Yang Zhang, Huan Liang, Yajing Liu, Dong Li, Shuai Dong, Jing Wang, Weiwei Li, Ce-Wen Nan
Relaxor ferroelectric materials are promising for next-generation capacitors due to their high energy storage capacity. Polymorphic phase engineering, where different ferroelectric phases coexist, has been widely demonstrated as an effective approach to further boost capacitive energy storage performance of relaxor ferroelectrics, but the reasons for these improvements and how they compare to single-phase systems remain unclear. Here, taking dendrite-like PbZr1-xTixO3/MgO nanocomposites with defected as a model system, we systematically examine properties and capacitive energy storage performance for rhombohedral-dominant, rhombohedral/tetragonal-mixed, and tetragonal-dominant phases through phase-field simulations. We find that the rhombohedral/tetragonal mixtures deliver the best results in most cases, mainly due to their low switching barriers and substantial local inhomogeneity. These results offer a detailed view of improved energy storage in relaxor ferroelectrics and provide theoretical guidance for designing high-performance capacitors.
{"title":"Boosting capacitive energy storage in relaxor ferroelectrics through polymorphic phase engineering","authors":"Yang Zhang, Huan Liang, Yajing Liu, Dong Li, Shuai Dong, Jing Wang, Weiwei Li, Ce-Wen Nan","doi":"","DOIUrl":"","url":null,"abstract":"<div >Relaxor ferroelectric materials are promising for next-generation capacitors due to their high energy storage capacity. Polymorphic phase engineering, where different ferroelectric phases coexist, has been widely demonstrated as an effective approach to further boost capacitive energy storage performance of relaxor ferroelectrics, but the reasons for these improvements and how they compare to single-phase systems remain unclear. Here, taking dendrite-like PbZr<sub>1-<i>x</i></sub>Ti<i><sub>x</sub></i>O<sub>3</sub>/MgO nanocomposites with defected as a model system, we systematically examine properties and capacitive energy storage performance for rhombohedral-dominant, rhombohedral/tetragonal-mixed, and tetragonal-dominant phases through phase-field simulations. We find that the rhombohedral/tetragonal mixtures deliver the best results in most cases, mainly due to their low switching barriers and substantial local inhomogeneity. These results offer a detailed view of improved energy storage in relaxor ferroelectrics and provide theoretical guidance for designing high-performance capacitors.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224573","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}
Karolin Voßgröne, Francesco Favero, Krushanka Kashyap, Francisco G. Rodríguez-González, André V. Olsen, Xin Li, Balca R. Mardin, Joachim Weischenfeldt, Claus S. Sørensen
Cancer mutations perturb key processes, driving uncontrolled cell proliferation. With critical roles of enzymes in cell function and growth, we hypothesized that cancer driver mutations alter specific and recurrent enzymatic functions. Leveraging large pan-cancer genomic datasets and curated mutation catalogs, we identified frequent mutations in helicases, enzymes involved in nucleic acid unwinding and processing. Helicases emerged as the most commonly mutated cancer driver enzyme family, altered in two-thirds of all cancers. Functional screens and genomic analyses revealed that helicase dysfunctions contribute to genomic instability and faulty DNA repair. We observed a marked phenotype of Aquarius helicase (AQR), which was recurrently hemizygously deleted as an early clonal event in cancer genomes. These deletions were associated with high genomic instability and homologous recombination deficiency signatures. Furthermore, we found hemizygous loss to be a common tumor suppression mechanism among helicases, present in 35% of all cancers. Overall, our enzyme-family approach highlights helicases, including AQR, as key potential cancer drivers.
