生物学最新文献

{"title":"Blood virome profiling reveals subtype-specific viral signatures and reduced diversity in non-Hodgkin lymphoma.","authors":"Shaokun Pan, Wang Li, Xingyue Zhao, Huijie Wang, Jing Liu, Wen Zhang, Chenglin Zhou, Youhua Xie","doi":"10.1080/21505594.2025.2542457","DOIUrl":"10.1080/21505594.2025.2542457","url":null,"abstract":"<p><p>Non-Hodgkin lymphoma (NHL), a heterogeneous lymphoid malignancy, demonstrates molecular diversity linked to genetic and immune factors, with emerging roles for viral infections in pathogenesis. Yet, the blood virome's composition and dynamics in NHL remain poorly characterized. This study characterizes the blood virome in NHL subtypes using viral metagenomic sequencing of serum from 217 patients (B-cell: BCL, T-cell: TCL, NK-cell: NKCL) and 40 healthy controls. Bioinformatic analysis identified 45 viral families, revealing subtype-specific viromic signatures. BCL exhibited a dominance of <i>Anelloviridae</i>, which accounted for 86% of eukaryotic viruses, compared with only 3% in controls, correlating with immunosuppression. Additionally, picobirnavirus, an opportunistic pathogen particularly in hosts with compromised immune systems, also showed a significant difference compared to controls. NKCL showed <i>Flaviviridae</i> enrichment, accounting for 82% of eukaryotic viruses, with nearly all of them being human pegivirus-1 (HPgV-1). Compared with healthy controls, patients with NHL exhibited significantly lower blood virome α-diversity at the genus level, and T-cell lymphomas showed the lowest species-level richness (140 vs. 332 in controls). Beta diversity highlighted BCL-specific viral heterogeneity, contrasting conserved T/NKCL viral profiles. <i>Anelloviridae</i> and Picobirnavirus expansion aligns with immune dysfunction, whereas NKCL-restricted HPgV-1 prevalence underscores biomarker potential. These findings implicate blood virome alterations marked by viral family predominance and diversity loss in NHL pathogenesis via immune modulation or oncogenesis. This first comprehensive NHL virome profile identifies subtype-specific signatures (<i>Anelloviridae</i>/Picobirnavirus/HPgV-1) for potential diagnostic and therapeutic targeting. Validation of these biomarkers may refine NHL subtyping and elucidate virome-lymphomagenesis mechanisms.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2542457"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manipulation of macrophage signaling by <i>Leishmania</i> virulence factors.","authors":"Dhiraj Gurjar, Neelam Bodhale, Divanshu Shukla, Debadatta Nayak, Nibedita Lenka, Bhaskar Saha","doi":"10.1080/21505594.2025.2549802","DOIUrl":"10.1080/21505594.2025.2549802","url":null,"abstract":"<p><p><i>Leishmania</i>, a macrophage-residing parasite, expresses virulence factors that intercept macrophage signaling and inflicts leishmaniasis. Recently described virulence factors- eEF-1α (eukaryotic elongation factor), LmjF_36_3850 (<i>Leishmania major</i> F_36_3850), LdTyrPIP_22 (LDBPK_220120.1) and LmjMAPK (<i>L. major</i> mitogen activated protein kinase)-4/12 selectively modulate the activities of kinases, phosphatases and metabolism of phosphatidylinositol influencing the infection outcome. LmjF_36_3850, abundant in virulent <i>L. major</i>, interferes with PKC (Protein kinase C) activation; OAG (1-oleoyl-2-acetyl-sn-glycerol) supplementation enhanced PKC phosphorylation, increasing IL-12, but reducing IL-10, production and increased disease-promoting T cells. LdTyrPIP_22, a dual-specificity phosphatase, dephosphorylates phosphotyrosine residues and PI(3)P/PI(4)P, within the flagellar pocket and vesicles, suggesting a role in phosphoinositide (PI) signaling during differentiation. Its <i>L. mexicana</i> ortholog, LmDUSP1 (Dual-specificity Phosphatase), is a virulence factor linked to infectivity. 170 PX-domain-containing proteins in Kinetoplastea are implicated in phosphoinositide-mediated signaling, transport, and membrane trafficking. This review constructs a new framework of virulence factor-modulated host cell signaling as a bi-directional host-parasite interaction.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2549802"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of oxidative stress and the Neuropilin-2-induced neuroinflammatory pathway by EMO ameliorates epileptic seizures in the preclinical model of epilepsy.","authors":"Haiting Li, Yujia Zhang, Yangyang Zhang, Yuehui Li, Huifang Wang","doi":"10.1080/13510002.2025.2547405","DOIUrl":"10.1080/13510002.2025.2547405","url":null,"abstract":"<p><strong>Objective: </strong>Epilepsy is a chronic neurological condition characterized by recurrent seizures, often linked to neuroinflammation and oxidative stress that exacerbate neuronal injury. Neuropilin-2 (NRP2) and Nuclear Factor-Kappa B (NF-κB) are key mediators in these pathways. This study evaluated the neuroprotective effects of emodin, a bioactive anthraquinone with antioxidant and anti-inflammatory properties, in a pentylenetetrazole (PTZ)-induced mouse model of epilepsy.