Science Advances最新文献_第7页

Cryo-EM structure of Nipah virus RNA polymerase complex.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adr7116

Yiru Wang, Lixia Zhao, Yi Zhang, Yuhan Wang, Jiao Tang, Simiao Liu, Huihan Gao, Xiaoxiao Zhang, Luca Zinzula, Roger D Kornberg, Heqiao Zhang

引用次数: 0

Endomicroscopic AI-driven morphochemical imaging and fs-laser ablation for selective tumor identification and selective tissue removal.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.ado9721

Matteo Calvarese, Elena Corbetta, Jhonatan Contreras, Hyeonsoo Bae, Chenting Lai, Karl Reichwald, Tobias Meyer-Zedler, David Pertzborn, Anna Mühlig, Franziska Hoffmann, Bernhard Messerschmidt, Orlando Guntinas-Lichius, Michael Schmitt, Thomas Bocklitz, Juergen Popp

{"title":"Endomicroscopic AI-driven morphochemical imaging and fs-laser ablation for selective tumor identification and selective tissue removal.","authors":"Matteo Calvarese, Elena Corbetta, Jhonatan Contreras, Hyeonsoo Bae, Chenting Lai, Karl Reichwald, Tobias Meyer-Zedler, David Pertzborn, Anna Mühlig, Franziska Hoffmann, Bernhard Messerschmidt, Orlando Guntinas-Lichius, Michael Schmitt, Thomas Bocklitz, Juergen Popp","doi":"10.1126/sciadv.ado9721","DOIUrl":"10.1126/sciadv.ado9721","url":null,"abstract":"The rising incidence of head and neck cancer represents a serious global health challenge, requiring more accurate diagnosis and innovative surgical approaches. Multimodal nonlinear optical microscopy, combining coherent anti-Stokes Raman scattering (CARS), two-photon excited fluorescence (TPEF), and second-harmonic generation (SHG) with deep learning-based analysis routines, offers label-free assessment of the tissue's morphochemical composition and allows early-stage and automatic detection of disease. For clinical intraoperative application, compact devices are required. In this preclinical study, a cohort of 15 patients was examined with a newly developed rigid CARS/TPEF/SHG endomicroscope. To detect head and neck tumor from the multimodal data, deep learning-based semantic segmentation models were used. This preclinical study yields in a diagnostic sensitivity of 88% and a specificity of 96%. To combine diagnostics with therapy, machine learning-inspired image-guided selective tissue removal was used by integrating femtosecond laser ablation into the endomicroscope. This enables a powerful approach of intraoperative \"seek and treat,\" paving the way to advanced surgical treatment.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eado9721"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MLL/WDR5 complex recruits centriolar satellite protein Cep72 to regulate microtubule nucleation and spindle formation.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adn0086

Swathi Chodisetty, Aditi Arora, Kausika Kumar Malik, Himanshu Goel, Shweta Tyagi

{"title":"MLL/WDR5 complex recruits centriolar satellite protein Cep72 to regulate microtubule nucleation and spindle formation.","authors":"Swathi Chodisetty, Aditi Arora, Kausika Kumar Malik, Himanshu Goel, Shweta Tyagi","doi":"10.1126/sciadv.adn0086","DOIUrl":"10.1126/sciadv.adn0086","url":null,"abstract":"Dysfunction of the centrosome, the major microtubule-organizing center of the cell, is implicated in microcephaly. Haploinsufficiency of mixed-lineage leukemia (MLL/KMT2A) protein causes Wiedemann-Steiner syndrome (WSS), a neurodevelopmental disorder associated with microcephaly. However, whether MLL has a function at the centrosome is not clear. Here, we show that loss of the MLL/WDR5 complex affects microtubule nucleation and regrowth. MLL/WDR5 localize to the pericentriolar material and interact with centriolar satellite protein Cep72 and γ-tubulin ring complex proteins (γ-TuRCs). MLL/WDR5 promote the localization of γ-TuRCs and structural proteins like AKAP9 to the centrosome during interphase and mitosis, a phenotype also observed in cells derived from patients with WSS. During mitosis, loss of MLL, WDR5, and Cep72 affects spindle formation and leads to misaligned chromosomes. Last, we show that MLL and WDR5 recruit Cep72 to the centrosome. Our studies provide insight into an undiscovered role of MLL at the centrosome and elucidate how centriolar satellite proteins like Cep72 can be recruited to the centrosome.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadn0086"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid prediction of acute thrombosis via nanoengineered immunosensors with unsupervised clustering for multiple circulating biomarkers.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adq6778

Kaidong Wang, Shaolei Wang, Samuel Margolis, Jae Min Cho, Enbo Zhu, Alexander Dupuy, Junyi Yin, Seul-Ki Park, Clara E Magyar, Oladunni B Adeyiga, Kristin Schwab Jensen, John A Belperio, Freda Passam, Peng Zhao, Tzung K Hsiai

