Chiral discrimination of enantiomeric biomolecules is vital in chemistry, biology, and medicine. Conventional methods, relying on circularly polarized light, face weak chiroptical signals and potential photodamage. Despite extensive efforts to improve sensitivity under low-photon exposure, classical chiral probes remain fundamentally bound by the shot noise limit due to quantum fluctuations. To beat these limitations, we demonstrate quantum-elevated chiral discrimination using continuous-variable polarization-entangled states as moderate–photon flux, high-sensitivity, quantum noise–squeezed chiral probes. We achieve a 5-decibel improvement beyond the shot noise limit in distinguishing l- and d-amino acids in liquid phase. This nondestructive, biocompatible protocol enables high-sensitivity chiral analysis, with broad implications for drug development, biochemical research, environmental monitoring, and asymmetric synthesis.
{"title":"Quantum-elevated chiral discrimination for biomolecules","authors":"Yiquan Yang, Xiaolong Hu, Wei Du, Shuhe Wu, Peiyu Yang, Guzhi Bao, Weiping Zhang","doi":"10.1126/sciadv.aea8201","DOIUrl":"10.1126/sciadv.aea8201","url":null,"abstract":"<div >Chiral discrimination of enantiomeric biomolecules is vital in chemistry, biology, and medicine. Conventional methods, relying on circularly polarized light, face weak chiroptical signals and potential photodamage. Despite extensive efforts to improve sensitivity under low-photon exposure, classical chiral probes remain fundamentally bound by the shot noise limit due to quantum fluctuations. To beat these limitations, we demonstrate quantum-elevated chiral discrimination using continuous-variable polarization-entangled states as moderate–photon flux, high-sensitivity, quantum noise–squeezed chiral probes. We achieve a 5-decibel improvement beyond the shot noise limit in distinguishing <span>l</span>- and <span>d</span>-amino acids in liquid phase. This nondestructive, biocompatible protocol enables high-sensitivity chiral analysis, with broad implications for drug development, biochemical research, environmental monitoring, and asymmetric synthesis.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964493","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}
Jishan Wu, Minhao Xiao, Jinlong He, Rachel Tang, Katie Soares, Ziwei Hou, Xinyi Wang, David Jassby, Menachem Elimelech, Eric M. V. Hoek
Conventional thin-film composite (TFC) reverse osmosis (RO) membranes experience irreversible performance loss at high temperatures, restricting their use in industries with high-temperature streams, including oil and gas, pharmaceuticals, electronics, power generation, food production, and hybrid desalination plants. However, the mechanisms driving the performance decline of TFC membranes at high temperatures remain poorly understood. Herein, we combine controlled experiments, molecular dynamics simulations, and micromechanical modeling to elucidate TFC failure mechanisms and to evaluate thermally resilient thin-film cross-linked (TFX) composite membrane. Upon exposure to elevated temperatures (>60°C), salt rejection of TFC dropped from ~99 to <90%, with irreversible structural damage in the polysulfone layer, confirmed by scanning electron microscopy. In contrast, the TFX membrane maintained ~99% salt rejection and showed no signs of physical degradation up to 80°C. Our combined analyses revealed that TFC membrane failure arises from irreversible pore expansion in the thermoplastic polysulfone support, leading to polyamide film rupture and delamination. TFX membranes resist thermal deformation, enabling ultrahigh-temperature RO desalination and water reuse.
