Jeongmin Hwang, Tonatiuh A. Ocampo, Vinzenz Mayer, Janice Kang, Krishna S. Paranandi, Young Jun Kim, Zhenyu Han, John P. Cavaliere, Sergej Kudruk, Jochen H. Lorch, Chad A. Mirkin
To develop effective nanostructured immunotherapeutics, identifying structural parameters that maximize immune response is essential. Spherical nucleic acids (SNAs) provide a modular platform for coordinated antigen-adjuvant delivery, where subtle structural differences can markedly influence potency. Herein, three SNAs were designed with HLA-A2–restricted HPV16 E7 11-19 peptide and CpG adjuvant, nearly identical in composition but differing in antigen presentation. All enhanced dendritic cell activation and CD8 + T cell cytotoxicity in primary human cells compared to peptide-CpG admixture; however, one variant, N-HSNA, elicited the strongest response, inducing ~8-fold higher interferon-γ secretion and ~2.5-fold greater cytotoxicity. In tumor-bearing AAD mice, N-HSNA reduced tumor burden by ~3.5-fold, prolonged survival, and expanded CD8 + T cells. Transcriptomic profiling revealed up-regulation of activation genes and suppression of exhaustion markers. In patient-derived HPV + head and neck cancer spheroids, N-HSNA enhanced cytotoxicity ~2.5-fold, establishing antigen placement and orientation as key parameters for translational cancer immunotherapy.
{"title":"E7 11-19 placement and orientation dictate CD8 + T cell response in structurally defined spherical nucleic acid vaccines","authors":"Jeongmin Hwang, Tonatiuh A. Ocampo, Vinzenz Mayer, Janice Kang, Krishna S. Paranandi, Young Jun Kim, Zhenyu Han, John P. Cavaliere, Sergej Kudruk, Jochen H. Lorch, Chad A. Mirkin","doi":"10.1126/sciadv.aec3876","DOIUrl":"https://doi.org/10.1126/sciadv.aec3876","url":null,"abstract":"To develop effective nanostructured immunotherapeutics, identifying structural parameters that maximize immune response is essential. Spherical nucleic acids (SNAs) provide a modular platform for coordinated antigen-adjuvant delivery, where subtle structural differences can markedly influence potency. Herein, three SNAs were designed with HLA-A2–restricted HPV16 E7 <jats:sub>11-19</jats:sub> peptide and CpG adjuvant, nearly identical in composition but differing in antigen presentation. All enhanced dendritic cell activation and CD8 <jats:sup>+</jats:sup> T cell cytotoxicity in primary human cells compared to peptide-CpG admixture; however, one variant, N-HSNA, elicited the strongest response, inducing ~8-fold higher interferon-γ secretion and ~2.5-fold greater cytotoxicity. In tumor-bearing AAD mice, N-HSNA reduced tumor burden by ~3.5-fold, prolonged survival, and expanded CD8 <jats:sup>+</jats:sup> T cells. Transcriptomic profiling revealed up-regulation of activation genes and suppression of exhaustion markers. In patient-derived HPV <jats:sup>+</jats:sup> head and neck cancer spheroids, N-HSNA enhanced cytotoxicity ~2.5-fold, establishing antigen placement and orientation as key parameters for translational cancer immunotherapy.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"59 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153615","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}
Michael Antesberger, Mariana M. E. Schmid, Huan Cao, Borivoje Dakić, Lee A. Rozema, Philip Walther
Entangled quantum states are essential ingredients for many quantum technologies, but they must be validated before they are used. As a full characterization is prohibitively resource intensive, recent work has focused on developing methods to efficiently extract a few parameters of interest, in a so-called verification framework. Most existing approaches are based on preparing an ensemble of nominally identical and independently distributed (IID) quantum states and then measuring each copy of the ensemble. However, this leaves no states left for the intended quantum tasks and the IID assumptions do not always hold experimentally. To overcome these challenges, we experimentally implement quantum state certification (QSC), which measures only a subset of the ensemble, certifying the fidelity of multiple copies of the remaining states. We use active optical switches to randomly sample from sources of two-photon Bell states and three-photon GHZ (Greenberger-Horn-Zeilinger) states, reporting statistically sound fidelities in real time without destroying the entire ensemble. In addition, our QSC protocol removes the assumption that the states are identically distributed (but still assumes independent copies); can achieve close N−1 scaling, in the number of states measured N ; and can be implemented in a device-independent manner. Together, these benefits make our QSC protocol suitable for benchmarking large-scale quantum computing devices and deployed quantum communication setups relying on entanglement in both standard and adversarial situations.