{"title":"Rapid prediction of acute thrombosis via nanoengineered immunosensors with unsupervised clustering for multiple circulating biomarkers.","authors":"Kaidong Wang, Shaolei Wang, Samuel Margolis, Jae Min Cho, Enbo Zhu, Alexander Dupuy, Junyi Yin, Seul-Ki Park, Clara E Magyar, Oladunni B Adeyiga, Kristin Schwab Jensen, John A Belperio, Freda Passam, Peng Zhao, Tzung K Hsiai","doi":"10.1126/sciadv.adq6778","DOIUrl":"10.1126/sciadv.adq6778","url":null,"abstract":"The recent SARS-CoV-2 pandemic underscores the need for rapid and accurate prediction of clinical thrombotic events. Here, we developed nanoengineered multichannel immunosensors for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. We fabricated the immunosensors using fiber laser engraving of carbon nanotubes and CO2 laser cutting of microfluidic channels, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody. Using unsupervised clustering based on four biomarker concentrations, we predicted thrombotic events in 49 of 53 patients. The four-biomarker combination yielded an area under the receiver operating characteristic curve (AUC) of 0.95, demonstrating high sensitivity and specificity for acute thrombosis prediction compared to the AUC values for individual biomarkers: CRP (0.773), calprotectin (0.711), sP-selectin (0.683), and D-dimer (0.739). Thus, a nanoengineered multichannel platform with unsupervised clustering provides accurate and efficient methods for predicting thrombosis, guiding personalized medicine.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadq6778"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cretaceous coastal mountain building and potential impacts on climate change in East Asia

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.ads0587

Jianhua Li, Shuwen Dong, Guochun Zhao, Peter A. Cawood, Stephen T. Johnston, Jian Zhang, Yujia Xin, Jinming Wang

{"title":"Cretaceous coastal mountain building and potential impacts on climate change in East Asia","authors":"Jianhua Li, Shuwen Dong, Guochun Zhao, Peter A. Cawood, Stephen T. Johnston, Jian Zhang, Yujia Xin, Jinming Wang","doi":"10.1126/sciadv.ads0587","DOIUrl":"https://doi.org/10.1126/sciadv.ads0587","url":null,"abstract":"Crustal thickness and elevation variations control mountain building and climate change at convergent margins. As an archetypal Andean-type convergent margin, eastern Asia preserves voluminous magmas ideal for quantifying these processes and their impacts on climate. Here, we use Sr/Y and Ce/Y proxies to show that the crust experienced alternating thickening and thinning during the Late Mesozoic. We identify a noticeably thickened (50 to 55 kilometers) crust associated with tectonic shortening at 120 to 105 million years, corresponding to a >2500-meter-high coastal mountain range. Using climate simulation with the Community Earth System Model, we demonstrate that the mountain uplift changed Asian atmospheric circulation and precipitation patterns, increased inland aridity (~15%), and prompted the eastward desert expansion, contributing substantially to the arid zonal belt across mid- to low-latitude Asia. These findings—compatible with independent geological, geophysical, and climatic observations—have global implications for broadening our understanding of Earth-system interactions in the Cretaceous greenhouse world.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820804","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}

引用次数: 0

Onsite ammonia synthesis from water vapor and nitrogen in the air

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.ads4443

Xiaowei Song, Chanbasha Basheer, Jinheng Xu, Richard N. Zare

引用次数: 0

Effect of pandemic influenza A virus PB1 genes of avian origin on viral RNA polymerase activity and pathogenicity

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.ads5735

Stephanie L. Williams, Li Qi, Zong-Mei Sheng, Yongli Xiao, Ashley Freeman, Lex Matthews, Sharon Fong Legaspi, Ervin Fodor, Jeffery K. Taubenberger

{"title":"Effect of pandemic influenza A virus PB1 genes of avian origin on viral RNA polymerase activity and pathogenicity","authors":"Stephanie L. Williams, Li Qi, Zong-Mei Sheng, Yongli Xiao, Ashley Freeman, Lex Matthews, Sharon Fong Legaspi, Ervin Fodor, Jeffery K. Taubenberger","doi":"10.1126/sciadv.ads5735","DOIUrl":"https://doi.org/10.1126/sciadv.ads5735","url":null,"abstract":"Zoonotic influenza A virus (IAV) infections pose a substantial threat to global health. The influenza RNA-dependent RNA polymerase (RdRp) comprises the PB2, PB1, and PA proteins. Of the last four pandemic IAVs, three featured avian-origin PB1 genes. Prior research linked these avian PB1 genes to increased viral fitness when reassorted with human IAV genes. This study evaluated chimeric RdRps with PB1 genes from the 1918, 1957, and 1968 pandemic IAVs in a low pathogenic avian influenza (LPAI) virus background to assess polymerase activity and pathogenicity. Substituting in the pandemic PB1 genes reduced polymerase activity, virulence, and altered lung pathology, while the native LPAI PB1 showed the highest pathogenicity and polymerase activity. The native LPAI PB1 virus caused severe pneumonia and high early viral RNA levels, correlating with elevated host cytokine signaling. Increased genetic distance from the LPAI PB1 sequence correlated with reduced polymerase activity, IFN-β expression, viral replication, and pathogenicity.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"49 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820571","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}

