Amy C. Pickering, Jamie Gorzynski, Grace Taylor-Joyce, Rhodri Evans, Willow Fox, Pedro Melo, Joana Alves, Hannah Schlauch, Fiona Sargison, Gonzalo Yebra, Natalie Ring, J. Ross Fitzgerald
New pathogens typically arise from host jump events between species. Staphylococcus aureus is a multihost pathogen responsible for a global burden of human disease and a leading cause of intramammary infection in dairy cattle. Here, we demonstrate that following historical human-to-bovine host switch events, S. aureus has undergone adaptive metabolic remodeling in response to distinct nutrient availability in the dairy niche. In particular, we found that bovine S. aureus has evolved the capacity for protease-mediated degradation of casein, a protein abundant in bovine milk, to access nutrients for proliferation. This phenotype has evolved convergently in different S. aureus lineages via mutations in distinct gene loci driving overexpression of the protease aureolysin. Together, we have dissected a key host-adaptive trait, which facilitates the enzymatic release of nutrients from a substrate specific to the new host milieu. These findings highlight the remarkable evolutionary plasticity of a major bacterial pathogen underpinning its multihost species tropism.
{"title":"Bacterial metabolic remodeling by convergent evolution unlocks nutrient availability after a host switch","authors":"Amy C. Pickering, Jamie Gorzynski, Grace Taylor-Joyce, Rhodri Evans, Willow Fox, Pedro Melo, Joana Alves, Hannah Schlauch, Fiona Sargison, Gonzalo Yebra, Natalie Ring, J. Ross Fitzgerald","doi":"10.1126/sciadv.adw9419","DOIUrl":"https://doi.org/10.1126/sciadv.adw9419","url":null,"abstract":"New pathogens typically arise from host jump events between species. <jats:italic toggle=\"yes\">Staphylococcus aureus</jats:italic> is a multihost pathogen responsible for a global burden of human disease and a leading cause of intramammary infection in dairy cattle. Here, we demonstrate that following historical human-to-bovine host switch events, <jats:italic toggle=\"yes\">S. aureus</jats:italic> has undergone adaptive metabolic remodeling in response to distinct nutrient availability in the dairy niche. In particular, we found that bovine <jats:italic toggle=\"yes\">S. aureus</jats:italic> has evolved the capacity for protease-mediated degradation of casein, a protein abundant in bovine milk, to access nutrients for proliferation. This phenotype has evolved convergently in different <jats:italic toggle=\"yes\">S. aureus</jats:italic> lineages via mutations in distinct gene loci driving overexpression of the protease aureolysin. Together, we have dissected a key host-adaptive trait, which facilitates the enzymatic release of nutrients from a substrate specific to the new host milieu. These findings highlight the remarkable evolutionary plasticity of a major bacterial pathogen underpinning its multihost species tropism.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"84 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129402","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}
Vasileios Voutsinos, Kristoffer E. Johansson, Fia B. Larsen, Martin Grønbæk-Thygesen, Nicolas Jonsson, Emma Holm-Olesen, Giulio Tesei, Amelie Stein, Douglas M. Fowler, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Degrons are short protein segments that direct proteins for degradation via the ubiquitin-proteasome system, ensuring the removal of signaling proteins and clearance of misfolded proteins. We have performed a large-scale screen of more than 200,000 30-residue peptides from more than 5000 human cytosolic proteins, achieving 99.7% coverage. We find that 19% of peptides act as strong degrons, 30% as intermediate, and 51% as non-degrons. We identify both known and previously unidentified degradation signals and show that most depend on the E1 ubiquitin-activating enzyme and the proteasome. Structural mapping shows that many degrons are buried and likely become active upon protein unfolding. Training of a machine learning model allowed us to describe the degron properties and predict the cellular abundance of missense variants that operate by forming degrons in exposed and disordered protein regions, thus providing a mechanism of pathogenicity for germline coding variants at such positions.