{"title":"Experimental quantum state certification by actively sampling photonic entangled states","authors":"Michael Antesberger, Mariana M. E. Schmid, Huan Cao, Borivoje Dakić, Lee A. Rozema, Philip Walther","doi":"10.1126/sciadv.aea4144","DOIUrl":"https://doi.org/10.1126/sciadv.aea4144","url":null,"abstract":"Entangled quantum states are essential ingredients for many quantum technologies, but they must be validated before they are used. As a full characterization is prohibitively resource intensive, recent work has focused on developing methods to efficiently extract a few parameters of interest, in a so-called verification framework. Most existing approaches are based on preparing an ensemble of nominally identical and independently distributed (IID) quantum states and then measuring each copy of the ensemble. However, this leaves no states left for the intended quantum tasks and the IID assumptions do not always hold experimentally. To overcome these challenges, we experimentally implement quantum state certification (QSC), which measures only a subset of the ensemble, certifying the fidelity of multiple copies of the remaining states. We use active optical switches to randomly sample from sources of two-photon Bell states and three-photon GHZ (Greenberger-Horn-Zeilinger) states, reporting statistically sound fidelities in real time without destroying the entire ensemble. In addition, our QSC protocol removes the assumption that the states are identically distributed (but still assumes independent copies); can achieve close <jats:italic toggle=\"yes\">N</jats:italic> <jats:sup>−1</jats:sup> scaling, in the number of states measured <jats:italic toggle=\"yes\">N</jats:italic> ; and can be implemented in a device-independent manner. Together, these benefits make our QSC protocol suitable for benchmarking large-scale quantum computing devices and deployed quantum communication setups relying on entanglement in both standard and adversarial situations.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"59 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153716","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}
Chiral boundary states with perfect conducting channels are essential characteristics of magnetic topological materials. Prominent examples include the one-dimensional (1D) chiral edge and 2D chiral surface states found in 2D and 3D quantum Hall materials under magnetic fields, respectively. However, these boundary states are restricted to specific fixed dimensions, so they hardly facilitate cross-dimensional energy and information transport. Here, we fabricate a unique 3D photonic antiferromagnetic topological insulator with net zero magnetization that can simultaneously support different-dimensional hinge states and unpaired surface Dirac cones on neighboring facets. Owing to the chiral anomaly present in a finite-size sample, the gapless surface Dirac cone, neighbored by facets with surface Dirac masses of opposite signs, is further converted, exhibiting 2D planar one-way propagation. In conjunction with 1D hinge states, we experimentally observe a closed chiral loop for nonreciprocal hinge–surface transport across dimensions in topological photonics, similar to that theoretically proposed in 3D quantum anomalous Hall materials. Our findings enrich the chiral boundary features of 3D magnetic topological insulators and offer a topological strategy for exploring ideal cross-dimensional devices.
