Amar Singh, Adam Herman, Devanjan Dey, Samuel Menge, Shilpi Singh, Anna Tran, Anders Matson, Ahmed Mourad, Parthasarathy Rangarajan, Ravi Masuria, Naoya Sato, Sarah Vadnais, Joseph Sushil Rao, Gatikrushna Singh, Melanie L. Graham, Sabarinathan Ramachandran, Bernhard J. Hering
Inducing stable tolerance to transplants remains a challenge in immunology. Previously, we induced tolerance to allogeneic islets in nonhuman primates by preemptive alloantigen delivery to antigen-presenting cells in situ. Here, mass cytometry phenotyping with incorporated donor-derived MHC-I peptide–loaded MHC-II tetramers revealed accumulation of allospecific CD4+ T cell clusters in the spleen of tolerant recipients. Areg+Tr1 regulatory and terminally exhausted EGFRhi T (Tex) cells represented the predominant allospecific subsets. Trajectory analysis showed that antigen-experienced effector memory T cells differentiated into suppressive Areg+Tr1 and EGFR+TOX+Nur77+TCF-1− Tex subsets. Cell-cell communication mapping showed that exhausted and effector memory T cells engaged with allospecific Tr1 cells via the Areg-EGFR axis. Gene silencing studies confirmed that Tr1 cells use Areg-EGFR signaling to drive the metabolic suppression and epigenetic reprogramming of CD4+ T cells through a Nur77-dependent pathway. These findings point to the splenic Areg+Tr1 cell-EGFR+Teff cell axis as a critical immunoregulatory pathway in peripheral transplant tolerance.
{"title":"Allospecific splenic Tr1 cells drive effector T cell exhaustion through up-regulated Areg-EGFR signaling to promote transplant tolerance","authors":"Amar Singh, Adam Herman, Devanjan Dey, Samuel Menge, Shilpi Singh, Anna Tran, Anders Matson, Ahmed Mourad, Parthasarathy Rangarajan, Ravi Masuria, Naoya Sato, Sarah Vadnais, Joseph Sushil Rao, Gatikrushna Singh, Melanie L. Graham, Sabarinathan Ramachandran, Bernhard J. Hering","doi":"10.1126/sciadv.aea0567","DOIUrl":"10.1126/sciadv.aea0567","url":null,"abstract":"<div >Inducing stable tolerance to transplants remains a challenge in immunology. Previously, we induced tolerance to allogeneic islets in nonhuman primates by preemptive alloantigen delivery to antigen-presenting cells in situ. Here, mass cytometry phenotyping with incorporated donor-derived MHC-I peptide–loaded MHC-II tetramers revealed accumulation of allospecific CD4<sup>+</sup> T cell clusters in the spleen of tolerant recipients. Areg<sup>+</sup>Tr1 regulatory and terminally exhausted EGFR<sup>hi</sup> T (Tex) cells represented the predominant allospecific subsets. Trajectory analysis showed that antigen-experienced effector memory T cells differentiated into suppressive Areg<sup>+</sup>Tr1 and EGFR<sup>+</sup>TOX<sup>+</sup>Nur77<sup>+</sup>TCF-1<sup>−</sup> Tex subsets. Cell-cell communication mapping showed that exhausted and effector memory T cells engaged with allospecific Tr1 cells via the Areg-EGFR axis. Gene silencing studies confirmed that Tr1 cells use Areg-EGFR signaling to drive the metabolic suppression and epigenetic reprogramming of CD4<sup>+</sup> T cells through a Nur77-dependent pathway. These findings point to the splenic Areg<sup>+</sup>Tr1 cell-EGFR<sup>+</sup>Teff cell axis as a critical immunoregulatory pathway in peripheral transplant tolerance.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 2","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908250","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}
This study proposes a perforated, soft millirobot with dual functions: in situ mechanostimulation to enhance cell functionality and local cell delivery. Following protein modification and silica coating, the soft millirobots exhibit excellent biocompatibility, promoting cell adhesion and tissue ingrowth within their perforated architectures under both in vitro and in vivo conditions. They can apply in situ mechanostimulation to various cellular morphologies, including two-dimensional (2D) cell sheets, 3D cell–laden hydrogels, and ex vivo tissue models. The mechanical stimulation improves the functionality of muscle cells by enhancing cellular orientation, myotube contraction, and myocyte differentiation. In parallel, we develop an integrated robotic platform combining magnetic actuation with ultrasound imaging. It demonstrates the proof of principle that delivers 2D cell-sheet and 3D cell–laden biohybrid millirobots to narrow regions in an ex vivo pig liver model. This work expands the potential applications of soft millirobots in mechanobiology studies and future cell-based therapies.