{"title":"Resilient high-temperature reverse osmosis desalination membranes","authors":"Jishan Wu, Minhao Xiao, Jinlong He, Rachel Tang, Katie Soares, Ziwei Hou, Xinyi Wang, David Jassby, Menachem Elimelech, Eric M. V. Hoek","doi":"10.1126/sciadv.aea1505","DOIUrl":"10.1126/sciadv.aea1505","url":null,"abstract":"<div >Conventional thin-film composite (TFC) reverse osmosis (RO) membranes experience irreversible performance loss at high temperatures, restricting their use in industries with high-temperature streams, including oil and gas, pharmaceuticals, electronics, power generation, food production, and hybrid desalination plants. However, the mechanisms driving the performance decline of TFC membranes at high temperatures remain poorly understood. Herein, we combine controlled experiments, molecular dynamics simulations, and micromechanical modeling to elucidate TFC failure mechanisms and to evaluate thermally resilient thin-film cross-linked (TFX) composite membrane. Upon exposure to elevated temperatures (>60°C), salt rejection of TFC dropped from ~99 to <90%, with irreversible structural damage in the polysulfone layer, confirmed by scanning electron microscopy. In contrast, the TFX membrane maintained ~99% salt rejection and showed no signs of physical degradation up to 80°C. Our combined analyses revealed that TFC membrane failure arises from irreversible pore expansion in the thermoplastic polysulfone support, leading to polyamide film rupture and delamination. TFX membranes resist thermal deformation, enabling ultrahigh-temperature RO desalination and water reuse.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964494","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}
Jinzhu Chen, Wenhao Li, Qin Peng, Hongwei Zhu, Tan Dai, Jianqiang Miao, Xili Liu
Redox balance is essential for normal cellular functions. PsAF5, a FYVE domain–containing protein, functions as an essential sensor and adapter, particularly in mitophagy triggered by reactive oxygen species in Phytophthora sojae. However, the regulatory role of PsAF5 in maintaining the dynamic equilibrium of the intracellular redox state has not yet been fully elucidated. Here, we identify that specific cysteine residues in the FYVE domain of PsAF5 sense cellular redox states to form and resolve disulfide bonds in a redox-dependent manner. Under reducing conditions, PsAF5 undergoes redox-dependent phase separation to form cytoplasmic condensates that are functionally decoupled from mitophagy execution. Under oxidative conditions, PsAF5 exhibits increased cytosolic solubility and enhanced interaction with PsATG8, thereby promoting mitophagy. This mechanism enables P. sojae to toggle between “detoxification” (oxidizing stress) and “metabolic resilience” (reducing stress) states, ensuring survival across hostile host niches.
{"title":"Reversible phase dynamics of PsAF5 regulate mitophagy to balance redox levels in Phytophthora sojae","authors":"Jinzhu Chen, Wenhao Li, Qin Peng, Hongwei Zhu, Tan Dai, Jianqiang Miao, Xili Liu","doi":"10.1126/sciadv.adz2785","DOIUrl":"10.1126/sciadv.adz2785","url":null,"abstract":"<div >Redox balance is essential for normal cellular functions. PsAF5, a FYVE domain–containing protein, functions as an essential sensor and adapter, particularly in mitophagy triggered by reactive oxygen species in <i>Phytophthora sojae</i>. However, the regulatory role of PsAF5 in maintaining the dynamic equilibrium of the intracellular redox state has not yet been fully elucidated. Here, we identify that specific cysteine residues in the FYVE domain of PsAF5 sense cellular redox states to form and resolve disulfide bonds in a redox-dependent manner. Under reducing conditions, PsAF5 undergoes redox-dependent phase separation to form cytoplasmic condensates that are functionally decoupled from mitophagy execution. Under oxidative conditions, PsAF5 exhibits increased cytosolic solubility and enhanced interaction with PsATG8, thereby promoting mitophagy. This mechanism enables <i>P. sojae</i> to toggle between “detoxification” (oxidizing stress) and “metabolic resilience” (reducing stress) states, ensuring survival across hostile host niches.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964495","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}
