Cao, Barry L. Winn, Andrey A. Podlesnyak, Daniel M. Pajerowski, Ruidan Zhong, Xianghan Xu, N. P. Armitage, Robert Cava, Collin Broholm
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引用次数: 0
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