Science Advances最新文献

Violation of Bell inequality with unentangled photons 非纠缠光子对贝尔不等式的违反

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adr1794

Kai Wang, Zhaohua Hou, Kaiyi Qian, Leizhen Chen, Mario Krenn, Markus Aspelmeyer, Anton Zeilinger, Shining Zhu, Xiao-Song Ma

{"title":"Violation of Bell inequality with unentangled photons","authors":"Kai Wang, Zhaohua Hou, Kaiyi Qian, Leizhen Chen, Mario Krenn, Markus Aspelmeyer, Anton Zeilinger, Shining Zhu, Xiao-Song Ma","doi":"10.1126/sciadv.adr1794","DOIUrl":"10.1126/sciadv.adr1794","url":null,"abstract":"<div >Violation of local realism via Bell inequality—a profound and counterintuitive manifestation of quantum theory that conflicts with the prediction of local realism—is viewed to be intimately linked with quantum entanglement. Experimental demonstrations of such a phenomenon using quantum entangled states are among the landmark experiments of modern physics and paved the way for quantum technology. Here, we report the violation of the Bell inequality that cannot be described by quantum entanglement in the system but arises from quantum indistinguishability by path identity, shown by the multiphoton frustrated interference. By analyzing the measurement of four-photon frustrated interference within the standard Bell-test formalism, we find a violation of Bell inequality by more than four SDs. Our work establishes a connection between quantum correlation and quantum indistinguishability, providing insights into the fundamental origin of the counterintuitive characteristics observed in quantum physics.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr1794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756413","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

eIF2A regulates cell migration in a translation-independent manner eIF2A以与翻译无关的方式调节细胞迁移

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adu5668

Jennifer Jungfleisch, Neus Mestre-Farràs, Raúl Gómez-Riera, Oriane Pourcelot, Edouard Bertrand, Nadia Halidi, Fátima Gebauer

{"title":"eIF2A regulates cell migration in a translation-independent manner","authors":"Jennifer Jungfleisch, Neus Mestre-Farràs, Raúl Gómez-Riera, Oriane Pourcelot, Edouard Bertrand, Nadia Halidi, Fátima Gebauer","doi":"10.1126/sciadv.adu5668","DOIUrl":"10.1126/sciadv.adu5668","url":null,"abstract":"<div >The RNA-binding protein eukaryotic translation initiation factor 2A (eIF2A) is an alternative translation initiation factor shown to drive tumor formation by facilitating translation from near-cognate initiation codons. Here, we uncover a function for eIF2A in regulating cell migration in a manner independent of overt control of translation. Using a melanoma cell model consisting of nontumoral melanocytic Mel-ST cells and their metastatic counterpart obtained by <i>H-Ras</i> transformation, we unexpectedly find minimal effects of eIF2A depletion on translation. Interactome studies identified centrosomal proteins as major binding partners of eIF2A. We found that eIF2A colocalizes with the centrosome, enhances centrosome composition, and promotes centrosome orientation during cell migration. Migration requires the C-terminal disordered region of eIF2A, involved in mRNA binding. Interaction with mRNA, however, does not require ongoing translation. These findings reveal a role for eIF2A in centrosome dynamics beyond its traditional function in translation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu5668","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756541","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

BACH2 drives the development and function of group 2 innate lymphoid cells BACH2驱动2组先天淋巴样细胞的发育和功能

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.ads4323

Gaoyu Liu, Ying Wang, Xianfu Yi, Jianye Wang, Jun Zhang, Xixi Feng, Haitao Wang, Chun Chen, Qiang Liu, Jun Wang, Jie Zhou

