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Targeted protein degradation via cellular trafficking of nanoparticles 通过纳米粒子的细胞贩运实现有针对性的蛋白质降解
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-28 DOI: 10.1038/s41565-024-01801-3
Yang Liu, Runhan Liu, Jiawei Dong, Xue Xia, Haoying Yang, Sijun Wei, Linlin Fan, Mengke Fang, Yan Zou, Meng Zheng, Kam W. Leong, Bingyang Shi

Strategies that selectively bind proteins of interest and target them to the intracellular protein recycling machinery for targeted protein degradation have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmaceutical industry. However, targeting any new protein of interest with current degradation tools requires a laborious case-by-case design for different diseases and cell types, especially for extracellular targets. Here we observe that nanoparticles can mediate specific receptor-independent internalization of a bound protein and further develop a general strategy for degradation of extracellular proteins of interest by making full use of clinically approved components. This extremely flexible strategy aids in targeted protein degradation tool development and provides knowledge for targeted drug therapies and nanomedicine design.

在生物医学研究和制药业中,选择性结合感兴趣的蛋白质并将其靶向到细胞内蛋白质回收机制以实现有针对性的蛋白质降解的策略,最近已成为治疗无法药物靶点的有力工具。然而,利用目前的降解工具靶向任何新的感兴趣的蛋白质需要针对不同的疾病和细胞类型,特别是细胞外靶点进行逐个设计。在这里,我们观察到纳米粒子可以介导特异性受体独立于结合蛋白的内化,并充分利用临床认可的成分,进一步开发了降解细胞外相关蛋白的通用策略。这种极其灵活的策略有助于开发靶向蛋白质降解工具,并为靶向药物疗法和纳米药物设计提供知识。
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引用次数: 0
Unravelling topological states in quantum spin chains 揭示量子自旋链中的拓扑状态
IF 38.1 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-28 DOI: 10.1038/s41565-024-01806-y
Deung-Jang Choi, Dario Bercioux
Scanning tunnelling microscopy experiments enable the realization of artificially built topological quantum magnets with titanium atoms and graphene goblets.
通过扫描隧道显微镜实验,实现了用钛原子和石墨烯小球人工制造拓扑量子磁体。
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引用次数: 0
Filamentous phages as tumour-targeting immunotherapeutic bionanofibres 丝状噬菌体作为肿瘤靶向免疫治疗仿生纤维
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-28 DOI: 10.1038/s41565-024-01800-4
Hui Yue, Yan Li, Tao Yang, Yecheng Wang, Qing Bao, Yajing Xu, Xiangyu Liu, Yao Miao, Mingying Yang, Chuanbin Mao

Programmed cell death-ligand 1 (PD-L1) blockers have advanced immunotherapy, but their lack of tumour homing capability represents a substantial challenge. Here we show that genetically engineered filamentous phages can be used as tumour-targeting immunotherapeutic agents that reduce the side effects caused by untargeted delivery of PD-L1 blockers. Specifically, we improved biopanning to discover a peptide binding the extracellular domain of PD-L1 and another targeting both melanoma tissues and cancer cells. The two peptides were genetically fused to the sidewall protein and tip protein of fd phages, respectively. The intravenously injected phages homed to tumours and bound PD-L1 on cancer cells, effectively blocking PD-1/PD-L1 recognition to trigger targeted immunotherapy without body weight loss, organ abnormalities and haematological aberrations. The phages, cost-effectively replicated by bacteria, are cancer-targeting immunotherapeutic nanofibres that can be flexibly designed to target different cancer types and immune checkpoints.

程序性细胞死亡配体 1(PD-L1)阻断剂推动了免疫疗法的发展,但它们缺乏肿瘤归巢能力是一个巨大的挑战。在这里,我们展示了经过基因工程改造的丝状噬菌体可用作肿瘤靶向免疫治疗药物,从而减少 PD-L1 阻断剂非靶向递送所带来的副作用。具体来说,我们改进了生物扫描,发现了一种结合 PD-L1 细胞外结构域的多肽,以及另一种同时靶向黑色素瘤组织和癌细胞的多肽。这两种肽分别与 fd 噬菌体的侧壁蛋白和尖端蛋白进行了基因融合。静脉注射噬菌体后,噬菌体会进入肿瘤并与癌细胞上的PD-L1结合,有效阻断PD-1/PD-L1的识别,从而引发靶向免疫疗法,且不会导致体重减轻、器官异常和血液畸变。噬菌体通过细菌复制,成本效益高,是一种癌症靶向免疫治疗纳米纤维,可灵活设计为针对不同癌症类型和免疫检查点。
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引用次数: 0
Self-cleaning electrode for stable synthesis of alkaline-earth metal peroxides 用于稳定合成碱土金属过氧化物的自清洁电极
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-28 DOI: 10.1038/s41565-024-01815-x
Minli Wang, Jinhuan Cheng, Wenwen Xu, Dandan Zhu, Wuyong Zhang, Yingjie Wen, Wanbing Guan, Jinping Jia, Zhiyi Lu

