Esmailie, F. | bioRxiv Science

bioRxiv2026

Physiological limits of localized hypothermia in the human cochlea: The role of vascular heat transport

PurposeMild therapeutic hypothermia (MTH) preserves cochlear function in animal models and is now entering early-phase human trials for hearing preservation. However, the extent to which the human cochlea can actually be cooled, and the mechanisms underlying MTH, remain unclear, in part because blood perfusion is expected to oppose localized cooling. In this study we evaluated the impact of blood flow on human cochlear temperature exposed to the MTH device using a combined experimental and computational approach. MethodsTemperature measurements were obtained from a human cadaver skull exposed to a commercial MTH device. These data were used to validate a three-dimensional bioheat transfer model incorporating realistic skull anatomy. The validated model was subsequently extended to include physiological blood perfusion in the internal carotid artery; a major heat source located near the cochlea. Finally, the in silico model was further expanded to incorporate the surrounding skin and brain tissues. ResultsIncorporating blood flow in internal carotid artery substantially altered predicted cochlear temperature distributions, highlighting the importance of localized vascular heat transport in the human cochlea during MTH. Although cochlear cooling was attenuated in the presence of perfusion, the therapeutic effects of MTH may not depend solely on the magnitude of local intracochlear temperature reduction. Additional mechanisms, such as reduced facial surface temperature, may also contribute to its efficacy. ConclusionThe validated in silico model provides a physiologically realistic framework for evaluating human cochlear thermal responses, investigating MTH mechanisms, and optimizing temperature-based strategies for hearing preservation.

bioengineering↗

bioRxiv2026

Engineered probiotics that sequester arsensite in a mouse gastrointestinal system

Chronic exposure to inorganic arsenic remains a major global health concern, as arsenite is frequently present in contaminated food and drinking water and readily absorbed through the gastrointestinal (GI) tract. Once internalized, arsenite accumulates in tissues and contributes to long-term health effects, including cancer, organ dysfunction, and neurological disorders. Despite extensive efforts to reduce environmental contamination, there are currently no practical strategies to prevent dietary arsenite from entering the human body during digestion. Here, we report a synthetic biology-based approach that uses engineered probiotics to detect and sequester arsenite directly within the GI tract before systemic absorption occurs. We engineered Escherichia coli Nissle 1917 (EcN), a probiotic strain, to function as a living arsenite-interception system. Central to this design is an arsenite-responsive genetic toggle switch that activates chelator expression upon exposure and sustains production under biostatic conditions, while automatically shutting off during active cell division to limit metabolic burden and enhance biosafety. In parallel, we engineered an arsenite-binding protein derived from the transcriptional regulator ArsR to eliminate DNA-binding activity while retaining high-affinity metal binding, yielding a non-toxic chelator suitable for intracellular sequestration. The resulting engineered strain efficiently removed arsenite from its surrounding environment in vitro while maintaining robust cell viability and growth. To translate these findings to an in vivo context, we developed a mass-transfer model describing arsenite distribution among the stomach lumen, engineered bacteria, and epithelial cells. This model guided the selection of a bacterial dose predicted to substantially deplete lumenal arsenite prior to epithelial uptake. Using this strategy, we demonstrated in a mouse GI model that oral administration of engineered EcN markedly reduced arsenite entry into the bloodstream compared with wild-type EcN or no-bacteria controls. Together, these results establish a programmable probiotic platform for intercepting dietary arsenite and highlight a potential strategy for preventing absorption of environmental toxicants using living microbial therapeutics.

synthetic biology↗