{"title":"A near-complete map of human cytosolic degrons and their relevance for disease","authors":"Vasileios Voutsinos, Kristoffer E. Johansson, Fia B. Larsen, Martin Grønbæk-Thygesen, Nicolas Jonsson, Emma Holm-Olesen, Giulio Tesei, Amelie Stein, Douglas M. Fowler, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen","doi":"10.1126/sciadv.adz3483","DOIUrl":"https://doi.org/10.1126/sciadv.adz3483","url":null,"abstract":"Degrons are short protein segments that direct proteins for degradation via the ubiquitin-proteasome system, ensuring the removal of signaling proteins and clearance of misfolded proteins. We have performed a large-scale screen of more than 200,000 30-residue peptides from more than 5000 human cytosolic proteins, achieving 99.7% coverage. We find that 19% of peptides act as strong degrons, 30% as intermediate, and 51% as non-degrons. We identify both known and previously unidentified degradation signals and show that most depend on the E1 ubiquitin-activating enzyme and the proteasome. Structural mapping shows that many degrons are buried and likely become active upon protein unfolding. Training of a machine learning model allowed us to describe the degron properties and predict the cellular abundance of missense variants that operate by forming degrons in exposed and disordered protein regions, thus providing a mechanism of pathogenicity for germline coding variants at such positions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"29 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129407","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}
Jia-Hao Lü, Wen Ning, Fan Wu, Ri-Hua Zheng, Ken Chen, Xin Zhu, Zhen-Biao Yang, Huai-Zhi Wu, Shi-Biao Zheng
Critical systems near quantum phase transitions were predicted to be useful for improvement of metrological precision, thanks to their ultrasensitive response to tiny variations of the control Hamiltonian. However, realizing criticality enhanced quantum metrology is experimentally challenging, mainly owing to decoherence and critical slowing down associated with the corresponding quantum state preparation. We circumvent these problems by making use of the critical behaviors in the Jaynes-Cummings model, to which the signal field is coupled. The information is encoded in the qubit’s excitation number, which displays a divergent changing rate at the critical point, and is extremely robust against decoherence and nonadiabatic effects. We demonstrate such a metrological protocol in a superconducting circuit, where an Xmon qubit, interacting with a resonator, is used as a probe for estimating the amplitude of a microwave field. The measured quantum Fisher information exhibits a critical quantum enhancement, confirming the potential for quantum metrology.
{"title":"Critical quantum metrology robust against dissipation and nonadiabaticity","authors":"Jia-Hao Lü, Wen Ning, Fan Wu, Ri-Hua Zheng, Ken Chen, Xin Zhu, Zhen-Biao Yang, Huai-Zhi Wu, Shi-Biao Zheng","doi":"10.1126/sciadv.ady2358","DOIUrl":"https://doi.org/10.1126/sciadv.ady2358","url":null,"abstract":"Critical systems near quantum phase transitions were predicted to be useful for improvement of metrological precision, thanks to their ultrasensitive response to tiny variations of the control Hamiltonian. However, realizing criticality enhanced quantum metrology is experimentally challenging, mainly owing to decoherence and critical slowing down associated with the corresponding quantum state preparation. We circumvent these problems by making use of the critical behaviors in the Jaynes-Cummings model, to which the signal field is coupled. The information is encoded in the qubit’s excitation number, which displays a divergent changing rate at the critical point, and is extremely robust against decoherence and nonadiabatic effects. We demonstrate such a metrological protocol in a superconducting circuit, where an Xmon qubit, interacting with a resonator, is used as a probe for estimating the amplitude of a microwave field. The measured quantum Fisher information exhibits a critical quantum enhancement, confirming the potential for quantum metrology.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"2 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129408","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}
Jian Teng, Samuel H. Hales, Xin Yang, Jared Anklam, Saebom Lee, Yu Liu, Dwipak Prasad Sahu, Leibin Li, Cordelia Latham, Xi Tian, Derrick Wong, Taylor E. Greenwood, John S. Ho, Yong Lin Kong
Three-dimensional (3D) printing can create freeform architectures and electronics with unprecedented versatility. However, the full potential of electronic 3D printing has so far been limited by the inability to selectively anneal the printed materials, especially on temperature-sensitive substrates. Here, we achieve highly selective and rapid volumetric heating of 3D-printed nanomaterials and polymers in situ by focusing microwaves using a metamaterial-inspired near-field electromagnetic structure (Meta-NFS). In contrast to previous work, the Meta-NFS achieves the spatial resolution and power density needed to 3D print freeform microstructures where the electronic and mechanical properties can be locally programmed even within optically opaque materials. By broadening the material palettes compatible with 3D printing, near-field microwave 3D printing with Meta-NFS enables classes of electronics that are otherwise challenging to create.
