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Engineering two-in-one DNA nanohybrids to evaluate anti-cancer effects through activatable RNA imaging 设计二合一 DNA 纳米混合物,通过可激活的 RNA 成像评估抗癌效果
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-14 DOI: 10.1016/j.nantod.2024.102496
Dejie Lu , Caichang Xiong , Lele Li , Jian Zhao , Yaoxuan Chen , Li Zheng

The development of DNA-based imaging techniques provides a promising way for theranostic applications. However, the dramatic chemical difference between DNA probes and therapeutics significantly hinders the construction of an ideal theranostic system for evaluation of therapeutic effects via in situ molecular imaging. In this work, we report a simple approach for the construction of a two-in-one DNA nanohybrid via one-step assembly of DNA probes and small molecular drugs, enabling evaluation of therapeutic effects via sensitive imaging of apoptosis-related mRNA. The nanohybrid was self-assembled from a rationally designed molecular beacon (MB) probe, doxorubicin (DOX, a chemotherapeutic drug) and Fe (II) ions through coordination interactions, which possesses anti-cancer effects from chemotherapeutics and the capability of efficient co-delivery of DNA probes without transfection agents. By tracking pro-apoptotic Bax mRNA expression with the MB, this system allows real-time monitoring of cell apoptotic process in response to drug treatment, enabling assessment of therapeutic effects of small molecular drugs. In addition, the approach is extended to the imaging of target microRNA in the drug treatment based on flexible DNA probe design, demonstrating the universality of this strategy. Moreover, the modular design of this DNA nanohybrid allows the introduction of photosensitizers into this system for efficient photodynamic therapy and simultaneous mRNA monitoring. This strategy expands the theranostic toolbox for the in situ evaluation of treatment response and screening anticancer drugs.

基于 DNA 的成像技术的发展为治疗学应用提供了一条前景广阔的途径。然而,DNA 探针与治疗药物之间巨大的化学差异极大地阻碍了通过原位分子成像评估治疗效果的理想治疗系统的构建。在这项工作中,我们报告了一种简单的方法,即通过一步组装 DNA 探针和小分子药物来构建二合一 DNA 纳米杂交系统,从而通过对细胞凋亡相关 mRNA 的灵敏成像来评估治疗效果。该纳米杂交体由合理设计的分子信标(MB)探针、多柔比星(DOX,一种化疗药物)和铁(II)离子通过配位相互作用自组装而成,不仅具有化疗药物的抗癌效果,还能在不使用转染剂的情况下高效地共同递送DNA探针。通过利用 MB 跟踪促凋亡 Bax mRNA 的表达,该系统可实时监测细胞凋亡过程对药物治疗的反应,从而评估小分子药物的治疗效果。此外,基于灵活的 DNA 探针设计,该方法还可扩展到药物治疗中的目标 microRNA 成像,从而证明了这一策略的通用性。此外,这种 DNA 纳米杂交技术的模块化设计允许在该系统中引入光敏剂,以实现高效的光动力疗法和同步 mRNA 监测。这一策略为原位评估治疗反应和筛选抗癌药物扩展了治疗工具箱。
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引用次数: 0
Protein denaturation for in-depth serum proteome profiling and enhanced cancer diagnosis 蛋白质变性用于深入分析血清蛋白质组和强化癌症诊断
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-14 DOI: 10.1016/j.nantod.2024.102488
Yueli Xie , Mengjie Wang , Haoxiang Guo , Baichuan Jin , Chenlu Xu , Xin Dai , Yiyang Fu , Ze Wang , Weizhao Yao , Yuan Liu , Weihong Tan