Luz Jubierre Zapater, Sara A. Lewis, Rodrigo Lopez Gutierrez, Makiko Yamada, Elias Rodriguez-Fos, Merce Planas-Felix, Daniel Cameron, Phillip Demarest, Anika Nabila, Helen S. Mueller, Junfei Zhao, Paul Bergin, Casie Reed, Tzippora Chwat-Edelstein, Alex Pagnozzi, Caroline Nava, Emilie Bourel-Ponchel, Patricia Cornejo, Ali Dursun, R. Köksal Özgül, Halil Tuna Akar, Henry Houlden, Huma Arshad Cheema, Muhammad Nadeem Anjum, Giovanni Zifarelli, Peter Bauer, Miriam Essid, Hanene Benrhouma, Meriem Ben Hafsa, Ichraf Kraoua, Carolina I. Galaz-Montoya, Alex Proekt, Xiaolan Zhao, Nicholas D. Socci, Matthew Hayes, Yves Bigot, Raul Rabadan, Reza Maroofian, David Torrents, Claudia L Kleinmann, Michael C. Kruer, Miklos Toth, Alex Kentsis
Vertebrate brain development is associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. DNA transposable elements could contribute to somatic genome rearrangements; however, their contributions to brain development are largely unknown. PiggyBac transposable element derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase–derived gene with DNA remodeling activities in human cells. Here, we show that PGBD5 contributes to normal brain development in mice and humans, and its deficiency causes disorder of intellectual disability, movement disorders, and epilepsy. In mice, Pgbd5 is required for the developmental induction of postmitotic DNA breaks and recurrent somatic brain genome rearrangements. In the cerebral cortex, loss of Pgbd5 leads to aberrant neuronal gene expression, including of specific types of glutamatergic neurons, which partly explains the features of PGBD5 deficiency in humans. Thus, PGBD5 is a transposase-derived gene required for brain development in mammals.
{"title":"A transposase-derived gene required for human brain development","authors":"Luz Jubierre Zapater, Sara A. Lewis, Rodrigo Lopez Gutierrez, Makiko Yamada, Elias Rodriguez-Fos, Merce Planas-Felix, Daniel Cameron, Phillip Demarest, Anika Nabila, Helen S. Mueller, Junfei Zhao, Paul Bergin, Casie Reed, Tzippora Chwat-Edelstein, Alex Pagnozzi, Caroline Nava, Emilie Bourel-Ponchel, Patricia Cornejo, Ali Dursun, R. Köksal Özgül, Halil Tuna Akar, Henry Houlden, Huma Arshad Cheema, Muhammad Nadeem Anjum, Giovanni Zifarelli, Peter Bauer, Miriam Essid, Hanene Benrhouma, Meriem Ben Hafsa, Ichraf Kraoua, Carolina I. Galaz-Montoya, Alex Proekt, Xiaolan Zhao, Nicholas D. Socci, Matthew Hayes, Yves Bigot, Raul Rabadan, Reza Maroofian, David Torrents, Claudia L Kleinmann, Michael C. Kruer, Miklos Toth, Alex Kentsis","doi":"10.1126/sciadv.adv7530","DOIUrl":"10.1126/sciadv.adv7530","url":null,"abstract":"<div >Vertebrate brain development is associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. DNA transposable elements could contribute to somatic genome rearrangements; however, their contributions to brain development are largely unknown. PiggyBac transposable element derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase–derived gene with DNA remodeling activities in human cells. Here, we show that PGBD5 contributes to normal brain development in mice and humans, and its deficiency causes disorder of intellectual disability, movement disorders, and epilepsy. In mice, Pgbd5 is required for the developmental induction of postmitotic DNA breaks and recurrent somatic brain genome rearrangements. In the cerebral cortex, loss of Pgbd5 leads to aberrant neuronal gene expression, including of specific types of glutamatergic neurons, which partly explains the features of PGBD5 deficiency in humans. Thus, PGBD5 is a transposase-derived gene required for brain development in mammals.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964490","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}
Key appendage innovations have driven the origin and expansion of arthropods, such as spinnerets enabling spiders to occupy three-dimensional space and diversify into more than 53,000 species. Here, we investigate the genetic basis of spinneret emergence in spiders by examining the complex history and functional importance of arachnid genome evolution. Using chromosome-scale genomes from newly sequenced spiders and the whip scorpion, we integrate evidence from macrosynteny and phylogenetic analyses to provide further strong support for a whole-genome duplication (WGD) event that occurred during early Arachnopulmonata evolution. Following this event, the abdominal-A gene pair not only exhibits functional divergence but also jointly facilitates the emergence of spinnerets. Furthermore, we integrated single-cell transcriptomic analyses and functional validation to confirm that the dachshund-1 gene also regulates spinneret development. The network of duplicated gene pairs may form a cornerstone in the origin and evolution of key morphological traits, revealing that the long-term effects of ancient WGDs on innovation and diversification also occurred in arthropods.