{"title":"In situ mechanostimulation of biohybrid millirobots for enhanced cell functionality and delivery","authors":"Jianhua Zhang, Xianqiang Bao, Zhou Zhu, Rongjing Zhang, Chunxiang Wang, Mingtong Li, Kaichen Xu, Yong He, Dietmar W. Hutmacher, Ziyu Ren, Metin Sitti","doi":"10.1126/sciadv.adx9616","DOIUrl":"10.1126/sciadv.adx9616","url":null,"abstract":"<div >This study proposes a perforated, soft millirobot with dual functions: in situ mechanostimulation to enhance cell functionality and local cell delivery. Following protein modification and silica coating, the soft millirobots exhibit excellent biocompatibility, promoting cell adhesion and tissue ingrowth within their perforated architectures under both in vitro and in vivo conditions. They can apply in situ mechanostimulation to various cellular morphologies, including two-dimensional (2D) cell sheets, 3D cell–laden hydrogels, and ex vivo tissue models. The mechanical stimulation improves the functionality of muscle cells by enhancing cellular orientation, myotube contraction, and myocyte differentiation. In parallel, we develop an integrated robotic platform combining magnetic actuation with ultrasound imaging. It demonstrates the proof of principle that delivers 2D cell-sheet and 3D cell–laden biohybrid millirobots to narrow regions in an ex vivo pig liver model. This work expands the potential applications of soft millirobots in mechanobiology studies and future cell-based therapies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888016","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}
Karishma Bisht, Daniel R. Weilandt, Caitlin H. Lamb, Elizaveta Elshina, Cameron Myhrvold, Aartjan J.W. te Velthuis
Fever during influenza A virus (IAV) infection is triggered by the innate immune response. Various factors contribute to this response, including IAV mini viral RNAs (mvRNA), which trigger RIG-I signaling when their replication and transcription are dysregulated by template loops (t-loops). It is presently not well understood whether the fever response to IAV infection affects subsequent viral replication and innate immune activation. Here, we show that IAV infection at temperatures that simulate fever leads to increased antiviral signaling in H1N1 and H3N2 infections. Mathematical modeling and experimental analyses reveal that differential IAV nucleoprotein and RNA polymerase production increase mvRNA and interferon production. Moreover, at the higher infection temperature, mvRNAs with dysregulating t-loops contribute most to the innate immune activation. We propose that fever during IAV infection can establish a positive feedback loop in which elevated aberrant RNA synthesis and innate immune activation can contribute to the dysregulation of cytokine production.
{"title":"Febrile temperature activates the innate immune response by promoting aberrant influenza A virus RNA synthesis","authors":"Karishma Bisht, Daniel R. Weilandt, Caitlin H. Lamb, Elizaveta Elshina, Cameron Myhrvold, Aartjan J.W. te Velthuis","doi":"10.1126/sciadv.aeb2700","DOIUrl":"10.1126/sciadv.aeb2700","url":null,"abstract":"<div >Fever during influenza A virus (IAV) infection is triggered by the innate immune response. Various factors contribute to this response, including IAV mini viral RNAs (mvRNA), which trigger RIG-I signaling when their replication and transcription are dysregulated by template loops (t-loops). It is presently not well understood whether the fever response to IAV infection affects subsequent viral replication and innate immune activation. Here, we show that IAV infection at temperatures that simulate fever leads to increased antiviral signaling in H1N1 and H3N2 infections. Mathematical modeling and experimental analyses reveal that differential IAV nucleoprotein and RNA polymerase production increase mvRNA and interferon production. Moreover, at the higher infection temperature, mvRNAs with dysregulating t-loops contribute most to the innate immune activation. We propose that fever during IAV infection can establish a positive feedback loop in which elevated aberrant RNA synthesis and innate immune activation can contribute to the dysregulation of cytokine production.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888025","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}
Joseph R. Podojil, Andrew C. Cogswell, Tobias Neef, Ming-Yi Chiang, Sara A. Beddow, Gabriel Arellano, Sandeep Kakade, Derrick P. McCarthy, Adam Elhofy, Chris T. Harp, Mairah Khan, Joshua J. Meeks, Dan Xu, Lonnie D. Shea, Stephen D. Miller
