Proceedings of the National Academy of Sciences of the United States of America最新文献

{"title":"Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1.","authors":"Sitao Zhang, Amalia H Megarioti, Joseph M Hendricks, Junshu Zhou, Qingxiang Sun, Da Jia, James A Olzmann","doi":"10.1073/pnas.2505197122","DOIUrl":"https://doi.org/10.1073/pnas.2505197122","url":null,"abstract":"<p><p>FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 and vitamin K. These quinone antioxidants function as radical scavenging agents that prevent the propagation of lipid peroxidation and the induction of ferroptosis. Although several small-molecule inhibitors of FSP1 have been developed and found to sensitize cancer cells to ferroptosis, our understanding of their molecular mechanisms remains limited and no structures of FSP1 in complex with its inhibitors have been solved. Here, we solve the cocrystal structure of FSP1 in complex with the FSP1 inhibitor FSEN1, revealing that FSEN1 binds within the FSP1 substrate-binding pocket. FSEN1 makes key interactions with a critical phenylalanine, which is absent in mouse FSP1, providing an explanation for the selectivity of FSEN1 for human FSP1. These conclusions are supported by mutagenesis of FSP1 and biochemical and cellular assays of FSP1 function. Our findings provide the first cocrystal structure of FSP1 in complex with an inhibitor, enhancing our understanding of the mechanism of FSP1 inhibition and enabling future rational medicinal chemistry efforts to advance FSP1 inhibitors as therapeutics.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2505197122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174670","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}

{"title":"Maximum spreading of impacting shear-thinning and shear-thickening drops.","authors":"Anahita Mobaseri, Satish Kumar, Xiang Cheng","doi":"10.1073/pnas.2500163122","DOIUrl":"https://doi.org/10.1073/pnas.2500163122","url":null,"abstract":"<p><p>The maximum spreading of an impacting liquid drop is a key metric for characterizing the fundamental fluid process of drop impact. While extensively studied for Newtonian liquids, how far a non-Newtonian drop can spread upon impacting a solid substrate remains an open question. Here, by combining simulations, experiments, and scaling analyses, we establish a general framework for predicting the maximum spreading of drops of generalized Newtonian liquids, encompassing both shear-thinning and shear-thickening behaviors. Through an analysis of the energy budget at maximum spreading, we identify a characteristic shear rate that governs the viscous dissipation during drop impact. The finding allows us to map the spreading of non-Newtonian drops onto that of Newtonian drops, revealing the quantitative dependence of the maximum spreading diameter on various impact parameters and rheological properties of liquids. Our study addresses the long-standing challenge of understanding the impact dynamics of non-Newtonian drops, and provides valuable guidance for designing non-Newtonian liquids to achieve desired impact outcomes.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2500163122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174501","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}

{"title":"Nanoimmunomodulation of the Aβ-STING feedback machinery in microglia for Alzheimer's disease treatment.","authors":"Limin Tian, Guangyu Long, Siqi Zhu, Yuelong Wang, Pengcheng Xu, Lifeng Liu, Hong Yao, Shentong Fang, Shuqing Chen, Suxin Li","doi":"10.1073/pnas.2427257122","DOIUrl":"https://doi.org/10.1073/pnas.2427257122","url":null,"abstract":"<p><p>Imbalanced production and clearance of amyloid-β (Aβ) is a hallmark pathological feature of Alzheimer's disease (AD). While several monoclonal antibodies targeting Aβ have shown reductions in amyloid burden, their impact on cognitive function remains controversial, with the added risk of inflammatory side effects. Dysregulated stimulator of interferon genes (STING) signaling is implicated in neurodegenerative disorders, yet the biological interaction between this pathway and Aβ, as well as their combined influence on AD progression, is poorly understood. Here, we show that while microglia play a protective role in clearing extracellular Aβ, excessive Aβ engulfment triggers the cytosolic leakage of mitochondrial DNA for cGAS-STING cascade. This creates a negative feedback loop that not only exacerbates neuroinflammation but also impairs further Aβ clearance. To address this, we present a nanomedicine approach termed \"Aβ-STING Synergistic ImmunoSilencing Therapy (ASSIST)\". ASSIST comprises STING inhibitors encapsulated within a blood-brain barrier (BBB)-permeable polymeric micelle that also serves as an Aβ scavenger. Through a multivalent interaction mechanism, ASSIST efficiently destabilizes Aβ plaques and prevents monomer aggregation, subsequently promoting the engulfment of the dissociated Aβ by microglia rather than neurocytes. Furthermore, the STING signaling induced by excessive Aβ uptake is blocked, reducing inflammation and restoring microglial homeostatic functions involved in Aβ clearance. Intravenous administration of ASSIST significantly reduces Aβ burden and improves cognition in AD mice, with minimal cerebral amyloid angiopathy or microhemorrhages. We provide a proof-of-concept nanoengineering strategy to target the maladaptive immune feedback loop arising from conventional immunotherapy for AD treatment.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2427257122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161721","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}