{"title":"Hemizygous loss of helicases promotes genomic instability and cancer development","authors":"Karolin Voßgröne, Francesco Favero, Krushanka Kashyap, Francisco G. Rodríguez-González, André V. Olsen, Xin Li, Balca R. Mardin, Joachim Weischenfeldt, Claus S. Sørensen","doi":"","DOIUrl":"","url":null,"abstract":"<div >Cancer mutations perturb key processes, driving uncontrolled cell proliferation. With critical roles of enzymes in cell function and growth, we hypothesized that cancer driver mutations alter specific and recurrent enzymatic functions. Leveraging large pan-cancer genomic datasets and curated mutation catalogs, we identified frequent mutations in helicases, enzymes involved in nucleic acid unwinding and processing. Helicases emerged as the most commonly mutated cancer driver enzyme family, altered in two-thirds of all cancers. Functional screens and genomic analyses revealed that helicase dysfunctions contribute to genomic instability and faulty DNA repair. We observed a marked phenotype of Aquarius helicase (<i>AQR</i>), which was recurrently hemizygously deleted as an early clonal event in cancer genomes. These deletions were associated with high genomic instability and homologous recombination deficiency signatures. Furthermore, we found hemizygous loss to be a common tumor suppression mechanism among helicases, present in 35% of all cancers. Overall, our enzyme-family approach highlights helicases, including <i>AQR</i>, as key potential cancer drivers.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224583","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}
Subhash B. Arya, Fatima Jordan-Javed, Kristen Loesel, Yehyun Choi, Samuel P. Collie, Lauren E. Hein, Brendon M. Baker, Euisik Yoon, Carole A. Parent
Efficient neutrophil chemotaxis requires the integration of mechanical forces and lipid-mediated signaling. While the signaling lipid leukotriene B4 (LTB 4 ) reinforces cellular polarity, how mechanical cues regulate its production remains unclear. We now show that cytosolic phospholipase A2α (cPLA 2 α), which is essential for the synthesis of LTB 4 , functions as a nuclear curvosensor. cPLA 2 α responds to nuclear squeezing by localizing to ceramide-rich inner nuclear membrane microdomains and incorporating onto the exofacial surface of nuclear envelope–derived exosomes. This unique topology enables localized LTB 4 synthesis, which synchronizes calcium spikes, promotes myosin light chain II phosphorylation, and sustains polarity and directional persistence after constriction. In neutrophils passing through tight spaces, cPLA 2 α activity drives the chemotactic response to nuclear squeezing by promoting exosomal LTB 4 production and persistence after constriction. These findings uncover a cPLA 2 α-dependent mechanochemical axis linking nuclear architecture to chemotactic efficiency and offer alternative strategies to modulate inflammatory responses.
{"title":"cPLA 2 α targeting to exosomes connects nuclear deformation to LTB 4 -signaling during neutrophil chemotaxis","authors":"Subhash B. Arya, Fatima Jordan-Javed, Kristen Loesel, Yehyun Choi, Samuel P. Collie, Lauren E. Hein, Brendon M. Baker, Euisik Yoon, Carole A. Parent","doi":"10.1126/sciadv.aea2784","DOIUrl":"https://doi.org/10.1126/sciadv.aea2784","url":null,"abstract":"Efficient neutrophil chemotaxis requires the integration of mechanical forces and lipid-mediated signaling. While the signaling lipid leukotriene B4 (LTB <jats:sub>4</jats:sub> ) reinforces cellular polarity, how mechanical cues regulate its production remains unclear. We now show that cytosolic phospholipase A2α (cPLA <jats:sub>2</jats:sub> α), which is essential for the synthesis of LTB <jats:sub>4</jats:sub> , functions as a nuclear curvosensor. cPLA <jats:sub>2</jats:sub> α responds to nuclear squeezing by localizing to ceramide-rich inner nuclear membrane microdomains and incorporating onto the exofacial surface of nuclear envelope–derived exosomes. This unique topology enables localized LTB <jats:sub>4</jats:sub> synthesis, which synchronizes calcium spikes, promotes myosin light chain II phosphorylation, and sustains polarity and directional persistence after constriction. In neutrophils passing through tight spaces, cPLA <jats:sub>2</jats:sub> α activity drives the chemotactic response to nuclear squeezing by promoting exosomal LTB <jats:sub>4</jats:sub> production and persistence after constriction. These findings uncover a cPLA <jats:sub>2</jats:sub> α-dependent mechanochemical axis linking nuclear architecture to chemotactic efficiency and offer alternative strategies to modulate inflammatory responses.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"49 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222818","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}
With increasing understanding of cadmium (Cd) exposure levels and toxicity mechanisms, the adequacy of current Cd limit standards for protecting public health requires comprehensive evaluation. Here, we found that 39.04% of rice Cd content surpassed the fifth percentile of benchmark dose lower limit (BMDL 5 ; 17.100 micrograms per day) threshold for dietary Cd associated with chronic kidney disease in Jiangsu Province. Moreover, more than 90% of rice Cd levels posed potential health hazards, with some samples presenting lifetime carcinogenic risks. Blood and urinary Cd levels demonstrated age-dependent increases, with 48.40 and 20.61% of participants exceeding BMDL 5 levels for blood Cd (0.640 micrograms per liter) and urinary Cd (0.120 micrograms per liter), respectively. The derived reference values for dietary Cd were 0.149 and 0.018 micrograms per kilogram of body weight per day for adults and children, respectively. The lowest concentrations of Cd in rice consumed by adults and children were also observed, which indicated that current Cd limit standards appear insufficient to protect public health, indicating a need for more stringent safety thresholds.