{"title":"BACH2 drives the development and function of group 2 innate lymphoid cells","authors":"Gaoyu Liu, Ying Wang, Xianfu Yi, Jianye Wang, Jun Zhang, Xixi Feng, Haitao Wang, Chun Chen, Qiang Liu, Jun Wang, Jie Zhou","doi":"10.1126/sciadv.ads4323","DOIUrl":"10.1126/sciadv.ads4323","url":null,"abstract":"<div >Group 2 innate lymphoid cells (ILC2s) represent one of the major drivers of allergic inflammation; however, the precise mechanisms governing the development and function of ILC2s remain unknown. Here, we show that the transcription factor BACH2 was abundantly expressed and epigenetically activated in ILC2s and their progenitors. Conditional ablation of BACH2 diminished the ability of ILC2 progenitors to differentiate into ILC2s. Integration of the scRNA-seq, ATAC-seq, and CUT&Tag-seq techniques revealed that BACH2 modulated the transcriptional profiles and epigenetic landscapes of ILC2 progenitors. Furthermore, BACH2 ablation compromised the functionality of ILC2s, resulting in a resolution of allergic airway inflammation. Notably, the different binding sites of BACH2 in ILC2s and T<sub>H</sub>2 cells suggested that BACH2 binds to IRF4 to control the function of ILC2, underscoring its context-specific effects on allergic airway inflammation. These findings shed promising light on the importance of BACH2 in type 2 immunity and its multifaceted role in asthma.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads4323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756591","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

A scalable ultra-long-acting tenofovir phosphonate prodrug sustains HBV suppression 可扩展的超长效替诺福韦磷酸盐前药维持HBV抑制

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adw2286

Samiksha S. Raut, Srijanee Das, Grace Bybee, Haritha Chava, Mojisola Ogunnaike, Weimin Wang, Anup S. Pathania, Brandon W. Hanson, Nam Thai Hoang Le, Samuel M. Cohen, Howard E. Gendelman, Larisa Y. Poluektova, Benson J. Edagwa, Natalia A. Osna

{"title":"A scalable ultra-long-acting tenofovir phosphonate prodrug sustains HBV suppression","authors":"Samiksha S. Raut, Srijanee Das, Grace Bybee, Haritha Chava, Mojisola Ogunnaike, Weimin Wang, Anup S. Pathania, Brandon W. Hanson, Nam Thai Hoang Le, Samuel M. Cohen, Howard E. Gendelman, Larisa Y. Poluektova, Benson J. Edagwa, Natalia A. Osna","doi":"10.1126/sciadv.adw2286","DOIUrl":"10.1126/sciadv.adw2286","url":null,"abstract":"<div >Long-acting (LA) extended-release formulations are revolutionizing treatment and prevention of HIV infection. However, none of the existing LA therapies are active against hepatitis B virus (HBV), a common coinfection with HIV. Managing coinfection requires therapy to be effective against both viruses. Notable candidates are tenofovir (TFV) prodrugs. We have previously developed an LA TFV through a modified lipophilic ProTide strategy. Given the process chemistry challenges presented by amino acid chiral centers in ProTides, a simplified lipophilic amino acid–free crystalline phosphonate prodrug of TFV (M5TFV) has been created. Intramuscular injections of M5TFV nanosuspension (NM5TFV) were well tolerated in Sprague-Dawley rats and HBV transgenic mice. Notably, single doses at 200 and 400 milligrams per kilogram TFV equivalents produced >2.5 log<sub>10</sub> reduction in HBV DNA beyond 2 months in transgenic mice. Reductions of covalently closed circular DNA were seen in hepatocyte-like cells. These promising findings support further development of NM5TFV as an ultra-LA formulation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adw2286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756596","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

Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A 5-羟色胺受体5-HT1A上G蛋白亚型选择性的结构决定因素

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adu9851

Audrey L. Warren, Gregory Zilberg, Anwar Abbassi, Alejandro Abraham, Shifan Yang, Daniel Wacker

{"title":"Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A","authors":"Audrey L. Warren, Gregory Zilberg, Anwar Abbassi, Alejandro Abraham, Shifan Yang, Daniel Wacker","doi":"10.1126/sciadv.adu9851","DOIUrl":"10.1126/sciadv.adu9851","url":null,"abstract":"<div >Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the receptor signals through inhibitory G proteins, more work is necessary to understand differences in transducer coupling and its relation to functional activity. To develop a molecular understanding of the differences underlying transducer coupling and activation, we performed structure-activity relationship studies of 5-HT1A with distinct G proteins. Through a combination of in vitro assays, we identified a potent partial agonist that selectively engages a G protein subtype. We further investigated the differences in G protein engagement at 5-HT1A with cryo–electron microscopy, determining structures of 5-HT1A bound to distinct ligands and G protein subtypes. Combined with subsequent structure-guided mutagenesis and signaling assays, our studies uncover both orthosteric and allosteric determinants of agonist-specific stimulation of distinct transducers.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu9851","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756536","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