{"title":"Three-dimensional printing of nanomaterials-based electronics with a metamaterial-inspired near-field electromagnetic structure","authors":"Jian Teng, Samuel H. Hales, Xin Yang, Jared Anklam, Saebom Lee, Yu Liu, Dwipak Prasad Sahu, Leibin Li, Cordelia Latham, Xi Tian, Derrick Wong, Taylor E. Greenwood, John S. Ho, Yong Lin Kong","doi":"10.1126/sciadv.adz7415","DOIUrl":"https://doi.org/10.1126/sciadv.adz7415","url":null,"abstract":"Three-dimensional (3D) printing can create freeform architectures and electronics with unprecedented versatility. However, the full potential of electronic 3D printing has so far been limited by the inability to selectively anneal the printed materials, especially on temperature-sensitive substrates. Here, we achieve highly selective and rapid volumetric heating of 3D-printed nanomaterials and polymers in situ by focusing microwaves using a metamaterial-inspired near-field electromagnetic structure (Meta-NFS). In contrast to previous work, the Meta-NFS achieves the spatial resolution and power density needed to 3D print freeform microstructures where the electronic and mechanical properties can be locally programmed even within optically opaque materials. By broadening the material palettes compatible with 3D printing, near-field microwave 3D printing with Meta-NFS enables classes of electronics that are otherwise challenging to create.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"119 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129411","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}
Deuterium-labeled silanes are of great significance in organic synthesis and drug discoveries, yet obtaining versatile deuterated silanes efficiently and selectively under electrochemical conditions using green deuterium sources remains enormously challenging. Herein, facile and general electrochemical deuteration of silanes using D 2 O as the economical deuterium source was reported. A variety of alkyl- and aryl-substituted silanes can be smoothly converted into the corresponding products with excellent levels of deuterium incorporation and yields. Furthermore, this protocol enables 10-gram-scale preparation under high current conditions, underscoring the potential in industry applications. Mechanistic studies have revealed that a catalytic amount of nickel may form a pivotal silicon-nickel intermediate, reversing the polarity of silicon and thereby facilitating the subsequent reactions.
{"title":"Electrochemically deuterated silane synthesis with D 2 O","authors":"Chao Gao, Min Liu, Youai Qiu","doi":"10.1126/sciadv.aeb7677","DOIUrl":"https://doi.org/10.1126/sciadv.aeb7677","url":null,"abstract":"Deuterium-labeled silanes are of great significance in organic synthesis and drug discoveries, yet obtaining versatile deuterated silanes efficiently and selectively under electrochemical conditions using green deuterium sources remains enormously challenging. Herein, facile and general electrochemical deuteration of silanes using D <jats:sub>2</jats:sub> O as the economical deuterium source was reported. A variety of alkyl- and aryl-substituted silanes can be smoothly converted into the corresponding products with excellent levels of deuterium incorporation and yields. Furthermore, this protocol enables 10-gram-scale preparation under high current conditions, underscoring the potential in industry applications. Mechanistic studies have revealed that a catalytic amount of nickel may form a pivotal silicon-nickel intermediate, reversing the polarity of silicon and thereby facilitating the subsequent reactions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"34 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129413","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}
Seungmin Shin, Yae-Jin Kim, Bernard J. C. Macatangay, Joshua C. Cyktor, Margaret G. Hines, Ze-Yu Sun, Kong Chen, John W. Mellors, Dimiter S. Dimitrov, Wei Li, Du-San Baek
NK and T cells are key effectors that eliminate cancer cells, but upregulation of the inhibitory receptor NKG2A on these cells attenuates antitumor immune responses. To counteract NKG2A inhibitory signaling, we identified two specific fully human monoclonal anti-NKG2A antibodies that block HLA-E ligand binding. These antibodies activated NK cells and enhanced antibody-dependent cellular cytotoxicity of tumor-targeting IgG1s both in vitro and in vivo. Bispecific engagers (BiNKs), generated by fusing NKG2A antibodies with tumor targeting binders, promoted immune synapse formation and directed cytotoxicity of NK and CD8+ T cells toward cancer cells. In a human PBMC-engrafted NSG mouse xenograft lung cancer model, an anti-HER2 × anti-NKG2A BiNK markedly inhibited tumor growth as a monotherapy or in combination with pertuzumab. Cell depletion studies revealed that the BiNK enhanced antitumor activity of both NK and T cells. NKG2A blockade with potent and specific, fully human antibodies and BiNKs show promise for further development as cancer immunotherapeutics.