{"title":"Assessing the health risks of rice cadmium content standards in China","authors":"Haiyan Chu, Huilin Zhang, Dahua Ren, Xuanying Jiang, Yang Yu, Jialei Zhu, Kexin Li, Haiping Liu, Linfan Xu, Xiaoting Li, Zhen Ding","doi":"10.1126/sciadv.adw4382","DOIUrl":"https://doi.org/10.1126/sciadv.adw4382","url":null,"abstract":"With increasing understanding of cadmium (Cd) exposure levels and toxicity mechanisms, the adequacy of current Cd limit standards for protecting public health requires comprehensive evaluation. Here, we found that 39.04% of rice Cd content surpassed the fifth percentile of benchmark dose lower limit (BMDL <jats:sub>5</jats:sub> ; 17.100 micrograms per day) threshold for dietary Cd associated with chronic kidney disease in Jiangsu Province. Moreover, more than 90% of rice Cd levels posed potential health hazards, with some samples presenting lifetime carcinogenic risks. Blood and urinary Cd levels demonstrated age-dependent increases, with 48.40 and 20.61% of participants exceeding BMDL <jats:sub>5</jats:sub> levels for blood Cd (0.640 micrograms per liter) and urinary Cd (0.120 micrograms per liter), respectively. The derived reference values for dietary Cd were 0.149 and 0.018 micrograms per kilogram of body weight per day for adults and children, respectively. The lowest concentrations of Cd in rice consumed by adults and children were also observed, which indicated that current Cd limit standards appear insufficient to protect public health, indicating a need for more stringent safety thresholds.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222952","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}
Guoyu Cheng, Xuan Jiang, Lingxuan Zhu, Xinjie Chen, Rucheng Liu, Liang Zhu, Xiao Hu, Shaosen Zhang, Wen Tan, Dongxin Lin, Li Zhang, Chen Wu, Mingkun Li
Intratumoral microbiota has emerged as a notable factor influencing cancer initiation and progression. However, its composition and functional impact in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. Here, we performed metagenomic sequencing on 119 paired tumor-normal tissues from patients with ESCC and single-cell RNA sequencing on 45 samples to investigate microbe-host interactions. We identified Parvimonas micra (P. micra), an anaerobic oral-derived bacterium, as significantly enriched in tumor tissues and associated with poor prognosis. Moreover, the abundance of P. micra correlated with increased regulatory T cell (Treg cell) infiltration in the ESCC tumor microenvironment. Through cellular and animal experiments, we demonstrate that P. micra promotes tumor growth by secreting p-cresol, a metabolite of amino acid fermentation, which elevates reactive oxygen species levels and induces FOXP3+ Treg differentiation, thereby fostering immunosuppression and tumor growth. Our study establishes a mechanistic link between intratumoral microbiota and the immune microenvironment, highlighting the microbial contribution to ESCC progression and prognosis.
