Vagus nerve stimulation has shown promising neuroprotective and anti-inflammatory effects in progressive neurodegenerative disorders such as Parkinson’s disease. However, its invasive nature introduces procedural and device-related risks. Here we introduce a magnetoelectric particulate system for oral delivery and non-invasive vagus nerve stimulation through the gut. The system comprises a magneto-responsive nickel ferrite core and a piezoelectric barium titanate shell, conjugated with capsaicin to specifically target TRPV1 receptors, ensuring effective adherence to the stomach lining after oral administration. Upon magnetic field stimulation, the particles generate electrical pulses that activate vagal afferent fibres, engaging the nucleus tractus solitarius in the brainstem via the gut−brain axis. This activation enhances norepinephrine production in the locus coeruleus and dopamine synthesis in the substantia nigra. Vagal efferent activation triggers the cholinergic anti-inflammatory pathway, mitigating both neuroinflammation and systemic inflammation. This non-invasive approach demonstrates potential for alleviating motor symptoms and non-motor anxiety in Parkinson’s disease, offering valuable insights into its mechanisms and clinical applications. Orally delivered magnetoelectric particles activate vagal afferent fibres in the gut−brain axis and influence neurodegeneration and neuroinflammation in mouse models of Parkinson’s disease.
There is an urgent global need for affordable, large-scale health screening to enhance preventive care in the ageing population. Using low-cost, non-invasive retinal photographs and leveraging large foundation models, we developed a deep learning-based biomarker, Retinal Mortality Equivalent (RetiME), that directly mapped retinal features to individual mortality risk. Trained on a European cohort and externally validated across three independent external cohorts spanning Southeast Asia, Eurasia and North America, RetiME showed robust associations with all-cause and cause-specific mortality and predicted the incidence of a wide range of systemic and ocular diseases. Crucially, beyond static risk estimation, RetiME re-timed mortality risk by reconstructing personalized lifespan trajectories that were associated with observed mortality outcomes (for example, age of death). Clustering of these trajectories revealed distinct mortality patterns, spanning cancer-predominant, cardiometabolic and neurodegenerative risks, reflecting diverse ageing pathways captured by RetiME. Interpretability analyses showed that RetiME captures diverse biological and retinal features underlying mortality risk. Genome-wide analyses further identified genetic loci associated with RetiME. Collectively, these findings support further evaluation of retinal imaging and trajectory modelling as one component of a comprehensive assessment of mortality risk. RetiME is a deep learning-based biomarker that maps retinal features to individual mortality risks and can reconstruct personalized lifespan trajectories associated with observed mortality outcomes with distinct disease-related mortality patterns.
Gastrointestinal fistulas (GFs) represent one of the main causes of morbidity and mortality. While endoscopic techniques provide a minimally invasive approach to GF repair, offering advantages over conventional surgical approaches, the integration of endoscopic delivery with hydrogel sealants in user-friendly and easy processes approaches remains a great challenge. Here we develop a thermoresponsive positively charged poly(N-isopropylacrylamide) (PNIPAM)/Ga3+ (PGaIII) hydrogel sealant, formed by slug-inspired biomimetic self-assembly. The PGaIII integrated injectability and single-step-formed Janus-type adhesion to tissues, simultaneously featuring excellent biocompatibility, water/acid resistance, active shrinkage and antibacterial properties, enabling its effective ready-to-use biological sealant for endoscopic repair of GFs and prevention of postoperative adhesions. To validate the efficacy of PGaIII in treating GFs, we demonstrate its effectiveness in repairing GFs and its convenience in non-invasive endoscopic surgery in living Sprague–Dawley rat and Bama miniature pig models. The proposed PGaIII holds potential for the repair of fistulas in other organs in vivo, thereby promoting the establishment of safer and more effective clinical treatment options for related diseases. A thermoresponsive hydrogel sealant, prepared in a user-friendly and single-step process, and featuring Janus-type adhesion, is injected endoscopically and repairs gastrointestinal fistulas in rat and minipig models.
After spinal cord injury, clinical management aims to support tissue perfusion, but current methods rely on the indirect control of arterial blood pressure without direct measurement of the local blood flow. This limits the ability to tailor drug delivery to the injured tissue. Here, we show that spinal cord blood flow can be regulated using a closed-loop controller that adjusts vasopressor infusion on the basis of real-time ultrasound flow measurement. We characterize the dynamic relationship between drug infusion, arterial pressure and spinal cord blood flow, and we use these data to design a feedback controller that targets a predefined flow level. We validate the system in simulations, implement the controller in real time in rodents and translate it to pigs. We show that the controller reduced blood flow deviations and variability compared with constant dosing and supported functional recovery in a rodent survival model. These results show a closed-loop spinal cord perfusion control strategy that leverages clinically available measurements and pharmacological interventions, supporting its translation to clinical settings for the management of acute spinal cord injury. A closed-loop control strategy regulates spinal cord blood flow by adjusting norepinephrine infusion using real-time flow measurements, enabling direct flow targeting after acute injury.
