bioRxiv : the preprint server for biology最新文献

{"title":"RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA.","authors":"Pim P B America, Subhas C Bera, Arnab Das, Thomas K Anderson, John C Marecki, Flávia S Papini, Jamie J Arnold, Robert N Kirchdoerfer, Craig E Cameron, Kevin D Raney, Martin Depken, David Dulin","doi":"10.1101/2025.03.05.641625","DOIUrl":"10.1101/2025.03.05.641625","url":null,"abstract":"<p><p>Positive-sense (+) RNA viruses often encode helicases presumed to support replication. Their precise role remains unresolved though, especially in coronaviruses (CoV) where the helicase translocates in the opposite direction to the polymerase. Using high-throughput single-molecule magnetic tweezers, we show that the coronavirus helicase enhances RNA synthesis through duplex RNA by tenfold, forming a directional complex with the viral polymerase. Despite opposing polarity, the helicase coordinates elongation by engaging the non-template strand. A detailed kinetic model derived from large datasets reveals distinct dynamic states, including fast bursting and slow, backtracking-prone modes, which are governed by helicase engagement. These results uncover an active coupling mechanism that modulates replication dynamics and provide a mechanistic basis for continuous versus discontinuous RNA synthesis in coronaviruses. Our findings establish the viral helicase as a central regulator of RNA replication rather than a passive accessory enzyme.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropixels reveal structure-function relationships in monkey V1 <i>in vivo</i>.","authors":"Nicole Carr, Shude Zhu, Xiaomo Chen, Kenji Lee, Alec Perliss, Tirin Moore, Chandramouli Chandrasekaran","doi":"10.1101/2025.05.14.653875","DOIUrl":"10.1101/2025.05.14.653875","url":null,"abstract":"<p><p>The relationship between structural properties of diverse neuronal populations in monkey primary visual cortex (V1) and their <i>in vivo</i> functional responses is not fully understood. We combined high-density Neuropixels recordings across cortical layers of macaque V1 with non-linear dimensionality reduction on waveform shape to delineate nine putative cell classes: 4 narrow-spiking (NS), 4 broad-spiking (BS) and 1 tri-phasic (TP). Using targeted analyses of laminar organization, spike amplitude, multichannel waveforms, functional properties, and network connectivity of these cell classes, we demonstrate four aspects of the V1 microcircuit predicted by anatomical studies but never fully demonstrated <i>in vivo</i> . First, NS neurons were concentrated in layer 4. Second, a large-amplitude NS cell class in layer 4B showed strong direction selectivity. Third, another layer 4B NS class exhibited robust bursting and orientation selectivity. Finally, cross-correlation analysis revealed functional interactions between cells in different layers. Our results highlight how high-resolution electrophysiology can reveal novel relationships between <i>in vivo</i> function of neurons and the underlying circuit.</p><p><strong>Teaser: </strong>High-resolution electrophysiology used with machine learning reveals links between function and the underlying neural circuitry.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a prototype Orbitrap Astral Zoom mass spectrometer for quantitative proteomics - Beyond identification lists.","authors":"Chris Hsu, Nicholas Shulman, Hamish Stewart, Johannes Petzoldt, Anna Pashkova, Deanna L Plubell, Eduard Denisov, Bernd Hagedorn, Eugen Damoc, Brendan X MacLean, Philip Remes, Jesse D Canterbury, Alexander Makarov, Christian Hock, Vlad Zabrouskov, Christine C Wu, Michael J MacCoss","doi":"10.1101/2025.05.30.657132","DOIUrl":"10.1101/2025.05.30.657132","url":null,"abstract":"<p><p>Mass spectrometry instrumentation continues to evolve rapidly yet quantifying these advances beyond conventional peptide and protein detections remain challenging. Here, we evaluate a modified Orbitrap Astral Zoom mass spectrometer (MS) prototype and compare its performance to the standard Orbitrap Astral MS. Across a range of acquisition methods and sample inputs, the prototype instrument outperformed the standard Orbitrap Astral MS in precursor and protein identifications, ion beam utilization, and quantitative precision. To enable meaningful cross-platform comparisons, we implemented an ion calibration framework that converts signal intensity from arbitrary units to ion per second. This benchmarking strategy showed that the prototype sampled 30% more ions per peptide than the original Orbitrap Astral MS. This increase in the ion beam utilization resulted in improved sensitivity and quantitative precision. To make these metrics broadly accessible, we added new metrics to the Skyline document grid to report the number of ions measured in a spectrum at the apex of the elution peak or the sum of ions between the peak integration boundaries. Taken together, our results demonstrate the prototype Orbitrap Astral Zoom as a high-performance platform for DIA proteomics and establish a generalizable framework for evaluation of mass spectrometer performance based on the number of ions detected for each analyte. Data are available on Panorama Public and on ProteomeXchange under the identifier PXD064536.