Science Advances最新文献_第5页

A dual chemodrug-loaded hyaluronan nanogel for differentiation induction therapy of refractory AML via disrupting lysosomal homeostasis

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.ado3923

Shilin Xu, Tao Wang, Xuechun Hu, Hong Deng, Yiyi Zhang, Lei Xu, Yang Zeng, Jia Yu, Weiqi Zhang, Lin Wang, Haiyan Xu

{"title":"A dual chemodrug-loaded hyaluronan nanogel for differentiation induction therapy of refractory AML via disrupting lysosomal homeostasis","authors":"Shilin Xu, Tao Wang, Xuechun Hu, Hong Deng, Yiyi Zhang, Lei Xu, Yang Zeng, Jia Yu, Weiqi Zhang, Lin Wang, Haiyan Xu","doi":"10.1126/sciadv.ado3923","DOIUrl":"10.1126/sciadv.ado3923","url":null,"abstract":"<div >Relapsed/refractory acute myeloid leukemia (rrAML) is a malignant blood cancer with an extremely poor prognosis, largely ascribed to the drug-resistant leukemia stem cells (LSCs). Most patients suffer from a risk of difficult-to-cure as well as severe systemic toxicity when receiving standard chemotherapies. As hyaluronic acid (HA) is a specific ligand of CD44 highly expressed by LSCs, we had HA self-assembled with cisplatin and daunorubicin to form a dual chemodrug nanogel (HA/Cis/Dau) to afford the targeted therapeutic interventions of rrAML. HA/Cis/Dau displayed an extra therapeutic function of inducing the granulocyte-monocyte differentiation in CD44<sup>+</sup> rrAML cells, an rrAML mouse model, and primary blasts isolated from patients with AML. Unlike free drugs directly diffusing and killing rrAML cells, HA/Cis/Dau transported the drugs into lysosomes, causing lysosomal membrane permeabilization, ROS accumulation, and thus a metabolic reprogramming of the rrAML cells. Moreover, HA/Cis/Dau was featured with alleviated side effects, ease of preparation, and cost effectiveness, therefore holding great promises for the targeted treatment of rrAML.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado3923","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723919","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

Circadian clock is critical for fungal pathogenesis by regulating zinc starvation response and secondary metabolism

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.ads1341

Qiaojia Lu, Muqun Yu, Xianyun Sun, Xin Zhou, Rui Zhang, Yahao Zhang, Xiao-Lan Liu, Zhanbiao Li, Lei Cai, Hongwei Liu, Shaojie Li, Yunkun Dang, Xiaodong Xu, Qun He, Yi Liu, Xiao Liu

{"title":"Circadian clock is critical for fungal pathogenesis by regulating zinc starvation response and secondary metabolism","authors":"Qiaojia Lu, Muqun Yu, Xianyun Sun, Xin Zhou, Rui Zhang, Yahao Zhang, Xiao-Lan Liu, Zhanbiao Li, Lei Cai, Hongwei Liu, Shaojie Li, Yunkun Dang, Xiaodong Xu, Qun He, Yi Liu, Xiao Liu","doi":"10.1126/sciadv.ads1341","DOIUrl":"10.1126/sciadv.ads1341","url":null,"abstract":"<div >Circadian clocks are known to modulate host immune responses to pathogen infections, yet their role in influencing pathogen pathogenesis remains unclear. Here, we investigated the role of circadian clocks in regulating the pathogenesis of the fungal pathogen <i>Fusarium oxysporum</i>, which has multiple genes homologous to the <i>Neurospora crassa frq</i> due to gene duplication events, with <i>Fofrq1</i> being the primary circadian clock gene. The pathogenesis of <i>F. oxysporum</i> in plants is controlled by its circadian clock, with infections causing severe disease symptoms at dawn. Notably, disruption of clock genes dramatically reduces fungal pathogenicity. Circadian clocks regulate the rhythmic expression of several transcription factors, including FoZafA, which enables the pathogen to adapt to zinc starvation within the plant, and FoCzf1, which governs the production of the toxin fusaric acid. Together, our findings highlight the critical roles of circadian clocks in <i>F. oxysporum</i> pathogenicity by regulating zinc starvation response and secondary metabolite production.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads1341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723920","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