{"title":"Intratumoral Parvimonas micra promotes esophageal squamous cell carcinoma via p-cresol–induced Treg differentiation","authors":"Guoyu Cheng, Xuan Jiang, Lingxuan Zhu, Xinjie Chen, Rucheng Liu, Liang Zhu, Xiao Hu, Shaosen Zhang, Wen Tan, Dongxin Lin, Li Zhang, Chen Wu, Mingkun Li","doi":"","DOIUrl":"","url":null,"abstract":"<div >Intratumoral microbiota has emerged as a notable factor influencing cancer initiation and progression. However, its composition and functional impact in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. Here, we performed metagenomic sequencing on 119 paired tumor-normal tissues from patients with ESCC and single-cell RNA sequencing on 45 samples to investigate microbe-host interactions. We identified <i>Parvimonas micra</i> (<i>P. micra</i>), an anaerobic oral-derived bacterium, as significantly enriched in tumor tissues and associated with poor prognosis. Moreover, the abundance of <i>P. micra</i> correlated with increased regulatory T cell (T<sub>reg</sub> cell) infiltration in the ESCC tumor microenvironment. Through cellular and animal experiments, we demonstrate that <i>P. micra</i> promotes tumor growth by secreting <i>p</i>-cresol, a metabolite of amino acid fermentation, which elevates reactive oxygen species levels and induces FOXP3<sup>+</sup> T<sub>reg</sub> differentiation, thereby fostering immunosuppression and tumor growth. Our study establishes a mechanistic link between intratumoral microbiota and the immune microenvironment, highlighting the microbial contribution to ESCC progression and prognosis.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224608","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}
Min Li, Fantao Kong, Hao Zhuo, Wenshu Luo, Xiangzhi Cui, Jianlin Shi
The electrochemical conversion of oxalic acid (OX) to glycolic acid (GC) offers a sustainable route for biomass valorization yet suffers from inefficient proton-coupled electron transfer and competitive hydrogen evolution. We report an oxygen vacancy (OV)–mediated atomic interface strategy to construct Feδ--OV-Ti3+ dual-active sites in TiO2, enabling tandem activation of H+ and C═O bond through a (2e− + 2e−) relay mechanism. The Fe-TiOX/titanium paper electrocatalyst achieves a faradaic efficiency of 74.3% with >60% GC selectivity at industrially relevant current densities (~100 milliamperes per square centimeter), stable for ~60 hours, which is a record high in electrochemical conversion of OX to GC. In situ spectroscopy and density functional theory calculations reveal that the Feδ- sites dynamically stabilize H* intermediates while inhibiting H2 formation, while Ti3+ sites form a σ─π coordination bond with the carbonyl oxygen in OX, lowering the energy barrier of the rate-determining step. This work provides a paradigm for designing a dual site in electrochemical tandem reactions, offering fundamental insights in sustainable chemical synthesis.
{"title":"Electrochemical conversion of oxalic acid to glycolic acid via oxygen vacancy–mediated tandem catalysis","authors":"Min Li, Fantao Kong, Hao Zhuo, Wenshu Luo, Xiangzhi Cui, Jianlin Shi","doi":"","DOIUrl":"","url":null,"abstract":"<div >The electrochemical conversion of oxalic acid (OX) to glycolic acid (GC) offers a sustainable route for biomass valorization yet suffers from inefficient proton-coupled electron transfer and competitive hydrogen evolution. We report an oxygen vacancy (O<sub>V</sub>)–mediated atomic interface strategy to construct Fe<sup>δ-</sup>-O<sub>V</sub>-Ti<sup>3+</sup> dual-active sites in TiO<sub>2</sub>, enabling tandem activation of H<sup>+</sup> and C═O bond through a (2e<sup>−</sup> + 2e<sup>−</sup>) relay mechanism. The Fe-TiO<sub>X</sub>/titanium paper electrocatalyst achieves a faradaic efficiency of 74.3% with >60% GC selectivity at industrially relevant current densities (~100 milliamperes per square centimeter), stable for ~60 hours, which is a record high in electrochemical conversion of OX to GC. In situ spectroscopy and density functional theory calculations reveal that the Fe<sup>δ-</sup> sites dynamically stabilize H* intermediates while inhibiting H<sub>2</sub> formation, while Ti<sup>3+</sup> sites form a σ─π coordination bond with the carbonyl oxygen in OX, lowering the energy barrier of the rate-determining step. This work provides a paradigm for designing a dual site in electrochemical tandem reactions, offering fundamental insights in sustainable chemical synthesis.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224609","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}
Oluwaseun D. Akanbi, Michael L. Felder, Daniel Kupor, Jiachen Feng, Luana Janaína de Campos, Lisa J. Bain, Crystal Sanchez, Hanieh Safari, Thi Vo, Martin Conda-Sheridan, Omolola Eniola-Adefeso
Steroids, specifically bile salts and corticosteroids, treat bile synthesis disorders, liver dysfunction, and inflammation. However, these water-soluble steroid drugs are rapidly cleared from the desired sites of action in the body, necessitating multiple doses. Therefore, the development of particle-based steroid medications that offer elongated therapeutic activity is of paramount medical importance. Accordingly, steroid microparticles were developed via three fabrication processes in this work, where a metal or an organic acid facilitates steroid microparticle formation. Particles fabricated using these methods exhibit consistent shape, size, and crystallinity. Furthermore, results from our coarse-grained computational model show that hydrogen bonding dictates steroid monomer-monomer interactions that determine overall particle shape and size. In addition, we demonstrate the ability to induce steroid particle formation and tune the morphology of steroid drug particles by replacing the C21 side group (tail) with chemical analogs. Thus, this study opens opportunities for the clinical translation of particle-based steroid therapeutics as an alternative to the current steroid drug formulations.
