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Ocean weather systems on icy moons, with application to Enceladus 冰卫星上的海洋天气系统,并应用于土卫二
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-06 DOI: 10.1126/sciadv.adn6857
Yixiao Zhang, Wanying Kang, John Marshall
We explore ocean circulation on a rotating icy moon driven by temperature gradients imposed at its upper surface due to the suppression of the freezing point of water with pressure, as might be induced by ice thickness variations on Enceladus. Using high-resolution simulations, we find that eddies dominate the circulation and arise from baroclinic instability, analogous to Earth’s weather systems. Multiple alternating jets, resembling those of Jupiter’s atmosphere, are sustained by these baroclinic eddies. We establish a theoretical model of the stratification and circulation and present scaling laws for the magnitude of the meridional heat transport. These are tested against numerical simulations. Through identification of key nondimensional numbers, our simplified model is applied to other icy moons. We conclude that baroclinic instability is central to the general circulation of icy moons.
我们探索了旋转冰卫星上的海洋环流,该环流是由其上表面的温度梯度驱动的,温度梯度是由于水的凝固点随压力的变化而受到抑制,这可能是由冰封土上的冰厚度变化引起的。通过高分辨率模拟,我们发现漩涡在环流中占主导地位,它产生于气压不稳定性,类似于地球的天气系统。这些气压漩涡维持着多个交替的喷流,与木星大气中的喷流相似。我们建立了分层和环流的理论模型,并提出了经向热传输量的比例定律。这些都经过了数值模拟的检验。通过确定关键的非维数,我们的简化模型被应用于其他冰卫星。我们的结论是,气压不稳定性是冰卫星一般环流的核心。
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引用次数: 0
Tailored ultrasound propagation in microscale metamaterials via inertia design 通过惯性设计实现微尺度超材料中的定制超声波传播
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-06 DOI: 10.1126/sciadv.adq6425
Rachel Sun, Jet Lem, Yun Kai, Washington DeLima, Carlos M. Portela
The quasi-static properties of micro-architected (meta)materials have been extensively studied over the past decade, but their dynamic responses, especially in acoustic metamaterials with engineered wave propagation behavior, represent a new frontier. However, challenges in miniaturizing and characterizing acoustic metamaterials in high-frequency (megahertz) regimes have hindered progress toward experimentally implementing ultrasonic-wave control. Here, we present an inertia design framework based on positioning microspheres to tune responses of 3D microscale metamaterials. We demonstrate tunable quasi-static stiffness by up to 75% and dynamic longitudinal-wave velocities by up to 25% while maintaining identical material density. Using noncontact laser-based dynamic experiments of tunable elastodynamic properties and numerical demonstrations of spatio-temporal ultrasound wave propagation, we explore the tunable static and elastodynamic property relation. This design framework expands the quasi-static and dynamic metamaterial property space through simple geometric changes, enabling facile design and fabrication of metamaterials for applications in medical ultrasound and analog computing.
在过去十年中,人们对微结构(超)材料的准静态特性进行了广泛研究,但它们的动态响应,尤其是具有工程波传播行为的声学超材料的动态响应,则是一个新的前沿领域。然而,高频(兆赫兹)声学超材料的微型化和表征所面临的挑战阻碍了超声波控制实验的进展。在此,我们提出了一种基于定位微球的惯性设计框架,以调整三维微尺度超材料的响应。我们展示了在保持材料密度相同的情况下,可调准静态刚度达 75%,动态纵波速度达 25%。利用基于非接触激光的可调弹性动力学特性动态实验和时空超声波传播的数值演示,我们探索了可调静态和弹性动力学特性的关系。这种设计框架通过简单的几何变化扩展了超材料的准静态和动态特性空间,使超材料的设计和制造变得简单,可应用于医疗超声和模拟计算领域。
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引用次数: 0
Dormancy-inducing 3D engineered matrix uncovers mechanosensitive and drug-protective FHL2-p21 signaling axis 诱导休眠的三维工程基质揭示了机械敏感性和药物保护性FHL2-p21信号轴
IF 13.6 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-06 DOI: 10.1126/sciadv.adr3997
Sadra Bakhshandeh, Unai Heras, Hubert M. Taïeb, Adithi R. Varadarajan, Susanna M. Lissek, Sarah M. Hücker, Xin Lu, Daniela S. Garske, Sarah A. E. Young, Andrea Abaurrea, Maria M Caffarel, Ana Riestra, Paloma Bragado, Jörg Contzen, Manfred Gossen, Stefan Kirsch, Jens Warfsmann, Kamran Honarnejad, Christoph A. Klein, Amaia Cipitria
Solid cancers frequently relapse with distant metastasis, despite local and systemic treatment. Cellular dormancy has been identified as an important mechanism underlying drug resistance enabling late relapse. Therefore, relapse from invisible, minimal residual cancer of seemingly disease-free patients call for in vitro models of dormant cells suited for drug discovery. Here, we explore dormancy-inducing 3D engineered matrices, which generate mechanical confinement and induce growth arrest and survival against chemotherapy in cancer cells. We characterized the dormant phenotype of solitary cells by P-ERK low :P-p38 high dormancy signaling ratio, along with Ki67 expression. As underlying mechanism, we identified stiffness-dependent nuclear localization of the four-and-a-half LIM domain 2 (FHL2) protein, leading to p53-independent high p21 Cip1/Waf1 nuclear expression, validated in murine and human tissue. Suggestive of a resistance-causing role, cells in the dormancy-inducing matrix became sensitive against chemotherapy upon FHL2 down-regulation. Thus, our biomaterial-based approach will enable systematic screens for previously unidentified compounds suited to eradicate potentially relapsing dormant cancer cells.