Autoreactive CD4+ T cell infiltration, tissue destruction, and spread epitope–specific CD4+ T cell activation underly CD4+ T cell–mediated autoimmune disease pathogenesis. Here, we identify previously unknown pathways required for antigen (Ag)–specific tolerogenic immune-modifying particle/Cour nanoparticle (TIMP/CNP)–induced tolerance. The data show that myeloid cells phagocytose CNPs, undergo apoptosis, and release oxidized DNA [8-hydroxy-2′-deoxyguanosine (8-OHG)]. Subsequently, Ag-specific CNP treatment increases the number of PD-L1+ cDC2 dendritic cells and the number of FoxP3+, CTLA-4+, PD-1+, and IL-10+ regulatory CD4+ T cells via a stimulator of interferon genes (STING)/interferon-α/β receptor (IFNAR)–dependent pathway. In addition, these same pathways were found to be required for both Ag-coupled apoptotic leukocyte–induced and Ag-coupled red blood cell treatment–induced CD4+ T cell tolerance. Together, these results show that Ag-specific tolerance induced by the presence of apoptotic cells, and by CNP-induced apoptosis, requires the STING/IFNAR pathway, thereby illustrating a previously unknown function of this pathway.
{"title":"STING/type I interferon pathway is required for antigen-containing PLGA nanoparticle- and apoptotic cell–induced CD4+ T cell tolerance","authors":"Joseph R. Podojil, Andrew C. Cogswell, Tobias Neef, Ming-Yi Chiang, Sara A. Beddow, Gabriel Arellano, Sandeep Kakade, Derrick P. McCarthy, Adam Elhofy, Chris T. Harp, Mairah Khan, Joshua J. Meeks, Dan Xu, Lonnie D. Shea, Stephen D. Miller","doi":"10.1126/sciadv.adv8860","DOIUrl":"10.1126/sciadv.adv8860","url":null,"abstract":"<div >Autoreactive CD4<sup>+</sup> T cell infiltration, tissue destruction, and spread epitope–specific CD4<sup>+</sup> T cell activation underly CD4<sup>+</sup> T cell–mediated autoimmune disease pathogenesis. Here, we identify previously unknown pathways required for antigen (Ag)–specific tolerogenic immune-modifying particle/Cour nanoparticle (TIMP/CNP)–induced tolerance. The data show that myeloid cells phagocytose CNPs, undergo apoptosis, and release oxidized DNA [8-hydroxy-2′-deoxyguanosine (8-OHG)]. Subsequently, Ag-specific CNP treatment increases the number of PD-L1<sup>+</sup> cDC2 dendritic cells and the number of FoxP3<sup>+</sup>, CTLA-4<sup>+</sup>, PD-1<sup>+</sup>, and IL-10<sup>+</sup> regulatory CD4<sup>+</sup> T cells via a stimulator of interferon genes (STING)/interferon-α/β receptor (IFNAR)–dependent pathway. In addition, these same pathways were found to be required for both Ag-coupled apoptotic leukocyte–induced and Ag-coupled red blood cell treatment–induced CD4<sup>+</sup> T cell tolerance. Together, these results show that Ag-specific tolerance induced by the presence of apoptotic cells, and by CNP-induced apoptosis, requires the STING/IFNAR pathway, thereby illustrating a previously unknown function of this pathway.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888029","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}
Antibiotic-tolerant persisters use dormancy as a bet-hedging strategy to evade lethal antibiotics, undermining therapeutic efficacy. Protein condensates have been implicated in bacterial dormancy, yet how these assemblies orchestrate dormancy entry remains unclear. We evolved persisters that enter dormancy before the stationary phase, most harboring mutations in serS, encoding seryl-transfer RNA synthetase (SerRS). These variants recapitulated persistence induced by serine hydroxamate (SHX), a serine analog and SerRS inhibitor. Both the serS mutation and SHX treatment trigger SerRS sequestration into conserved DEAD-box adenosine triphosphatase–associated condensates, coinciding with growth arrest and dormancy. In vitro, the SerRS variant preferentially partitions into DeaD granules, consistent with its distinct in vivo localization. Microscopy revealed spatially restricted translation silencing within condensates upon SerRS partitioning. Together, these phase-separated condensates act as hubs that coordinate the transition from proliferation to dormancy, paralleling eukaryotic cell fate control via localized translation. Our findings provide mechanistic insight into bacterial persistence and suggest that targeting condensates could help combat antibiotic tolerance and delay resistance.
