Science Advances最新文献

Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy 针对肿瘤特异性递送可点击抑制剂，降解 PD-L1 并减轻放射免疫疗法的抗药性

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq3940

Bo Hou, Jiayi Ye, Lujia Huang, Wenhao Cheng, Fangmin Chen, Huiling Zhou, Jiaxing Pan, Jing Gao, Yi Lai, Yujun Zhao, Wei Huang, Haijun Yu, Zhiai Xu

{"title":"Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy","authors":"Bo Hou, Jiayi Ye, Lujia Huang, Wenhao Cheng, Fangmin Chen, Huiling Zhou, Jiaxing Pan, Jing Gao, Yi Lai, Yujun Zhao, Wei Huang, Haijun Yu, Zhiai Xu","doi":"10.1126/sciadv.adq3940","DOIUrl":"10.1126/sciadv.adq3940","url":null,"abstract":"<div >Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes was labeled with highly active azide groups. This enables covalently binding of the clickable inhibitor with PD-L1 and subsequent PD-L1 degradation. A pH-activatable nanoparticle responding to extracellular acidic pH of tumor was subsequently used to deliver the clickable PD-L1 inhibitor into extracellular tumor microenvironment for depleting PD-L1 on the surface of tumor cell and macrophage membranes in vivo. We further demonstrated that a combination of the clickable PD-L1 inhibitor with radiotherapy (RT) eradicated the established tumor by inhibiting RT–up-regulated PD-L1 in the tumor tissue. Therefore, selective PD-L1 blockade in tumors via the clickable PD-L1 inhibitor offers a versatile approach to promote cancer immunotherapy.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq3940","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637709","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

Landscape burning facilitated Aboriginal migration into Lutruwita/Tasmania 41,600 years ago 4.16 万年前，焚烧地貌为原住民迁徙到路特鲁维塔/塔斯马尼亚提供了便利

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adp6579

Matthew A. Adeleye, Felicitas Hopf, Simon G. Haberle, Georgia L. Stannard, David B. Mcwethy, Stephen Harris, David M. J. S. Bowman

引用次数: 0

Gas-phase preparation of silylacetylene (SiH3CCH) through a counterintuitive ethynyl radical (C2H) insertion 通过反直觉乙炔基（C 2 H）插入气相制备硅乙炔（SiH 3 CCH）

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq5018

Shane J. Goettl, Allen Vincent, Mateus X. Silva, Zhenghai Yang, Breno R. L. Galvão, Rui Sun, Ralf I. Kaiser

引用次数: 0

Projected increase in the frequency of extremely active Atlantic hurricane seasons 预计大西洋飓风极端活跃季节的频率将增加

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq7856

Hosmay Lopez, Sang-Ki Lee, Robert West, Dongmin Kim, Gregory R. Foltz, Ghassan J. Alaka Jr., Hiroyuki Murakami

{"title":"Projected increase in the frequency of extremely active Atlantic hurricane seasons","authors":"Hosmay Lopez, Sang-Ki Lee, Robert West, Dongmin Kim, Gregory R. Foltz, Ghassan J. Alaka Jr., Hiroyuki Murakami","doi":"10.1126/sciadv.adq7856","DOIUrl":"10.1126/sciadv.adq7856","url":null,"abstract":"<div >Future changes to the year-to-year swings between active and inactive North Atlantic tropical cyclone (TC) seasons have received little attention, yet may have great societal implications in areas prone to hurricane landfalls. This work investigates past and future changes in North Atlantic TC activity, focusing on interannual variability and evaluating the contributions from anthropogenic forcing. We show that interannual variability of Atlantic TC activity has already increased, evidenced by an increase in the occurrence of both extremely active and inactive TC seasons. TC-resolving general circulation models project a 36% increase in the variance of North Atlantic TC activity, measured by accumulated cyclone energy, by the middle of the 21st century. These changes are the result of increased variability in vertical wind shear and atmospheric stability, in response to enhanced Pacific-to-Atlantic interbasin sea surface temperature variations. Robust anthropogenic-forced intensification in the variability of Atlantic TC activity will continue in the future, with important implications for emergency planning and societal preparedness.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq7856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637767","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

Generative adversarial networks accurately reconstruct pan-cancer histology from pathologic, genomic, and radiographic latent features 生成式对抗网络从病理学、基因组学和放射学潜特征中准确重建泛癌症组织学

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq0856

Frederick M. Howard, Hanna M. Hieromnimon, Siddhi Ramesh, James Dolezal, Sara Kochanny, Qianchen Zhang, Brad Feiger, Joseph Peterson, Cheng Fan, Charles M. Perou, Jasmine Vickery, Megan Sullivan, Kimberly Cole, Galina Khramtsova, Alexander T. Pearson