尽管进行了局部和全身治疗,实体瘤仍经常复发并出现远处转移。细胞休眠已被确定为导致晚期复发的重要耐药机制。因此,看似无病的患者因隐形、微小残留癌复发,需要适合药物发现的体外休眠细胞模型。在这里,我们探索了诱导休眠的三维工程基质,它能产生机械限制,诱导癌细胞生长停滞并在化疗中存活。我们通过 P-ERK 低:P-p38 高休眠信号传导比和 Ki67 表达来描述单个细胞的休眠表型。作为基本机制,我们确定了四半 LIM 结构域 2(FHL2)蛋白的僵化依赖性核定位,导致 p53 依赖性的 p21 Cip1/Waf1 高核表达,这在小鼠和人体组织中得到了验证。FHL2下调后,休眠诱导基质中的细胞对化疗变得敏感,这表明FHL2具有导致抗药性的作用。因此,我们这种基于生物材料的方法将能系统地筛选出适合消灭潜在复发休眠癌细胞的以前未发现的化合物。
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引用次数: 0
Stem cell–homing biomimetic hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling 干细胞归巢生物仿生水凝胶通过成骨和血管生成耦合促进骨质疏松性骨缺损的修复
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adq6700
Fei-Long Wei, Yuan Zhai, Tian-Fu Wang, Jing-Wei Zhao, Chao-Li Wang, Zhen Tang, Kuo Shen, Hao Wu, Rui Zheng, Ming-Rui Du, Wei Heng, Xiao-Xiang Li, Xiao-Dong Yan, Quan-You Gao, Zheng Guo, Ji-Xian Qian, Cheng-Pei Zhou
Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca2+, promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.
骨质疏松症骨缺损是指骨质疏松症患者的骨结构完整性遭到破坏,给骨科医生带来了巨大挑战。在这项研究中,我们开发了一种仿生水凝胶,以改善成骨微环境并促进干细胞归巢。这种水凝胶可作为 S-亚硝基谷胱甘肽和 Ca 2+ 的容器,促进骨髓间充质干细胞(BMSCs)和人类血管内皮细胞释放生物活性一氧化氮(NO),并激活 NO/ 环鸟苷一磷酸信号通路。这些变化促进了成骨和血管生成的耦合。该水凝胶同时通过连接干细胞归巢肽 SKPPGTSS 来招募 BMSCs。利用大鼠股骨远端缺损模型证明,这种水凝胶能有效增加骨组织和新生血管的形成,并具有免疫调节功能。我们设想,这种水凝胶可能是一种微创但高效的策略,可加快骨质疏松性骨缺损的愈合。
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引用次数: 0
Polymer semiconductor films and bacteria hybrid artificial bio-leaves 聚合物半导体薄膜和细菌混合人造生物叶
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adp8567
Na Wen, Qianqing Jiang, Dianyi Liu
Bio-artificial photosynthetic systems can reduce CO2 into multicarbon compounds by simulating natural photosynthesis. Here, inspired by organic photovoltaic structures, we demonstrate a bio-artificial photosynthetic system based on the hybridization of polymer semiconductor films and bacteria. The study suggests that the polymer-based semiconductor film can efficiently drive the non-photosynthetic bacteria to convert CO2 to acetate. By systematically characterizing the charge transport behavior of the bio-artificial photosynthetic system, the bulk-heterojunction structure and charge transport layers are proven to enhance the system performance markedly. The scalable floating artificial bio-leaf system can produce acetate to gram scale in a week. Notably, the semiconductor film is easy to recycle and maintains stable performance, showing good sustainable production capability of the system. A quasi–solid-state artificial bio-leaf is successfully prepared using agar to simulate the morphology and function of natural leaves. Last, the acetate production converted from CO2 was used to grow yeast for food production, thus achieving a complete simulation of natural photosynthesis.