</p><p><strong>Methods: </strong>Seizure severity, anxiety-like behavior (Elevated Plus Maze), and cognitive function (Morris Water Maze) were assessed. Oxidative stress markers including glutathione (GSH), catalase, lipid peroxidation (LPO), and glutathione-S-transferase (GST) were measured. Expression of NRP2, NF-κB, and proinflammatory cytokines (TNF-α, IL-6) was quantified. Docking studies examined emodin's binding affinity to NRP2 and NF-κB.</p><p><strong>Results: </strong>Emodin (200 mg/kg) significantly reduced seizure frequency and severity, improved anxiety-like behavior, and enhanced cognition. Biochemical analysis showed restored oxidative balance, with increased GSH and catalase activity and reduced LPO and GST dysfunction. Molecular studies revealed downregulation of NRP2, NF-κB, and cytokines. Docking confirmed strong binding affinity to NRP2 and NF-κB.</p><p><strong>Conclusion: </strong>Emodin alleviates oxidative stress and neuroinflammation by modulating NRP2 and NF-κB pathways, suggesting therapeutic potential in epilepsy.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2547405"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological protection and molecular regulation of cystatin B in Nile tilapia (<i>Oreochromis niloticus</i>) bacterial disease.","authors":"Yongxiong Huang, Xuyan Tan, Yuwen Li, Zhiqiang Zhang, Yu Huang, Jichang Jian","doi":"10.1080/21505594.2025.2563010","DOIUrl":"10.1080/21505594.2025.2563010","url":null,"abstract":"<p><p>Cystatin B (CSTB) is an endogenous cysteine protease inhibitor that plays a critical role in the modulation of numerous biological processes, involving immune responses, apoptosis, and inflammation in mammals. However, its immunological functions in teleost, particularly Nile tilapia (<i>Oreochromis niloticus</i>) remain unclear. In the present study, the <i>CSTB</i> was cloned and characterized from Nile tilapia (<i>On-CSTB</i>) and its role in bacterial infection was revealed. The On-CSTB open reading frame is 300 bp encoding 99 amino acids that contains a conserved cystatin domain. Multiple sequence alignment analysis revealed that On-CSTB share over 75% identity with fish lineages, and 45% identity with mammals. qPCR analysis showed that <i>On-CSTB</i> is widely expressed across various tissues and highly expressed in blood cells and intestines and can be significantly inducted by <i>Streptococcus agalactiae</i> (<i>S. agalactiae</i>) and <i>Aeromonas hydrophila</i> (<i>A. hydrophila</i>). In vivo experiments demonstrated that On-CSTB protein could suppress inflammation while participating in the MyD88/NF-κB signaling pathway and inflammasome activation, affecting apoptosis and pyroptosis processes. Moreover, On-CSTB contributed to enhanced tissue integrity and alleviated pathological damage. These findings collectively highlight On-CSTB as a crucial immunomodulator that contributes to host defense and tissue protection in fish. The present study offers novel perspectives on the immunomodulatory role of CSTB in tilapia, providing a basis for disease resistance strategies in aquaculture.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2563010"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular survival of <i>Staphylococcus aureus</i> in macrophages during osteomyelitis.","authors":"William A Lathram, Christopher D Radka","doi":"10.1080/21505594.2025.2553789","DOIUrl":"10.1080/21505594.2025.2553789","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i>, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, <i>S. aureus</i> exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies - including biofilm formation, small colony variants, and inhibition of phagolysosomal killing - further enhance persistence and immune evasion. While these mechanisms are well studied in extracellular infections, their role in intracellular survival is increasingly evident. This review synthesizes emerging insights into how <i>S. aureus</i> manipulates macrophage function to establish chronic bone infection and highlights therapeutic opportunities targeting macrophage polarization to improve immune-mediated clearance and bone repair in osteomyelitis.