Potential Application of Modified mRNA in Cardiac Regeneration.

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

Combined Phloretin and Human Platelet-rich Plasma Effectively Preserved Integrities of Brain Structure and Neurological Function in Rat after Traumatic Brain Damage.

BACKGROUND: This study tested whether phloretin (a brain-edema inhibitors) would augment therapeutic impact of human-derived platelet-rich plasma (hPRP) on attenuating brain-hemorrhagic volume (BHV) and preserving the neurologic function in rodent following acute traumatic brain damage (TBD). METHODS: Rats (n=40) were separated into group-1 (sham-control), group-2 (TBD), group-3 [TBD + phloretin (80mg/kg/dose by intra-peritoneal administration at 30min and days 2/3 followed-by TBD), group-4 (TBD + PRP/80µL by left intra-carotid-artery injection at 3h after TBD) and group-5 (TBD + phloretin + hPRP) and cerebral tissues were harvested by day 28 after TBD. RESULTS: The brain MRI at day 28 revealed that the BHV was lowest in group 1, highest in group 2 and significantly lower in group 5 than in groups 3/4, but it was similar between groups 3/4, whereas neurological function displayed a opposite pattern of BHV among the groups (all p<0.0001). By 72h, the protein levels of upstream (HGMB1/TLR-2/TLR-4/MyD88/Mal/TRAM/ TRIF/TRAF6/IKK-α/IKK-ß/p-NF-κB) and downstream (IL-1ß/TNF-α/iNOS) inflammation signalings, apoptosis (caspase3/PARP) and fibrosis (Smad3/TGF-ß) biomarkers and flow cytometric assessment of inflammation cells (CD11b/c+//Ly6G+/PMO+) and early (AN-V+/PI-)/late (AN-V+/PI+) mononuclear-cell apoptosis displayed a similar manner of BHV among the groups (all p<0.0001). Cell number of inflammatory (CD68+/MMP9+) and brain-swelling/myelin-damaged (AQP4+/ GFAP+) mediators revealed a similar way, whereas the neuronal-myelin (Doublecortin+/NeuN/nestin) mediators exhibited an inverse manner of BHV among the groups (all p<0.0001). CONCLUSION: Combination of phloretin and hPRP regimen was better than just one treatment to offer synergic benefits for protecting the brain against TBD.

Embedded Hybrid-Dimensional Heterointerface for Filament Modulation in 2D Material-Based Artificial Nociceptor.

Nociceptors are key sensory receptors that transmit warning signals to the central nervous system in response to painful stimuli. This fundamental process is emulated in an electronic device by developing a novel artificial nociceptor with an ultrathin, nonstoichiometric gallium oxide (GaOx)-silicon oxide heterostructure. A large-area 2D-GaOx film is printed on a substrate through liquid metal printing to facilitate the production of conductive filaments. This nociceptive structure exhibits a unique short-term temporal response following stimulation, enabling a facile demonstration of threshold-switching physics. The developed heterointerface 2D-GaOx film enables the fabrication of fast-switching, low-energy, and compliance-free 2D-GaOx nociceptors, as confirmed through experiments. The accumulation and extrusion of Ag in the oxide matrix are significant for inducing plastic changes in artificial biological sensors. High-resolution transmission electron microscopy and electron energy loss spectroscopy demonstrate that Ag clusters in the material dispersed under electrical bias and regrouped spontaneously when the bias is removed owing to interfacial energy minimization. Moreover, 2D nociceptors are stable; thus, heterointerface engineering can enable effective control of charge transfer in 2D heterostructural devices. Furthermore, the diffusive 2D-GaOx device and its Ag dynamics enable the direct emulation of biological nociceptors, marking an advancement in the hardware implementation of artificial human sensory systems.

Bimetallic nanoalloys planted on super-hydrophilic carbon nanocages featuring tip-intensified hydrogen evolution electrocatalysis.

The insufficient availability and activity of interfacial water remain a major challenge for alkaline hydrogen evolution reaction (HER). Here, we propose an "on-site disruption and near-site compensation" strategy to reform the interfacial water hydrogen bonding network via deliberate cation penetration and catalyst support engineering. This concept is validated using tip-like bimetallic RuNi nanoalloys planted on super-hydrophilic and high-curvature carbon nanocages (RuNi/NC). Theoretical simulations suggest that tip-induced localized concentration of hydrated K+ facilitates optimization of interfacial water dynamics and intermediate adsorption. In situ synchrotron X-ray spectroscopy endorses an H* spillover-bridged Volmer‒Tafel mechanism synergistically relayed between Ru and Ni. Consequently, RuNi/NC exhibits low overpotential of 12 mV and high durability of 1600 h at 10 mA cm‒2 for alkaline HER, and demonstrates high performance in both water electrolysis and chlor-alkali electrolysis. This strategy offers a microscopic perspective on catalyst design for manipulation of the local interfacial water structure toward enhanced HER kinetics.