Science Advances最新文献_第9页

From synthetic vesicles to living cells: Anchoring conducting polymers to cell membrane.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adr2882

Hanne Biesmans, Alex Bersellini Farinotti, Tobias Abrahamsson, Katriann Arja, Caroline Lindholm, Xenofon Strakosas, Jennifer Y Gerasimov, Daniel T Simon, Camilla I Svensson, Chiara Musumeci, Magnus Berggren

{"title":"From synthetic vesicles to living cells: Anchoring conducting polymers to cell membrane.","authors":"Hanne Biesmans, Alex Bersellini Farinotti, Tobias Abrahamsson, Katriann Arja, Caroline Lindholm, Xenofon Strakosas, Jennifer Y Gerasimov, Daniel T Simon, Camilla I Svensson, Chiara Musumeci, Magnus Berggren","doi":"10.1126/sciadv.adr2882","DOIUrl":"10.1126/sciadv.adr2882","url":null,"abstract":"Coupling biology with electronics is emerging as a transformative approach in developing advanced medical treatments, with examples ranging from implants for treating neurological disorders to biosensors for real-time monitoring of physiological parameters. The electrodes used for these purposes often face challenges such as signal degradation due to biofouling and limited biocompatibility, which can lead to inaccurate readings and tissue damage over time. Conducting organic polymers are a promising alternative because of their mechanical, chemical, and physical properties, which better match the ones of biological systems. They also can be synthesized in vivo to form bio-templated structures through biologically compatible manufacturing processes. Here, we report a method to achieve conductive polymer structures anchored to cell membranes, creating an intimate interface between the polymer electrode and single cells. We show that the polymer is nontoxic to cells and does not interfere with its activation, thereby making this process an interesting alternative to existing materials and electrode techniques.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadr2882"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813945","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

Noninvasive identification of carbon-based black pigments with pump-probe microscopy.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adp0005

Heidi V Kastenholz, Michael I Topper, Warren S Warren, Martin C Fischer, David Grass

引用次数: 0

SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adq4274

Xinxin Song, Zhuan Zhou, Ammar Elmezayen, Runliu Wu, Chunhua Yu, Boning Gao, John D Minna, Kenneth D Westover, Herbert J Zeh, Guido Kroemer, Lynn E Heasley, Rui Kang, Daolin Tang

{"title":"SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.","authors":"Xinxin Song, Zhuan Zhou, Ammar Elmezayen, Runliu Wu, Chunhua Yu, Boning Gao, John D Minna, Kenneth D Westover, Herbert J Zeh, Guido Kroemer, Lynn E Heasley, Rui Kang, Daolin Tang","doi":"10.1126/sciadv.adq4274","DOIUrl":"10.1126/sciadv.adq4274","url":null,"abstract":"Direct targeting of the KRAS-G12C-mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the KRAS-G12C mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma. A genome-wide CRISPR screen revealed that the adenosine triphosphate binding cassette transporter ABCC1 mediates MRTX849 resistance. Functional studies demonstrated that the transcription factor JUN drives ABCC1 expression, resulting in multidrug resistance. An unbiased drug screen identified the tyrosine kinase inhibitor dasatinib that potentiates MRTX849 efficacy by inhibiting SRC-dependent JUN activation, avoiding multidrug resistance and tumor suppression in vitro as well as in suitable preclinical mouse models and patient-derived organoids. SRC inhibitors (DGY-06-116, dasatinib, and bosutinib) also exhibit synergistic effects with MRTX849 in eliminating various tumor cell lines carrying KRAS-G12C mutations. Thus, SRC inhibitors amplify the therapeutic utility of G12Ci.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadq4274"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814174","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

Model predictions of global geologic hydrogen resources 全球地质氢资源模型预测

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.ado0955

Geoffrey S. Ellis, Sarah E. Gelman

引用次数: 0

Composition and in situ structure of the Methanospirillum hungatei cell envelope and surface layer

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adr8596

Hui Wang, Jiayan Zhang, Shiqing Liao, Anne M. Henstra, Deborah Leon, Jonathan Erde, Joseph A. Loo, Rachel R. Ogorzalek Loo, Z. Hong Zhou, Robert P. Gunsalus