{"title":"DEAD-box ATPase–marked condensates coordinate compartmentalized translation and antibiotic persistence","authors":"Ziyin Zhang, Daqian Li, Bo Zheng, Jia-feng Liu","doi":"10.1126/sciadv.ady1930","DOIUrl":"10.1126/sciadv.ady1930","url":null,"abstract":"<div >Antibiotic-tolerant persisters use dormancy as a bet-hedging strategy to evade lethal antibiotics, undermining therapeutic efficacy. Protein condensates have been implicated in bacterial dormancy, yet how these assemblies orchestrate dormancy entry remains unclear. We evolved persisters that enter dormancy before the stationary phase, most harboring mutations in <i>serS</i>, encoding seryl-transfer RNA synthetase (SerRS). These variants recapitulated persistence induced by serine hydroxamate (SHX), a serine analog and SerRS inhibitor. Both the <i>serS</i> mutation and SHX treatment trigger SerRS sequestration into conserved DEAD-box adenosine triphosphatase–associated condensates, coinciding with growth arrest and dormancy. In vitro, the SerRS variant preferentially partitions into DeaD granules, consistent with its distinct in vivo localization. Microscopy revealed spatially restricted translation silencing within condensates upon SerRS partitioning. Together, these phase-separated condensates act as hubs that coordinate the transition from proliferation to dormancy, paralleling eukaryotic cell fate control via localized translation. Our findings provide mechanistic insight into bacterial persistence and suggest that targeting condensates could help combat antibiotic tolerance and delay resistance.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888032","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}
Scott A. Williams, Xue Wang, Isabella Araiza, Jordan S. Guerra, Marc R. Meyer, Jeffrey K. Spear
Bipedalism is a key adaptation that differentiates hominins (humans and our extinct relatives) from living and fossil apes. The earliest putative hominin, Sahelanthropus tchadensis (~7 million years old), was originally represented by a cranium, the reconstruction of which suggested to its discoverers that Sahelanthropus carried its head in a manner similar to known bipedal hominins. Recently, two partial ulnae and a femur shaft were announced as evidence in support of the contention that Sahelanthropus was an early biped, but those interpretations have been challenged. Here, while we find that both limb bones are most similar in size and geometric morphometric shape to chimpanzees (genus Pan), we demonstrate that their relative proportion is more hominin-like. Furthermore, we confirm two features linked to hominin-like hip and knee function and identify a femoral tubercle, a feature only found in bipedal hominins. Our results suggest that Sahelanthropus was an early biped that evolved from a Pan-like Miocene ape ancestor.
{"title":"Earliest evidence of hominin bipedalism in Sahelanthropus tchadensis","authors":"Scott A. Williams, Xue Wang, Isabella Araiza, Jordan S. Guerra, Marc R. Meyer, Jeffrey K. Spear","doi":"10.1126/sciadv.adv0130","DOIUrl":"10.1126/sciadv.adv0130","url":null,"abstract":"<div >Bipedalism is a key adaptation that differentiates hominins (humans and our extinct relatives) from living and fossil apes. The earliest putative hominin, <i>Sahelanthropus tchadensis</i> (~7 million years old), was originally represented by a cranium, the reconstruction of which suggested to its discoverers that <i>Sahelanthropus</i> carried its head in a manner similar to known bipedal hominins. Recently, two partial ulnae and a femur shaft were announced as evidence in support of the contention that <i>Sahelanthropus</i> was an early biped, but those interpretations have been challenged. Here, while we find that both limb bones are most similar in size and geometric morphometric shape to chimpanzees (genus <i>Pan</i>), we demonstrate that their relative proportion is more hominin-like. Furthermore, we confirm two features linked to hominin-like hip and knee function and identify a femoral tubercle, a feature only found in bipedal hominins. Our results suggest that <i>Sahelanthropus</i> was an early biped that evolved from a <i>Pan</i>-like Miocene ape ancestor.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888004","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}
Antibiotic persistence, typically attributed to dormant bacteria, is known to be a major cause of treatment failure. However, despite many years of intense research, no clear consensus on its mechanism has emerged. Here, we demonstrate that high survival under antibiotics may originate from two fundamentally different growth-arrest archetypes: either from a regulated growth arrest, leading to a protected dormant cellular state, or from a dysregulated disrupted growth arrest. Using modeling and experimental approaches including transcriptomics, microcalorimetry, and microfluidics, we unveil the characteristics and vulnerabilities of each growth-arrest archetype. In particular, disrupted bacteria show a general impairment of membrane homeostasis. This understanding resolves previous conflicting results regarding characteristics of persisters and allows tailoring treatments that target the different growth-arrested bacteria. The fundamental distinction between regulated and disrupted growth arrests should be broadly relevant for the description of cells under stress.