The in-depth blood-based proteomics is significantly limited owing to the intrinsic wide dynamic range of protein concentrations (over 10 orders of magnitude) and highly abundant proteins (albumin, etc.) in blood. Here, we developed a protein denaturation strategy to enhance the serum proteomic depth via nanoparticle-protein corona for enhanced non-small cell lung cancer (NSCLC) diagnosis. We developed an optimal denaturant panel consists of nature, 30 % acetonitrile, 40 % RapiGest, and 4 M urea respectively treated serum to form various nanoparticle-protein coronas with magnetic nanoparticles (MNPs). Based on this panel, we have identified 1846 proteins by profiling 172 NSCLC serum samples, significantly enhancing the depth of serum proteomics. Furthermore, we selected 15 key proteins with random forest algorithm to distinguish the benign and malignant nodules and achieved an ROC-AUC of 98.44 %. Differentially expressed protein-based pathway analysis revealed that metabolic and immune-related pathways were significantly enriched, in which apolipoproteins play pivotal role in the transfer from benign to malignant nodules. Our study demonstrated a facile serum denaturation strategy for enhanced depth of serum proteomics which will benefit the cancer biomarker discovery and diagnosis.

由于血液中蛋白质浓度的内在动态范围很宽(超过 10 个数量级)且蛋白质(白蛋白等)含量很高,因此基于血液的深度蛋白质组学研究受到很大限制。在此,我们开发了一种蛋白质变性策略,通过纳米粒子-蛋白质电晕来提高血清蛋白质组学的深度,从而增强非小细胞肺癌(NSCLC)的诊断能力。我们开发了一种最佳变性剂面板,由自然、30 % 乙腈、40 % RapiGest 和 4 M 尿素组成,分别处理血清,与磁性纳米粒子(MNPs)形成各种纳米粒子-蛋白质冠。在此基础上,我们对 172 份 NSCLC 血清样本进行了分析,鉴定出 1846 个蛋白质,大大提高了血清蛋白质组学的深度。此外,我们还利用随机森林算法筛选出了15个关键蛋白来区分良性和恶性结节,其ROC-AUC达到了98.44%。基于差异表达蛋白的通路分析表明,代谢和免疫相关通路显著富集,其中脂蛋白在良性结节向恶性结节的转移中起着关键作用。我们的研究展示了一种简便的血清变性策略,可提高血清蛋白质组学的深度,这将有利于癌症生物标志物的发现和诊断。
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引用次数: 0
Strategic structural design of transition metal electrocatalysts for efficient water splitting: A comprehensive review 用于高效水分离的过渡金属电催化剂的战略结构设计:全面综述
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-13 DOI: 10.1016/j.nantod.2024.102487
Jagadis Gautam, Seul-Yi Lee, Soo-Jin Park

Electrochemical water splitting (EWS) is a pivotal method for sustainable hydrogen (H2) generation, yet it faces challenges due to limited accessibility and high costs associated with precious metal electrocatalysts. Efforts in research have thus been directed toward developing cost-effective alternatives to drive widespread adoption. Transition metals (TMs) emerge as promising candidates to replace noble metal-based electrocatalysts in EWS, offering abundance and affordability. This review surveys recent advancements and innovative methodologies in designing TM-based electrocatalysts, focusing on strategies such as defect engineering of MXene. This approach demonstrates considerable potential in enhancing EWS technology. Moreover, the review underscores the necessity of comprehending the fundamental mechanisms and activity-limiting factors inherent in EWS. It advocates for catalyst engineering strategies, integration of theoretical calculations, and modern in situ characterization techniques to facilitate the commercialization of electrocatalysts for sustainable hydrogen production. By integrating recent progress and ongoing challenges, this review seeks to present insights into the frontier of TM-based electrocatalysts and their role in advancing the field of EWS toward a more sustainable future.