{"title":"Composition and in situ structure of the Methanospirillum hungatei cell envelope and surface layer","authors":"Hui Wang, Jiayan Zhang, Shiqing Liao, Anne M. Henstra, Deborah Leon, Jonathan Erde, Joseph A. Loo, Rachel R. Ogorzalek Loo, Z. Hong Zhou, Robert P. Gunsalus","doi":"10.1126/sciadv.adr8596","DOIUrl":"https://doi.org/10.1126/sciadv.adr8596","url":null,"abstract":"Archaea share genomic similarities with Eukarya and cellular architectural similarities with Bacteria, though archaeal and bacterial surface layers (S-layers) differ. Using cellular cryo–electron tomography, we visualized the S-layer lattice surrounding Methanospirillum hungatei , a methanogenic archaeon. Though more compact than known structures, M. hungatei ’s S-layer is a flexible hexagonal lattice of dome-shaped tiles, uniformly spaced from both the overlying cell sheath and the underlying cell membrane. Subtomogram averaging resolved the S-layer hexamer tile at 6.4-angstrom resolution. By fitting an AlphaFold model into hexamer tiles in flat and curved conformations, we uncover intra- and intertile interactions that contribute to the S-layer’s cylindrical and flexible architecture, along with a spacer extension for cell membrane attachment. M. hungatei cell’s end plug structure, likely composed of S-layer isoforms, further highlights the uniqueness of this archaeal cell. These structural features offer advantages for methane release and reflect divergent evolutionary adaptations to environmental pressures during early microbial emergence.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-precision chemical quantum sensing in flowing monodisperse microdroplets.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adp4033

Adrisha Sarkar, Zachary R Jones, Madhur Parashar, Emanuel Druga, Amala Akkiraju, Sophie Conti, Pranav Krishnamoorthi, Srisai Nachuri, Parker Aman, Mohammad Hashemi, Nicholas Nunn, Marco D Torelli, Benjamin Gilbert, Kevin R Wilson, Olga A Shenderova, Deepti Tanjore, Ashok Ajoy

{"title":"High-precision chemical quantum sensing in flowing monodisperse microdroplets.","authors":"Adrisha Sarkar, Zachary R Jones, Madhur Parashar, Emanuel Druga, Amala Akkiraju, Sophie Conti, Pranav Krishnamoorthi, Srisai Nachuri, Parker Aman, Mohammad Hashemi, Nicholas Nunn, Marco D Torelli, Benjamin Gilbert, Kevin R Wilson, Olga A Shenderova, Deepti Tanjore, Ashok Ajoy","doi":"10.1126/sciadv.adp4033","DOIUrl":"10.1126/sciadv.adp4033","url":null,"abstract":"A method is presented for high-precision chemical detection that integrates quantum sensing with droplet microfluidics. Using nanodiamonds (ND) with fluorescent nitrogen-vacancy (NV) centers as quantum sensors, rapidly flowing microdroplets containing analyte molecules are analyzed. A noise-suppressed mode of optically detected magnetic resonance is enabled by pairing controllable flow with microwave control of NV electronic spins, to detect analyte-induced signals of a few hundredths of a percent of the ND fluorescence. Using this method, paramagnetic ions in droplets are detected with low limit-of-detection using small analyte volumes, with exceptional measurement stability over >103 s. In addition, these droplets are used as microconfinement chambers by co-encapsulating ND quantum sensors with various analytes such as single cells, suggesting wide-ranging applications including single-cell metabolomics and real-time intracellular measurements from bioreactors. Important advances are enabled by this work, including portable chemical testing devices, amplification-free chemical assays, and chemical imaging tools for probing reactions within microenvironments.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadp4033"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814064","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

Deep and dynamic metabolic and structural imaging in living tissues.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adp2438

Kunzan Liu, Honghao Cao, Kasey Shashaty, Li-Yu Yu, Sarah Spitz, Francesca Michela Pramotton, Zhengpeng Wan, Ellen L Kan, Erin N Tevonian, Manuel Levy, Eva Lendaro, Roger D Kamm, Linda G Griffith, Fan Wang, Tong Qiu, Sixian You

{"title":"Deep and dynamic metabolic and structural imaging in living tissues.","authors":"Kunzan Liu, Honghao Cao, Kasey Shashaty, Li-Yu Yu, Sarah Spitz, Francesca Michela Pramotton, Zhengpeng Wan, Ellen L Kan, Erin N Tevonian, Manuel Levy, Eva Lendaro, Roger D Kamm, Linda G Griffith, Fan Wang, Tong Qiu, Sixian You","doi":"10.1126/sciadv.adp2438","DOIUrl":"10.1126/sciadv.adp2438","url":null,"abstract":"Label-free imaging through two-photon autofluorescence of NAD(P)H allows for nondestructive, high-resolution visualization of cellular activities in living systems. However, its application to thick tissues has been restricted by its limited penetration depth within 300 μm, largely due to light scattering. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to more than 700 μm in living engineered human multicellular microtissues by adopting multimode fiber-based, low repetition rate, high peak power, three-photon excitation of NAD(P)H at 1100 nm. This is achieved by having more than 0.5 megawatts peak power at the band of 1100 ± 25 nm through adaptively modulating multimodal nonlinear pulse propagation with a compact fiber shaper. Moreover, the eightfold increase in pulse energy enables faster imaging of monocyte behaviors in the living multicellular models. These results represent a substantial advance for deep and dynamic imaging of intact living biosystems. The modular design is anticipated to allow wide adoption for demanding imaging applications, including cancer research, immune responses, and tissue engineering.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadp2438"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813783","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