{"title":"Chiral hinge–surface transport across dimensions in three-dimensional magneto-optical topological materials","authors":"Hua-Shan Lai, Yan-Chen Zhou, Ze-Qun Sun, Cheng He, Yan-Feng Chen","doi":"10.1126/sciadv.aeb4171","DOIUrl":"https://doi.org/10.1126/sciadv.aeb4171","url":null,"abstract":"Chiral boundary states with perfect conducting channels are essential characteristics of magnetic topological materials. Prominent examples include the one-dimensional (1D) chiral edge and 2D chiral surface states found in 2D and 3D quantum Hall materials under magnetic fields, respectively. However, these boundary states are restricted to specific fixed dimensions, so they hardly facilitate cross-dimensional energy and information transport. Here, we fabricate a unique 3D photonic antiferromagnetic topological insulator with net zero magnetization that can simultaneously support different-dimensional hinge states and unpaired surface Dirac cones on neighboring facets. Owing to the chiral anomaly present in a finite-size sample, the gapless surface Dirac cone, neighbored by facets with surface Dirac masses of opposite signs, is further converted, exhibiting 2D planar one-way propagation. In conjunction with 1D hinge states, we experimentally observe a closed chiral loop for nonreciprocal hinge–surface transport across dimensions in topological photonics, similar to that theoretically proposed in 3D quantum anomalous Hall materials. Our findings enrich the chiral boundary features of 3D magnetic topological insulators and offer a topological strategy for exploring ideal cross-dimensional devices.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"3 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153378","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}
Leonie M. Heger, Francesco Gubinelli, Andreas J. Huber, Aida Cardona-Alberich, Matteo Rovere, Ulf Matti, Stephan A. Müller, Sankarshana R. Nagaraja, Lena Jaschkowitz, Martina Schifferer, Wolfgang Wurst, Stefan F. Lichtenthaler, Christian Behrends, Sivakumar Sambandan, Lena F. Burbulla
Parkinson’s disease (PD) is characterized by α-synuclein accumulation and dopaminergic neuron degeneration, with dopamine (DA) oxidation emerging as a key pathological driver. However, the mechanisms underlying this neurotoxic process remain unclear. Using PD patient-derived and CRISPR-engineered induced pluripotent stem cell midbrain dopaminergic neurons lacking DJ-1, we identified defective sequestration of cytosolic DA into synaptic vesicles, which culminated in DA oxidation and α-synuclein pathology. In-depth proteomics, state-of-the-art imaging, and ultrasensitive DA probes uncovered that decreased vesicular monoamine transporter 2 (VMAT2) protein and function impaired vesicular DA uptake, resulting in reduced vesicle availability and abnormal vesicle morphology. Furthermore, VMAT2 activity and vesicle endocytosis are processes dependent on adenosine 5′-triphosphate (ATP), which is notably reduced in DJ-1–deficient dopaminergic neurons. ATP supplementation restored vesicular function and alleviated DA-related pathologies in mutant dopaminergic neurons. This study reveals an ATP-sensitive mechanism that regulates DA homeostasis through VMAT2 and vesicle dynamics in midbrain dopaminergic neurons, highlighting enhanced DA sequestration as a promising therapeutic strategy for PD.