Alkaline-earth metal peroxides (MO2, M = Ca, Sr, Ba) represent a category of versatile and clean solid oxidizers, while the synthesis process usually consumes excessive hydrogen peroxide (H2O2). Here we discover that H2O2 synthesized via two-electron electrochemical oxygen reduction (2e ORR) on the electrode surface can be efficiently and durably consumed to produce high-purity MO2 in an alkaline environment. The crucial factor lies in the in-time detachment of in situ-generated MO2 from the self-cleaning electrode, where the solid products spontaneously detach from the electrode to solve the block issue. The self-cleaning electrode is achieved by constructing micro-/nanostructure of a highly active catalyst with appropriate surface modification. In experiments, an unprecedented accumulated selectivity (~99%) and durability (>1,000 h, 50 mA cm2) are achieved for electrochemical synthesis of MO2. Moreover, the comparability of CaO2 and H2O2 for tetracycline degradation with hydrodynamic cavitation is validated in terms of their close efficacies (degradation efficiency of 87.9% and 93.6% for H2O2 and CaO2, respectively).

碱土金属过氧化物(MO2,M = Ca、Sr、Ba)是一类多功能、清洁的固体氧化剂,而合成过程通常会消耗过量的过氧化氢(H2O2)。在这里,我们发现通过电极表面的双电子电化学氧还原(2e- ORR)合成的 H2O2 可以在碱性环境中高效、持久地消耗,从而生产出高纯度的 MO2。关键因素在于原位生成的 MO2 能及时从自清洁电极上脱离,固体产物自发地从电极上脱离,从而解决了堵塞问题。自清洁电极是通过构建高活性催化剂的微/纳米结构并进行适当的表面修饰实现的。在实验中,MO2 的电化学合成实现了前所未有的累积选择性(约 99%)和持久性(1,000 h,50 mA cm-2)。此外,还验证了 CaO2 和 H2O2 在水动力空化作用下降解四环素的相似效率(H2O2 和 CaO2 的降解效率分别为 87.9% 和 93.6%)。
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引用次数: 0
Small structural changes in siloxane-based lipidoids improve tissue-specific mRNA delivery 硅氧烷类脂质的微小结构变化可改善组织特异性 mRNA 递送
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-28 DOI: 10.1038/s41565-024-01748-5
From a single library of siloxane-based lipidoids, siloxane-incorporated lipid nanoparticles (SiLNPs) involving minor alterations in lipid chemistry yield tissue-specific mRNA delivery to the liver, lung, or spleen. Upon enhanced intracellular delivery, these SiLNPs show clinical promise for protein replacement therapies, regenerative medicine, and CRISPR–Cas-based gene editing applications.
从单一的硅氧烷类脂质库中,硅氧烷包合脂质纳米颗粒(SiLNPs)在脂质化学性质上稍作改变,就能将组织特异性 mRNA 运送到肝脏、肺部或脾脏。这些 SiLNPs 在增强细胞内递送后,在蛋白质替代疗法、再生医学和基于 CRISPR-Cas 的基因编辑应用方面显示出临床前景。
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引用次数: 0
Silk protein connecting water and nanofabrication 连接水与纳米制造的蚕丝蛋白
IF 38.1 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-25 DOI: 10.1038/s41565-024-01808-w
Sunghwan Kim
The amphiphilic silk fibroin is a natural surfactant. It influences interface interactions and enables wetting hydrophobic surfaces with aqueous solutions. This offers a sustainable route for fabricating water-processed nanodevices without prior surface modification.
两亲性蚕丝纤维素是一种天然表面活性剂。它能影响界面相互作用,并能用水溶液润湿疏水性表面。这为制造水处理纳米器件提供了一条可持续的途径,而无需事先进行表面改性。
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引用次数: 0
Out-of-plane coordination of iridium single atoms with organic molecules and cobalt–iron hydroxides to boost oxygen evolution reaction 铱单原子与有机分子和钴铁氢氧化物平面外配位,促进氧进化反应
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-21 DOI: 10.1038/s41565-024-01807-x
Jie Zhao, Yue Guo, Zhiqi Zhang, Xilin Zhang, Qianqian Ji, Hua Zhang, Zhaoqi Song, Dongqing Liu, Jianrong Zeng, Chenghao Chuang, Erhuan Zhang, Yuhao Wang, Guangzhi Hu, Muhammad Asim Mushtaq, Waseem Raza, Xingke Cai, Francesco Ciucci