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Neuron Shape Reasoning with Point Affinity Transformers.","authors":"J Troidl, J Knittel, W Li, F Zhan, H Pfister, S Turaga","doi":"10.1101/2024.11.24.625067","DOIUrl":"10.1101/2024.11.24.625067","url":null,"abstract":"<p><p>Connectomics is a field of neuroscience that maps the brain's intricate wiring diagram. Accurate neuron segmentation from microscopy volumes is essential for automating connectome reconstruction. However, state-of-the-art algorithms use image-based convolutional neural networks limited to local neuron shape context. Thus, we introduce a new framework that reasons over global neuron shape with a novel point affinity transformer. Our framework embeds a (multi-)neuron point cloud into a fixed-length feature set from which we can decode any point pair affinities, enabling clustering neuron point clouds for automatic proofreading. We also show that the learned feature set can easily be mapped to a contrastive embedding space that enables neuron type classification using a simple classifier. Our approach excels in two demanding connectomics tasks: correcting segmentation errors and classifying neuron types. Evaluated on three benchmark datasets derived from state-of-the-art connectomes, our method outperforms point transformers, graph neural networks, and unsupervised clustering baselines.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive mechanosensory connectome reveals a somatotopically organized neural circuit architecture controlling stimulus-aimed grooming of the <i>Drosophila</i> head.","authors":"Steven A Calle-Schuler, Alexis E Santana-Cruz, Lucia Kmecová, Stefanie Hampel, Andrew M Seeds","doi":"10.1101/2025.05.19.654894","DOIUrl":"10.1101/2025.05.19.654894","url":null,"abstract":"<p><p>Animals respond to tactile stimulations of the body with location-appropriate behavior, such as aimed grooming. These responses are mediated by mechanosensory neurons distributed across the body, whose axons project into somatotopically organized brain regions corresponding to body location. How mechanosensory neurons interface with brain circuits to transform mechanical stimulations into location-appropriate behavior is unclear. We previously described the somatotopic organization of bristle mechanosensory neurons (BMNs) around the <i>Drosophila</i> head that elicit a sequence of location-aimed grooming movements (Eichler et al., 2024). Here, we use a serial section electron microscopy reconstruction of a full adult fly brain to identify nearly all of BMN pre-and postsynaptic partners, uncovering circuit pathways that control head grooming. Postsynaptic partners dominate the connectome, and are both excitatory and inhibitory. We identified an excitatory hemilineage of cholinergic interneurons (hemilineage 23b) that elicit aimed head grooming and exhibit varied connectivity to BMNs from different head locations, revealing lineage-based development of a somatotopic parallel circuit architecture. Presynaptic partners provide extensive BMN presynaptic inhibition, consistent with models of sensory gain control as a mechanism of suppressing grooming movements and controlling the sequence. This work provides the first comprehensive map of a somatotopically organized connectome, and reveals how this organization could shape grooming. It also reveals the mechanosensory interface with the brain, illuminating fundamental features of mechanosensory processing, including feedforward excitation and inhibition, feedback inhibition, somatotopic circuit organization, and developmental origins.