{"title":"VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1–linked Parkinson’s neurons","authors":"Leonie M. Heger, Francesco Gubinelli, Andreas J. Huber, Aida Cardona-Alberich, Matteo Rovere, Ulf Matti, Stephan A. Müller, Sankarshana R. Nagaraja, Lena Jaschkowitz, Martina Schifferer, Wolfgang Wurst, Stefan F. Lichtenthaler, Christian Behrends, Sivakumar Sambandan, Lena F. Burbulla","doi":"10.1126/sciadv.adz5645","DOIUrl":"https://doi.org/10.1126/sciadv.adz5645","url":null,"abstract":"Parkinson’s disease (PD) is characterized by α-synuclein accumulation and dopaminergic neuron degeneration, with dopamine (DA) oxidation emerging as a key pathological driver. However, the mechanisms underlying this neurotoxic process remain unclear. Using PD patient-derived and CRISPR-engineered induced pluripotent stem cell midbrain dopaminergic neurons lacking DJ-1, we identified defective sequestration of cytosolic DA into synaptic vesicles, which culminated in DA oxidation and α-synuclein pathology. In-depth proteomics, state-of-the-art imaging, and ultrasensitive DA probes uncovered that decreased vesicular monoamine transporter 2 (VMAT2) protein and function impaired vesicular DA uptake, resulting in reduced vesicle availability and abnormal vesicle morphology. Furthermore, VMAT2 activity and vesicle endocytosis are processes dependent on adenosine 5′-triphosphate (ATP), which is notably reduced in DJ-1–deficient dopaminergic neurons. ATP supplementation restored vesicular function and alleviated DA-related pathologies in mutant dopaminergic neurons. This study reveals an ATP-sensitive mechanism that regulates DA homeostasis through VMAT2 and vesicle dynamics in midbrain dopaminergic neurons, highlighting enhanced DA sequestration as a promising therapeutic strategy for PD.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"31 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153381","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}
Optimizing organic photovoltaic (OPV) performance requires navigating the high-dimensional, interdependent processing parameters governing bulk heterojunction morphology. To address this, we have constructed a standardized database integrating donor/acceptor pairs, nine key fabrication parameters, and device efficiencies, consolidating over a decade of experimental results. Leveraging this resource, we developed a three-tiered machine learning framework using gradient boosting regression trees. The strategy progresses from single-parameter baseline models to stage-combined models that capture intraprocess synergies, culminating in a global nine-parameter optimization model. This final model achieves a Pearson correlation of >0.9 and a success rate of >80% in identifying optimal multiparameter configurations. Validation on 78 external systems, each containing a previously unseen donor or acceptor, demonstrates robust generalization with >75% accuracy in predicting the optimal or secondary condition for individual parameters. This work establishes a practical, data-driven framework for accelerating the rational optimization of OPV photoactive layers.
{"title":"Navigating high-dimensional processing parameters in organic photovoltaics via a multitier machine learning framework","authors":"Yaping Wen, Yipu Zhang, Haibo Ma","doi":"10.1126/sciadv.aeb1323","DOIUrl":"https://doi.org/10.1126/sciadv.aeb1323","url":null,"abstract":"Optimizing organic photovoltaic (OPV) performance requires navigating the high-dimensional, interdependent processing parameters governing bulk heterojunction morphology. To address this, we have constructed a standardized database integrating donor/acceptor pairs, nine key fabrication parameters, and device efficiencies, consolidating over a decade of experimental results. Leveraging this resource, we developed a three-tiered machine learning framework using gradient boosting regression trees. The strategy progresses from single-parameter baseline models to stage-combined models that capture intraprocess synergies, culminating in a global nine-parameter optimization model. This final model achieves a Pearson correlation of >0.9 and a success rate of >80% in identifying optimal multiparameter configurations. Validation on 78 external systems, each containing a previously unseen donor or acceptor, demonstrates robust generalization with >75% accuracy in predicting the optimal or secondary condition for individual parameters. This work establishes a practical, data-driven framework for accelerating the rational optimization of OPV photoactive layers.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"46 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153612","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}
Meifei Su, Qianqian Qin, Jing Zhang, Yingdong Li, Ailin Ye, Suomin Wang, Suiwen Hou
Type one protein phosphatases (TOPPs) widely modulate phytohormone signaling and stress responses, but their roles in ethylene signaling remain unknown. This study reveals a reciprocal regulatory relationship between TOPPs and ethylene insensitive 2 (EIN2)–mediated ethylene signaling. We identified that ethylene can induce TOPPs ’ expression, and topp1/4/5 mutants exhibited partial ethylene insensitivity with reduced EIN3 protein. Mechanistically, TOPPs function upstream of EIN2 and interact with its carboxyl-terminal domain (CEND) to dephosphorylate the S655 residue. This site-specific dephosphorylation promotes EIN2 stability and EIN2 CEND nuclear accumulation, thereby activating ethylene responses. Notably, EIN2 S655A -YFP/ein2-5 plants displayed constitutive ethylene responses and improved salt tolerance. Further investigation showed that EIN3/EIN3 like 1 (EIL1) activates TOPPs ’ expression by binding to their promoters, amplifying ethylene signaling accordingly. Together, our finding establishes TOPPs as key regulators in ethylene signaling and reveal a dephosphorylation switch mechanism governing EIN2 function, providing critical insight into how EIN2 posttranslational modifications mediate plant stress adaptation.