{"title":"Engineering controlled-release steroid therapeutics: fabrication and molecular design of self-assembled microparticles","authors":"Oluwaseun D. Akanbi, Michael L. Felder, Daniel Kupor, Jiachen Feng, Luana Janaína de Campos, Lisa J. Bain, Crystal Sanchez, Hanieh Safari, Thi Vo, Martin Conda-Sheridan, Omolola Eniola-Adefeso","doi":"","DOIUrl":"","url":null,"abstract":"<div >Steroids, specifically bile salts and corticosteroids, treat bile synthesis disorders, liver dysfunction, and inflammation. However, these water-soluble steroid drugs are rapidly cleared from the desired sites of action in the body, necessitating multiple doses. Therefore, the development of particle-based steroid medications that offer elongated therapeutic activity is of paramount medical importance. Accordingly, steroid microparticles were developed via three fabrication processes in this work, where a metal or an organic acid facilitates steroid microparticle formation. Particles fabricated using these methods exhibit consistent shape, size, and crystallinity. Furthermore, results from our coarse-grained computational model show that hydrogen bonding dictates steroid monomer-monomer interactions that determine overall particle shape and size. In addition, we demonstrate the ability to induce steroid particle formation and tune the morphology of steroid drug particles by replacing the C21 side group (tail) with chemical analogs. Thus, this study opens opportunities for the clinical translation of particle-based steroid therapeutics as an alternative to the current steroid drug formulations.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 8","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224611","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}
Li-Kun Yang, Qishu Qin, Jin Zhang, Ziyu Zhang, Haiyan Yu, Chengtian Zhao, Bo Dong
Settlement of marine invertebrate larvae at suitable sites for metamorphosis, growth, and reproduction is crucial for propagating populations, but often causes ecological problems such as bioinvasion and biofouling. Chemosensation plays an essential role in larval settlement preferences. However, the mechanisms for sensing chemical cues underlying these preferences remain unknown. Using urochordate ascidian larvae, the prominent marine fouling organisms affecting coastal ecosystems, we explored the mechanism of larval chemosensation and its role in settlement preference. Here, we identified taurine, a specific sulfur-containing amino acid secreted from marine adult animals, as a chemical attractant for ascidian larvae to locate salubrious environments for metamorphosis. Taurine stimulates primary sensory neurons within larval papillae, and this neuronal excitation is integrated in the simple brain (also known as sensory vesicle) to elicit chemoattraction and attachment of swimming larvae. We discuss the implications of this study in the emerging field of marine Eco-Evo-Devo research by establishing a model system for understanding developmental mechanisms in the context of marine ecosystems and aquaculture. Of interest is the potential development of antifouling strategies by targeting taurine chemosensation.