{"title":"ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.","authors":"Nilam Bhandari, Ashutosh Prince, Mariam R Khan, C Alicia Traughber, Kalash Neupane, Shuhui W Lorkowski, Gregory Brubaker, Elif G Ertugral, Chandrasekhar R Kothapalli, George R Dubyak, Jonathan D Smith, Kailash Gulshan","doi":"10.1073/pnas.2502798122","DOIUrl":"https://doi.org/10.1073/pnas.2502798122","url":null,"abstract":"<p><p>Mutations in <i>ATP8B1</i> cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput studies showed interconnection between ATP8B1 and phosphoinositide (PIPs), but the mechanism linking ATP8B1, lipid metabolism, and inflammation remains unclear. <i>Atp8b1^G308V/G308V</i> mouse model, unbiased RNAseq, high-resolution-stimulation emission depltion (STED)-microscopy, and Crispr-Cas9 generated <i>ATP8B1^-/-</i> knockouts in hepatocytes/monocytes/macrophages were used to determine role of ATP8B1 in phosphatidylinositol,4-5-bisphosphate (PIP2) trafficking and inflammation. Human ATP8B1, purified from Sf9 insect cells and reconstituted in proteoliposomes, was used to test cell-free PIP2 flip. Various in-vitro techniques were used for testing direct interaction between PIP2 and ATP8B1. ATP8B1 maintains PIP2 at the inner leaflet of plasma membrane (PM). ATP8B1 flips PIP2 in cells, without altering flip of PE or bulk-endocytosis. ATP8b1 flips PIP2 in a cell-free system. ATP8B1 deletion promotes bile-salt-mediated cholesterol extraction from hepatocytes in a PIP2-dependent manner. PIP2 directly binds to the P-loop of ATP8B1. Unbiased RNAseq showed upregulation of inflammatory cytokines in ATP8b1^-/- immune cells. <i>ATP8B1^-/-</i> monocytes/macrophages showed aberrant lipopolysaccharide (LPS)-induced cleavage of GSDMD, formation of GSDMD pores, and interleukin-1beta (IL1β) release. Inflammation-resolving efferocytosis was impaired in <i>ATP8B1^-/-</i> macrophages. Biophysical properties of PM were altered in <i>ATP8b1^-/-</i> cells, with the mechanism being disrupted localization of PIP2. <i>Atp8b1^G308V/G308V</i> mice exposed to LPS showed higher plasma IL1β and lower survival rates vs. WT mice. ATP8B1 maintains PIP2 at the inner leaflet of PM. ATP8b1 directly flips and binds PIP2. ATP8B1 regulates LPS-induced GsdmD cleavage, formation of GsdmD pores, IL1β release, and mortality in mice.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2502798122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174669","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}