{"title":"Differentiation between regulated and disrupted growth arrests allows tailoring of effective treatments for antibiotic persistence","authors":"Adi Rotem, Yoav Kaplan, Orit Gefen, Irine Ronin, Alon Gutfreund, Hagai Rappeport, Raya Faigenbaum-Romm, Nitsan Naor, Elisheva Stav, Oded Agam, Nathalie Q. Balaban","doi":"10.1126/sciadv.adt6577","DOIUrl":"10.1126/sciadv.adt6577","url":null,"abstract":"<div >Antibiotic persistence, typically attributed to dormant bacteria, is known to be a major cause of treatment failure. However, despite many years of intense research, no clear consensus on its mechanism has emerged. Here, we demonstrate that high survival under antibiotics may originate from two fundamentally different growth-arrest archetypes: either from a regulated growth arrest, leading to a protected dormant cellular state, or from a dysregulated disrupted growth arrest. Using modeling and experimental approaches including transcriptomics, microcalorimetry, and microfluidics, we unveil the characteristics and vulnerabilities of each growth-arrest archetype. In particular, disrupted bacteria show a general impairment of membrane homeostasis. This understanding resolves previous conflicting results regarding characteristics of persisters and allows tailoring treatments that target the different growth-arrested bacteria. The fundamental distinction between regulated and disrupted growth arrests should be broadly relevant for the description of cells under stress.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888026","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}
Coherent one-way quantum key distribution (COW-QKD) has been widely investigated and even been deployed in real-world quantum network. However, the proposal of the zero-error attack has critically undermined its security guarantees, and existing experimental implementations have not yet established security against coherent attacks. In this work, we propose and experimentally demonstrate an information–theoretically secure COW-QKD protocol that can resist source side-channel attacks, with secure transmission distances up to 100 kilometers. Our system achieves a secure key rate on the order of kilobits per second over 50 kilometers in the finite-size regime, sufficient for real-time secure voice communication across metropolitan networks. Furthermore, we demonstrate the encrypted transmission of a logo with information-theoretic security over 100 kilometers of optical fiber. These results confirm that COW-QKD can simultaneously provide simplicity and security, establishing it as a strong candidate for deployment in small-scale quantum networks.
{"title":"Experimental coherent one-way quantum key distribution with simplicity and practical security","authors":"Xiao-Yu Cao, Xiao-Ran Sun, Ming-Yang Li, Yu-Shuo Lu, Hua-Lei Yin, Zeng-Bing Chen","doi":"10.1126/sciadv.aec2776","DOIUrl":"10.1126/sciadv.aec2776","url":null,"abstract":"<div >Coherent one-way quantum key distribution (COW-QKD) has been widely investigated and even been deployed in real-world quantum network. However, the proposal of the zero-error attack has critically undermined its security guarantees, and existing experimental implementations have not yet established security against coherent attacks. In this work, we propose and experimentally demonstrate an information–theoretically secure COW-QKD protocol that can resist source side-channel attacks, with secure transmission distances up to 100 kilometers. Our system achieves a secure key rate on the order of kilobits per second over 50 kilometers in the finite-size regime, sufficient for real-time secure voice communication across metropolitan networks. Furthermore, we demonstrate the encrypted transmission of a logo with information-theoretic security over 100 kilometers of optical fiber. These results confirm that COW-QKD can simultaneously provide simplicity and security, establishing it as a strong candidate for deployment in small-scale quantum networks.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888033","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 Yu, Yuting Bu, Chao Shen, Bingru Lin, Chao Lu, Lin Zhu, Zhe Shen, Chong Li, Xin Li
Intestinal fibrosis (IF), a severe complication of inflammatory bowel disease (IBD), remains a critical unmet clinical need. Although the LL37 peptide and probiotics demonstrate therapeutic potential against IF, their clinical translation is hampered by enzymatic hydrolysis and rapid clearance. Here, inspired by the strategy of bacteriocin transport by bacteria (BTB), we developed an orally administered biotherapeutic platform [BTB–alginate (Alg)] featuring an “all-in-one” architecture that enables spatiotemporal coordination of LL37 and probiotics. The BTB-Alg effectively restored intestinal homeostasis through inflammation resolution, immune modulation, and gut microbiota reconstitution. Notably, integrated multiomics analysis and molecular dynamics simulations revealed that LL37 exerts antifibrotic effects by inducing adenosine 5′-monophosphate–activated protein kinase/mammalian target of rapamycin–mediated autophagy, a mechanism validated in clinical specimens. BTB-Alg exhibited potent therapeutic efficacy in three murine models of acute colitis, IBD-associated IF, and Clostridioides difficile–complicated colitis, highlighting its potential as an IBD treatment paradigm. This study offers a clinically translatable strategy for broad gastrointestinal applications.