生物人工光合作用系统可以通过模拟自然光合作用将二氧化碳还原成多碳化合物。在此,我们受有机光伏结构的启发,展示了一种基于聚合物半导体薄膜和细菌杂交的生物人工光合系统。研究表明,基于聚合物的半导体薄膜可以有效地驱动非光合细菌将 CO 2 转化为醋酸。通过系统表征生物人工光合系统的电荷传输行为,证明了体外结结构和电荷传输层能显著提高系统性能。可扩展的浮动人工生物叶系统可在一周内生产出克级醋酸酯。值得注意的是,该半导体薄膜易于回收并能保持稳定的性能,显示了该系统良好的可持续生产能力。利用琼脂成功制备了准固态人工生物叶片,模拟了天然叶片的形态和功能。最后,利用从 CO 2 转化而来的醋酸生产物培养酵母,用于食品生产,从而实现了对自然光合作用的完全模拟。
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引用次数: 0
High mitochondrial DNA levels accelerate lung adenocarcinoma progression 线粒体 DNA 水平过高会加速肺腺癌的发展
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adp3481
Mara Mennuni, Stephen E. Wilkie, Pauline Michon, David Alsina, Roberta Filograna, Markus Lindberg, David E. Sanin, Florian Rosenberger, Alina Schaaf, Erik Larsson, Erika L. Pearce, Nils-Göran Larsson
Lung adenocarcinoma is a common aggressive cancer and a leading cause of mortality worldwide. Here, we report an important in vivo role for mitochondrial DNA (mtDNA) copy number during lung adenocarcinoma progression in the mouse. We found that lung tumors induced by KRASG12D expression have increased mtDNA levels and enhanced mitochondrial respiration. To experimentally assess a possible causative role in tumor progression, we induced lung cancer in transgenic mice with a general increase in mtDNA copy number and found that they developed a larger tumor burden, whereas mtDNA depletion in tumor cells reduced tumor growth. Immune cell populations in the lung and cytokine levels in plasma were not affected by increased mtDNA levels. Analyses of large cancer databases indicate that mtDNA copy number is also important in human lung cancer. Our study thus reports experimental evidence for a tumor-intrinsic causative role for mtDNA in lung cancer progression, which could be exploited for development of future cancer therapies.
肺腺癌是一种常见的侵袭性癌症,也是全球死亡的主要原因之一。在这里,我们报告了线粒体 DNA(mtDNA)拷贝数在小鼠肺腺癌进展过程中的重要作用。我们发现,由 KRAS G12D 表达诱导的肺部肿瘤具有 mtDNA 水平升高和线粒体呼吸增强的特点。为了实验性地评估 mtDNA 在肿瘤进展中的可能致病作用,我们用 mtDNA 拷贝数普遍增加的转基因小鼠诱导肺癌,结果发现它们的肿瘤负荷更大,而肿瘤细胞中的 mtDNA 消耗则减少了肿瘤的生长。肺部的免疫细胞群和血浆中的细胞因子水平不受 mtDNA 水平增加的影响。对大型癌症数据库的分析表明,mtDNA拷贝数在人类肺癌中也很重要。因此,我们的研究报告提供了实验证据,证明mtDNA在肺癌进展过程中具有肿瘤内在的致病作用,可用于开发未来的癌症疗法。
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引用次数: 0
Real-space investigation of polarons in hematite Fe2O3 赤铁矿 Fe 2 O 3 中极子的实空间研究
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adp7833
Jesus Redondo, Michele Reticcioli, Vit Gabriel, Dominik Wrana, Florian Ellinger, Michele Riva, Giada Franceschi, Erik Rheinfrank, Igor Sokolović, Zdenek Jakub, Florian Kraushofer, Aji Alexander, Eduard Belas, Laerte L. Patera, Jascha Repp, Michael Schmid, Ulrike Diebold, Gareth S. Parkinson, Cesare Franchini, Pavel Kocan, Martin Setvin
In polarizable materials, electronic charge carriers interact with the surrounding ions, leading to quasiparticle behavior. The resulting polarons play a central role in many materials properties including electrical transport, interaction with light, surface reactivity, and magnetoresistance, and polarons are typically investigated indirectly through these macroscopic characteristics. Here, noncontact atomic force microscopy (nc-AFM) is used to directly image polarons in Fe2O3 at the single quasiparticle limit. A combination of Kelvin probe force microscopy (KPFM) and kinetic Monte Carlo (KMC) simulations shows that the mobility of electron polarons can be markedly increased by Ti doping. Density functional theory (DFT) calculations indicate that a transition from polaronic to metastable free-carrier states can play a key role in migration of electron polarons. In contrast, hole polarons are significantly less mobile, and their hopping is hampered further by trapping centers.