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2553789"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AoVps18 regulates sporulation, trap morphogenesis, and nematode predation by modulating vacuole assembly and attractant synthesis in <i>Arthrobotrys oligospora</i>.","authors":"Meichen Zhu, Yankun Liu, Yi Chen, Qiyan Hu, Dake Zhao, Wenjie Wang, Jinkui Yang","doi":"10.1080/21505594.2025.2553782","DOIUrl":"10.1080/21505594.2025.2553782","url":null,"abstract":"<p><p>Vacuoles are essential organelles in eukaryotic cells, playing key roles in cellular homeostasis through nutrient sensing, osmoregulation, and autophagy. In filamentous fungi, vacuole dynamics are crucial for mycelial growth, stress response, and pathogenicity. The vacuolar functions and their regulation in nematode-trapping (NT) fungi remain poorly understood. Here, we characterized a vacuolar protein sorting (Vps) protein Vps18 (AoVps18) in a typical NT fungus <i>Arthrobotrys oligospora</i>, which is required for the proper regulation of mycelial growth, trap formation, and sporulation. Through integrated phenotypic and molecular analyses, we established that AoVps18 physically interacts with core mitogen-activated protein kinase (MAPK) signaling components (AoSte12 and AoFus3) to coordinate predation-related cellular processes, including vacuole assembly, mitochondrial dynamics, and lipid droplet accumulation. Notably, we identified a TGAAAC regulatory motif in the <i>Aovps18</i> promoter, suggesting direct transcriptional control by the MAPK effector, AoSte12. RNA sequencing and metabolomics further revealed that AoVps18 is involved in regulating multiple cellular processes and synthesizing compounds critical for the chemotaxis of nematodes toward <i>A. oligospora</i>. Overall, these findings elucidate the regulatory mechanisms by which AoVps18 coordinates vacuolar function with trap morphogenesis and mycelial growth in NT fungi, advancing both the fundamental understanding of Vps proteins regulation and potential biocontrol applications against plant-parasitic nematodes.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2553782"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping evolutionary paradigm of bovine viral diarrhea virus <i>Npro</i> associated with different organizations of nucleotide.","authors":"Xili Feng, Zeyu Liu, Xiaoting Ren, Lele An, Xiao-Xia Ma","doi":"10.1080/21505594.2025.2550620","DOIUrl":"10.1080/21505594.2025.2550620","url":null,"abstract":"<p><p>The non-structural protein (Npro) of bovine viral diarrhea virus (BVDV) is a crucial virulence factor that impairs the host's antiviral immune response and facilitates virus production. This study establishes a foundation for understanding how different selective pressures influence the formation of nucleotide pairs, synonymous codon, and context-dependent codon bias (CDCB) in BVDV <i>Npro</i>. BVDV genotype 1 exhibits a greater number of subgenotypes compared to other genotypes, yet its overall nucleotide usage bias in <i>Npro</i> is stronger. Within <i>Npro</i>, certain dinucleotides, specifically CpG and UpA, are notably suppressed, while UpG is selected with high frequency across all genotypes. The BVDV <i>Npro</i> region exhibits a pronounced bias in synonymous codon usage and possesses a genetic capacity to distinguish between genotypes. Unlike the patterns of mononucleotide and synonymous codon usage associated with BVDV genotyping, nucleotide pair usage and CDCB show significant variability due to the high mutation rate in the Npro coding sequence. Despite this variation, both nucleotide architectures demonstrate a unique evolutionary paradigm that goes beyond genotype-specific models. Aside from nucleotide composition constraints imposed by the high mutation rate in the viral genome, natural selective pressures arising from translational selection and host immune response also significantly influence the formation of various nucleotide architectures in the BVDV <i>Npro</i>. By analyzing the genetic characterizations associated with the different nucleotide architectures in the <i>Npro</i>, the diverse repertoire of nucleotide pairs, synonymous codons and CDCB may provide BVDV mutants with ample opportunities for direct adaptation and exaptation, thereby overcoming the robust immune defenses of the host.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2550620"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>miR-4484</i> suppresses hepatocellular carcinoma progression via targeting <i>KIF2C</i>.","authors":"Jianyang Lin, Yun Cai, Zhihong Chen, Jichun Ma, Kun Zhao","doi":"10.1080/15476286.2025.2569192","DOIUrl":"10.1080/15476286.2025.2569192","url":null,"abstract":"<p><p>Aberrantly expressed microRNA-4484 (<i>miR-4484</i>) has recently garnered attention for its involvement in human diseases, but its specific role in hepatocellular carcinoma (HCC) remains largely unexplored. This study investigates the function of <i>miR-4484</i> in HCC progression and its regulatory interaction with <i>KIF2C</i>. Analysis of the data from the TCGA-LIHC database revealed that <i>miR-4484</i> expression is significantly downregulated in HCC tissues, with lower levels correlating with worse prognosis. <i>In vitro</i> experiments confirmed that <i>miR-4484</i> expression is lower in HCC cell lines compared to a normal liver cell line. Functional assays demonstrated that <i>miR-4484</i> overexpression via a <i>miR-4484</i> mimic suppressed cell proliferation and induced G1 phase arrest, whereas <i>miR-4484</i> inhibition promoted proliferation and facilitated cell cycle progression from G1 to S and G2 phases. Additionally, <i>KIF2C</i> expression was significantly upregulated in HCC tissues and cell lines, exhibiting an inverse correlation with <i>miR-4484</i> levels. Dual-Luciferase Reporter Assays confirmed that <i>miR-4484</i> directly binds to <i>KIF2C</i>, thereby regulating its expression and influencing cell proliferation and cell cycle progression. <i>In vivo</i>, subcutaneous intratumoral injection of the <i>miR-4484</i> mimic in nude mice significantly inhibited HCC tumour growth. These findings highlight <i>miR-4484</i> as a potential tumour suppressor in HCC through its direct targeting of <i>KIF2C</i>, underscoring its promise as a therapeutic target for HCC treatment.