Advancements in single-atom-based catalysts are crucial for enhancing oxygen evolution reaction (OER) performance while reducing precious metal usage. A comprehensive understanding of underlying mechanisms will expedite this progress further. Here we report Ir single atoms coordinated out-of-plane with dimethylimidazole (MI) on CoFe hydroxide (Ir1/(Co,Fe)-OH/MI). This Ir1/(Co,Fe)-OH/MI catalyst, which was prepared using a simple immersion method, delivers ultralow overpotentials of 179 mV at a current density of 10 mA cm−2 and 257 mV at 600 mA cm−2 as well as an ultra-small Tafel slope of 24 mV dec−1. Furthermore, Ir1/(Co,Fe)-OH/MI has a total mass activity exceeding that of commercial IrO2 by a factor of 58.4. Ab initio simulations indicate that the coordination of MI leads to electron redistribution around the Ir sites. This causes a positive shift in the d-band centre at adjacent Ir and Co sites, facilitating an optimal energy pathway for OER.

单原子催化剂的进步对于提高氧进化反应(OER)性能并减少贵金属用量至关重要。全面了解潜在的机理将进一步加快这一进程。在此,我们报告了氢氧化钴铁上与二甲基咪唑(MI)平面外配位的 Ir 单原子(Ir1/(Co,Fe)-OH/MI)。这种Ir1/(Co,Fe)-OH/MI催化剂采用简单的浸泡法制备,在电流密度为10 mA cm-2时具有179 mV的超低过电位,在电流密度为600 mA cm-2时具有257 mV的超低过电位,以及24 mV dec-1的超小塔菲尔斜率。此外,Ir1/(Co,Fe)-OH/MI 的总质量活性比商用二氧化铱高出 58.4 倍。Ab initio 模拟表明,MI 的配位导致电子在 Ir 位点周围重新分布。这导致相邻 Ir 和 Co 位点的 d 带中心发生正向移动,从而为 OER 提供了最佳的能量途径。
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引用次数: 0
Synthetic syntrophy for adenine nucleotide cross-feeding between metabolically active nanoreactors 用于代谢活性纳米反应器之间腺嘌呤核苷酸交叉馈送的合成合成物
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-21 DOI: 10.1038/s41565-024-01811-1
Laura Heinen, Marco van den Noort, Martin S. King, Edmund R. S. Kunji, Bert Poolman

Living systems depend on continuous energy input for growth, replication and information processing. Cells use membrane proteins as nanomachines to convert light or chemical energy of nutrients into other forms of energy, such as ion gradients or adenosine triphosphate (ATP). However, engineering sustained fuel supply and metabolic energy conversion in synthetic systems is challenging. Here, inspired by endosymbionts that rely on the host cell for their nutrients, we introduce the concept of cross-feeding to exchange ATP and ADP between lipid-based compartments hundreds of nanometres in size. One population of vesicles enzymatically produces ATP in the mM concentration range and exports it. A second population of vesicles takes up this ATP to fuel internal reactions. The produced ADP feeds back to the first vesicles, and ATP-dependent reactions can be fuelled sustainably for up to at least 24 h. The vesicles are a platform technology to fuel ATP-dependent processes in a sustained fashion, with potential applications in synthetic cells and nanoreactors. Fundamentally, the vesicles enable studying non-equilibrium processes in an energy-controlled environment and promote the development and understanding of constructing life-like metabolic systems on the nanoscale.

