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Background: Bovine respiratory disease (BRD) remains a significant health and economic problem to the dairy cattle industry. Multiple risk factors contribute to BRD susceptibility including the bacterial pathobionts Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. Studies have characterized and quantified the abundance of these bacteria in the nasal cavity of cattle to infer and help disease diagnosis; nonetheless, there is still discrepancy in the results observed of when these microbes are commensal or pathogenic. Additionally, some of these studies are limited to a specific farm. The goal of this study is to compare the nasal microbiome community (diversity and composition) and the abundance of the four bacterial pathogens (by qPCR) in the nasal cavity to identify differences between dairy calves that are apparently healthy and those identified to have BRD. Nasal swabs were collected from approximately 50 apparently healthy and 50 BRD-affected calves sampled from five different dairy farms in the US (CA, IN, NY (two farms), and TX)., Results: Calves diagnosed with BRD in NY, and TX had lower nasal microbiome diversity compared to the apparently healthy calves. Differences in the nasal microbiome composition were observed between the different farms predicted by Bray-Curtis and weighted UniFrac dissimilarities. Commensal and pathobiont genera Acinetobacter, Moraxella, Psychrobacter, Histophilus, Mannheimia, Mycoplasma, and Pasteurella were prevalent in the bovine nasal microbiome regardless of farm or disease status. The BRD-pathobiont H. somni was the most prevalent pathobiont among all the samples and M. bovis the least prevalent. Only in CA was the abundance of a pathobiont different according to disease status, where M. haemolytica was significantly more abundant in the BRD-affected animals than apparently healthy animals., Conclusions: This study offers insight into the nasal microbiome community composition in both animals diagnosed with BRD and healthy animals, and shows that the farm effect plays a more significant role in determining the microbiome community than disease status in young dairy calves., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures involving animal use were approved by the Purdue University Animal Care and Use Committee (protocol #1906001911). Consent for publication: All authors provide consent to publish. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Modern medicine seeks precision targeting, imaging and therapy to maximize efficacy and avoid toxicities. Nanoparticles (NPs) have tremendous yet unmet clinical potential to carry and deliver imaging and therapeutic agents systemically with tissue precision. But their size contributes to rapid scavenging by the reticuloendothelial system and poor penetration of key endothelial cell (EC) barriers, limiting target tissue uptake, safety and efficacy. Here we discover the ability of the EC caveolae pumping system to outpace scavenging and deliver NPs rapidly and specifically into the lungs. Gold and dendritic NPs are conjugated to antibodies targeting caveolae of the lung microvascular endothelium. SPECT-CT imaging and biodistribution analyses reveal that rat lungs extract most of the intravenous dose within minutes to achieve precision lung imaging and targeting with high lung concentrations exceeding peak blood levels. These results reveal how much ECs can both limit and promote tissue penetration of NPs and the power and size-dependent limitations of the caveolae pumping system. This study provides a new retargeting paradigm for NPs to avoid reticuloendothelial system uptake and achieve rapid precision nanodelivery for future diagnostic and therapeutic applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)