{"title":"Generative adversarial networks accurately reconstruct pan-cancer histology from pathologic, genomic, and radiographic latent features","authors":"Frederick M. Howard, Hanna M. Hieromnimon, Siddhi Ramesh, James Dolezal, Sara Kochanny, Qianchen Zhang, Brad Feiger, Joseph Peterson, Cheng Fan, Charles M. Perou, Jasmine Vickery, Megan Sullivan, Kimberly Cole, Galina Khramtsova, Alexander T. Pearson","doi":"10.1126/sciadv.adq0856","DOIUrl":"10.1126/sciadv.adq0856","url":null,"abstract":"<div >Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of molecular features. These approaches distill cancer histologic images into high-level features, which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network—HistoXGAN—capable of reconstructing representative histology using feature vectors produced by common feature extractors. We evaluate HistoXGAN across 29 cancer subtypes and demonstrate that reconstructed images retain information regarding tumor grade, histologic subtype, and gene expression patterns. We leverage HistoXGAN to illustrate the underlying histologic features for deep learning models for actionable mutations, identify model reliance on histologic batch effect in predictions, and demonstrate accurate reconstruction of tumor histology from radiographic imaging for a “virtual biopsy.”</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq0856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637702","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

Mitochondrial pyruvate transport regulates presynaptic metabolism and neurotransmission 线粒体丙酮酸转运调节突触前代谢和神经传递

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adp7423

Anupama Tiwari, Jongyun Myeong, Arsalan Hashemiaghdam, Marion I. Stunault, Hao Zhang, Xiangfeng Niu, Marissa A. Laramie, Jasmin Sponagel, Leah P. Shriver, Gary J. Patti, Vitaly A. Klyachko, Ghazaleh Ashrafi

{"title":"Mitochondrial pyruvate transport regulates presynaptic metabolism and neurotransmission","authors":"Anupama Tiwari, Jongyun Myeong, Arsalan Hashemiaghdam, Marion I. Stunault, Hao Zhang, Xiangfeng Niu, Marissa A. Laramie, Jasmin Sponagel, Leah P. Shriver, Gary J. Patti, Vitaly A. Klyachko, Ghazaleh Ashrafi","doi":"10.1126/sciadv.adp7423","DOIUrl":"10.1126/sciadv.adp7423","url":null,"abstract":"<div >Glucose has long been considered the primary fuel source for the brain. However, glucose levels fluctuate in the brain during sleep or circuit activity, posing major metabolic stress. Here, we demonstrate that the mammalian brain uses pyruvate as a fuel source, and pyruvate can support neuronal viability in the absence of glucose. Nerve terminals are sites of metabolic vulnerability, and we show that mitochondrial pyruvate uptake is a critical step in oxidative ATP production in hippocampal terminals. We find that the mitochondrial pyruvate carrier is post-translationally modified by lysine acetylation, which, in turn, modulates mitochondrial pyruvate uptake. Our data reveal that the mitochondrial pyruvate carrier regulates distinct steps in neurotransmission, namely, the spatiotemporal pattern of synaptic vesicle release and the efficiency of vesicle retrieval—functions that have profound implications for synaptic plasticity. In summary, we identify pyruvate as a potent neuronal fuel and mitochondrial pyruvate uptake as a critical node for the metabolic control of neurotransmission in hippocampal terminals.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp7423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637703","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

CO2 capture, geological storage, and mineralization using biobased biodegradable chelating agents and seawater 使用生物基生物可降解螯合剂和海水进行二氧化碳捕获、地质封存和矿化

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq0515

Jiajie Wang, Ryota Sekiai, Ryota Tamura, Noriaki Watanabe

{"title":"CO2 capture, geological storage, and mineralization using biobased biodegradable chelating agents and seawater","authors":"Jiajie Wang, Ryota Sekiai, Ryota Tamura, Noriaki Watanabe","doi":"10.1126/sciadv.adq0515","DOIUrl":"10.1126/sciadv.adq0515","url":null,"abstract":"<div >Geological storage and mineralization of CO<sub>2</sub> in mafic/ultramafic reservoirs faces challenges including limited effective porosity, permeability, and rock reactivity; difficulties in using seawater for CO<sub>2</sub> capture; and uncontrolled carbonation. This study introduces a CO<sub>2</sub> capture, storage, and mineralization approach with the utilization of biobased biodegradable chelating agents and seawater. An acidic chelating agent solution is used to increase effective porosity and permeability through enhanced mineral dissolution. For instance, applying an acidic <i>N</i>,<i>N</i>-Bis(carboxymethyl)-<i>L</i>-glutamate solution to a porous basalt increased effective porosity by 16% and permeability by 26-fold in 120 hours. Subsequently, alkaline chelating agent–containing seawater improves CO<sub>2</sub> capture and storage by inhibiting mineralization, thus maintaining injectivity while providing ions for mineralization and further expanding storage space. Last, controlled mineralization is achieved by adjusting chelating agent biodegradation. Promising CO<sub>2</sub> storage and mineralization capacities two orders higher than current techniques, this approach reduces required reservoir volume while enhancing efficiency.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq0515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637765","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