{"title":"An ancient genome duplication event drives the development and evolution of spinnerets in spiders","authors":"Fengyuan Li, Han Yang, Yiming Zhang, Shuhui Wang, Qi Gu, Meiming Wu, Pengyu Jin, Xin Huang, Yu Zhong, Xianting Huang, Yejie Lin, Xinyue Guo, Yunyun Li, Wei Zhang, Shuqiang Li","doi":"10.1126/sciadv.adw2173","DOIUrl":"10.1126/sciadv.adw2173","url":null,"abstract":"<div >Key appendage innovations have driven the origin and expansion of arthropods, such as spinnerets enabling spiders to occupy three-dimensional space and diversify into more than 53,000 species. Here, we investigate the genetic basis of spinneret emergence in spiders by examining the complex history and functional importance of arachnid genome evolution. Using chromosome-scale genomes from newly sequenced spiders and the whip scorpion, we integrate evidence from macrosynteny and phylogenetic analyses to provide further strong support for a whole-genome duplication (WGD) event that occurred during early Arachnopulmonata evolution. Following this event, the <i>abdominal-A</i> gene pair not only exhibits functional divergence but also jointly facilitates the emergence of spinnerets. Furthermore, we integrated single-cell transcriptomic analyses and functional validation to confirm that the <i>dachshund-1</i> gene also regulates spinneret development. The network of duplicated gene pairs may form a cornerstone in the origin and evolution of key morphological traits, revealing that the long-term effects of ancient WGDs on innovation and diversification also occurred in arthropods.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964501","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}
Adrià Alcaide-Jiménez, Albert Canals, Florence Baudin, Cristina Machón, Montserrat Fàbrega-Ferrer, Olga Bantysh, Rosa Pérez-Luque, Brice Murciano, Ali A. Mohammad, Michael J. Rowse, Joseph M. Ferracciolo, Eric S. Krukonis, Christoph W. Müller, Miquel Coll
Activation of virulence in Vibrio cholerae, the etiological agent of cholera disease, is mediated by two transmembrane one-component signal-transduction proteins, ToxR and TcpP, which are also transcription factors. Using cryo–electron microscopy, we have solved five structures of the ompU and toxT transcription activation complexes, including the RNA polymerase (RNAP) holoenzyme, promoter DNAs, transcribed RNA, and their corresponding transcription factors, ToxR or TcpP and ToxR-TcpP, respectively. Activation is achieved through the interaction of ToxR or TcpP with the α–C-terminal repeat domain of RNAP where a single residue of the activator, a phenylalanine, appears to be the most critical contact, as confirmed by mutagenesis. No interactions of the transcription factors were observed with other subunits of the RNAP, i.e., the σ subunit as it occurs in the structurally related PhoB family of two-component transcription factors. The structures, and their comparison with our previously solved DNA promoter–ToxR x-ray structures, unveil the molecular mechanism of cholera virulence gene activation.