{"title":"Discovery and preclinical evaluation of monoclonal antibodies and bispecific engagers targeting the NKG2A inhibitory receptor","authors":"Seungmin Shin, Yae-Jin Kim, Bernard J. C. Macatangay, Joshua C. Cyktor, Margaret G. Hines, Ze-Yu Sun, Kong Chen, John W. Mellors, Dimiter S. Dimitrov, Wei Li, Du-San Baek","doi":"10.1126/sciadv.adu0690","DOIUrl":"10.1126/sciadv.adu0690","url":null,"abstract":"<div >NK and T cells are key effectors that eliminate cancer cells, but upregulation of the inhibitory receptor NKG2A on these cells attenuates antitumor immune responses. To counteract NKG2A inhibitory signaling, we identified two specific fully human monoclonal anti-NKG2A antibodies that block HLA-E ligand binding. These antibodies activated NK cells and enhanced antibody-dependent cellular cytotoxicity of tumor-targeting IgG1s both in vitro and in vivo. Bispecific engagers (BiNKs), generated by fusing NKG2A antibodies with tumor targeting binders, promoted immune synapse formation and directed cytotoxicity of NK and CD8<sup>+</sup> T cells toward cancer cells. In a human PBMC-engrafted NSG mouse xenograft lung cancer model, an anti-HER2 × anti-NKG2A BiNK markedly inhibited tumor growth as a monotherapy or in combination with pertuzumab. Cell depletion studies revealed that the BiNK enhanced antitumor activity of both NK and T cells. NKG2A blockade with potent and specific, fully human antibodies and BiNKs show promise for further development as cancer immunotherapeutics.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111424","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}
Hybrid incompatibility can lead to lethality and sterility of F1 hybrids, promoting speciation. The cell biological basis underlying hybrid incompatibility remains largely unknown, especially in mammals. Here, we found that female hybrids between Mus musculus domesticus and Mus spicilegus mice are sterile due to the failure of homologous-chromosome separation in oocyte meiosis, producing aneuploid eggs. This nondisjunction phenotype was driven by the mislocalization of the cohesin protector, SGO2, along the chromosome arms instead of its typical centromeric enrichment, resulting in cohesin overprotection. The upstream kinase, BUB1, showed a higher activity in hybrid oocytes, explaining SGO2 mistargeting. Higher BUB1 activity was not observed in mitosis, consistent with viable hybrid mice. Cohesion defects were also evident in hybrid mice from another genus, Peromyscus, wherein cohesin protection is weakened. Defective cohesion in oocytes is a leading cause of reduced fertility. Our work provides evidence that a major cause of human infertility may play a positive role in mammalian speciation.
{"title":"Hybrid female sterility due to cohesin protection errors in mouse oocytes","authors":"Warif El Yakoubi, Bo Pan, Takashi Akera","doi":"10.1126/sciadv.adx9729","DOIUrl":"10.1126/sciadv.adx9729","url":null,"abstract":"<div >Hybrid incompatibility can lead to lethality and sterility of F1 hybrids, promoting speciation. The cell biological basis underlying hybrid incompatibility remains largely unknown, especially in mammals. Here, we found that female hybrids between <i>Mus musculus domesticus</i> and <i>Mus spicilegus</i> mice are sterile due to the failure of homologous-chromosome separation in oocyte meiosis, producing aneuploid eggs. This nondisjunction phenotype was driven by the mislocalization of the cohesin protector, SGO2, along the chromosome arms instead of its typical centromeric enrichment, resulting in cohesin overprotection. The upstream kinase, BUB1, showed a higher activity in hybrid oocytes, explaining SGO2 mistargeting. Higher BUB1 activity was not observed in mitosis, consistent with viable hybrid mice. Cohesion defects were also evident in hybrid mice from another genus, <i>Peromyscus</i>, wherein cohesin protection is weakened. Defective cohesion in oocytes is a leading cause of reduced fertility. Our work provides evidence that a major cause of human infertility may play a positive role in mammalian speciation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111429","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}
Qiong Zhu, Jinning Zhang, Weichen Zhou, Shen-Ao Liang, Shengmiao Wang, Xinyu Cai, Fuyuan Li, Jin Li, Guojie Zhang, Huijuan Feng, Qiaomei Fu, Joshua M. Akey, Feng Zhang, Li Jin, Shuhua Xu, Hong-Xiang Zheng, Lu Chen
Archaic introgression introduced functionally relevant variants into modern humans, yet small-scale insertions remain understudied. Here, we leverage 2519 modern human genomes and four high-coverage archaic hominin genomes to systematically characterize nuclear mitochondrial DNA segments (NUMTs). We uncover 483 polymorphic NUMTs across globally diverse human populations and 10 in archaic genomes. By combining overlap with Neanderthal-derived and Denisovan-derived haplotypes, phylogenetic analyses, insertion time estimates, and haplotype colocalization, we identify five NUMTs introduced into modern humans via archaic hominin introgression. Functional analyses reveal that introgressed NUMTs can modulate gene expression, including allele-specific up-regulation of the immune-related gene RASGRP3, and reshape three-dimensional chromatin structure at loci such as SCD5 and HNRNPD. These findings highlight an underappreciated mechanism by which archaic mitochondrial fragments shape nuclear genome function and evolution. Our study reframes NUMTs not as passive genomic fossils but as dynamic elements influencing modern human diversity and adaptation.