电化学水分离(EWS)是可持续制氢(H2)的关键方法,但由于贵金属电催化剂的可获得性有限且成本高昂,这种方法面临着挑战。因此,研究人员一直致力于开发具有成本效益的替代品,以推动其广泛应用。过渡金属(TMs)以其丰富的资源和可负担性,成为替代 EWS 中贵金属电催化剂的理想候选材料。本综述探讨了设计基于 TM 的电催化剂的最新进展和创新方法,重点是 MXene 的缺陷工程等策略。这种方法在提高 EWS 技术方面具有相当大的潜力。此外,综述还强调了理解 EWS 固有的基本机制和活性限制因素的必要性。它倡导催化剂工程策略、理论计算与现代原位表征技术的整合,以促进可持续制氢电催化剂的商业化。通过整合最新进展和当前挑战,本综述旨在深入探讨基于 TM 的电催化剂的前沿及其在推动 EWS 领域迈向更可持续的未来中的作用。
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引用次数: 0
In situ revealing the dehydration and atomic structure evolution of protonated titanate nanotubes via environmental transmission electron microscopy 通过环境透射电子显微镜原位揭示质子化钛酸钡纳米管的脱水和原子结构演变过程
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-13 DOI: 10.1016/j.nantod.2024.102503
Chunxi Li , Xiaoyun Guo , Ying Jiang, Zhong-kang Han, Wentao Yuan, Hangsheng Yang, Yong Wang

The precise control of nanomaterial microstructure at the atomic level relies on the comprehensive understanding of atomic structural transition during the fabrication process at the atomic level. The phase transition from protonated titanate to TiO2 is a prevalent route to synthesize low dimensional TiO2-based nanomaterials, which exhibit excellent photocatalytic, lithium-ion battery performances, while the detailed phase transition mechanism remains to be clarified due to lack of atomic-level in situ information. Herein, the atomic structural transitions from one-dimensional H2Ti3O7 (HT) to TiO2(B) and anatase TiO2 (TB and TA) nanocrystals were revealed through in situ environmental transmission electron microscopy, which exhibited a two-step phase transition at 200–600 °C. (I) H2Ti3O7 to TiO2(B) transition began via an indirect pathway at ∼200 °C: The HT (200) interlayer dehydration occurred firstly with lattice shrinkage; Then TB discretely nucleated at the dehydrated H2Ti3O7 nanotube wall with a crystallographic relationship of (200)HT(200)TB {[001]HT[001]TB}; At higher temperature, the separated nuclei grew up with defects and distorted crystal lattice among them, which then connected and jointed to a single crystalline TB nanotube by atomic rearrangement. (II) The further transition of TiO2(B) to anatase TiO2 occurred via a direct pathway above 400 °C: Scarce nucleation event of TA phase was observed, which generated within TB nanocrystal with a crystallographic relationship of (200)TB(002)TA {[001]TB[010]TA}. Once a TA nucleus formed, it grew up to a large crystal by consuming the neighbor TB nanocrystals. These findings may contribute to comprehensively understanding phase transition and precisely manipulating the atomic structure of one-dimensional TiO2 nanocrystals.

