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Summary: Ischemic stroke is the second leading cause of death and disability worldwide, and efforts to prevent stroke, mitigate secondary neurological damage, and promote neurological recovery remain paramount. Recent findings highlight the critical importance of microbiome-related metabolites, including vitamin B12 (VB12), in alleviating toxic stroke-associated neuroinflammation. Here, we showed that VB12 tonically programmed genes supporting microglial cell division and activation and critically controlled cellular fatty acid metabolism in homeostasis. Intriguingly, VB12 promoted mitochondrial transcriptional and metabolic activities and significantly restricted stroke-associated gene alterations in microglia. Furthermore, VB12 differentially altered the functions of microglial subsets during the acute phase of ischemic stroke, resulting in reduced brain damage and improved neurological function. Pharmacological depletion of microglia before ischemic stroke abolished VB12-mediated neurological improvement. Thus, our preclinical studies highlight the relevance of VB12 in the functional programming of microglia to alleviate neuroinflammation, minimize ischemic injury, and improve host neurological recovery after ischemic stroke.

Triboelectric nanogenerators (TENGs) have recently drawn much attention in the field of biomechanical energy harvesting and motion monitoring. However, the electrode stretchability and contact-separation model induced complicated packed structure remain a problem that heavily affects output performance during various human movements and requires to be urgently addressed. Here, a single-electrode piezo-triboelectric hybrid nanogenerator (SEP-TENG) integrated with stretchable liquid-metal metal electrodes is reported, which simultaneously achieves outstanding energy harvesting performance and skin-comfort human motion monitoring. A polarized piezoelectric BaTiO3/silicon rubber (SR) composites film is served as the effective negative tribomaterial, benefiting from the improved dielectric constant and piezoelectric charge transfer, the optimized SEP-TENG generates a high peak power density of 5.7 W/m2 while contacted with human skin. Besides, owing to the ultralow Young's modulus of the SR encapsulation layer and tribo-piezoelectric hybrid layer, the homogeneous integrated multilayer composite serves no break till a 745% elongation, promoting that the SEP-TENG could effectively harvest biomechanical energy and realize stable power supplying for wearable electronics even under large deformation state. Furthermore, the SEP-TENG could comfortably attach to the finger joints and collect bending energy. This work provides a novel design methodology for a single-electrode TENG to realize omnidirectional biomechanical energy harvesting and motion monitoring.

Summary: Ischemic stroke critically impacts neurovascular homeostasis, potentially resulting in neurological disorders. However, the mechanisms through which stroke-induced inflammation modifies the molecular and metabolic circuits, particularly in ileal epithelial cells (iECs), currently remain elusive. Using multiomic approaches, we illustrated that stroke impaired the ileal microbiome and associated metabolites, leading to increased inflammatory signals and altered metabolites, potentially deteriorating the iEC homeostasis. Bulk transcriptomic and metabolomic profiling demonstrated that stroke enhanced fatty acid oxidation while reducing the tricarboxylic acid (TCA) cycle in iECs within the first day after stroke. Intriguingly, single-cell RNA sequencing analysis revealed that stroke dysregulated cell-type-specific gene responses within iECs and reduced frequencies of goblet and tuft cells. Additionally, stroke augmented interleukin-17A+ γδ T cells but decreased CD4+ T cells in the ileum. Collectively, our findings provide a comprehensive overview of stroke-induced intestinal dysbiosis and unveil responsive gene programming within iECs with implications for disease development.

Adropin is a highly-conserved peptide that has been shown to preserve endothelial barrier function. Blood-brain barrier (BBB) disruption is a key pathological event in cerebral ischemia. However, the effects of adropin on ischemic stroke outcomes remain unexplored. Hypothesizing that adropin exerts neuroprotective effects by maintaining BBB integrity, we investigated the role of adropin in stroke pathology utilizing loss- and gain-of-function genetic approaches combined with pharmacological treatment with synthetic adropin peptide. Long-term anatomical and functional outcomes were evaluated using histology, MRI, and a battery of sensorimotor and cognitive tests in mice subjected to ischemic stroke. Brain ischemia decreased endogenous adropin levels in the brain and plasma. Adropin treatment or transgenic adropin overexpression robustly reduced brain injury and improved long-term sensorimotor and cognitive function in young and aged mice subjected to ischemic stroke. In contrast, genetic deletion of adropin exacerbated ischemic brain injury, irrespective of sex. Mechanistically, adropin treatment reduced BBB damage, degradation of tight junction proteins, matrix metalloproteinase-9 activity, oxidative stress, and infiltration of neutrophils into the ischemic brain. Adropin significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS), Akt, and ERK1/2. While adropin therapy was remarkably protective in wild-type mice, it failed to reduce brain injury in eNOS-deficient animals, suggesting that eNOS is required for the protective effects of adropin in stroke. These data provide the first causal evidence that adropin exerts neurovascular protection in stroke through an eNOS-dependent mechanism. We identify adropin as a novel neuroprotective peptide with the potential to improve stroke outcomes.

Triboelectric nanogenerator (TENG) and piezoelectric nanogenerator (PENG) present excellent performances in harvesting multivariant mechanical energy. However, the conductivity of electrode has become one of the important factors restricting the mechanical energy acquisition under the large deformation and multiple freedom degrees. In this work, a highly conductive stretchable electrode based piezoelectric-enhanced triboelectric nanogenerator (P-TENG) with outstanding performance is reported. Ultra-flexible silicone rubber based triboelectric part with surface modification and piezoelectric part with BaTiO3 dispersed possess excellent electrical and mechanical property, at the same time, the stretchable electrode based on liquid metal could maintain low resistance even under large deformation. The peak to peak open-circuit voltage (VOC) and short-circuit current (ISC) of P-TENG could reach 1.38 kV and 36.13 μA, respectively. The instantaneous power density can reach 1.1 mW/cm2 and the charge quantity in single capacitor charging circle is approximately 0.30 μC. It also has the surpassing force-electrical linearity that the output voltage positively correlating to stretching speeds and stretching rates. The resistance increments of electrode below 0.32 Ω under stretching rate more than 200% and the percentage of breaking elongation could reach 645%. In applying experiments, the P-TENG could directly light 16 LEDs and effectively identify the motion signals. This work provides a new thought for nanogenerator (NG) with high stretchability and applied to collect irregular mechanical energy.