{"title":"Introgressed mitochondrial fragments from archaic hominins alter nuclear genome function in modern humans","authors":"Qiong Zhu, Jinning Zhang, Weichen Zhou, Shen-Ao Liang, Shengmiao Wang, Xinyu Cai, Fuyuan Li, Jin Li, Guojie Zhang, Huijuan Feng, Qiaomei Fu, Joshua M. Akey, Feng Zhang, Li Jin, Shuhua Xu, Hong-Xiang Zheng, Lu Chen","doi":"10.1126/sciadv.aea0706","DOIUrl":"10.1126/sciadv.aea0706","url":null,"abstract":"<div >Archaic introgression introduced functionally relevant variants into modern humans, yet small-scale insertions remain understudied. Here, we leverage 2519 modern human genomes and four high-coverage archaic hominin genomes to systematically characterize nuclear mitochondrial DNA segments (NUMTs). We uncover 483 polymorphic NUMTs across globally diverse human populations and 10 in archaic genomes. By combining overlap with Neanderthal-derived and Denisovan-derived haplotypes, phylogenetic analyses, insertion time estimates, and haplotype colocalization, we identify five NUMTs introduced into modern humans via archaic hominin introgression. Functional analyses reveal that introgressed NUMTs can modulate gene expression, including allele-specific up-regulation of the immune-related gene <i>RASGRP3</i>, and reshape three-dimensional chromatin structure at loci such as <i>SCD5</i> and <i>HNRNPD</i>. These findings highlight an underappreciated mechanism by which archaic mitochondrial fragments shape nuclear genome function and evolution. Our study reframes NUMTs not as passive genomic fossils but as dynamic elements influencing modern human diversity and adaptation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111415","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 Zhang, Edgar Castro, Alexandra Shtein, Adjani A. Peralta, Mahdieh Danesh Yazdi, Xiao Wu, Joel D. Schwartz, Robert O. Wright, Yaguang Wei
The relationships between chronic exposure to wildfire smoke PM2.5 (particulate matter with aerodynamic diameter of ≤2.5 μm) and mortality remain poorly understood, with causal evidence being particularly scarce. In this ecological study, we used a doubly robust method, incorporating flexible generalized propensity score estimation that captured potential nonlinearity and interactions among confounders and relaxed the distribution form assumption for exposure, to estimate the effects of annual exposure to wildfire smoke PM2.5 on all-cause and cause-specific mortality in the contiguous United States from 2006 to 2020. We found that wildfire smoke PM2.5 was associated with increased mortality rate for all studied outcomes, except for deaths from transport accidents or falls, which served as negative outcome controls. Wildfire smoke PM2.5 was responsible for ~24,100 all-cause deaths per year in the contiguous United States. The exposure-response curve for all-cause mortality increased monotonically, with no evidence of a “safe” threshold. Among the six cause-specific outcomes, mortality from neurological disease showed the greatest increase per 0.1 μg/m3 increase in smoke PM2.5 exposure. Our study provided robust evidence for the chronic effect of wildfire smoke PM2.5 on mortality, underscoring the urgent need for targeted measures to mitigate the substantial and escalating burden of wildfires.