1型蛋白磷酸酶（TOPPs）广泛调节植物激素信号和胁迫反应，但其在乙烯信号中的作用尚不清楚。这项研究揭示了TOPPs与乙烯不敏感2 （EIN2）介导的乙烯信号传导之间的相互调节关系。我们发现乙烯可以诱导TOPPs的表达，topp1/4/5突变体表现出部分乙烯不敏感，EIN3蛋白减少。从机制上讲，TOPPs在EIN2上游发挥作用，并与EIN2的羧基末端结构域（CEND）相互作用，使S655残基去磷酸化。这种位点特异性的去磷酸化促进了EIN2的稳定性和EIN2的CEND核积累，从而激活乙烯反应。值得注意的是，EIN2 S655A -YFP/ EIN2 -5植株表现出组分乙烯响应，耐盐性提高。进一步研究发现EIN3/EIN3 like 1 （EIL1）通过结合启动子激活TOPPs的表达，从而放大乙烯信号。总之，我们的发现确定了TOPPs是乙烯信号的关键调节因子，并揭示了控制EIN2功能的去磷酸化开关机制，为EIN2翻译后修饰如何介导植物胁迫适应提供了重要的见解。
{"title":"Type one protein phosphatases (TOPPs) catalyze EIN2 dephosphorylation to regulate ethylene signaling in Arabidopsis","authors":"Meifei Su, Qianqian Qin, Jing Zhang, Yingdong Li, Ailin Ye, Suomin Wang, Suiwen Hou","doi":"10.1126/sciadv.aec5937","DOIUrl":"https://doi.org/10.1126/sciadv.aec5937","url":null,"abstract":"Type one protein phosphatases (TOPPs) widely modulate phytohormone signaling and stress responses, but their roles in ethylene signaling remain unknown. This study reveals a reciprocal regulatory relationship between TOPPs and ethylene insensitive 2 (EIN2)–mediated ethylene signaling. We identified that ethylene can induce <jats:italic toggle=\"yes\">TOPPs</jats:italic> ’ expression, and <jats:italic toggle=\"yes\">topp1/4/5</jats:italic> mutants exhibited partial ethylene insensitivity with reduced EIN3 protein. Mechanistically, TOPPs function upstream of EIN2 and interact with its carboxyl-terminal domain (CEND) to dephosphorylate the S655 residue. This site-specific dephosphorylation promotes EIN2 stability and EIN2 CEND nuclear accumulation, thereby activating ethylene responses. Notably, <jats:italic toggle=\"yes\"> EIN2 <jats:sup>S655A</jats:sup> -YFP/ein2-5 </jats:italic> plants displayed constitutive ethylene responses and improved salt tolerance. Further investigation showed that EIN3/EIN3 like 1 (EIL1) activates <jats:italic toggle=\"yes\">TOPPs</jats:italic> ’ expression by binding to their promoters, amplifying ethylene signaling accordingly. Together, our finding establishes TOPPs as key regulators in ethylene signaling and reveal a dephosphorylation switch mechanism governing EIN2 function, providing critical insight into how EIN2 posttranslational modifications mediate plant stress adaptation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"20 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153379","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}
Héctor Capella-Monsonís, Jiayang Rong, Bharadwaj Chirravuri, William D’Angelo, Hēth R. Turnquist, George Hussey, Stephen F. Badylak
Extracellular vesicles (EV) represent a conserved and highly efficient mechanism for cell-to-cell communication. Matrix-bound nanovesicles (MBV) are a recently identified type of EV embedded within the extracellular matrix with potent local and systemic immunomodulatory effects on myeloid cells. These effects are durable and last beyond the predicted life span of differentiated myeloid cells such as macrophages. The present study investigated MBV-directed epigenetic modification in myeloid precursors as a potential explanation for their prolonged immunomodulatory effects. Flow cytometry and ATAC sequencing studies show that MBV are internalized by myeloid cell progenitors in the bone marrow and in macrophages after terminal differentiation. This internalization is coincident with epigenetic changes that are associated with modulation of macrophage responses to inflammatory stimuli. Furthermore, MBV treatment differentially alters chromatin accessibility as a function of cell differentiation state (i.e., myeloid progenitor versus macrophage). The present study shows the epigenetic effects of MBV on myeloid cells, representing a potential avenue to exploit the therapeutic potential of biologic scaffold materials.
