Science Advances最新文献_第5页

Nzf2 promotes oligodendrocyte differentiation and regeneration via repressing HDAC1-mediated histone deacetylation

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adf8405

Xiaofeng Xu, Minxi Fang, Lixia Chen, Hao Huang, Zhong-Min Dai, Junlin Yang, Mengsheng Qiu

{"title":"Nzf2 promotes oligodendrocyte differentiation and regeneration via repressing HDAC1-mediated histone deacetylation","authors":"Xiaofeng Xu, Minxi Fang, Lixia Chen, Hao Huang, Zhong-Min Dai, Junlin Yang, Mengsheng Qiu","doi":"10.1126/sciadv.adf8405","DOIUrl":"https://doi.org/10.1126/sciadv.adf8405","url":null,"abstract":"Proper axonal myelination and function of the vertebrate central nervous system rely largely on the timely differentiation of oligodendrocytes (OLs), yet key regulatory factors remain enigmatic. Our study reveals neural zinc finger (Nzf2) as a crucial orchestrator that controls the timing of OL differentiation both during development and myelin repair, contrasting with its previously suggested role in direct myelin gene regulation. Nzf2 ablation delays the onset of OL differentiation, while hyperactivation stimulates OL differentiation both during development and remyelination. Using RNA-seq and ChIP-seq, we pinpoint Nkx2.2 as a critical downstream target of Nzf2. Specific binding of Nzf2 in the Nkx2.2 gene locus inhibits histone deacetylation by disrupting the HDAC1 repressor complex and reducing deacetylase activity. Furthermore, Nzf2 overrides the inhibitory Notch signaling to initiate OL differentiation. Thus, we propose that the Notch-Nzf2-Nkx2.2 axis is a vital component of OL differentiation timing mechanism, suggesting Nzf2 as a potential therapeutic target for stimulating OL differentiation and boosting myelin repair in demyelinating diseases.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"84 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820588","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

Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adm7928

Shuyi Li, Zhi-Cheng Yao, Hanzhi Wang, Jonathan A. Ecker, Mary O. Omotoso, Jaechan Lee, Jiayuan Kong, Hexiang Feng, Worarat Chaisawangwong, Si-Sim Kang, Sydney R. Shannon, Natalie K. Livingston, Joan G. Bieler, Shweta Singh, Maya L. Zhang, Pilar O’Neal, Emily Ariail, Benjamin Biggs, John W. Hickey, Hai-Quan Mao, Jonathan P. Schneck

{"title":"Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy","authors":"Shuyi Li, Zhi-Cheng Yao, Hanzhi Wang, Jonathan A. Ecker, Mary O. Omotoso, Jaechan Lee, Jiayuan Kong, Hexiang Feng, Worarat Chaisawangwong, Si-Sim Kang, Sydney R. Shannon, Natalie K. Livingston, Joan G. Bieler, Shweta Singh, Maya L. Zhang, Pilar O’Neal, Emily Ariail, Benjamin Biggs, John W. Hickey, Hai-Quan Mao, Jonathan P. Schneck","doi":"10.1126/sciadv.adm7928","DOIUrl":"https://doi.org/10.1126/sciadv.adm7928","url":null,"abstract":"Tissue-resident memory T (T RM ) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T RM cells and delivering these cells in vivo hinders the exploration of T RM cell–mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for T RM cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human T RM -like CD8 + T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel to deliver T RM -like cells. T RM -like cells delivered in the optimized HA hydrogel trigger robust local and systemic antitumor immunity and show synergistic effects with anti–PD-1 treatment. Our findings suggest that nano-aAPC–induced T RM -like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of T RM cell–mediated cancer therapy.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"119 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820579","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

Gradient polaritonic surface with space-variant switchable light-matter interactions in 2D moiré superlattices

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adq7445

Zhen-Bing Dai, Hua Fan, Vyacheslav Semenenko, Xinyu Lv, Lu Wen, Zhen Zhang, Shijie Fang, Vasili Perebeinos, Yue Zhao, Zhiqiang Li

{"title":"Gradient polaritonic surface with space-variant switchable light-matter interactions in 2D moiré superlattices","authors":"Zhen-Bing Dai, Hua Fan, Vyacheslav Semenenko, Xinyu Lv, Lu Wen, Zhen Zhang, Shijie Fang, Vasili Perebeinos, Yue Zhao, Zhiqiang Li","doi":"10.1126/sciadv.adq7445","DOIUrl":"https://doi.org/10.1126/sciadv.adq7445","url":null,"abstract":"Polaritons in two-dimensional (2D) materials provide unique opportunities for controlling light at nanoscales. Tailoring these polaritons via gradient polaritonic surfaces with space-variant response can enable versatile light-matter interaction platforms with advanced functionalities. However, experimental progress has been hampered by the optical losses and poor light confinement of conventionally used artificial nanostructures. Here, we demonstrate natural gradient polaritonic surfaces based on superlattices of solitons—localized structural deformations—in a prototypical moiré system, twisted bilayer graphene on boron nitride. We demonstrate on-off switching and continuous modulation of local polariton-soliton interactions, which results from marked modifications of topological and conventional soliton states through variation of local strain direction. Furthermore, we reveal the capability of these structures to spatially modify the near-field profile, phase, and propagation direction of polaritons in record-small footprints, enabling generation and electrical switching of directional polaritons. Our findings open up new avenues toward nanoscale manipulation of light-matter interactions and spatial polariton engineering through gradient moiré superlattices.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"91 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816353","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

Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin–expressing cancers 二合一纳米粒子平台诱导靶向疗法对表达 P 选择素的癌症产生强大疗效

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adr4762

Shani Koshrovski-Michael, Daniel Rodriguez Ajamil, Pradip Dey, Ron Kleiner, Shahar Tevet, Yana Epshtein, Marina Green Buzhor, Rami Khoury, Sabina Pozzi, Gal Shenbach-Koltin, Eilam Yeini, Laura Woythe, Rachel Blau, Anna Scomparin, Iris Barshack, Helena F. Florindo, Shlomi Lazar, Lorenzo Albertazzi, Roey J. Amir, Ronit Satchi-Fainaro

{"title":"Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin–expressing cancers","authors":"Shani Koshrovski-Michael, Daniel Rodriguez Ajamil, Pradip Dey, Ron Kleiner, Shahar Tevet, Yana Epshtein, Marina Green Buzhor, Rami Khoury, Sabina Pozzi, Gal Shenbach-Koltin, Eilam Yeini, Laura Woythe, Rachel Blau, Anna Scomparin, Iris Barshack, Helena F. Florindo, Shlomi Lazar, Lorenzo Albertazzi, Roey J. Amir, Ronit Satchi-Fainaro","doi":"10.1126/sciadv.adr4762","DOIUrl":"https://doi.org/10.1126/sciadv.adr4762","url":null,"abstract":"Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG)–based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor. Nonetheless, extravasation-dependent tumor accumulation is susceptible to variations in tumor vasculature; therefore, PLGA-PEG was modified with sulfates to actively target P-selectin–expressing cancers. Here, we show the potential of our platform in unique three-dimensional (3D) in vitro and in vivo models. The P-selectin–targeted nanoparticles showed enhanced accumulation in 3D spheroids and tissues of P-selectin–expressing BRAF-mutated melanomas and BRCA-mutated breast cancers, resulting in superior in vivo efficacy and safety. This nanoplatform could advance the codelivery of a plethora of anticancer drug combinations to various P-selectin–expressing tumors.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"45 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820592","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

Absolute signal of stimulated Raman scattering microscopy: A quantum electrodynamics treatment.

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.adm8424

Wei Min, Xin Gao

引用次数: 0

Identification of the Wnt signal peptide that directs secretion on extracellular vesicles.

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.ado5914

Uxia Gurriaran-Rodriguez, David Datzkiw, Leandro G Radusky, Marie Esper, Ehsan Javandoost, Fan Xiao, Hong Ming, Solomon Fisher, Alberto Marina, Yves De Repentigny, Rashmi Kothary, Mikel Azkargorta, Felix Elortza, Adriana L Rojas, Luis Serrano, Aitor Hierro, Michael A Rudnicki

{"title":"Identification of the Wnt signal peptide that directs secretion on extracellular vesicles.","authors":"Uxia Gurriaran-Rodriguez, David Datzkiw, Leandro G Radusky, Marie Esper, Ehsan Javandoost, Fan Xiao, Hong Ming, Solomon Fisher, Alberto Marina, Yves De Repentigny, Rashmi Kothary, Mikel Azkargorta, Felix Elortza, Adriana L Rojas, Luis Serrano, Aitor Hierro, Michael A Rudnicki","doi":"10.1126/sciadv.ado5914","DOIUrl":"10.1126/sciadv.ado5914","url":null,"abstract":"Wnt proteins are hydrophobic glycoproteins that are nevertheless capable of long-range signaling. We found that Wnt7a is secreted long distance on the surface of extracellular vesicles (EVs) following muscle injury. We defined a signal peptide region in Wnts required for secretion on EVs, termed exosome-binding peptide (EBP). Addition of EBP to an unrelated protein directed secretion on EVs. Palmitoylation and the signal peptide were not required for Wnt7a-EV secretion. Coatomer was identified as the EV-binding protein for the EBP. Analysis of cocrystal structures, binding thermodynamics, and mutagenesis found that a dilysine motif mediates EBP binding to coatomer with a conserved function across the Wnt family. We showed that EBP is required for Wnt7a bioactivity when expressed in vivo during regeneration. Overall, our study has elucidated the structural basis and singularity of Wnt secretion on EVs, alternatively to canonical secretion, opening avenues for innovative therapeutic targeting strategies and systemic protein delivery.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eado5914"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814091","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

Spatiotemporal characterization of water diffusion anomalies in saline solutions using machine learning force field.

