The treatment of cystic fibrosis (CF) remains challenging due to formidable biological barriers in the lungs, including thick mucus and resilient biofilms that severely limit the efficacy of conventional therapies. Nanotechnology, engineered to overcome these barriers, is emerging as a transformative approach for CF therapy. This opinion highlighted the most recent and advanced nanotechnologies, categorizing them into four strategic frontiers: (1) nanocarriers that achieve mucus penetration through surface modifications; (2) nanoplatforms for efficient delivery of genetic therapeutics; (3) nanocarriers for antimicrobial delivery to cure infections associated with CF; and (4) combinatorial nanomedicines for synchronized delivery of multiple drugs. We concluded that, with the help of these nanotechnologies, therapies for CF will now undergo a paradigm shift, moving CF from a fatal disease to a treatable and potentially curable one. Although the clinical transition is challenging, it holds immense promise for revolutionizing CF management.
Milk production in developing African countries is a viable path for smallholders’ sustainable development. Supporting interventions should be shaped by evidence from comprehensive, context-specific analyses. Using survey data, this study contributes to the development-oriented literature on dairy productivity in African smallholder systems by conducting the first stochastic frontier analysis in the Malagasy context. Focusing on milk producers in central Madagascar’s crop-livestock family farms, a stochastic frontier production function with inefficiency effects is developed. The fitted frontier comprises the number of cows, annual purchased feed expenditure, farmer’s labor, and total household assets owned. Distance from the frontier is explained by the use of improved breeds, integration in the regional milk zone, farmer years of experience, the presence of off-farm income, and the number of oxen owned. Technical efficiency ranged from 4.6% to 90.8% around a mean of 55.5%. Results revealed how, in this context, cows are embedded in diversified family farming systems where resources are allocated across production activities and household needs. The study’s multidisciplinary stochastic frontier analysis provides a more complete picture to guide research and policy for smallholders’ sustainable rural development.
Extracellular vesicles (EVs) are molecularly very heterogeneous, and their characterization at the single-particle level is technically challenging. Existing approaches, such as nanoparticle tracking analysis, fluorescence microscopy, and nano-flow cytometry, provide important insights but often lack the flexibility to detect multiple molecular markers simultaneously. Here, we describe an optimized workflow for multiparametric EV phenotyping using a spectral flow cytometry instrument with enhanced small particle detection capacity. EVs were isolated from murine melanoma and melanocyte cell lines via size-exclusion chromatography and labeled with a fluorogenic membrane probe that enables robust, single EV detection. In this study, we systematically optimized staining conditions, EV concentrations, and fluorophore combinations for a 5-color antibody panel on single EVs. We show that single-particle flow cytometry can reliably detect and resolve multiple EV surface markers simultaneously. Data analysis by unsupervised clustering further enabled unbiased identification of distinct EV subsets, providing a practical approach for EV phenotyping in both research and clinical contexts.
Oral squamous cell carcinoma (OSCC) is a malignant epithelial neoplasm characterized by high aggressiveness and limited options for early diagnosis. In recent years, extracellular vesicles (EVs) have gained attention as mediators of intercellular communication in cancer, contributing to tumor progression and remodeling of the microenvironment. O-GlcNAcylation, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), participates in multiple tumor processes; however, its association with EVs in OSCC has not yet been explored. In this study, EVs were isolated from SCC-152, SCC-25, and HaCaT cell lines using differential centrifugation, and their identity was confirmed by detection of CD63 and TSG101 markers and by transmission electron microscopy (TEM). Immunocytochemistry revealed the nuclear and cytoplasmic localization of OGT and OGA in all analyzed cell lines. Importantly, both enzymes were detected in EVs cargo by Western blot analysis, with significant differences between tumor and non-tumor lines as determined by densitometric and fluorescence intensity analyses. Quantitative analysis indicated a higher relative signal for OGA compared with OGT across all cell lines (with an approximate ~1.5–2.2-fold difference depending on the cell line, p < 0.05), and cell line-derived samples showed a higher relative signal than non-tumoral HaCaT (corresponding to an approximate ~1.2–1.3-fold increase under the experimental conditions evaluated). All experiments were performed using three independent biological replicates (n = 3), and statistical significance was assessed using one-way or two-way ANOVA followed by Tukey’s post hoc test. These findings suggest that OSCC-derived EVs carry enzymatic components of the O-GlcNAcylation machinery as vesicular protein cargo, potentially influencing tumor microenvironment regulation and cancer progression. Overall, these results should be considered hypothesis-generating, opening new perspectives for their use as vesicular biomarkers.
The high-mountain steppes of South-eastern Altai are a valuable resource for pastoralism—almost the only possible type of economic activity in these places—and the conservation of near threatened species, such as the argali. Argali are the largest and most vulnerable wild sheep (Ovis ammon ammon L.), and are listed in the Red Data Book of the Russian Federation and on the IUCN Red List. The argali is also important in the food chain of another rare and protected species, the snow leopard. This paper presents the results of research into the productivity of argali’s high-mountain steppes habitation in various parts of the Sailugem Ridge, and assesses their pasture degradation. We predict how observed declining pasture productivity due to anthropogenic and climate pressure, as well as argali grazing, will threaten their survival. We propose special measures to reduce the impact of the argali population on the degradation of current pastures, while improving argali conservation in other areas of South-eastern Altai and adjacent territories where the species previously existed.