{"title":"Matrix-bound nanovesicles as epigenetic modulators of myeloid cells","authors":"Héctor Capella-Monsonís, Jiayang Rong, Bharadwaj Chirravuri, William D’Angelo, Hēth R. Turnquist, George Hussey, Stephen F. Badylak","doi":"10.1126/sciadv.adx9159","DOIUrl":"https://doi.org/10.1126/sciadv.adx9159","url":null,"abstract":"Extracellular vesicles (EV) represent a conserved and highly efficient mechanism for cell-to-cell communication. Matrix-bound nanovesicles (MBV) are a recently identified type of EV embedded within the extracellular matrix with potent local and systemic immunomodulatory effects on myeloid cells. These effects are durable and last beyond the predicted life span of differentiated myeloid cells such as macrophages. The present study investigated MBV-directed epigenetic modification in myeloid precursors as a potential explanation for their prolonged immunomodulatory effects. Flow cytometry and ATAC sequencing studies show that MBV are internalized by myeloid cell progenitors in the bone marrow and in macrophages after terminal differentiation. This internalization is coincident with epigenetic changes that are associated with modulation of macrophage responses to inflammatory stimuli. Furthermore, MBV treatment differentially alters chromatin accessibility as a function of cell differentiation state (i.e., myeloid progenitor versus macrophage). The present study shows the epigenetic effects of MBV on myeloid cells, representing a potential avenue to exploit the therapeutic potential of biologic scaffold materials.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"133 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153623","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}
Stimuli-responsive nanomaterials represent a promising platform for immunomodulation. However, their application in orchestrating T cell responses remains limited. Here, we develop a biomimetic magnetoelectric nanoparticle (DC@CFO/BFO) by coating core-shell CoFe 2 O 4 @BiFeO 3 particles with dendritic cell membranes to enable selective targeting of CD4 + T cells. Under magnetic field stimulation, DC@CFO/BFO localizes to ribosomes and enhances protein synthesis by modulating electrostatic interactions at the ribosomal exit tunnel. This ribosome-targeted modulation promotes type II immune response via IL-4 induction and TAF9B-dependent transcriptional programming, thereby enhancing T helper 2 (T H 2) cell proliferation. In murine models of colitis and arthritis, both systemic administration of DC@CFO/BFO and adoptive transfer of magnetoelectricity-responsive T H 2 cells attenuated inflammation and restored immune homeostasis. In contrast, these effects were abrogated in Taf9b -deficient T cells, underscoring the essential role of TAF9B in mediating this response. Collectively, our findings identify magnetoelectric nanocomposites as a potent tool for T cell engineering and highlight a translational strategy for the treatment of autoimmune inflammation.