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnesium depletion unleashes two unusual modes of colistin resistance with different fitness costs.","authors":"Yu-Ying Phoebe Hsieh, Ian P O'Keefe, Zeqi Wang, Wanting Sun, Hyojik Yang, Linda M Vu, Robert K Ernst, Ajai A Dandekar, Harmit S Malik","doi":"10.1101/2024.10.15.618514","DOIUrl":"10.1101/2024.10.15.618514","url":null,"abstract":"<p><p>Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. We previously reported that magnesium sequestration by <i>Candida albicans</i> enables <i>Pseudomonas aeruginosa</i> to become colistin-resistant. Here, we show that Mg²⁺ depletion drives <i>P. aeruginosa</i> to evolve greater colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg ²⁺ -sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway relies on early mutations in <i>htrB2</i> , a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of <i>htrB2</i> mutations without compromising membrane integrity. In both cases, reduced binding of colistin to the bacterial membrane underlies resistance. Our findings reveal that Mg ²⁺ scarcity unleashes two novel trajectories of colistin resistance evolution in <i>P. aeruginosa</i> . (160).</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11507728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tunable Pulmonary Organoid Model Demonstrates Compositionally Driven Epithelial Plasticity and Immune Polarization.","authors":"Sophie E Edelstein, Satoshi Mizoguchi, Maria Tomàs Gracia, Nuoya Wang, Vi Lee, Hahram Kim, Connor Haynes, Colten Danelski, Tomoshi Tsuchiya, Maor Sauler, Micha Sam Brickman Raredon","doi":"10.1101/2025.06.05.658120","DOIUrl":"10.1101/2025.06.05.658120","url":null,"abstract":"<p><p>Aberrant epithelial regeneration and immune remodeling are hallmarks of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), COPD, and post-viral syndromes. Yet how cellular context shapes these trajectories remains unresolved. We present a tunable, primary rat-derived lung organoid model that systematically varies immune, epithelial, and mesenchymal inputs to reveal how composition alone dictates epithelial plasticity and macrophage polarization. Across organoid conditions that varied by relative starting lineage ratios, we observed the spontaneous emergence of disease-relevant transitional cell states, including <i>Sox9 ⁺</i> stressed progenitors, RAS-like intermediates, and hillock-like cells, alongside distinct macrophage activation profiles. In mesenchyme-rich contexts, epithelial-immune-mesenchymal crosstalk appeared to reinforce inflammatory signaling and stabilize transitional persistence, while immune-dominant inputs favored ATI-like repair and squamous remodeling. Hillock-like cells displayed context-specific polarization and expressed immune-regulatory genes, suggesting a role as epithelial orchestrators that help calibrate inflammatory response during regeneration. Connectomic analysis via NICHES revealed that regenerative outcomes were associated with dynamic multicellular signaling networks that integrate stress sensing, immune coordination, and epithelial resilience. This platform provides a tractable system for modeling milieu-specific repair and regenerative mechanisms and could inform therapeutic strategies aimed at redirecting epithelial fate in chronic lung disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> CRISPR screening identifies <i>NF1/RASA1/TP53</i> co-mutations and downstream MEK signaling as a common key mechanism of sinonasal tumorigenesis.","authors":"Kenny Vu, Sreenivasulu Gunti, Ramya Viswanathan, Anjali Nandal, Riley Larkin, Sungwoo Cho, Jonathan Zou, Shivani Ramolia, Austin T K Hoke, Siani M Barbosa, Gary L Gallia, Lisa M Rooper, Charalampos S Floudas, Hui Cheng, Christine N Miller, Mary R Guest, Marco Notaro, Arati Raziuddin, Zhonghe Sun, Xiaolin Wu, Farhoud Faraji, Matt Lechner, Federico Comoglio, Elijah F Edmondson, Raj Chari, Nyall R London","doi":"10.1101/2025.05.19.654661","DOIUrl":"10.1101/2025.05.19.654661","url":null,"abstract":"<p><p>Genomic alterations driving tumorigenesis in sinonasal malignancies remain largely unexplored. Here, we perform an <i>in vivo</i> loss-of-function screen using a pooled custom single-guide library delivered to the sinonasal cavity by adeno-associated virus vector to identify cancer driver genes across diverse sinonasal malignancies. This approach yielded sinonasal malignancies with diverse histologies, including sinonasal squamous cell carcinoma, adenocarcinoma, poorly differentiated sinonasal carcinoma, and sinonasal neuroendocrine tumors characteristic of olfactory neuroblastoma. Surprisingly, rather than observing distinct sgRNA profiles across sinonasal tumor subtypes, common recurrent mutations were identified in <i>Nf1</i> (79%), <i>Rasa1</i> (74%), and <i>Trp53</i> (68%) across malignancies with distinct histologies. Utilizing an orthogonal approach, we confirmed that <i>Nf1/Trp53</i> were required for sinonasal tumorigenesis. Given that loss-of-function in <i>NF1</i> and <i>RASA1</i> may lead to increased Ras activity and downstream MEK signaling, we tested small molecule targeting of the RAS-MAPK pathway in sinonasal malignancies. Indeed, both tumor cell lines derived from our loss-of-function approach as well as from human sinonasal malignancies displayed significant sensitivity to MEK inhibition in standard <i>in vitro</i> culture and organoid models. These findings demonstrate that loss of NF1 and RASA1-mediated Ras-GAP activity leads to Ras activation and downstream MEK signaling which is a potential common target throughout major sinonasal tumor subtypes.