{"title":"Allelic variations and gene cluster modularity act as nonlinear bottlenecks for cholera emergence.","authors":"Mario López-Pérez, Deepak Balasubramanian, Alicia Campos-Lopez, Cole Crist, Trudy-Ann Grant, Jose M Haro-Moreno, Asier Zaragoza-Solas, Salvador Almagro-Moreno","doi":"10.1073/pnas.2417915122","DOIUrl":"https://doi.org/10.1073/pnas.2417915122","url":null,"abstract":"<p><p>The underlying factors that lead to specific strains within a species to emerge as human pathogens remain mostly enigmatic. The diarrheal disease cholera is caused by strains from a phylogenetically confined group within the <i>Vibrio cholerae</i> species, the pandemic cholera group (PCG), making it an ideal model system to tackle this puzzling phenomenon. Comprehensive analyses of over 1,840 <i>V. cholerae</i> genomes, including environmental isolates from this study, reveal that the species consists of eleven groups, with the PCG belonging to the largest and located within a lineage shared with environmental strains. This hierarchical classification provided us with a framework to unravel the ecoevolutionary dynamics of the genetic determinants associated with the emergence of toxigenic <i>V. cholerae</i>. Our analyses indicate that this phenomenon is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. We determined that certain PCG-associated alleles are essential for successful colonization whereas others provide a nonlinear competitive advantage, acting as a critical bottleneck that clarifies the isolated emergence of PCG. For instance, toxigenic strains encoding non-PCG alleles of a) <i>tcpF</i> or b) a sextuple allelic exchange mutant for genes <i>tcpA</i>, <i>toxT</i>, <i>VC0176</i>, <i>VC1791</i>, <i>rfbT,</i> and <i>ompU</i>, lose their ability to colonize the intestine. Interestingly, these alleles do not play a role in the colonization of newly established model environmental reservoirs. Our study uncovers the evolutionary roots of toxigenic <i>V. cholerae</i> offering a tractable approach for investigating the emergence of pathogenic clones within an environmental population.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2417915122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161724","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}

{"title":"Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins.","authors":"Adedeji M Aderounmu, Josephine Maus-Conn, Claudia D Consalvo, Peter S Shen, Brenda L Bass","doi":"10.1073/pnas.2500825122","DOIUrl":"https://doi.org/10.1073/pnas.2500825122","url":null,"abstract":"<p><p>A fully functional Dicer helicase, present in the modern arthropod, uses energy from ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA cleavage required for efficient antiviral defense. However, modern Dicer orthologs exhibit divergent helicase functions that affect their ability to contribute to antiviral defense. Moreover, mechanisms that couple ATP hydrolysis to Dicer helicase movement on dsRNA remain enigmatic. We used biochemical and structural analyses of ancestrally reconstructed Dicer helicases to map evolution of dsRNA binding affinity, ATP hydrolysis and translocation. Loss of affinity for dsRNA occurred early in Dicer evolution, coinciding with a decline in translocation activity, despite preservation of ATP hydrolysis activity. Ancestral nematode Dicer also exhibited significant decline in ATP hydrolysis and translocation, but studies of antiviral activities in the modern nematode <i>Caenorhabditis elegans</i> indicate Dicer retained a role in antiviral defense by recruiting a second helicase. Cryogenic electron microscopy (cryo-EM) analyses of an ancient metazoan Dicer allowed capture of multiple helicase states revealing the mechanism that connects each step of ATP hydrolysis to unidirectional movement along dsRNA. Our study rationalizes the diversity in modern Dicer helicases by connecting ancestral functions to observations in extant enzymes.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2500825122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161734","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}

{"title":"Ethanol induction of FGF21 in the liver is dependent on histone acetylation and ligand activation of ChREBP by glycerol-3-phosphate.","authors":"Mi Cheong Cheong, Bryan Mackowiak, Hyung Bum Kim, Genaro Hernandez, Tulip Nandu, Kevin Vale, Yuan Zhang, Lauren G Zacharias, Thomas P Mathews, Bin Gao, W Lee Kraus, Steven A Kliewer, David J Mangelsdorf","doi":"10.1073/pnas.2505263122","DOIUrl":"https://doi.org/10.1073/pnas.2505263122","url":null,"abstract":"<p><p>Ethanol rapidly stimulates the liver to synthesize the hormone fibroblast growth factor 21 (FGF21), which then acts on the brain to elicit a multifaceted protective response. We show that in mice, this induction of FGF21 occurs at the level of gene transcription and is regulated by two byproducts of ethanol metabolism, glycerol-3-phosphate (G3P) and acetyl-CoA. Using cell-based reporter and thermal shift binding assays, we show that G3P binds to a conserved domain and activates the transcription factor carbohydrate-responsive element-binding protein (ChREBP), which regulates the <i>Fgf21</i> gene promoter. The stimulation of <i>Fgf21</i> gene transcription by ethanol also requires its metabolism to acetyl-CoA and correlates with histone acetylation. Accordingly, a p300/CBP histone acetyltransferase inhibitor blocks histone acetylation, ChREBP recruitment, and transcriptional activation at the <i>Fgf21</i> promoter. Together, these findings reveal a dual regulatory mechanism driven by both G3P and acetyl-CoA that explains ethanol's robust stimulatory effect on <i>Fgf21</i> and possibly other ChREBP target genes in the liver.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 22","pages":"e2505263122"},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174324","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}