{"title":"Magnetoelectric nanoparticles drive TAF9B + T H 2 cell expansion to alleviate inflammation","authors":"Jia Song, Lulu Liu, Ziqi Liu, Shuo Liu, Zhang Zhang, Xinyu Liu, Boon Chin Heng, Yaojin Wang, Dan Lu, Xuehui Zhang, Xuliang Deng","doi":"10.1126/sciadv.adz3199","DOIUrl":"https://doi.org/10.1126/sciadv.adz3199","url":null,"abstract":"Stimuli-responsive nanomaterials represent a promising platform for immunomodulation. However, their application in orchestrating T cell responses remains limited. Here, we develop a biomimetic magnetoelectric nanoparticle (DC@CFO/BFO) by coating core-shell CoFe <jats:sub>2</jats:sub> O <jats:sub>4</jats:sub> @BiFeO <jats:sub>3</jats:sub> particles with dendritic cell membranes to enable selective targeting of CD4 <jats:sup>+</jats:sup> T cells. Under magnetic field stimulation, DC@CFO/BFO localizes to ribosomes and enhances protein synthesis by modulating electrostatic interactions at the ribosomal exit tunnel. This ribosome-targeted modulation promotes type II immune response via IL-4 induction and TAF9B-dependent transcriptional programming, thereby enhancing T helper 2 (T <jats:sub>H</jats:sub> 2) cell proliferation. In murine models of colitis and arthritis, both systemic administration of DC@CFO/BFO and adoptive transfer of magnetoelectricity-responsive T <jats:sub>H</jats:sub> 2 cells attenuated inflammation and restored immune homeostasis. In contrast, these effects were abrogated in <jats:italic toggle=\"yes\">Taf9b</jats:italic> -deficient T cells, underscoring the essential role of TAF9B in mediating this response. Collectively, our findings identify magnetoelectric nanocomposites as a potent tool for T cell engineering and highlight a translational strategy for the treatment of autoimmune inflammation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"394 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153712","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}
Jiaying Shen, Weng Fu Io, Chang Liu, Yiyang Wen, Han Wu, Yilin Cao, Yongtao Yang, Dianmeng Dong, Fan Zhang, Songhua Cai, Wei Ren, Xianran Xing, Yang Zhang, Zhenping Wu, Jianhua Hao
For decades, the integration of power handling and nonvolatile memory has been fundamentally impeded by the incompatibility between wide-bandgap semiconductors and ferroelectric materials. We resolve this challenge by demonstrating robust room-temperature ferroelectricity in epitaxial metastable κ-Ga 2 O 3 , grown via industry-compatible metal-organic chemical vapor deposition, creating an intrinsically ferroelectric wide-bandgap semiconductor. Through systematic characterization including piezoresponse force microscopy, polarization hysteresis measurements, and positive up–negative down tests, we provide conclusive evidence of stable ferroelectric switching down to 5-nanometer thickness—exceeding conventional ferroelectric limits—via a unique octahedral-tetrahedral transformation. Ferroelectric tunnel junctions achieve giant tunneling electroresistance exceeding 10 5 . This fundamental discovery in a mainstream semiconductor challenges conventional materials paradigms and enables monolithic integration of power and memory functionalities on a unified platform.