Alternatives to photorespiration: A system-level analysis reveals mechanisms of enhanced plant productivity

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.adt9287

Edward N. Smith, Marvin van Aalst, Andreas P. M. Weber, Oliver Ebenhöh, Matthias Heinemann

引用次数: 0

Tempests in the troposphere: Mapping the impact of giant storms on Jupiter’s deep atmosphere

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.ado9779

Chris Moeckel, Huazhi Ge, Imke de Pater

引用次数: 0

Permafrost thawing under overlaying salt water

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.adp2808

Yumin Wang, Jin-Han Xie, Wei Yang, Xiaotian Li, Zulikaer Abulaiti, Shuai Zheng, Jingwei Zhu, Ke Xu

{"title":"Permafrost thawing under overlaying salt water","authors":"Yumin Wang, Jin-Han Xie, Wei Yang, Xiaotian Li, Zulikaer Abulaiti, Shuai Zheng, Jingwei Zhu, Ke Xu","doi":"10.1126/sciadv.adp2808","DOIUrl":"10.1126/sciadv.adp2808","url":null,"abstract":"<div >Thawing of permafrost substantially affects the local environment and global energy balance. When salt water overlays permafrost, Rayleigh-Darcy (R-D) instability emerges because of the density mismatch and regulates melting (thawing) dynamics. Contrary to expectations that a higher Rayleigh number (<i>R</i>) would amplify instability, our experiments revealed fingering and stable melting fronts at low and high <i>R</i>, respectively. We attribute the occurrence of the two melting patterns to the interplay between two competing flow structures: local circumfluence modulated by front perturbation and transversal chaotic mixing. We propose theories that rationalize the melting pattern transition and finger-scale evolution. In addition, the classic mass transport theory for R-D convection drastically underestimates the melting rate and misses key variable(s). The presence of fingering patterns and accelerated dynamics may have led to earlier penetration of the permafrost layer than previously anticipated. These findings have implications for understanding similar processes in magma migration, carbon sequestration, and subsurface energy recovery.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp2808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723902","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

Ocean alkalinity destruction by anthropogenic seafloor disturbances generates a hidden CO2 emission

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.adp9112

Sebastiaan J. van de Velde, Astrid Hylén, Filip J. R. Meysman

{"title":"Ocean alkalinity destruction by anthropogenic seafloor disturbances generates a hidden CO2 emission","authors":"Sebastiaan J. van de Velde, Astrid Hylén, Filip J. R. Meysman","doi":"10.1126/sciadv.adp9112","DOIUrl":"10.1126/sciadv.adp9112","url":null,"abstract":"<div >The seafloor is responsible for 40% of the alkalinity input to the ocean, thus contributing to the ocean’s capacity to sequester atmospheric CO<sub>2</sub>. Anthropogenic seafloor disturbances induced by mobile bottom-contact fishing and dredging influence this natural carbon sink, yet the human impact on the ocean’s alkalinity cycle remains poorly quantified. Model simulations show that the combined impact of mobile bottom-contact fishing (e.g., trawling) and dredging reduces natural alkalinity generation by 60 to 220 gigaequivalent year<sup>−1</sup>, which is equivalent to a reduction of the natural marine carbon sink by 2 to 8 teragrams CO<sub>2</sub> year<sup>−1</sup>. Alkalinity destruction by anthropogenic seafloor disturbance hence generates a hidden CO<sub>2</sub> emission, of which the impact is comparable to the estimated reduction of organic carbon burial by mobile bottom-contact fishing. Our analysis emphasizes that carbon accounting in marine systems should consider the anthropogenic impact on both the organic and inorganic carbon cycles.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp9112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723916","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