引用次数: 0

Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adq9909

Yining Xu, Cécilia Bohns Michalowski, Jackie Koehler, Tamana Darwish, Nunzio Guccio, Constanza Alcaino, Inês Domingues, Wunan Zhang, Valentina Marotti, Matthias Van Hul, Paola Paone, Melitini Koutsoviti, Ben J. Boyd, Daniel J. Drucker, Patrice D. Cani, Frank Reimann, Fiona M. Gribble, Ana Beloqui

{"title":"Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion","authors":"Yining Xu, Cécilia Bohns Michalowski, Jackie Koehler, Tamana Darwish, Nunzio Guccio, Constanza Alcaino, Inês Domingues, Wunan Zhang, Valentina Marotti, Matthias Van Hul, Paola Paone, Melitini Koutsoviti, Ben J. Boyd, Daniel J. Drucker, Patrice D. Cani, Frank Reimann, Fiona M. Gribble, Ana Beloqui","doi":"10.1126/sciadv.adq9909","DOIUrl":"https://doi.org/10.1126/sciadv.adq9909","url":null,"abstract":"Modulating the endogenous stores of gastrointestinal hormones is considered a promising strategy to mimic gut endocrine function, improving metabolic dysfunction. Here, we exploit mouse and human knock-in and knockout intestinal organoids and show that agents used as commercial lipid excipients can activate nutrient-sensitive receptors on enteroendocrine cells (EECs) and, when formulated as lipid nanocarriers, can bestow biological effects through the release of GLP-1, GIP, and PYY from K and L cells. Studies in wild-type, dysglycemic, and gut Gcg knockout mice demonstrated that the effect exerted by lipid nanocarriers could be modulated by varying the excipients (e.g., nature and quantities), the formulation methodology, and their physiochemical properties (e.g., size and composition). This study demonstrates the therapeutic potential of using nanotechnology to modulate release of multiple endogenous hormones from the enteroendocrine system through a patient-friendly, inexpensive, and noninvasive manner.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"38 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820576","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}

引用次数: 0

Sustainable high-entropy materials?

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.ads3926

Liuliu Han, Wangzhong Mu, Shaolou Wei, Peter K Liaw, Dierk Raabe

{"title":"Sustainable high-entropy materials?","authors":"Liuliu Han, Wangzhong Mu, Shaolou Wei, Peter K Liaw, Dierk Raabe","doi":"10.1126/sciadv.ads3926","DOIUrl":"10.1126/sciadv.ads3926","url":null,"abstract":"High-entropy materials (HEMs) show inspiring structural and functional properties due to their multi-elemental compositions. However, most HEMs are burdened by cost-, energy-, and carbon-intensive extraction, synthesis, and manufacturing protocols. Recycling and reusing HEMs are challenging because their design relies on high fractions of expensive and limited-supply elements in massive solid solutions. Therefore, we review the basic sustainability aspects of HEMs. Solutions include using feedstock with lower carbon and energy footprints, sustainable primary synthesis routes from minerals, attenuation of the equimolar alloying rule, and a preference for scrap and dumped waste for secondary and tertiary synthesis. The high solubility, compositional flexibility, and chemical robustness of HEMs offer pathways for using higher fractions of mixed and contaminated scrap and waste feedstocks, which are not admissible for synthesizing conventional materials. We also discuss thermodynamic and kinetic design strategies to reconcile good material properties with high impurity tolerance and variable compositions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eads3926"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated analysis of immunometabolic interactions in Down syndrome 综合分析唐氏综合征的免疫代谢相互作用

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adq3073

Lucas A. Gillenwater, Matthew D. Galbraith, Angela L. Rachubinski, Neetha Paul Eduthan, Kelly D. Sullivan, Joaquin M. Espinosa, James C. Costello

{"title":"Integrated analysis of immunometabolic interactions in Down syndrome","authors":"Lucas A. Gillenwater, Matthew D. Galbraith, Angela L. Rachubinski, Neetha Paul Eduthan, Kelly D. Sullivan, Joaquin M. Espinosa, James C. Costello","doi":"10.1126/sciadv.adq3073","DOIUrl":"https://doi.org/10.1126/sciadv.adq3073","url":null,"abstract":"Down syndrome (DS), caused by trisomy 21 (T21), results in immune and metabolic dysregulation. People with DS experience co-occurring conditions at higher rates than the euploid population. However, the interplay between immune and metabolic alterations and the clinical manifestations of DS are poorly understood. Here, we report an integrated analysis of immunometabolic pathways in DS. Using multi-omics data, we infered cytokine-metabolite relationships mediated by specific transcriptional programs. We observed increased mediation of immunometabolic interactions in those with DS compared to euploid controls by genes in interferon response, heme metabolism, and oxidative phosphorylation. Unsupervised clustering of immunometabolic relationships in people with DS revealed subgroups with different frequencies of co-occurring conditions. Across the subgroups, we observed distinct mediation by DNA repair, Hedgehog signaling, and angiogenesis. The molecular stratification associates with the clinical heterogeneity observed in DS, suggesting that integrating multiple omic profiles reveals axes of coordinated dysregulation specific to DS co-occurring conditions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"45 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820575","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}

引用次数: 0