{"title":"Taurine-driven chemotaxis and metamorphosis in ascidian tadpole larvae","authors":"Li-Kun Yang, Qishu Qin, Jin Zhang, Ziyu Zhang, Haiyan Yu, Chengtian Zhao, Bo Dong","doi":"10.1126/sciadv.aeb9574","DOIUrl":"https://doi.org/10.1126/sciadv.aeb9574","url":null,"abstract":"Settlement of marine invertebrate larvae at suitable sites for metamorphosis, growth, and reproduction is crucial for propagating populations, but often causes ecological problems such as bioinvasion and biofouling. Chemosensation plays an essential role in larval settlement preferences. However, the mechanisms for sensing chemical cues underlying these preferences remain unknown. Using urochordate ascidian larvae, the prominent marine fouling organisms affecting coastal ecosystems, we explored the mechanism of larval chemosensation and its role in settlement preference. Here, we identified taurine, a specific sulfur-containing amino acid secreted from marine adult animals, as a chemical attractant for ascidian larvae to locate salubrious environments for metamorphosis. Taurine stimulates primary sensory neurons within larval papillae, and this neuronal excitation is integrated in the simple brain (also known as sensory vesicle) to elicit chemoattraction and attachment of swimming larvae. We discuss the implications of this study in the emerging field of marine Eco-Evo-Devo research by establishing a model system for understanding developmental mechanisms in the context of marine ecosystems and aquaculture. Of interest is the potential development of antifouling strategies by targeting taurine chemosensation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"402 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222847","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}
Karolin Voßgröne, Francesco Favero, Krushanka Kashyap, Francisco G. Rodríguez-González, André V. Olsen, Xin Li, Balca R. Mardin, Joachim Weischenfeldt, Claus S. Sørensen
Cancer mutations perturb key processes, driving uncontrolled cell proliferation. With critical roles of enzymes in cell function and growth, we hypothesized that cancer driver mutations alter specific and recurrent enzymatic functions. Leveraging large pan-cancer genomic datasets and curated mutation catalogs, we identified frequent mutations in helicases, enzymes involved in nucleic acid unwinding and processing. Helicases emerged as the most commonly mutated cancer driver enzyme family, altered in two-thirds of all cancers. Functional screens and genomic analyses revealed that helicase dysfunctions contribute to genomic instability and faulty DNA repair. We observed a marked phenotype of Aquarius helicase ( AQR ), which was recurrently hemizygously deleted as an early clonal event in cancer genomes. These deletions were associated with high genomic instability and homologous recombination deficiency signatures. Furthermore, we found hemizygous loss to be a common tumor suppression mechanism among helicases, present in 35% of all cancers. Overall, our enzyme-family approach highlights helicases, including AQR , as key potential cancer drivers.
{"title":"Hemizygous loss of helicases promotes genomic instability and cancer development","authors":"Karolin Voßgröne, Francesco Favero, Krushanka Kashyap, Francisco G. Rodríguez-González, André V. Olsen, Xin Li, Balca R. Mardin, Joachim Weischenfeldt, Claus S. Sørensen","doi":"10.1126/sciadv.adv4540","DOIUrl":"https://doi.org/10.1126/sciadv.adv4540","url":null,"abstract":"Cancer mutations perturb key processes, driving uncontrolled cell proliferation. With critical roles of enzymes in cell function and growth, we hypothesized that cancer driver mutations alter specific and recurrent enzymatic functions. Leveraging large pan-cancer genomic datasets and curated mutation catalogs, we identified frequent mutations in helicases, enzymes involved in nucleic acid unwinding and processing. Helicases emerged as the most commonly mutated cancer driver enzyme family, altered in two-thirds of all cancers. Functional screens and genomic analyses revealed that helicase dysfunctions contribute to genomic instability and faulty DNA repair. We observed a marked phenotype of Aquarius helicase ( <jats:italic toggle=\"yes\">AQR</jats:italic> ), which was recurrently hemizygously deleted as an early clonal event in cancer genomes. These deletions were associated with high genomic instability and homologous recombination deficiency signatures. Furthermore, we found hemizygous loss to be a common tumor suppression mechanism among helicases, present in 35% of all cancers. Overall, our enzyme-family approach highlights helicases, including <jats:italic toggle=\"yes\">AQR</jats:italic> , as key potential cancer drivers.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"50 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222946","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}
Huimin Shao, Fei Xu, Jiangyue Xu, Lingjie Zhou, Yao Wu, Lianjun He, Xueyi Qian, Weijie He, Nanlin Jiao, Yabin Xia, Jun Zhao, Lili Sheng, Guoliang Mao, Tao Ma, Wei Wang, Shaoxiang Luo, Li Fu, Zhenyu Xu
Despite advances in chimeric antigen receptor T cell (CAR T cell) therapy for leukemia and lymphoma, solid tumors remain challenging because of limited target specificity and safety concerns. Neoantigens like KRAS G12V , a highly prevalent yet undruggable mutation in solid tumors, offer tumor-exclusive specificity. This study developed CAR T cells targeting KRAS G12V /HLA-A*02:01 using phage antibody display to identify high-affinity single-chain variable fragments. Engineered B9 CAR T cells specifically lysed tumor cells and patient-derived cancer organoids expressing KRAS G12V /HLA-A*02:01, demonstrating potent antitumor activity. Animal studies showed that B9 CAR T cells effectively controlled tumor growth in subcutaneous pancreatic ductal adenocarcinoma (PDAC) xenografts, as well as in metastatic and peritoneal PDAC models. Safety assessments in NCG-HLA-A2.1 and C57BL/6 mice revealed no detectable in vivo toxicity, supporting the clinical applicability of B9 CAR T cells. Collectively, our neoantigen-targeted CAR T cell therapy against solid tumors shows great potential for future clinical trials in patients with KRAS G12V /HLA-A*02:01, paving the way for clinical translation.