Ultrahigh-density nested polar nanovortices with independently controllable conduction for ferroelectric memristor 具有独立可控导电性的超高密度嵌套极性纳米涡旋铁电忆阻器

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adx0372

Wael Ben Taazayet, Jing Wang, Yixuan Zhang, Shuangquan Qu, Huayu Yang, Yuanyuan Fan, Haojie Han, Jing Ma, Ruiwen Shao, Houbing Huang, Ce-Wen Nan

{"title":"Ultrahigh-density nested polar nanovortices with independently controllable conduction for ferroelectric memristor","authors":"Wael Ben Taazayet, Jing Wang, Yixuan Zhang, Shuangquan Qu, Huayu Yang, Yuanyuan Fan, Haojie Han, Jing Ma, Ruiwen Shao, Houbing Huang, Ce-Wen Nan","doi":"10.1126/sciadv.adx0372","DOIUrl":"10.1126/sciadv.adx0372","url":null,"abstract":"<div >Ferroelectric vortices have received much attention in the past decade due to their functionalities and potential applications in nanoelectronics. However, most of the vortices fabricated in the nanoislands have a size of more than a hundred nanometers, which limits the miniaturization of electronic devices. Here, we show the realization of a high-density vortex lattice with ~10- to 20-nanometer size in ultrathin bismuth ferrite/barium titanate bilayer by strain engineering. The obtained vortex shows a nested structure, e.g., an outer center-type structure with a nested inner ring included, which is well supported by piezoelectric force microscopy, transmission electron microscopy, and phase-field simulations. The nested vortex structure is not only more stable than the center-type vortex structure but also exhibits controllable multistate conduction with low energy consumption (<100 zeptojoules, e.g., 10<sup>−19</sup> joules), good stability (>1 year), and high endurance. This is of great interest for high-density [~2 terabits per square inch (3100 terabits per square meter)] ferroelectric memristor conception for neuromorphic computing.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx0372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756542","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

Static three-dimensional structures determine fast dynamics between distal loci pairs in interphase chromosomes 静态三维结构决定了间期染色体远端位点对之间的快速动力学

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adx1763

Guang Shi, Sucheol Shin, D. Thirumalai

{"title":"Static three-dimensional structures determine fast dynamics between distal loci pairs in interphase chromosomes","authors":"Guang Shi, Sucheol Shin, D. Thirumalai","doi":"10.1126/sciadv.adx1763","DOIUrl":"10.1126/sciadv.adx1763","url":null,"abstract":"<div >Live-cell imaging experiments have shown that the distal dynamics between enhancers and promoters are unexpectedly rapid and incompatible with standard polymer models. The discordance between the compact static chromatin organization and dynamics is a conundrum that violates the expected structure–function relationship. We developed a theory to predict chromatin dynamics by accurately determining three-dimensional (3D) structures from static Hi-C contact maps or fixed-cell imaging data. Using the calculated 3D coordinates, the theory accurately forecasts experimentally observed two-point chromatin dynamics. It predicts rapid enhancer–promoter interactions and uncovers a scaling relationship between two-point relaxation time and genomic separation, closely matching recent measurements. The theory predicts that cohesin depletion accelerates single-locus diffusion while significantly slowing relaxation dynamics within topologically associating domains. Our results demonstrate that chromatin dynamics can be reliably inferred from static structural data, reinforcing the notion that 3D chromatin structure governs dynamic behavior. This general framework offers powerful tools for exploring chromatin dynamics across diverse biological contexts.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adx1763","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756544","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

Glia-derived noncanonical fatty acid binding protein modulates brain lipid storage and clearance 胶质细胞衍生的非典型脂肪酸结合蛋白调节脑脂质储存和清除