Liquid palladium for high-turnover carbon-carbon bond formation

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.adt9037

Md. Hasan Al Banna, Nieves Flores, Ziqi Zhou, Nastaran Meftahi, Salvy P. Russo, Pramod Koshy, Francois-Marie Allioux, Mohammad B. Ghasemian, Junma Tang, Sarina Sarina, Jianbo Tang, Andrew J. Christofferson, Kourosh Kalantar-Zadeh, Md. Arifur Rahim

{"title":"Liquid palladium for high-turnover carbon-carbon bond formation","authors":"Md. Hasan Al Banna, Nieves Flores, Ziqi Zhou, Nastaran Meftahi, Salvy P. Russo, Pramod Koshy, Francois-Marie Allioux, Mohammad B. Ghasemian, Junma Tang, Sarina Sarina, Jianbo Tang, Andrew J. Christofferson, Kourosh Kalantar-Zadeh, Md. Arifur Rahim","doi":"10.1126/sciadv.adt9037","DOIUrl":"10.1126/sciadv.adt9037","url":null,"abstract":"<div >Carbon-carbon (C─C) bond formation is a key step in diverse chemical processes and requires high-performance catalysts to enable energy-efficient technologies. Here, we present liquid Pd catalysts, formed by dissolving Pd in liquid Ga, for high-turnover C─C coupling reactions. The liquid Pd catalyst achieved a turnover frequency of 2.5 × 10<sup>8</sup> hour<sup>−1</sup> for a model coupling reaction at 70°C, surpassing all reported Pd catalysts by 1000-fold. Our results show that Pd atoms in the Ga matrix are liquid-like, exhibiting unique electronic and interfacial properties that substantially lower the energy barrier and enhance reaction kinetics. The system retained full activity over five cycles and showed no Pd leaching, highlighting the transformative potential of liquid-phase metals to advance high-throughput and sustainable C─C bond-forming strategies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723921","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

μSonic-hand: Biomedical micromanipulation driven by acoustic gas-liquid-solid interactions

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.ads8167

Xiaoming Liu, Yuyang Li, Fengyu Liu, Qing Shi, Lixin Dong, Qiang Huang, Tatsuo Arai, Toshio Fukuda

{"title":"μSonic-hand: Biomedical micromanipulation driven by acoustic gas-liquid-solid interactions","authors":"Xiaoming Liu, Yuyang Li, Fengyu Liu, Qing Shi, Lixin Dong, Qiang Huang, Tatsuo Arai, Toshio Fukuda","doi":"10.1126/sciadv.ads8167","DOIUrl":"10.1126/sciadv.ads8167","url":null,"abstract":"<div >Micromanipulation is crucial for operating and analyzing microobjects in advanced biomedical applications. However, safe, low-cost, multifunctional micromanipulation for operating bio-objects across scales and modalities remains inaccessible. Here, we propose a versatile micromanipulation method driven by acoustic gas-liquid-solid interactions, named μSonic-hand. The bubble contained at the end of a micropipette and the surrounding liquid form a gas-liquid multiphase system susceptible to acoustic waves. Driven by a piezoelectric transducer, the oscillating gas-liquid interface induces acoustic microstreaming, markedly increasing the mass transfer efficiency. It enables multiple liquid micromanipulations, including mixing, dispersion, enhancing cell membrane permeability, and harvesting selected cells. Furthermore, a controllable three-dimensional axisymmetric vortex in an open environment overcomes the constraints of microfluidic chip, enabling stable trapping, rapid transportation, and multidirectional rotation of HeLa cells, embryos, and other bio-objects ranging from micrometers to millimeters. A variety of applications demonstrate that the μSonic-hand, with its wide-range capabilities, inherent biocompatibility, and extremely low cost could remarkably advance biomedical science.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads8167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723922","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

Neuraminidase-specific antibodies drive differential cross-protection between contemporary FLUBV lineages