在可极化材料中,电子电荷载流子与周围的离子相互作用,导致准粒子行为。由此产生的极子在许多材料特性中发挥着核心作用,包括电传输、与光的相互作用、表面反应性和磁阻,而极子通常是通过这些宏观特性间接研究的。在这里,非接触式原子力显微镜(nc-AFM)被用来直接对 Fe 2 O 3 中的极子进行单准粒子极限成像。开尔文探针力显微镜(KPFM)和动力学蒙特卡罗(KMC)模拟相结合的结果表明,电子极子的迁移率可通过掺杂钛而显著提高。密度泛函理论(DFT)计算表明,从极子态到可陨落自由载流子态的转变在电子极子迁移中起着关键作用。相比之下,空穴极子的流动性要小得多,而且它们的跳跃会受到捕获中心的进一步阻碍。
{"title":"Real-space investigation of polarons in hematite Fe2O3","authors":"Jesus Redondo,&nbsp;Michele Reticcioli,&nbsp;Vit Gabriel,&nbsp;Dominik Wrana,&nbsp;Florian Ellinger,&nbsp;Michele Riva,&nbsp;Giada Franceschi,&nbsp;Erik Rheinfrank,&nbsp;Igor Sokolović,&nbsp;Zdenek Jakub,&nbsp;Florian Kraushofer,&nbsp;Aji Alexander,&nbsp;Eduard Belas,&nbsp;Laerte L. Patera,&nbsp;Jascha Repp,&nbsp;Michael Schmid,&nbsp;Ulrike Diebold,&nbsp;Gareth S. Parkinson,&nbsp;Cesare Franchini,&nbsp;Pavel Kocan,&nbsp;Martin Setvin","doi":"10.1126/sciadv.adp7833","DOIUrl":"10.1126/sciadv.adp7833","url":null,"abstract":"<div >In polarizable materials, electronic charge carriers interact with the surrounding ions, leading to quasiparticle behavior. The resulting polarons play a central role in many materials properties including electrical transport, interaction with light, surface reactivity, and magnetoresistance, and polarons are typically investigated indirectly through these macroscopic characteristics. Here, noncontact atomic force microscopy (nc-AFM) is used to directly image polarons in Fe<sub>2</sub>O<sub>3</sub> at the single quasiparticle limit. A combination of Kelvin probe force microscopy (KPFM) and kinetic Monte Carlo (KMC) simulations shows that the mobility of electron polarons can be markedly increased by Ti doping. Density functional theory (DFT) calculations indicate that a transition from polaronic to metastable free-carrier states can play a key role in migration of electron polarons. In contrast, hole polarons are significantly less mobile, and their hopping is hampered further by trapping centers.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp7833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dedicated developmental programing for group-supporting behaviors in eusocial honeybees 群居蜜蜂群体支持行为的专用发展程序
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adp3953
Vivien Sommer, Jana Seiler, Alina Sturm, Sven Köhnen, Anna Wagner, Christina Blut, Wolfgang Rössler, Stephen F. Goodwin, Bernd Grünewald, Martin Beye
The evolutionary changes from solitary to eusocial living in vertebrates and invertebrates are associated with the diversification of social interactions and the development of queen and worker castes. Despite strong innate patterns, our understanding of the mechanisms manifesting these sophisticated behaviors is still rudimentary. Here, we show that doublesex (dsx) manifests group-supporting behaviors in the honeybee (Apis mellifera) worker caste. Computer-based individual behavioral tracking of worker bees with biallelic stop mutations in colonies revealed that the dsx gene is required for the rate and duration of group-supporting behavior that scales the relationship between bees and their work. General sensorimotor functions remained unaffected. Unexpectedly, unlike in other insects, the dsx gene is required for the neuronal wiring of the mushroom body in which the gene is spatially restricted expressed. Together, our study establishes dedicated programming for group-supporting behaviors and provides insight into the connection between development in the neuronal circuitry and behaviors regulating the formation of a eusocial society.