{"title":"Bacteriocin-transport–inspired oral peptide-probiotic delivery ameliorates IBD complications via autophagy and gut homeostasis","authors":"Yang Yu, Yuting Bu, Chao Shen, Bingru Lin, Chao Lu, Lin Zhu, Zhe Shen, Chong Li, Xin Li","doi":"10.1126/sciadv.adz9069","DOIUrl":"10.1126/sciadv.adz9069","url":null,"abstract":"<div >Intestinal fibrosis (IF), a severe complication of inflammatory bowel disease (IBD), remains a critical unmet clinical need. Although the LL37 peptide and probiotics demonstrate therapeutic potential against IF, their clinical translation is hampered by enzymatic hydrolysis and rapid clearance. Here, inspired by the strategy of bacteriocin transport by bacteria (BTB), we developed an orally administered biotherapeutic platform [BTB–alginate (Alg)] featuring an “all-in-one” architecture that enables spatiotemporal coordination of LL37 and probiotics. The BTB-Alg effectively restored intestinal homeostasis through inflammation resolution, immune modulation, and gut microbiota reconstitution. Notably, integrated multiomics analysis and molecular dynamics simulations revealed that LL37 exerts antifibrotic effects by inducing adenosine 5′-monophosphate–activated protein kinase/mammalian target of rapamycin–mediated autophagy, a mechanism validated in clinical specimens. BTB-Alg exhibited potent therapeutic efficacy in three murine models of acute colitis, IBD-associated IF, and <i>Clostridioides difficile</i>–complicated colitis, highlighting its potential as an IBD treatment paradigm. This study offers a clinically translatable strategy for broad gastrointestinal applications.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 1","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888041","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}
Xiaoyu Huang, Zhouao Zhang, Dan Liu, Tiancheng Luo, Xueting An, Mingjin Yang, Shengli Li, Gang Wang, Huizhong Li, Jiang Cao, Zengtian Sun, Xue Du, Zhouyi Wang, Xinyan Guo, Tianyu Ma, Deyou Peng, Guoyan Qi, Shenghua Zong, Yanting Ding, Guiyun Cui, Ming Shi, Junnian Zheng, Yong Zhang
Myasthenia gravis (MG) is an autoimmune disorder characterized by B cell dysfunction. Here, we designed B cell maturation antigen (BCMA)/CD19 chimeric antigen receptor T cell (CAR T cell) therapy for six refractory MGs, demonstrating favorable safety with grade 1 cytokine release syndrome observed. CAR T cell expansion induced profound B cell depletion, a sustained reduction in acetylcholine receptor (AChR) antibody titers, and symptom improvement. Five patients achieved drug-free remission with minimal manifestations by month 6, persisting through the 12-month follow-up despite B cell reconstitution. Reconstituted B cells showed naïve predominance with diminished AChR specificity and functional capacities. Olink proteomics revealed up-regulation of anti-inflammatory factors, along with down-regulation of proinflammatory molecules. Single-cell sequencing revealed that age-associated B cells (ABCs) were up-regulated in a relapsed patient, and differential gene analysis indicated that Fc receptor-like 5 (FCRL5) expression was elevated in ABCs, whereas CAR T cell responders exhibited a down-regulated trend. Notably, similar ABC expansion and FCRL5 up-regulation occurred in rituximab-relapsed patients. Our findings support BCMA/CD19 CAR T cell therapy as feasible, tolerable, and effective in MG, identifying FCRL5 as a previously unidentified target in relapse.
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