{"title":"Structures of Vibrio cholerae transcription complexes reveal how ToxR and TcpP recruit the RNA polymerase and activate virulence genes","authors":"Adrià Alcaide-Jiménez, Albert Canals, Florence Baudin, Cristina Machón, Montserrat Fàbrega-Ferrer, Olga Bantysh, Rosa Pérez-Luque, Brice Murciano, Ali A. Mohammad, Michael J. Rowse, Joseph M. Ferracciolo, Eric S. Krukonis, Christoph W. Müller, Miquel Coll","doi":"10.1126/sciadv.adx9680","DOIUrl":"10.1126/sciadv.adx9680","url":null,"abstract":"<div >Activation of virulence in <i>Vibrio cholerae</i>, the etiological agent of cholera disease, is mediated by two transmembrane one-component signal-transduction proteins, ToxR and TcpP, which are also transcription factors. Using cryo–electron microscopy, we have solved five structures of the <i>ompU</i> and <i>toxT</i> transcription activation complexes, including the RNA polymerase (RNAP) holoenzyme, promoter DNAs, transcribed RNA, and their corresponding transcription factors, ToxR or TcpP and ToxR-TcpP, respectively. Activation is achieved through the interaction of ToxR or TcpP with the α–C-terminal repeat domain of RNAP where a single residue of the activator, a phenylalanine, appears to be the most critical contact, as confirmed by mutagenesis. No interactions of the transcription factors were observed with other subunits of the RNAP, i.e., the σ subunit as it occurs in the structurally related PhoB family of two-component transcription factors. The structures, and their comparison with our previously solved DNA promoter–ToxR x-ray structures, unveil the molecular mechanism of cholera virulence gene activation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 3","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964508","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}
Yang Xu, Xiaoqiang Su, Fusheng Deng, Yuqian Wang, Yaping Yang, Pablo Alonso-González, Hong Chen, Jiafang Li, Jiahua Duan, Zhiwei Guo
The topological transition of polariton dispersion in twisted van der Waals layers at the photonic magic angle results in the diffraction-less and collimated propagation state, termed canalization regime. This type of robust transport of polaritons (i.e., polariton canalization) holds promise for subwavelength control of energy flows. However, the lack of in situ dynamic tunability of canalized polaritons hinders such control because the canalization direction is fixed in the fabricated device. Here, we overcome this limitation by demonstrating programmable polariton canalization in a reconfigurable single-layer metasurface. By engineering the orientation of metasurface unit cells, the direction of canalized magnetic polaritons can be programmed along any in-plane direction (i.e., dynamic all-angle tunability). On-demand steering of canalized polaritons allows customized near-field patterns to be obtained at any desired location—a proof of concept for canalization-based information display applications. These findings offer opportunities to transcend conventional diffraction constraints for integrated photonic devices, thus opening the door for photonic applications where on-demand control is crucial.
{"title":"Programmable polariton canalization in reconfigurable metasurfaces","authors":"Yang Xu, Xiaoqiang Su, Fusheng Deng, Yuqian Wang, Yaping Yang, Pablo Alonso-González, Hong Chen, Jiafang Li, Jiahua Duan, Zhiwei Guo","doi":"10.1126/sciadv.aea0072","DOIUrl":"10.1126/sciadv.aea0072","url":null,"abstract":"<div >The topological transition of polariton dispersion in twisted van der Waals layers at the photonic magic angle results in the diffraction-less and collimated propagation state, termed canalization regime. This type of robust transport of polaritons (i.e., polariton canalization) holds promise for subwavelength control of energy flows. However, the lack of in situ dynamic tunability of canalized polaritons hinders such control because the canalization direction is fixed in the fabricated device. Here, we overcome this limitation by demonstrating programmable polariton canalization in a reconfigurable single-layer metasurface. By engineering the orientation of metasurface unit cells, the direction of canalized magnetic polaritons can be programmed along any in-plane direction (i.e., dynamic all-angle tunability). On-demand steering of canalized polaritons allows customized near-field patterns to be obtained at any desired location—a proof of concept for canalization-based information display applications. These findings offer opportunities to transcend conventional diffraction constraints for integrated photonic devices, thus opening the door for photonic applications where on-demand control is crucial.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 2","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941836","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}
The nonspecific distribution of tertiary lymph node (TLS)–inducing drugs may trigger autoimmune diseases. We developed a self-transforming chitosan hydrogel to act as a biomimetic TLS. The chitosan hydrogel solution was peritumorally injected in bacteria-colonized tumors in mice followed by the rapid in situ gelation. After killing tumor cells and intratumoral bacteria by doxorubicin and cefotaxime, the hydrogel efficiently adsorbed bacterial pathogen-associated molecular patterns, tumor cell–derived damage-associated molecular patterns, and tumor-associated antigens. These danger signals greatly potentiated immune cell recruitment into the hydrogel and sufficiently activated dendritic cells (DCs) by the absorbed DNA-mediated cGAS-STING activation. The activated DCs converted T cells into cytotoxic T cells, and these activated immune cells migrated through the pores of hydrogels into the tumor tissues, effectively remodeling the immunosuppressive microenvironment, thereby inhibiting the tumor growth and metastasis. These findings demonstrate a previously unidentified method to establish a safe, easy-to-control, and effective biomimetic TLS that offers a promising strategy for updating current combined immunotherapy against various tumors.