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-20"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altering rRNA 2'O-methylation pattern during neuronal differentiation is regulated by FMRP.","authors":"Michelle Ninochka D'Souza, Naveen Kumar Chandappa Gowda, Nivedita Hariharan, Syed Wasifa Qadri, Dasaradhi Palakodeti, Ravi S Muddashetty","doi":"10.1080/15476286.2025.2563986","DOIUrl":"10.1080/15476286.2025.2563986","url":null,"abstract":"<p><p>The Fragile X Messenger Ribonucleoprotein (FMRP) is a selective RNA-binding protein that localizes to the cytoplasm and the nucleus. The loss of FMRP results in Fragile X Syndrome (FXS), an autism spectrum disorder. FMRP interacts with ribosomes and regulates the translation of mRNAs essential for neuronal development and synaptic plasticity. However, the biochemical nature of this translation regulation is unknown. Here, we report that a potential feature of FMRP-mediated translation regulation during neuronal differentiation is the modulation of 2'-O-methylation of ribosomal RNA. 2'O-methylation, facilitated by C/D box snoRNAs in the nucleus, is a major epitranscriptome mark on rRNA, essential for ribosome assembly and function. We found that FMRP influences a distinct rRNA 2'O-Methylation pattern across neuronal differentiation. We show that in H9 ESCs, FMRP interacts with a selected set of C/D box snoRNA in the nucleus, resulting in the generation of ribosomes with a distinct pattern of rRNA 2'O-Methylation. This epitranscriptome pattern on rRNA undergoes a significant change during the differentiation of ESCs to neuronal precursors and cortical neurons. ESCs exhibit substantial levels of hypomethylated residues on rRNA, which progressively decrease in neuronal precursors and post-mitotic cortical neurons. This reduction correlates with changes in global protein synthesis across different stages of differentiation. Importantly, this stepwise change in the 2'O-methylation pattern during neuronal differentiation is altered in the absence of FMRP, which could impact neuronal development and contribute to dysregulated protein synthesis observed in Fragile X Syndrome.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-22"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal mechanism of ketone volatile organic compounds against <i>Pseudogymnoascus destructans</i>.","authors":"Yaping Lu, Yue Zhu, Long Huang, Yingting Pu, Xiaoyu Sun, Jiang Feng, Keping Sun","doi":"10.1080/21505594.2025.2569627","DOIUrl":"10.1080/21505594.2025.2569627","url":null,"abstract":"<p><p>Ketone volatile organic compounds have demonstrated favorable inhibitory activity against a wide range of pathogenic fungi, including <i>Pseudogymnoascus destructans</i> (<i>Pd</i>), the lethal pathogenic fungus responsible for white-nose syndrome in bats. However, the mechanism of fungal inhibition by ketones remains unclear. In this study, we employed transcriptomic analysis to conduct RNA sequencing on <i>Pd</i> treated with 2-undecanone and 2-nonanone, aiming to investigate the effects of these ketones on the gene expression profiles of <i>Pd</i>. The results indicated that 2-undecanone and 2-nonanone inhibit spore germination in <i>Pd</i> and cause significant damage to its mycelium. The minimum inhibitory concentrations (MIC) were determined to be 25.94 μg/mL and 135.41 μg/mL, respectively. Transcriptomic analysis revealed these ketones affects <i>Pd</i> through multiple pathways, inducing lesions in the cell wall and membrane, and disrupting ribosomal stability by interfering with rRNA modifications and ribosome assembly. Additionally, we found that 2-undecanone impacts enzymes involved in the tricarboxylic acid cycle, disrupting energy metabolism by interfering with critical metabolic pathways in aerobic organisms. In contrast, 2-nonanone directly damages <i>Pd</i> DNA, triggering the activation of DNA damage repair mechanisms. This study provides a theoretical basis for exploring novel antifungal strategies targeting <i>Pd</i>, suggesting that ketones may serve as potential in vitro defense and control tools, laying the groundwork for the subsequent development of efficient fumigants.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2569627"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}