Larocque, A. | Search bioRxiv

bioRxiv2026

Mechanically-mediated low-pressure cell membrane poration enables tunable intracellular delivery of traditionally impermeable cargoes in high throughput and clinical scale formats

Traditional intracellular delivery methods suffer from cargo inefficiencies, non-linear delivery kinetics, and cellular trauma. We designed a mechanically-mediated poration platform governed by deterministic, passive diffusion operating at low pressure which enables dose-dependent, cargo-agnostic intracellular delivery and preserves cellular homeostasis; key advantages include high-fidelity multiplexing, transient cell engineering, and direct-to-biology live-cell target engagement enabling development of novel intracellular delivery applications across drug discovery and cell therapy. We demonstrate examples including live-cell DEL discovery and MOA studies, complex and rapid cell therapy manufacturing, and assay development in sensitive primary cell types.

cell biology↗

bioRxiv2026

Spatiotemporal differences in salmon nutrient inputs restructure functional and taxonomic fungal communities in riparian system

O_LISpawning salmon transport marine-derived nutrients (MDN) into riparian forests, influencing soil, plant, and animal communities, yet their effects on fungal communities remain poorly understood. C_LIO_LIWe used DNA metabarcoding to examine fungal responses to three spatial patterns of salmon-derived nitrogen (N) in southwest Alaska: (i) patchy inputs from wildlife-deposited carcasses, (ii) a 21-year carcass relocation experiment, and (iii) natural N gradients with distance from streams. C_LIO_LIDecomposing carcasses increased saprotrophic fungal diversity, identifying taxa responsible for salmon carcass decomposition. Long-term carcass relocation reduced diversity of medium-distance fringe ectomycorrhizal fungi (EMF), whereas recent, patchy carcass inputs increased diversity of both medium-distance fringe and long-distance EMF--guilds often associated with low-nutrient environments. Along natural stream N gradients, EMF responses varied markedly within functional guilds and genera, revealing unexpected variation in N sensitivity among closely related taxa. C_LIO_LIPulsed, spatially heterogeneous nutrient inputs enhanced diversity of typically nitrophobic EMF, likely reflecting their capacity to maintain extensive mycelial networks, exploit nutrient hotspots, and mobilize organic N and phosphorus. The diversity of responses along natural N gradients suggests that mechanisms linking EMF traits to nutrient acquisition and tolerance remain unresolved. Our findings emphasize the importance of linking fungal community composition with functional attributes and nutrient dynamics. C_LI

ecology↗

bioRxiv2026

Plasma β-hydroxybutyrate Concentrations in Young Adult Females After a High-Fat Meal Under Normoxemia, Intermittent Hypoxemia, and Continuous Hypoxemia

Hypoxemia occurs in intermittent forms, such as obstructive sleep apnea, and in continuous forms, such as at high altitude, and is increasingly recognized as a modulator of cardiometabolic risk. Although hypoxemia alters postprandial glucose and lipid metabolism, its effects on ketone bodies remain unclear. Using a randomized crossover design, we examined whether six hours of normoxemia or intermittent hypoxemia (15 hypoxemic cycles/hour targeting [~]85% peripheral oxyhemoglobin saturation with 100% medical-grade nitrogen) alters plasma {beta}-hydroxybutyrate (BHB) concentrations in 12 young adult females (mean [SD]: 21 [3] years) following a high-fat meal (33% of estimated daily energy requirements; 59% of calories from fat). In a follow-up session, a subset (n = 8) completed six hours of continuous hypoxemia (fraction of inspired oxygen [~]12.0% in a normobaric chamber). Postprandial data were analyzed using baseline-adjusted linear mixed-effects models, with Bonferroni post hoc tests. A time x condition interaction (P = 0.010) indicated that BHB concentrations at 360 minutes were higher during continuous hypoxemia (0.247 mmol/L; 95% CI: 0.218-0.275) than normoxemia (0.176 mmol/L; 95% CI: 0.153-0.200; PBonferroni = 0.029) and intermittent hypoxemia (0.163 mmol/L; 95% CI: 0.139-0.186; PBonferroni = 0.002), representing increases of 13.0% and 14.2% in estimated marginal means, respectively. This response was accompanied by higher postprandial plasma glucose and triglyceride concentrations during continuous hypoxemia than during normoxemia and intermittent hypoxemia (PBonferroni [≤] 0.002), despite similar plasma insulin and non-esterified fatty acid responses across conditions (P [≥] 0.081). These findings indicate that continuous hypoxemia increases late postprandial plasma BHB concentrations in young adult females. New FindingsO_ST_ABSWhat is the central question of this study?C_ST_ABSWhat are the effects of normoxemia, intermittent hypoxemia, and continuous hypoxemia on plasma {beta}-hydroxybutyrate (BHB) concentrations in young adult females after a high-fat meal? What is the main finding and its importance?Compared to normoxemia, young adult females showed higher postprandial plasma BHB concentrations during continuous hypoxemia, but not during intermittent hypoxemia, despite similar changes in plasma concentrations of two main regulators of BHB production (non-esterified fatty acids and insulin) across experimental conditions. These findings suggest that continuous hypoxemia modifies postprandial BHB concentrations through mechanisms not fully explained by circulating non-esterified fatty acids or insulin concentrations alone.

physiology↗