要在原子水平上精确控制纳米材料的微观结构,就必须在原子水平上全面了解制备过程中的原子结构转变。从质子化钛酸酯到TiO2的相变是合成低维TiO2基纳米材料的普遍途径,这种材料具有优异的光催化、锂离子电池性能,但由于缺乏原子水平的原位信息,其详细的相变机制仍有待阐明。本文通过原位环境透射电子显微镜揭示了从一维H2Ti3O7(HT)到TiO2(B)和锐钛型TiO2(TB和TA)纳米晶体的原子结构转变,在200-600 ℃时呈现出两步相变。(I) H2Ti3O7 到 TiO2(B) 的转变在 ∼200 °C 时通过间接途径开始:首先,HT(200)层间脱水,晶格收缩;然后,TB 在脱水的 H2Ti3O7 纳米管壁上离散成核,其晶体学关系为(200)HT∥(200)TB {[001]HT∥[001]TB};在更高温度下,分离的晶核长大,它们之间存在缺陷和扭曲的晶格,然后通过原子重排连接成单晶的 TB 纳米管。(II) TiO2(B) 在 400 °C 以上通过直接途径进一步转变为锐钛矿型 TiO2:观察到 TA 相的稀少成核事件,它在 TB 纳米晶体内生成,其晶体学关系为 (200)TB∥(002)TA {[001]TB∥[010]TA}。一旦 TA 核形成,它就会通过吞噬邻近的 TB 纳米晶体而成长为大晶体。这些发现可能有助于全面理解相变和精确操纵一维二氧化钛纳米晶体的原子结构。
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引用次数: 0
Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information 封底外页 - 双栏图文摘要 TOC/TOC/封面图像图例(如适用)、条形码、摘要和索引信息
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-13 DOI: 10.1016/S1748-0132(24)00351-7
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引用次数: 0
Inside Back Cover - Graphical abstract TOC/TOC in double column continued from OBC if required, otherwise blank page 封底内页--图文摘要 TOC/TOC 双栏,如需要可从 OBC 续页,否则为空白页
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-13 DOI: 10.1016/S1748-0132(24)00350-5
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引用次数: 0
Photoferroptosis as a potent strategy for neuroblastoma treatment 光变态反应是治疗神经母细胞瘤的有效策略
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-12 DOI: 10.1016/j.nantod.2024.102498
Wenxin Zhang , Xiaodie Li , Chengyu Feng , Zihan Huang , Chao Zhang , Xintao Shuai , Lihua Yang

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been developed to treat tumors with potential of clinical applications due to their high spatiotemporal selectivity and non-invasiveness. Nevertheless, the hypoxia within the tumor microenvironment (TME) limits the efficacy of PDT. PTT has the risk of damaging surrounding normal tissues due to the high temperatures essential for killing tumor cells. Herein, we propose a new tumor treatment strategy based on photo-triggered ferroptosis of tumor cells, which is termed photoferroptosis therapy (PFT). The PFT agent (CuS&AIPH@PEG-PAE@PM) was synthesized by encapsulating a radical generator (2,2’-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) and a photothermal agent (copper sulfide, CuS) into an amphiphilic polymer (poly(ethylene glycol)-poly(β-amino ester), PEG-PAE) via self-assembly and a following coating with platelet membrane (PM). Under near-infrared (NIR) irradiation, the PFT agent CuS&AIPH@PEG-PAE@PM generates abundant alkyl radicals (R●) to trigger tumor cell ferroptosis in a moderate temperature and oxygen-independent manner. Meanwhile, the PFT agent also reduces the GSH level and thus suppresses GPX4 expression to promote ferroptosis, which further consolidates the antitumor effect of PFT. The PFT is expected to establish a promising phototherapy strategy against tumors, which has the potential to overcome the limitations of PDT and PTT.

光动力疗法(PDT)和光热疗法(PTT)因其高时空选择性和非侵入性,已被开发用于治疗肿瘤,并具有临床应用潜力。然而,肿瘤微环境(TME)中的缺氧限制了光热疗法的疗效。由于杀死肿瘤细胞所需的温度较高,PTT 有可能损伤周围的正常组织。在此,我们提出了一种基于光诱导肿瘤细胞铁突变的新型肿瘤治疗策略,即光铁突变疗法(PFT)。PFT 药剂(CuS&;AIPH@PEG-PAE@PM)是通过自组装将自由基发生器(2,2'-偶氮双[2-(2-咪唑啉-2-基)丙烷]二盐酸盐,AIPH)和光热剂(硫化铜,CuS)封装到两亲性聚合物(聚乙二醇-聚(β-氨基酯),PEG-PAE)中,然后包覆血小板膜(PM)而合成的。在近红外(NIR)照射下,PFT剂CuS&AIPH@PEG-PAE@PM会产生大量的烷基自由基(R●),以一种与温度和氧气无关的适度方式引发肿瘤细胞铁凋亡。同时,PFT 药剂还能降低 GSH 水平,从而抑制 GPX4 的表达,促进铁凋亡,进一步巩固 PFT 的抗肿瘤作用。PFT有望成为一种前景广阔的肿瘤光疗策略,有望克服PDT和PTT的局限性。
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引用次数: 0
A multi-adjuvant nanovaccine platform based on targeted delivery of specific antigens for cancer immunotherapy 基于特定抗原靶向递送的多辅助纳米疫苗平台,用于癌症免疫疗法
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-11 DOI: 10.1016/j.nantod.2024.102481
Wen Li, Qiu-Ling Zhang, Xiang-Yu Ma, Xuan Zeng, Xian-Zheng Zhang