脊椎动物和无脊椎动物从独居到群居的进化变化与社会互动的多样化以及蚁后和工蚁种群的发展有关。尽管有很强的先天模式,但我们对这些复杂行为的表现机制的了解仍然很有限。在这里,我们展示了蜜蜂(Apis mellifera)工蜂种姓中的双性(dsx)表现出的群体支持行为。通过计算机对蜂群中带有双重停止突变的工蜂进行个体行为跟踪,发现dsx基因是蜜蜂群体支持行为的速率和持续时间所必需的,这种行为能够调节蜜蜂与其工作之间的关系。一般的感觉运动功能未受影响。意想不到的是,与其他昆虫不同,dsx基因是蘑菇体神经元布线所必需的,该基因在其中的表达受到空间限制。总之,我们的研究为支持群体的行为建立了专门的程序,并为神经元回路的发育与调节形成社会的行为之间的联系提供了见解。
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引用次数: 0
Gated off-site radical injection: Bidirectional conductance modulation in single-molecule junctions 门控异位自由基注入:单分子结中的双向电导调制
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adp7307
Hanjun Zhang, Lichuan Chen, Xiaodong Liu, Fanxi Sun, Maolin Zhang, Sergio Moles Quintero, Qian Zhan, Shenqing Jiang, Jiayu Li, Dongsheng Wang, Juan Casado, Wenjing Hong, Yonghao Zheng
Uncovering the effects of radical injection into responsive organic molecules is a long-sought goal, and the single-molecule junctions provide a unique way to investigate molecular conductance evolution during the radical injection. We can modulate the main channel conductance by using electronic injection from off-site neutral radicals acting as gating terminals. Two families of cyclopentadienone derivatives were synthesized, featuring the inter-pyridyl main conductance channel and the inter-radical paths that are linear (FCF) or cross conjugated (PCP). Using a scanning tunneling microscope break junction technique, we find that the injection of mono- and diradicals in the PCP system unexpectedly decreases the conductance regarding the closed-shell analog, while that of FCF systems increases. Through-bond and through-space conductance mechanisms are found in the FCF and PCP series, respectively, and jointly modulate the overall charge transmission. This off-site injection concept offers a promising approach for developing molecular devices by manipulating electrical conductance in single-molecule junctions.
揭示自由基注入反应性有机分子的效应是一个长期追求的目标,而单分子结则为研究自由基注入过程中分子电导的演变提供了一种独特的方法。我们可以利用作为门控终端的异位中性自由基的电子注入来调节主通道电导。我们合成了两个系列的环戊二烯酮衍生物,它们具有吡啶基间主传导通道以及线性(FCF)或交叉共轭(PCP)的自由基间路径。利用扫描隧道显微镜断点技术,我们发现在 PCP 体系中注入一元和二元自由基会意外地降低闭壳类似物的电导率,而 FCF 体系的电导率则会增加。在 FCF 和 PCP 系列中分别发现了穿键和穿空传导机制,它们共同调节了整体电荷传输。这种场外注入概念为通过操纵单分子结中的电导来开发分子器件提供了一种前景广阔的方法。
{"title":"Gated off-site radical injection: Bidirectional conductance modulation in single-molecule junctions","authors":"Hanjun Zhang,&nbsp;Lichuan Chen,&nbsp;Xiaodong Liu,&nbsp;Fanxi Sun,&nbsp;Maolin Zhang,&nbsp;Sergio Moles Quintero,&nbsp;Qian Zhan,&nbsp;Shenqing Jiang,&nbsp;Jiayu Li,&nbsp;Dongsheng Wang,&nbsp;Juan Casado,&nbsp;Wenjing Hong,&nbsp;Yonghao Zheng","doi":"10.1126/sciadv.adp7307","DOIUrl":"10.1126/sciadv.adp7307","url":null,"abstract":"<div >Uncovering the effects of radical injection into responsive organic molecules is a long-sought goal, and the single-molecule junctions provide a unique way to investigate molecular conductance evolution during the radical injection. We can modulate the main channel conductance by using electronic injection from off-site neutral radicals acting as gating terminals. Two families of cyclopentadienone derivatives were synthesized, featuring the inter-pyridyl main conductance channel and the inter-radical paths that are linear (FCF) or cross conjugated (PCP). Using a scanning tunneling microscope break junction technique, we find that the injection of mono- and diradicals in the PCP system unexpectedly decreases the conductance regarding the closed-shell analog, while that of FCF systems increases. Through-bond and through-space conductance mechanisms are found in the FCF and PCP series, respectively, and jointly modulate the overall charge transmission. This off-site injection concept offers a promising approach for developing molecular devices by manipulating electrical conductance in single-molecule junctions.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp7307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Membrane potential stimulates ADP import and ATP export by the mitochondrial ADP/ATP carrier due to its positively charged binding site 由于线粒体 ADP/ATP 载体的结合部位带正电,膜电位可刺激 ADP 输入和 ATP 输出