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.adp9662

Ji Woong Yu, Sebin Kim, Jae Hyun Ryu, Won Bo Lee, Tae Jun Yoon

{"title":"Spatiotemporal characterization of water diffusion anomalies in saline solutions using machine learning force field.","authors":"Ji Woong Yu, Sebin Kim, Jae Hyun Ryu, Won Bo Lee, Tae Jun Yoon","doi":"10.1126/sciadv.adp9662","DOIUrl":"10.1126/sciadv.adp9662","url":null,"abstract":"Understanding water behavior in salt solutions remains a notable challenge in computational chemistry. Conventional force fields have shown limitations in accurately representing water's properties across different salt types (chaotropes and kosmotropes) and concentrations, demonstrating the need for better methods. Machine learning force field applications in computational chemistry, especially through deep potential molecular dynamics (DPMD), offer a promising alternative that closely aligns with the accuracy of first-principles methods. Our research used DPMD to study how salts affect water by comparing its results with ab initio molecular dynamics, SPC/Fw, AMOEBA, and MB-Pol models. We studied water's behavior in salt solutions by examining its spatiotemporally correlated movement. Our findings showed that each model's accuracy in depicting water's behavior in salt solutions is strongly connected to spatiotemporal correlation. This study demonstrates both DPMD's advanced abilities in studying water-salt interactions and contributes to our understanding of the basic mechanisms that control these interactions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadp9662"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814171","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

All eukaryotic SMC proteins induce a twist of −0.6 at each DNA loop extrusion step

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adt1832

Richard Janissen, Roman Barth, Iain F. Davidson, Jan-Michael Peters, Cees Dekker

{"title":"All eukaryotic SMC proteins induce a twist of −0.6 at each DNA loop extrusion step","authors":"Richard Janissen, Roman Barth, Iain F. Davidson, Jan-Michael Peters, Cees Dekker","doi":"10.1126/sciadv.adt1832","DOIUrl":"https://doi.org/10.1126/sciadv.adt1832","url":null,"abstract":"Eukaryotes carry three types of structural maintenance of chromosome (SMC) protein complexes, condensin, cohesin, and SMC5/6, which are ATP-dependent motor proteins that remodel the genome via DNA loop extrusion (LE). SMCs modulate DNA supercoiling but remains incompletely understood how this is achieved. Using a single-molecule magnetic tweezers assay that directly measures how much twist is induced by individual SMCs in each LE step, we demonstrate that all three SMC complexes induce the same large negative twist (i.e., linking number change <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mrow> <mml:mi mathvariant=\"normal\">Δ</mml:mi> <mml:msub> <mml:mi>L</mml:mi> <mml:mi mathvariant=\"normal\">k</mml:mi> </mml:msub> </mml:mrow> </mml:math> of ~−0.6 at each LE step) into the extruded loop, independent of step size and DNA tension. Using ATP hydrolysis mutants and nonhydrolyzable ATP analogs, we find that ATP binding is the twist-inducing event during the ATPase cycle, coinciding with the force-generating LE step. The fact that all three eukaryotic SMC proteins induce the same amount of twist indicates a common DNA-LE mechanism among these SMC complexes.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820590","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

Erratum for the Research Article: "Genomic imprinting-like monoallelic paternal expression determines sex of channel catfish" by W. Wang et al.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adu7669

引用次数: 0

Highly multiplexed fluorescence microscopy with spectrally tunable semiconducting polymer dots.

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.adk8829

Ziyu Guo, Chetan Poudel, Margaret C Sarfatis, Jiangbo Yu, Madeline Wong, Daniel T Chiu, Joshua C Vaughan

{"title":"Highly multiplexed fluorescence microscopy with spectrally tunable semiconducting polymer dots.","authors":"Ziyu Guo, Chetan Poudel, Margaret C Sarfatis, Jiangbo Yu, Madeline Wong, Daniel T Chiu, Joshua C Vaughan","doi":"10.1126/sciadv.adk8829","DOIUrl":"10.1126/sciadv.adk8829","url":null,"abstract":"Current studies of biological tissues require visualizing diverse cell types and molecular interactions, creating a growing need for versatile techniques to simultaneously probe numerous targets. Traditional multiplexed imaging is limited to around five targets at once. Emerging methods using sequential rounds of staining, imaging, and signal removal can probe tens of targets but require specialized hardware and time-consuming workflows and face challenges with sample distortion and artifacts. We present a highly multiplexed fluorescence microscopy method using semiconducting polymer dots (Pdots) in a single round of staining and imaging. Pdots are small, bright, and photostable fluorescent probes with a wide range of tunable Stokes shifts (20 to 450 nanometers). Multiple series of Pdots with varying excitation wavelengths allow for fast (<1 minute) and single-round imaging of up to 21 targets in the brain and kidney. This method is based on a simple immunofluorescence workflow, efficient use of spectral space, standard hardware, and straightforward analysis, making it widely applicable for bioimaging laboratories.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadk8829"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813946","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