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adv2902

Jun Yin, Hsueh-Ling Chen, Anna Grigsby-Brown, Yi He, Myriam L. Cotten, Jacob Short, Aidan Dermady, Jingce Lei, Mary Gibbs, Ethan S. Cheng, Dean Zhang, Caixia Long, Jennifer Tabet, Lele Xu, Tiffany Zhong, Rinat Abzalimov, Mariam Haider, Rong Sun, Ye He, Qiangjun Zhou, Nico Tjandra, Quan Yuan

{"title":"Glia-derived noncanonical fatty acid binding protein modulates brain lipid storage and clearance","authors":"Jun Yin, Hsueh-Ling Chen, Anna Grigsby-Brown, Yi He, Myriam L. Cotten, Jacob Short, Aidan Dermady, Jingce Lei, Mary Gibbs, Ethan S. Cheng, Dean Zhang, Caixia Long, Jennifer Tabet, Lele Xu, Tiffany Zhong, Rinat Abzalimov, Mariam Haider, Rong Sun, Ye He, Qiangjun Zhou, Nico Tjandra, Quan Yuan","doi":"10.1126/sciadv.adv2902","DOIUrl":"10.1126/sciadv.adv2902","url":null,"abstract":"<div >Glia-derived secretory factors are essential for brain development, physiology, and homeostasis, with their dysfunction linked to a variety of neurological disorders. Through genetic and biochemical approaches, we identified odorant binding protein 44a (Obp44a), a noncanonical α-helical fatty acid binding protein (FABP) highly expressed in <i>Drosophila</i> central nervous system glia. Obp44a binds long-chain fatty acids and shuttles between glia and neurons, acting as a secretory lipid chaperone and scavenger to support lipid storage, efflux, and redox homeostasis. Notably, Obp44a is recruited to apoptotic cells and injured axons, especially when glial engulfment is impaired, demonstrating its role in lipid waste management and clearance of cellular debris during development and in pathological states. Our findings highlight FABPs’ importance in regulating brain lipid dynamics and neuronal response to stress and injury. By visualizing FABP function in vivo, this study provides insights into how defective lipid regulation may contribute to neuronal stress and disease progression.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv2902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756398","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

Noise-enhanced stability in synchronized systems 同步系统的噪声增强稳定性

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.adx1338

Zhan Shi, Qiangfeng Lv, Mengqi Fu, Xuefeng Wang, Zhilong Huang, Xueyong Wei, Marco Amabili, Ronghua Huan

引用次数: 0

GTP hydrolysis triggers membrane remodeling by AMPH-1 GTP水解通过AMPH-1触发膜重塑

IF 12.5 1区综合性期刊

Science Advances Pub Date : 2025-08-01 DOI: 10.1126/sciadv.ads9443

Wei Gai, Yuhang Wang, Brianna Martin, Junjie Zhang, Chavela M. Carr, Hays S. Rye

{"title":"GTP hydrolysis triggers membrane remodeling by AMPH-1","authors":"Wei Gai, Yuhang Wang, Brianna Martin, Junjie Zhang, Chavela M. Carr, Hays S. Rye","doi":"10.1126/sciadv.ads9443","DOIUrl":"10.1126/sciadv.ads9443","url":null,"abstract":"<div >Membrane-enclosed transport carriers return biological molecules from the recycling endosome to the plasma membrane using a mechanism that is not well understood. In <i>Caenorhabditis elegans</i>, the formation of carriers from the recycling endosome requires the amphiphysin protein AMPH-1. Recently, we found that purified AMPH-1 is sufficient for tubulation and vesiculation of liposomes in a mechanism that is regulated by guanine nucleotides. Here, we propose a model linking guanosine 5′-triphosphate (GTP) binding and hydrolysis to the membrane binding and tubulation required for transport carrier formation. We find that GTP binding stabilizes interactions between AMPH-1 and the membrane through amphipathic, amino-terminal α helices, which are found at the tips of the arc-shaped, homodimeric structure. By contrast, in the posthydrolysis, guanosine diphosphate–bound state, these helices are repositioned to interact with the amino-terminal helices of other homodimers, to form an oligomeric AMPH-1 lattice that tubulates the membrane, in preparation for carrier formation by membrane fission.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 31","pages":""},"PeriodicalIF":12.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads9443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756576","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