IF 11.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-01 DOI: 10.1126/sciadv.adp7725
Vasiliki Mavridou, Martin S. King, Andre Bazzone, Roger Springett, Edmund R. S. Kunji
The mitochondrial adenosine 5′-diphosphate (ADP)/adenosine 5′-triphosphate (ATP) carrier imports ADP into the mitochondrion and exports ATP to the cell. Here, we demonstrate that 3.3 positive charges are translocated with the negatively charged substrate in each transport step. They can be assigned to three positively charged residues of the central substrate-binding site and two asparagine/arginine pairs. In this way, the membrane potential stimulates not only the ATP4− export step, as a net −0.7 charge is transported, but also the ADP3− import step, as a net +0.3 charge is transported with the electric field. These positive charge movements also inhibit the import of ATP and export of ADP in the presence of a membrane potential, allowing these nucleotides to be maintained at high concentrations in the cytosol and mitochondrial matrix to drive the hydrolysis and synthesis of ATP, respectively. Thus, this is the mechanism by which the membrane potential drives adenine nucleotide exchange with high directional fluxes to fuel the cellular processes.
线粒体 5′-二磷酸腺苷(ADP)/5′-三磷酸腺苷(ATP)载体将 ADP 输入线粒体,并将 ATP 输出到细胞。在这里,我们证明了在每个运输步骤中,有 3.3 个正电荷与带负电荷的底物一起转运。它们可归属于底物结合位点中央的三个带正电的残基和两个天冬酰胺/精氨酸对。这样,膜电位不仅刺激了 ATP 4 的输出步骤(净电荷为-0.7),还刺激了 ADP 3 的输入步骤(净电荷为+0.3),因为电场会随之传输。在膜电位存在的情况下,这些正电荷移动也会抑制 ATP 的输入和 ADP 的输出,从而使这些核苷酸在细胞质和线粒体基质中保持高浓度,分别驱动 ATP 的水解和合成。因此,这就是膜电位驱动腺嘌呤核苷酸以高定向通量进行交换以促进细胞过程的机制。
{"title":"Membrane potential stimulates ADP import and ATP export by the mitochondrial ADP/ATP carrier due to its positively charged binding site","authors":"Vasiliki Mavridou,&nbsp;Martin S. King,&nbsp;Andre Bazzone,&nbsp;Roger Springett,&nbsp;Edmund R. S. Kunji","doi":"10.1126/sciadv.adp7725","DOIUrl":"10.1126/sciadv.adp7725","url":null,"abstract":"<div >The mitochondrial adenosine 5′-diphosphate (ADP)/adenosine 5′-triphosphate (ATP) carrier imports ADP into the mitochondrion and exports ATP to the cell. Here, we demonstrate that 3.3 positive charges are translocated with the negatively charged substrate in each transport step. They can be assigned to three positively charged residues of the central substrate-binding site and two asparagine/arginine pairs. In this way, the membrane potential stimulates not only the ATP<sup>4−</sup> export step, as a net −0.7 charge is transported, but also the ADP<sup>3−</sup> import step, as a net +0.3 charge is transported with the electric field. These positive charge movements also inhibit the import of ATP and export of ADP in the presence of a membrane potential, allowing these nucleotides to be maintained at high concentrations in the cytosol and mitochondrial matrix to drive the hydrolysis and synthesis of ATP, respectively. Thus, this is the mechanism by which the membrane potential drives adenine nucleotide exchange with high directional fluxes to fuel the cellular processes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp7725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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