Electrochemical imaging of neurotransmitter release with fast-scan voltammetric ion conductance microscopy.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.ado9322

Yunong Wang, Cristobal Rodriguez, Sasha E Alden, Myung-Hoon Choi, Kristen Alanis, Rahul Srinivasan, Lane A Baker

{"title":"Electrochemical imaging of neurotransmitter release with fast-scan voltammetric ion conductance microscopy.","authors":"Yunong Wang, Cristobal Rodriguez, Sasha E Alden, Myung-Hoon Choi, Kristen Alanis, Rahul Srinivasan, Lane A Baker","doi":"10.1126/sciadv.ado9322","DOIUrl":"10.1126/sciadv.ado9322","url":null,"abstract":"Understanding the dynamic spatial and temporal release of neurotransmitters can help resolve long-standing questions related to chemical modulation of neurological circuits. Dopamine modulates function in a range of physiological processes and is key to transmission in addiction and neurological disorders. Studies at subcellular scales promise to help develop a broader understanding of dopamine release, diffusion, and receptor activation and how these processes lead to functional outcomes. Electrochemical measurements of dopamine release at individual cells have proven especially informative. We describe incorporation of fast-scan cyclic voltammetry for detection of dopamine release with subcellular spatial resolution and millisecond time resolution. The platform is benchmarked with standard redox probes and then applied to imaging stimulated release from subcellular locations of a coculture of dopaminergic neurons and astrocytes. Voltammetry reveals heterogeneity in release based on time, location, and neuron identity. We believe that this platform ultimately offers a window to understanding neurotransmission in pathophysiological models of disease where cell-cell communication is key.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eado9322"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813992","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

Raman microscopy of cryofixed biological specimens for high-resolution and high-sensitivity chemical imaging.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adn0110

Kenta Mizushima, Yasuaki Kumamoto, Shoko Tamura, Masahito Yamanaka, Kentaro Mochizuki, Menglu Li, Syusuke Egoshi, Kosuke Dodo, Yoshinori Harada, Nicholas I Smith, Mikiko Sodeoka, Hideo Tanaka, Katsumasa Fujita

{"title":"Raman microscopy of cryofixed biological specimens for high-resolution and high-sensitivity chemical imaging.","authors":"Kenta Mizushima, Yasuaki Kumamoto, Shoko Tamura, Masahito Yamanaka, Kentaro Mochizuki, Menglu Li, Syusuke Egoshi, Kosuke Dodo, Yoshinori Harada, Nicholas I Smith, Mikiko Sodeoka, Hideo Tanaka, Katsumasa Fujita","doi":"10.1126/sciadv.adn0110","DOIUrl":"10.1126/sciadv.adn0110","url":null,"abstract":"Raman microscopy is an emerging molecular imaging technology, yet its signal-to-noise ratio (SNR) in measurements of biological specimens is severely limited because of the small cross section of Raman scattering. Here, we present Raman imaging techniques of cryofixed specimens to overcome SNR limitations by enabling long exposure of specimens under highly stabilized low-temperature conditions. The observation of frozen specimens in a cryostat at a constant low temperature immediately after rapid freezing enabled the improvement of SNR and enhanced the spatial and spectral resolution. We also confirmed that the cryofixation can preserve physicochemical states of specimens by observing alkyne-labeled coenzyme Q in cytosol and hemeproteins in acute ischemic myocardium, which cannot be done by fixation using chemical reagents. Last, we applied the technique for multiplex Raman imaging of label-free endogenous molecules and alkyne-tagged molecules in cryofixed HeLa cells, demonstrating its capability of high-content imaging of complex biological phenomena while maintaining physiological conditions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadn0110"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814167","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

Tunable elliptical cylinders for rotational mechanical studies of single DNA molecules

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adr4519

Yifeng Hong, Fan Ye, Xiang Gao, James T. Inman, Michelle D. Wang

引用次数: 0