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.adu3344

Caroline K. Page, Justin D. Shepard, Sean D. Ray, James A. Ferguson, Alesandra J. Rodriguez, Julianna Han, Joel C. Jacob, Dawne K Rowe-Haas, Jasmine Y. Akinpelu, Lilach M. Friedman, Tomer Hertz, Andrew B. Ward, Stephen M. Tompkins

{"title":"Neuraminidase-specific antibodies drive differential cross-protection between contemporary FLUBV lineages","authors":"Caroline K. Page, Justin D. Shepard, Sean D. Ray, James A. Ferguson, Alesandra J. Rodriguez, Julianna Han, Joel C. Jacob, Dawne K Rowe-Haas, Jasmine Y. Akinpelu, Lilach M. Friedman, Tomer Hertz, Andrew B. Ward, Stephen M. Tompkins","doi":"10.1126/sciadv.adu3344","DOIUrl":"10.1126/sciadv.adu3344","url":null,"abstract":"<div >The two influenza B virus (FLUBV) lineages have continuously diverged from each other since the 1980s, with recent (post-2015) viruses exhibiting accelerated evolutionary rates. Emerging data from human studies and epidemiological models suggest that increased divergence in contemporary viruses may drive differential cross-protection, where infection with Yamagata lineage viruses provides limited immunity against Victoria lineage viruses. Here, we developed animal models to investigate the mechanisms behind asymmetric cross-protection between contemporary FLUBV lineages. Our results show that contemporary Victoria immunity provides robust cross-protection against the Yamagata lineage, whereas Yamagata immunity offers limited protection against the Victoria lineage. This differential cross-protection is driven by Victoria-elicited neuraminidase (NA)–specific antibodies, which show cross-lineage reactivity, unlike those from Yamagata infections. These findings identify a phenomenon in contemporary FLUBV that may help explain the recent disappearance of the Yamagata lineage from circulation, highlighting the crucial role of targeting NA in vaccination strategies to enhance cross-lineage FLUBV protection.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu3344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723875","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

Replication-dependent histone labeling dissects the physical properties of euchromatin/heterochromatin in living human cells

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-03-28 DOI: 10.1126/sciadv.adu8400

Katsuhiko Minami, Kako Nakazato, Satoru Ide, Kazunari Kaizu, Koichi Higashi, Sachiko Tamura, Atsushi Toyoda, Koichi Takahashi, Ken Kurokawa, Kazuhiro Maeshima

{"title":"Replication-dependent histone labeling dissects the physical properties of euchromatin/heterochromatin in living human cells","authors":"Katsuhiko Minami, Kako Nakazato, Satoru Ide, Kazunari Kaizu, Koichi Higashi, Sachiko Tamura, Atsushi Toyoda, Koichi Takahashi, Ken Kurokawa, Kazuhiro Maeshima","doi":"10.1126/sciadv.adu8400","DOIUrl":"10.1126/sciadv.adu8400","url":null,"abstract":"<div >A string of nucleosomes, where genomic DNA is wrapped around histones, is organized in the cell as chromatin, ranging from euchromatin to heterochromatin, with distinct genome functions. Understanding physical differences between euchromatin and heterochromatin is crucial, yet specific labeling methods in living cells remain limited. Here, we have developed replication-dependent histone (Repli-Histo) labeling to mark nucleosomes in euchromatin and heterochromatin based on DNA replication timing. Using this approach, we investigated local nucleosome motion in the four known chromatin classes, from euchromatin to heterochromatin, of living human and mouse cells. The more euchromatic (earlier-replicated) and more heterochromatic (later-replicated) regions exhibit greater and lesser nucleosome motions, respectively. Notably, the motion profile in each chromatin class persists throughout interphase. Genome chromatin is essentially replicated from regions with greater nucleosome motions, although the replication timing is perturbed. Our findings, combined with computational modeling, suggest that earlier-replicated regions have more accessibility, and local chromatin motion can be a major determinant of genome-wide replication timing.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 13","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu8400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723914","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