{"title":"Self-transforming hydrogel mimicking tertiary lymph nodes to activate cGAS-STING pathway for enhanced antitumor immunotherapy","authors":"Fei Wang, Yukun Zeng, Manqi Yan, Ziqi Zhou, Lingzi Feng, Fei Yang, Wei Zhao, Yong Hu","doi":"10.1126/sciadv.adz5078","DOIUrl":"10.1126/sciadv.adz5078","url":null,"abstract":"<div >The nonspecific distribution of tertiary lymph node (TLS)–inducing drugs may trigger autoimmune diseases. We developed a self-transforming chitosan hydrogel to act as a biomimetic TLS. The chitosan hydrogel solution was peritumorally injected in bacteria-colonized tumors in mice followed by the rapid in situ gelation. After killing tumor cells and intratumoral bacteria by doxorubicin and cefotaxime, the hydrogel efficiently adsorbed bacterial pathogen-associated molecular patterns, tumor cell–derived damage-associated molecular patterns, and tumor-associated antigens. These danger signals greatly potentiated immune cell recruitment into the hydrogel and sufficiently activated dendritic cells (DCs) by the absorbed DNA-mediated cGAS-STING activation. The activated DCs converted T cells into cytotoxic T cells, and these activated immune cells migrated through the pores of hydrogels into the tumor tissues, effectively remodeling the immunosuppressive microenvironment, thereby inhibiting the tumor growth and metastasis. These findings demonstrate a previously unidentified method to establish a safe, easy-to-control, and effective biomimetic TLS that offers a promising strategy for updating current combined immunotherapy against various tumors.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 2","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937649","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}
The interaction between a single microscopic object such as a cell or a molecule and electromagnetic field is fundamental in single-object manipulation such as optical trap and magnetic trap. Function-on-demand, single-object manipulation requires local high-freedom control of electromagnetic field, which remains challenging. Here, we propose a manipulation concept: programmable single-object manipulation, based on programming the electromagnetic field in a multibit electrode system realized on a programmable electric tweezer (PET) with four individually addressed electrodes. Its probe-integrated electrode array supports spatial-selective manipulation, while the adjustable electrode gaps enable manipulating multiscale targets. The independent programming of the electrical signals of each electrode further allows using multiple electric principles to achieve multiscale and spatiotemporal programmable control and in situ measurements, marking a transition from function-fixed single-object manipulation to function-on-demand single-object manipulation. Last, with integrated functions of PET, we demonstrate multistep manipulation to measure the spontaneous relaxation of DNA supercoiling, highlighting the versatility of PET in uncovering stochastic biophysical phenomena at the single-molecule level.
