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Background: Pine wood nematode (Bursaphelenchus xylophilus, PWN), a devastating pine parasite, induces widespread mortality in host trees. Chemical pesticides have been conventionally used for PWN control; however, their prolonged use drives the evolution of pesticide resistance in PWN and poses environmental risks. RNA interference (RNAi)-based biopesticides represent a promising alternative, offering species-specific targeting, high efficacy and a reduced ecological footprint.
Results: To engineer RNAi biopesticides against PWN, we systematically investigated eight V1-domain subunits (A-H) of the V-type proton ATPase (V-ATPase) family using integrated transcriptomic profiling and bioinformatic analyses. Eight corresponding double stranded (ds) RNAs were designed, synthesized, and functionally evaluated. RNAi targeting these subunits significantly impaired PWN viability, motility, feeding efficiency, and fecundity. Notably, dsV-ATPase-H exhibited the most pronounced interference efficacy: 72 h exposure to 700 ng μL dsRNA induced 80.12% corrected mortality in J4-stage nematodes. This treatment reduced egg production from 7 to 1 egg per nematode and population density from 8136 to 705 individuals. Transmission electron microscopy further revealed that RNAi disrupted nematode ultrastructure, manifesting as altered cuticle thickness and reduced intestinal microvilli density, thereby compromising structural and functional integrity.
Conclusions: Our study demonstrates the potential use of V-ATPase subunits (A-H) as molecular targets for RNAi-based PWN control. This study is the first to reveal, at the ultrastructural level, the regulatory effects of RNAi targeting V-ATPase (A-H) subunits in PWN on their critical life activities. It proposes a sustainable RNAi-based strategy for controlling pine wilt disease. © 2025 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.70047 | DOI Listing |
Ecotoxicol Environ Saf
September 2025
Center for Global Health, the Key Laboratory of Modern Toxicology, Ministry of Education, Department of Hygienic Analysis and Detection, School of Public Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Bisphenol F (BPF), a widely used substitute for bisphenol A (BPA), has raised growing concerns due to its potential metabolic toxicity. Recent studies suggest that BPF exposure is associated with lipid accumulation and non-alcoholic fatty liver disease (NAFLD)-like changes, however, the underlying mechanisms remain poorly understood. This study was performed to investigate the BPF-induced NAFLD-like changes through the lipid degradative pathway, which via an unrecognized defect of lipophagy mediated by Adipose Triglyceride Lipase (ATGL)-Sirtuin 1 (SIRT1)-Peroxisome proliferator-activated receptor α (PPARα) signaling axis.
View Article and Find Full Text PDFJ Biol Chem
August 2025
Department of Medicine, Division of Endocrinology, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address:
Pathologic loss of insulin-producing pancreatic β-cells is a hallmark of diabetes that is potentially reversible through regenerative therapy. However, existing replication-promoting compounds lack β-cell specificity, limiting their clinical application. To overcome this challenge, we generated βRepZnC, a zinc-chelating replication compound designed to leverage the uniquely high zinc content of β-cells for targeted delivery.
View Article and Find Full Text PDFCell Rep
August 2025
Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China; College of Pharmacy, Ningxia Medical University, Yinchuan
Cells adapt to nutrient limitation by activating catabolic and inhibiting anabolic pathways, yet prolonged stress may lead to cell death. How cells orchestrate metabolic adaptation and cell death to nutrient stress is poorly understood. We conduct a genome-wide CRISPR-Cas9 screen to identify regulators in glucose-starvation-induced cell death and find a group of genes in lysosomal pathway is enriched following glucose starvation.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210.
In yeast, early adaptation to hyperosmotic stress involves organelle-based mechanisms, including synthesis of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P) at the vacuole. This low-level signaling lipid drives vacuolar fragmentation and activates the V-ATPase proton pump, which acidifies the vacuole and drives salt sequestration. The vacuole-resident V-ATPase subunit Vph1 interacts with PI(3,5)P via its N-terminal domain (Vph1NT), directly linking lipid signaling to proton pump regulation.
View Article and Find Full Text PDFbioRxiv
July 2025
Department of Biological Sciences, Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina, 29634.
Tissue-resident macrophages efficiently internalize spores, forming a critical first line of defense against infection. However, the mechanisms that these cells use to control spores in vivo remain incompletely defined. Here, we used the live imaging capabilities of the larval zebrafish host model to assess the role of the v-ATPase complex in macrophage-mediated defense against in a whole vertebrate animal.
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