Cancer vaccines have become a milestone in immunotherapy, but inadequate activation rate of antigen presenting cells (APCs) and low delivery efficiency of specific antigen have widely limited their clinical application. Here we design an engineered vaccine platform based on targeted delivery of specific antigens to activated APCs. This vaccine platform is implemented by loading an agonist for stimulator of interferon genes and tumor lysate protein with calcium phosphate as adjuvants, and coating the surface with mannose-modified liposomes. By loading different types of tumor antigen proteins, this nanovaccine platform successfully achieves tumor immunotherapy in breast and colon cancer bearing mice. In addition, personalized nanovaccine prepared from surgically removed tumor lysate proteins also significantly suppresses postsurgical distant tumor. Through the design of nanovaccine platform, we provide an efficient multi-adjuvant delivery platform for multiple types of tumor antigens, and also offer more ideas for personalized vaccine immunization. This nanovaccine platform has great prospects for transformation due to the designability and simplicity for the preparation.

癌症疫苗已成为免疫疗法的一个里程碑,但抗原呈递细胞(APC)活化率不足和特异性抗原递送效率低普遍限制了其临床应用。在此,我们设计了一种基于向活化的抗原呈递细胞定向递送特异性抗原的工程疫苗平台。这种疫苗平台的实现方法是:以磷酸钙为佐剂,加入刺激干扰素基因的激动剂和肿瘤裂解蛋白,并在其表面涂上甘露糖修饰的脂质体。通过负载不同类型的肿瘤抗原蛋白,该纳米疫苗平台成功实现了对乳腺癌和结肠癌小鼠的肿瘤免疫治疗。此外,用手术切除的肿瘤裂解蛋白制备的个性化纳米疫苗也能显著抑制手术后的远处肿瘤。通过纳米疫苗平台的设计,我们为多种类型的肿瘤抗原提供了一个高效的多辅助给药平台,也为个性化疫苗免疫提供了更多的思路。该纳米疫苗平台的可设计性和制备的简便性使其具有广阔的转化前景。
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引用次数: 0
NIR-II light-activated and Cu nanocatalyst-enabled bioorthogonal reaction in living systems for efficient tumor therapy 近红外-II 光激活和铜纳米催化剂在活体系统中的生物正交反应,用于高效肿瘤治疗
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-11 DOI: 10.1016/j.nantod.2024.102483
Hui Huang , Wendi Xuan , Jiakang Hai , Xue Wang , Meng Chen , Guobing Hong , Xinyue Dai , Lili Xia , Wei Feng , Yu Chen

Bioorthogonal reaction refers to chemical reactions that occur within a biological system without interfering the normal biochemical process, offering the unprecedented versatility in engineering chemical reactions within cells. However, the precise regulation of bioorthogonal reaction in living systems is mired by the complexity of the physiological environment and the toxicity of catalysts. Herein, considering the deeper tissue penetration and reduced phototoxicity compared to visible light and ultraviolet, a second near infrared (NIR-II) light-activated Cu-based bioorthogonal reaction is developed to achieve precise spatiotemporal control and effective switching for Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) mediated chemical transformations in tumor, reducing the off-target effects. The catalytic activity of Cu catalyst through valence state interconversion between Cu(II) and Cu(I) can be precisely regulated in a reversible manner under NIR-II light irradiation-induced photoelectron transfer, which controls the extent of desired drug synthesis in bioorthogonal reaction. Meanwhile, the adverse effects of Cu(I) can be substantially mitigated within normal tissues due to their oxygen-rich condition. By utilizing NIR-II light and oxygen level, the Cu bioorthogonal catalyst achieves a balance between catalytic activity and biocompatibility. The ability to achieve precise spatiotemporal control and reversible catalysis makes this NIR-II light-mediated CuAAC platform an efficient and adaptable tool for bioorthogonal chemistry in living systems.