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-Supported, Rapid, and Electronic Detection of SARS-CoV-2 Antibodies and Antigens at Sub-Femtomolar Level.","authors":"Yeji Choi, Seyedsina Mirjalili, Md Ashif Ikbal, Sean McClure, Maziyar Kalateh Mohammadi, Scott Clemens, Jose Solano, John Heggland, Tingting Zhang, Jiawei Zuo, Chao Wang","doi":"10.1101/2024.09.04.611305","DOIUrl":"10.1101/2024.09.04.611305","url":null,"abstract":"<p><p>Major challenges remain to precisely detect low-abundance proteins from diverse biofluids in a rapid and cost-effective manner. Here we present a gold nanoparticle (AuNP)-supported, rapid electronic detection (NasRED) platform with sub-femtomolar sensitivity and high specificity. Surface-functionalized AuNPs act as multivalent detectors to recognize target antigens and antibodies through high-affinity binding, subsequently forming aggregates precipitated in a microcentrifuge tube and producing a solution color change. The optical extinction of residual floating AuNPs is digitized using a customized circuitry incorporating inexpensive optoelectronic elements and feedback mechanisms for stabilized readout. Uniquely, NasRED introduces active fluidic forces through engineered centrifugation and vortex agitation, effectively promoting protein detection at low concentrations and accelerating signal generation. Using SARS-CoV-2 as a demonstration, NasRED enables detection of both antibodies and antigens from a small sample volume (6 µL), distinguishes the viral antigens from those of human coronaviruses, and delivers test results in a short time (as fast as <15 min). The limits of detection (LoDs) for antibody detection are approximately 49 aM (7 fg/mL) in phosphate-buffered saline, or >3,000 times more sensitive than Enzyme-Linked Immunosorbent Assay (ELISA), ∼76 aM (11 fg/mL) in human pooled serum and in the femtomolar range in diluted whole blood. For nucleocapsid protein detection, NasRED LoDs are ∼190 aM (10 fg/mL) in human saliva and ∼2 fM (100 fg/mL) in nasal fluid. Unlike laboratory-based ELISA platforms, NasRED is a one-pot, in-solution assay that eliminates the needs for washing, labeling, expensive instrumentation or highly trained operators. With low reagent costs and a compact system footprint, this modular digital platform is well-suited for accurate, near-patient diagnosis and screening of a wide range of infectious and chronic diseases.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalable Perfluorocarbon RNA Nanocapsules Bypass Immune Clearance While Targeting Lung Epithelial and Lung Tumor Cells.","authors":"Kasturi Siddhanta, Atefehsadat Monirvaghefi, Aditya Sundar, Braeden R Pinkerton, Neha Kumari, Ling Ding, C J Woslager, Marjina Akter Kalpana, Chinmay M Jogdeo, Ashley R Ravnholdt, Jill A Poole, Joshua L Santarpia, James E Talmadge, David Oupický","doi":"10.1101/2025.06.05.658088","DOIUrl":"10.1101/2025.06.05.658088","url":null,"abstract":"<p><p>Inhalation RNA therapy offers to transform treatment of pulmonary diseases, yet mucus trapping, immune clearance, and navigation of heterogeneous lung tissue architecture still prevents RNA from reaching its target cells. Here, we develop perfluorocarbon (PFC) RNA nanocapsules that show negligible immune clearance, minimal inflammatory response, and efficient mucus transport, while passively homing to lung epithelial and tumor cells. After a single aerosolized dose in orthotopic lung metastasis model, more than 60% of tumor cells and most type II alveolar and bronchial epithelial cells internalized the nanocapsules, with observed pulmonary retention exceeding 48 h. The nanocapsule provoke negligible cytokine release, enabling repeated dosing. Treatment with therapeutic miR34-a suppresses metastatic outgrowth, potentiates anti-tumor immunity, and almost doubles median survival relative to control paclitaxel chemotherapy. By combining unique PFC disposition with RNA versatility, the delivery platform overcomes the main biological barriers for inhalable RNA medicines and opens a translatable path for treating diverse pulmonary diseases.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12157478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}