{"title":"Measuring historical pollution: Natural history collections as tools for public health and environmental justice research","authors":"Shane DuBay, Brian C. Weeks, Pamela E. Davis-Kean, Carl Fuldner, Nyeema C. Harris, Sara Hughes, Bruce O’Brien, Marie Perkins, Cheryl Weyant","doi":"10.1073/pnas.2403781122","DOIUrl":"https://doi.org/10.1073/pnas.2403781122","url":null,"abstract":"Through the industrial era, pollutants have been unevenly distributed in the environment, disproportionately impacting disenfranchised communities. Redressing the unequal distribution of environmental pollution is thus a question of environmental justice and public health that requires policy solutions. However, data on pollutants for many locations and time periods are limited because environmental monitoring is largely reactive—i.e., pollutants are monitored only after they are recognized as harmful and are circulating in the environment at elevated levels. Without comprehensive historical pollution data, it is difficult to understand the full, intergenerational consequences of pollutants on environmental and human health. We assert that biological specimens in natural history collections are an underutilized source of quantitative pollution data for tracking environmental pollutants over two centuries to inform justice-centered policy solutions. Specifically, we: 1) discuss the need for quantitative pollution data in environmental research and its implications for public health and policy, 2) examine the capacity of biological specimens as tools for tracking environmental pollutants through space and time, 3) present a framework for integrating pollution datasets from specimens with spatially and temporally matched human health datasets to inform and evaluate policy, and 4) identify challenges and research directions associated with the use of quantitative pollution datasets. Biological specimens present a unique opportunity to fill critical gaps that address environmental challenges relevant to public health and policy. This work demands interdisciplinary partnerships and inclusive practices to connect data generated from specimens with urgent questions about environmental health and justice.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"49 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184167","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}

{"title":"Estimating wage disparities using foundation models","authors":"Keyon Vafa, Susan Athey, David M. Blei","doi":"10.1073/pnas.2427298122","DOIUrl":"https://doi.org/10.1073/pnas.2427298122","url":null,"abstract":"The rise of foundation models marks a paradigm shift in machine learning: instead of training specialized models from scratch, foundation models are trained on massive datasets before being adjusted or fine-tuned to make predictions on smaller datasets. Initially developed for text, foundation models have also excelled at making predictions about social science data. However, while many estimation problems in the social sciences use prediction as an intermediate step, they ultimately require different criteria for success. In this paper, we develop methods for fine-tuning foundation models to perform these estimation problems. We first characterize an omitted variable bias that can arise when a foundation model is fine-tuned in the standard way: to minimize predictive error. We then provide a set of conditions for fine-tuning under which estimates derived from a foundation model are <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:msqrt> <mml:mi>n</mml:mi> </mml:msqrt> </mml:math> </jats:inline-formula> -consistent. Based on this theory, we develop fine-tuning algorithms that empirically mitigate this omitted variable bias. To demonstrate our ideas, we study gender wage gap estimation. Classical methods for estimating the adjusted wage gap employ simple predictive models of wages, which can induce omitted variable bias because they condition on coarse summaries of career history. Instead, we use a custom-built foundation model, capturing a richer representation of career history. Using data from the Panel Study of Income Dynamics, we find that career history explains more of the gender wage gap than standard econometric models can measure, and we identify elements of career history that are omitted by standard models but are important for explaining the gap.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"134 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184164","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}

{"title":"Phage-induced protection against lethal bacterial reinfection","authors":"Yikun Xing, Haroldo J. Hernandez Santos, Ling Qiu, Samantha R. Ritter, Jacob J. Zulk, Rachel Lahowetz, Kathryn A. Patras, Austen L. Terwilliger, Anthony W. Maresso","doi":"10.1073/pnas.2423286122","DOIUrl":"https://doi.org/10.1073/pnas.2423286122","url":null,"abstract":"Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"12 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183981","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}