{"title":"Robust room-temperature ferroelectricity in the wide-bandgap semiconductor Ga 2 O 3","authors":"Jiaying Shen, Weng Fu Io, Chang Liu, Yiyang Wen, Han Wu, Yilin Cao, Yongtao Yang, Dianmeng Dong, Fan Zhang, Songhua Cai, Wei Ren, Xianran Xing, Yang Zhang, Zhenping Wu, Jianhua Hao","doi":"10.1126/sciadv.aec5225","DOIUrl":"https://doi.org/10.1126/sciadv.aec5225","url":null,"abstract":"For decades, the integration of power handling and nonvolatile memory has been fundamentally impeded by the incompatibility between wide-bandgap semiconductors and ferroelectric materials. We resolve this challenge by demonstrating robust room-temperature ferroelectricity in epitaxial metastable κ-Ga <jats:sub>2</jats:sub> O <jats:sub>3</jats:sub> , grown via industry-compatible metal-organic chemical vapor deposition, creating an intrinsically ferroelectric wide-bandgap semiconductor. Through systematic characterization including piezoresponse force microscopy, polarization hysteresis measurements, and positive up–negative down tests, we provide conclusive evidence of stable ferroelectric switching down to 5-nanometer thickness—exceeding conventional ferroelectric limits—via a unique octahedral-tetrahedral transformation. Ferroelectric tunnel junctions achieve giant tunneling electroresistance exceeding 10 <jats:sup>5</jats:sup> . This fundamental discovery in a mainstream semiconductor challenges conventional materials paradigms and enables monolithic integration of power and memory functionalities on a unified platform.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"394 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153398","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}
Lester P. Sands, Hong Lei, Seth R. Batten, Alec Hartle, Terry Lohrenz, Leonardo Barbosa, Dan Bang, Peter Dayan, William M. Howe, Brian H. Smith, Pendleton R. Montague
Biogenic amines are fundamental for physiological homeostasis and behavioral control in both vertebrates and invertebrates. Monoamine neurotransmitters released in target brain regions conjointly regulate adaptive learning and plasticity. However, our understanding of these multianalyte mechanisms remains nascent, in part due to limitations in measurement technology. Here, during associative conditioning in honey bees, we concurrently tracked subsecond fluctuations in octopamine, tyramine, dopamine, and serotonin in the antennal lobe, where plasticity influences odorant representations. By repeatedly pairing an odorant with subsequent sucrose delivery, we observed individual differences in the conditioned response to odor, which occurred after a variable number of pairings (learners) or not at all (non-learners). The distinction between learners and non-learners was reflected in neurotransmitter responses across experimental conditions. The speed of learning, the number of pairings prior to a proboscis extension reflex, could be predicted from monoamine opponent signaling (octopamine-tyramine), from both the first presentation of the odorant alone, prior to any pairing with sucrose, and the first conditioned response to the odorant, coming after a number of sucrose pairings. These results suggest that monoamine signaling phenotypes may relate directly to the now widely reported socially relevant genetic differences in honey bee learning.
{"title":"Octopamine and tyramine dynamics predict learning rate phenotypes during associative conditioning in honey bees","authors":"Lester P. Sands, Hong Lei, Seth R. Batten, Alec Hartle, Terry Lohrenz, Leonardo Barbosa, Dan Bang, Peter Dayan, William M. Howe, Brian H. Smith, Pendleton R. Montague","doi":"10.1126/sciadv.aea8433","DOIUrl":"https://doi.org/10.1126/sciadv.aea8433","url":null,"abstract":"Biogenic amines are fundamental for physiological homeostasis and behavioral control in both vertebrates and invertebrates. Monoamine neurotransmitters released in target brain regions conjointly regulate adaptive learning and plasticity. However, our understanding of these multianalyte mechanisms remains nascent, in part due to limitations in measurement technology. Here, during associative conditioning in honey bees, we concurrently tracked subsecond fluctuations in octopamine, tyramine, dopamine, and serotonin in the antennal lobe, where plasticity influences odorant representations. By repeatedly pairing an odorant with subsequent sucrose delivery, we observed individual differences in the conditioned response to odor, which occurred after a variable number of pairings (learners) or not at all (non-learners). The distinction between learners and non-learners was reflected in neurotransmitter responses across experimental conditions. The speed of learning, the number of pairings prior to a proboscis extension reflex, could be predicted from monoamine opponent signaling (octopamine-tyramine), from both the first presentation of the odorant alone, prior to any pairing with sucrose, and the first conditioned response to the odorant, coming after a number of sucrose pairings. These results suggest that monoamine signaling phenotypes may relate directly to the now widely reported socially relevant genetic differences in honey bee learning.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153441","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}
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