生物正交反应是指在不干扰正常生化过程的情况下,在生物系统内发生的化学反应,为细胞内化学反应的工程化提供了前所未有的多功能性。然而,由于生理环境的复杂性和催化剂的毒性,生物系统中生物正交反应的精确调控陷入困境。在此,考虑到与可见光和紫外线相比,近红外光具有更深的组织穿透性和更低的光毒性,我们开发了第二种近红外(NIR-II)光催化的铜基生物正交反应,以实现对Cu(I)催化的叠氮-炔环加成(CuAAC)介导的肿瘤化学转化的精确时空控制和有效切换,减少脱靶效应。在近红外-II光照射诱导的光电子转移作用下,通过Cu(II)和Cu(I)之间的价态相互转化,Cu催化剂的催化活性可被以可逆的方式精确调控,从而控制生物正交反应中理想药物的合成程度。同时,由于正常组织富氧,Cu(I)的不良影响在正常组织内可以得到极大缓解。通过利用近红外-II 光和氧气水平,铜生物正交催化剂实现了催化活性和生物相容性之间的平衡。实现精确时空控制和可逆催化的能力使这种近红外-II 光介导的 CuAAC 平台成为活体系统中生物正交化学的一种高效、适应性强的工具。
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引用次数: 0
Device engineering of monolayer-based electronics 单层电子器件工程
IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-09-11 DOI: 10.1016/j.nantod.2024.102472
Chunyan Gao , Wei Si , Yani Huo , Yating Xiang , Guangwu Li , Jinying Wang , Chuancheng Jia , Xuefeng Guo

Monolayer-based electronics have emerged as a promising solution that solves the limitations of miniaturization in microelectronic circuits and paves the way for advanced electronic performance applications. Over the past few years, there have been significant advances in monolayer-based electronics from the refinement of fabrication techniques to the elucidation of fundamental mechanisms and the achievement of sophisticated electronic functionalities. In this review, we provide a timely, systematic overview of monolayer-based electronics, covering the preparation processes, charge transport mechanisms, thermoelectric effect, performance regulations, and functional applications. We also offer a detailed summary of devices that leverage either horizontal charge transport or vertical tunneling, along with their respective applications. Furthermore, we delve into the opportunities and challenges inherent in the realm of monolayer- or even single-molecule-based electronics, emphasizing potential breakthroughs that could revolutionize this swiftly evolving domain. Our review aims to provide a broad understanding of monolayer-based electronics and to inspire further research on their practical applications.

单层电子学是一种很有前途的解决方案,它解决了微电子电路微型化的局限性,并为先进的电子性能应用铺平了道路。在过去几年中,单层电子学从制造技术的完善到基本机制的阐明以及复杂电子功能的实现,都取得了重大进展。在这篇综述中,我们对单层电子学进行了及时、系统的概述,内容涵盖制备工艺、电荷传输机制、热电效应、性能规定和功能应用。我们还详细总结了利用水平电荷传输或垂直隧道的器件及其各自的应用。此外,我们还深入探讨了基于单层甚至单分子的电子学领域所固有的机遇和挑战,强调了可能给这一迅速发展的领域带来革命性变化的潜在突破。我们的综述旨在提供对单层电子学的广泛理解,并激发对其实际应用的进一步研究。
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引用次数: 0
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