{"title":"Programmable electric tweezers","authors":"Yuang Chen, Haojing Tan, Jiahua Zhuang, Yang Xu, Chen Zhang, Jiandong Feng","doi":"10.1126/sciadv.aec3443","DOIUrl":"10.1126/sciadv.aec3443","url":null,"abstract":"<div >The interaction between a single microscopic object such as a cell or a molecule and electromagnetic field is fundamental in single-object manipulation such as optical trap and magnetic trap. Function-on-demand, single-object manipulation requires local high-freedom control of electromagnetic field, which remains challenging. Here, we propose a manipulation concept: programmable single-object manipulation, based on programming the electromagnetic field in a multibit electrode system realized on a programmable electric tweezer (PET) with four individually addressed electrodes. Its probe-integrated electrode array supports spatial-selective manipulation, while the adjustable electrode gaps enable manipulating multiscale targets. The independent programming of the electrical signals of each electrode further allows using multiple electric principles to achieve multiscale and spatiotemporal programmable control and in situ measurements, marking a transition from function-fixed single-object manipulation to function-on-demand single-object manipulation. Last, with integrated functions of PET, we demonstrate multistep manipulation to measure the spontaneous relaxation of DNA supercoiling, highlighting the versatility of PET in uncovering stochastic biophysical phenomena at the single-molecule level.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 2","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938039","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}
Pengliang Yu, Agathe Eijsink, Junpeng Wang, Chris Marone, Derek Elsworth
Permeability evolves dynamically in the crust and mediates important natural and industrial processes in the subsurface. Episodic microearthquakes generate porosity and, thus, permeability by creating or reactivating fractures. We constrain the form of the scaling relationship linking seismic moment () to incremental permeability generation () through a series of laboratory fault reactivation experiments with absolute constraint on seismic moment. We demonstrate proportionality at centimeter scale but confirm predictive power-law scaling using a first-order model as from centimeter to subkilometer scale. Stress drop, fault roughness, and deformation modulus condition the prefactor , extending over 10 decades for reasonable natural parameter ranges. However, observed permeabilities are much more tightly constrained, with spanning only two orders of magnitude over length scales from centimeter to subkilometer, suggesting interdependencies in the controlling variables and rendering the relation as diagnostic in predicting fluid flow in crustal reservoirs.
{"title":"Seismicity diagnostic of permeability creation from centimeter to subkilometer scales in crystalline rock during shear stimulation","authors":"Pengliang Yu, Agathe Eijsink, Junpeng Wang, Chris Marone, Derek Elsworth","doi":"10.1126/sciadv.ady5201","DOIUrl":"10.1126/sciadv.ady5201","url":null,"abstract":"<div >Permeability evolves dynamically in the crust and mediates important natural and industrial processes in the subsurface. Episodic microearthquakes generate porosity and, thus, permeability by creating or reactivating fractures. We constrain the form of the scaling relationship linking seismic moment (<span><math><mrow><msub><mi>M</mi><mn>0</mn></msub></mrow></math></span>) to incremental permeability generation (<span><math><mrow><mi>Δ</mi><mi>k</mi></mrow></math></span>) through a series of laboratory fault reactivation experiments with absolute constraint on seismic moment. We demonstrate <span><math><mrow><mi>Δ</mi><mi>k</mi><mo>−</mo><msub><mi>M</mi><mn>0</mn></msub></mrow></math></span> proportionality at centimeter scale but confirm predictive power-law scaling using a first-order model as <span><math><mrow><mi>Δ</mi><mi>k</mi><mo>=</mo><mi>λ</mi><msubsup><mi>M</mi><mn>0</mn><mrow><mn>2</mn><mo>/</mo><mn>3</mn></mrow></msubsup></mrow></math></span> from centimeter to subkilometer scale. Stress drop, fault roughness, and deformation modulus condition the prefactor <span><math><mrow><mi>λ</mi></mrow></math></span>, extending over 10 decades for reasonable natural parameter ranges. However, observed permeabilities are much more tightly constrained, with <span><math><mrow><mi>λ</mi></mrow></math></span> spanning only two orders of magnitude over length scales from centimeter to subkilometer, suggesting interdependencies in the controlling variables and rendering the relation as diagnostic in predicting fluid flow in crustal reservoirs.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 2","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941820","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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