生命系统的生长、复制和信息处理都依赖于持续的能量输入。细胞利用膜蛋白作为纳米机器,将光或营养物质的化学能转化为其他形式的能量,如离子梯度或三磷酸腺苷(ATP)。然而,在合成系统中进行持续的燃料供应和代谢能量转换工程具有挑战性。在这里,受依赖宿主细胞获取营养的内共生体的启发,我们引入了交叉进食的概念,在数百纳米大小的脂质隔间交换 ATP 和 ADP。一个囊泡群以酶促方式产生毫摩尔浓度范围内的 ATP 并将其输出。第二组囊泡吸收这种 ATP,为内部反应提供燃料。这种囊泡是一种平台技术,可持续为依赖 ATP 的过程提供燃料,有望应用于合成细胞和纳米反应器。从根本上说,囊泡能够在能量受控的环境中研究非平衡过程,并促进在纳米尺度上构建类似生命的新陈代谢系统的发展和理解。
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引用次数: 0
Linearly programmable two-dimensional halide perovskite memristor arrays for neuromorphic computing 用于神经形态计算的线性可编程二维卤化物过氧化物忆阻器阵列
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-18 DOI: 10.1038/s41565-024-01790-3
Seung Ju Kim, In Hyuk Im, Ji Hyun Baek, Sungkyun Choi, Sung Hyuk Park, Da Eun Lee, Jae Young Kim, Soo Young Kim, Nam-Gyu Park, Donghwa Lee, J. Joshua Yang, Ho Won Jang

The exotic properties of three-dimensional halide perovskites, such as mixed ionic–electronic conductivity and feasible ion migration, have enabled them to challenge traditional memristive materials. However, the poor moisture stability and difficulty in controlling ion transport due to their polycrystalline nature have hindered their use as a neuromorphic hardware. Recently, two-dimensional (2D) halide perovskites have emerged as promising artificial synapses owing to their phase versatility, microstructural anisotropy in electrical and optoelectronic properties, and excellent moisture resistance. However, their asymmetrical and nonlinear conductance changes still limit the efficiency of training and accuracy of inference. Here we achieve highly linear and symmetrical conductance changes in Dion–Jacobson 2D perovskites. We further build a 7 × 7 crossbar array based on analogue perovskite synapses, achieving a high device yield, low variation with synaptic weight storing capability, multi-level analogue states with long retention, and moisture stability over 7 months. We explore the potential of such devices in large-scale image inference via simulations and show an accuracy within 0.08% of the theoretical limit. The excellent device performance is attributed to the elimination of gaps between inorganic layers, allowing the halide vacancies to migrate homogeneously regardless of grain boundaries. This was confirmed by first-principles calculations and experimental analysis.

三维卤化物包晶的奇特性质,如离子-电子混合导电性和可行的离子迁移,使它们能够挑战传统的记忆材料。然而,由于它们的多晶性质,湿度稳定性差,离子传输难以控制,这阻碍了它们作为神经形态硬件的应用。最近,二维(2D)卤化物包荧光体因其相位多变性、电学和光电特性的微结构各向异性以及优异的防潮性能而成为前景广阔的人工突触。然而,它们的非对称和非线性电导变化仍然限制了训练的效率和推断的准确性。在这里,我们在 Dion-Jacobson 二维包晶石中实现了高度线性和对称的电导变化。我们进一步构建了一个基于模拟包晶石突触的 7 × 7 横条阵列,实现了高器件产量、突触重量存储能力的低变化、多级模拟状态的长保持和 7 个月的湿度稳定性。我们通过模拟探索了这种器件在大规模图像推理中的潜力,结果表明其精确度在理论极限的 0.08% 以内。器件的优异性能归功于消除了无机层之间的间隙,使卤化物空位不受晶界的影响而均匀迁移。第一原理计算和实验分析证实了这一点。
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引用次数: 0
Energy-efficient magnetization manipulation using picosecond current pulses 利用皮秒电流脉冲进行高能效磁化控制
IF 38.3 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-10-16 DOI: 10.1038/s41565-024-01789-w
Reducing the duration of current pulses used to perform magnetization switching via spin–orbit torques in ferromagnetic and ferrimagnetic samples from microseconds to picoseconds leads to a continuous decrease in the energy consumption. These findings show that speed and efficiency of switching can be combined in various magnetic materials with different properties.
将铁磁性和铁磁性样品中通过自旋轨道力矩进行磁化切换的电流脉冲持续时间从微秒级缩短到皮秒级,可持续降低能耗。这些研究结果表明,在具有不同特性的各种磁性材料中,可以将切换速度和效率结合起来。
{"title":"Energy-efficient magnetization manipulation using picosecond current pulses","authors":"","doi":"10.1038/s41565-024-01789-w","DOIUrl":"https://doi.org/10.1038/s41565-024-01789-w","url":null,"abstract":"Reducing the duration of current pulses used to perform magnetization switching via spin–orbit torques in ferromagnetic and ferrimagnetic samples from microseconds to picoseconds leads to a continuous decrease in the energy consumption. These findings show that speed and efficiency of switching can be combined in various magnetic materials with different properties.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"44 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Nature nanotechnology
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