尽管嵌合抗原受体T细胞（CAR - T细胞）治疗白血病和淋巴瘤取得了进展，但由于有限的靶点特异性和安全性问题，实体肿瘤仍然具有挑战性。像KRAS G12V这样的新抗原，是一种在实体肿瘤中非常普遍但不可药物的突变，具有肿瘤特异性。本研究利用噬菌体抗体展示技术构建靶向KRAS G12V /HLA-A*02:01的CAR - T细胞，鉴定高亲和力单链可变片段。工程化的B9 CAR - T细胞特异性裂解表达KRAS G12V /HLA-A*02:01的肿瘤细胞和患者来源的癌症类器官，显示出有效的抗肿瘤活性。动物研究表明，B9 CAR - T细胞有效地控制了皮下胰腺导管腺癌（PDAC）异种移植以及转移性和腹膜性PDAC模型的肿瘤生长。在NCG-HLA-A2.1和C57BL/6小鼠中的安全性评估显示，没有检测到体内毒性，支持B9 CAR - T细胞的临床适用性。总的来说，我们的新抗原靶向CAR - T细胞治疗实体瘤在KRAS G12V /HLA-A*02:01患者的未来临床试验中显示出巨大的潜力，为临床转化铺平了道路。
{"title":"KRAS G12V /HLA-A*02:01–targeted chimeric antigen receptor T cells exhibit potent preclinical activity against solid tumors","authors":"Huimin Shao, Fei Xu, Jiangyue Xu, Lingjie Zhou, Yao Wu, Lianjun He, Xueyi Qian, Weijie He, Nanlin Jiao, Yabin Xia, Jun Zhao, Lili Sheng, Guoliang Mao, Tao Ma, Wei Wang, Shaoxiang Luo, Li Fu, Zhenyu Xu","doi":"10.1126/sciadv.aea2511","DOIUrl":"https://doi.org/10.1126/sciadv.aea2511","url":null,"abstract":"Despite advances in chimeric antigen receptor T cell (CAR T cell) therapy for leukemia and lymphoma, solid tumors remain challenging because of limited target specificity and safety concerns. Neoantigens like KRAS <jats:sup>G12V</jats:sup> , a highly prevalent yet undruggable mutation in solid tumors, offer tumor-exclusive specificity. This study developed CAR T cells targeting KRAS <jats:sup>G12V</jats:sup> /HLA-A*02:01 using phage antibody display to identify high-affinity single-chain variable fragments. Engineered B9 CAR T cells specifically lysed tumor cells and patient-derived cancer organoids expressing KRAS <jats:sup>G12V</jats:sup> /HLA-A*02:01, demonstrating potent antitumor activity. Animal studies showed that B9 CAR T cells effectively controlled tumor growth in subcutaneous pancreatic ductal adenocarcinoma (PDAC) xenografts, as well as in metastatic and peritoneal PDAC models. Safety assessments in NCG-HLA-A2.1 and C57BL/6 mice revealed no detectable in vivo toxicity, supporting the clinical applicability of B9 CAR T cells. Collectively, our neoantigen-targeted CAR T cell therapy against solid tumors shows great potential for future clinical trials in patients with KRAS <jats:sup>G12V</jats:sup> /HLA-A*02:01, paving the way for clinical translation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222978","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号