{"title":"Wildfire smoke PM2.5 and mortality rate in the contiguous United States: A causal modeling study","authors":"Min Zhang, Edgar Castro, Alexandra Shtein, Adjani A. Peralta, Mahdieh Danesh Yazdi, Xiao Wu, Joel D. Schwartz, Robert O. Wright, Yaguang Wei","doi":"10.1126/sciadv.adw5890","DOIUrl":"10.1126/sciadv.adw5890","url":null,"abstract":"<div >The relationships between chronic exposure to wildfire smoke PM<sub>2.5</sub> (particulate matter with aerodynamic diameter of ≤2.5 μm) and mortality remain poorly understood, with causal evidence being particularly scarce. In this ecological study, we used a doubly robust method, incorporating flexible generalized propensity score estimation that captured potential nonlinearity and interactions among confounders and relaxed the distribution form assumption for exposure, to estimate the effects of annual exposure to wildfire smoke PM<sub>2.5</sub> on all-cause and cause-specific mortality in the contiguous United States from 2006 to 2020. We found that wildfire smoke PM<sub>2.5</sub> was associated with increased mortality rate for all studied outcomes, except for deaths from transport accidents or falls, which served as negative outcome controls. Wildfire smoke PM<sub>2.5</sub> was responsible for ~24,100 all-cause deaths per year in the contiguous United States. The exposure-response curve for all-cause mortality increased monotonically, with no evidence of a “safe” threshold. Among the six cause-specific outcomes, mortality from neurological disease showed the greatest increase per 0.1 μg/m<sup>3</sup> increase in smoke PM<sub>2.5</sub> exposure. Our study provided robust evidence for the chronic effect of wildfire smoke PM<sub>2.5</sub> on mortality, underscoring the urgent need for targeted measures to mitigate the substantial and escalating burden of wildfires.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111414","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}
Patrick Eiring, Maximilian J. Steinhardt, Nele Bauer, Cornelia Vogt, Umair Munawar, Seungbin Han, Thomas Nerreter, Hermann Einsele, K. Martin Kortüm, Sören Doose, Markus Sauer
Super-resolution microscopy in combination with genetic labeling methods allows imaging of single proteins in cells. However, visualizing endogenous proteins on primary cells remains challenging due to the use of sterically demanding antibodies for labeling. Here, we demonstrate how immunolabeling conditions and antibody cross-linking influence the quantification and identification of membrane receptor stoichiometry on cells using single-molecule localization microscopy. We developed an optimized immunolabeling and analysis protocol and demonstrate the performance of the approach by resolving the molecular organization of endogenous CD45, CD69, and CD38 on Jurkat T cells. To demonstrate the usefulness of the method for immunotherapy applications, we investigated the interaction of primary multiple myeloma cells with the therapeutic monoclonal antibodies daratumumab and isatuximab and a polyclonal anti-CD38 antibody. Our approach might lay the foundation for improved personalized diagnostics and treatment with therapeutic antibodies.
{"title":"Single-molecule localization microscopy reveals the molecular organization of endogenous membrane receptors","authors":"Patrick Eiring, Maximilian J. Steinhardt, Nele Bauer, Cornelia Vogt, Umair Munawar, Seungbin Han, Thomas Nerreter, Hermann Einsele, K. Martin Kortüm, Sören Doose, Markus Sauer","doi":"10.1126/sciadv.aea2310","DOIUrl":"10.1126/sciadv.aea2310","url":null,"abstract":"<div >Super-resolution microscopy in combination with genetic labeling methods allows imaging of single proteins in cells. However, visualizing endogenous proteins on primary cells remains challenging due to the use of sterically demanding antibodies for labeling. Here, we demonstrate how immunolabeling conditions and antibody cross-linking influence the quantification and identification of membrane receptor stoichiometry on cells using single-molecule localization microscopy. We developed an optimized immunolabeling and analysis protocol and demonstrate the performance of the approach by resolving the molecular organization of endogenous CD45, CD69, and CD38 on Jurkat T cells. To demonstrate the usefulness of the method for immunotherapy applications, we investigated the interaction of primary multiple myeloma cells with the therapeutic monoclonal antibodies daratumumab and isatuximab and a polyclonal anti-CD38 antibody. Our approach might lay the foundation for improved personalized diagnostics and treatment with therapeutic antibodies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 6","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111418","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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