Gibbs states and Brownian models for coexisting haze and cloud droplets 雾霾与云滴共存的吉布斯状态和布朗模型

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq7518

Manuel Santos Gutiérrez, Mickaël David Chekroun, Ilan Koren

{"title":"Gibbs states and Brownian models for coexisting haze and cloud droplets","authors":"Manuel Santos Gutiérrez, Mickaël David Chekroun, Ilan Koren","doi":"10.1126/sciadv.adq7518","DOIUrl":"10.1126/sciadv.adq7518","url":null,"abstract":"<div >Cloud microphysics studies include how tiny cloud droplets grow and become rain. This is crucial for understanding cloud properties like size, life span, and impact on climate through radiative effects. Small weak-updraft clouds near the haze-to-cloud transition are especially difficult to measure and understand. They are abundant but hard to capture by satellites. Köhler’s theory explains initial droplet growth but struggles with large particle groups. Here, we present a stochastic, analytical framework building on Köhler’s theory to account for (monodisperse) aerosols and cloud droplet interaction through competitive growth in a limited water vapor field. These interactions are modeled by sink terms, while fluctuations in supersaturation affecting droplet growth are modeled by nonlinear white noise terms. Our results identify hysteresis mechanisms in the droplet activation and deactivation processes. Our approach allows for multimodal cloud’s droplet size distributions supported by laboratory experiments, offering a different perspective on haze-to-cloud transition and small cloud formation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq7518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637770","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

Gene-environment interactions in the influence of maternal education on adolescent neurodevelopment using ABCD study 利用 ABCD 研究分析母亲教育对青少年神经发育影响中的基因-环境相互作用。

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adp3751

Runye Shi, Xiao Chang, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot17,, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Nathalie Holz, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Xiaolei Lin, Jianfeng Feng, IMAGEN Consortium

{"title":"Gene-environment interactions in the influence of maternal education on adolescent neurodevelopment using ABCD study","authors":"Runye Shi, Xiao Chang, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot17,, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Nathalie Holz, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Xiaolei Lin, Jianfeng Feng, IMAGEN Consortium","doi":"10.1126/sciadv.adp3751","DOIUrl":"10.1126/sciadv.adp3751","url":null,"abstract":"<div >Maternal education was strongly correlated with adolescent brain morphology, cognitive performances, and mental health. However, the molecular basis for the effects of maternal education on the structural neurodevelopment remains unknown. Here, we conducted gene-environment–wide interaction study using the Adolescent Brain Cognitive Development cohort. Seven genomic loci with significant gene-environment interactions (G×E) on regional gray matter volumes were identified, with enriched biological functions related to metabolic process, inflammatory process, and synaptic plasticity. Additionally, genetic overlapping results with behavioral and disease-related phenotypes indicated shared biological mechanism between maternal education modified neurodevelopment and related behavioral traits. Finally, by decomposing the multidimensional components of maternal education, we found that socioeconomic status, rather than family environment, played a more important role in modifying the genetic effects on neurodevelopment. In summary, our study provided analytical evidence for G×E effects regarding adolescent neurodevelopment and explored potential biological mechanisms as well as social mechanisms through which maternal education could modify the genetic effects on regional brain development.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639705","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

Same rule, different genes: Blimp1 is a pair-rule gene in the milkweed bug Oncopeltus fasciatus 相同的规则，不同的基因Blimp1 是乳草虫 Oncopeltus fasciatus 的配对规则基因

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-11-15 DOI: 10.1126/sciadv.adq9045

Katie Reding, Matthew Chung, Abigail Heath, Julie Dunning Hotopp, Leslie Pick

{"title":"Same rule, different genes: Blimp1 is a pair-rule gene in the milkweed bug Oncopeltus fasciatus","authors":"Katie Reding, Matthew Chung, Abigail Heath, Julie Dunning Hotopp, Leslie Pick","doi":"10.1126/sciadv.adq9045","DOIUrl":"10.1126/sciadv.adq9045","url":null,"abstract":"<div >Morphological features of organismal body plans are often highly conserved within large taxa. For example, segmentation is a shared and defining feature of all insects. Screens in <i>Drosophila</i> identified genes responsible for the development of body segments, including the “pair-rule” genes (PRGs), which subdivide embryos into double-segment units in a previously unexpected pre-patterning step. Here we show that the milkweed bug <i>Oncopeltus fasciatus</i> also uses a pair rule for embryo subdivision but <i>Oncopeltus</i> employs different genes for this process. We identified the gene <i>Blimp1</i> as an <i>Oncopeltus</i> PRG based on its expression pattern, tested its function with RNA interference and CRISPR-Cas9, and generated the first PR mutant in this species. Although it does not have PR function in <i>Drosophila</i>, like <i>Drosophila</i> PRGs, <i>Blimp1</i> encodes a transcription factor required for embryonic viability. Thus, pair-rule subdivision of the insect body plan is more highly conserved than the factors mediating this process, suggesting a developmental constraint on this pre-patterning step.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq9045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637712","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