Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.spinal cord injury | NT3 | chitosan | functional recovery | endogenous neurogenesis
Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity, and reproducibility of ctDNA assays is poorly understood. Here we report the findings of a multi-site, cross-platform evaluation of the analytical performance of five industry-leading ctDNA assays. We evaluated each stage of the ctDNA sequencing workflow with simulations, synthetic DNA spike-in experiments, and proficiency testing on standardized cell line–derived reference samples. Above 0.5% variant allele frequency, ctDNA mutations were detected with high sensitivity, precision and reproducibility by all five assays, whereas below this limit detection became unreliable and varied widely between assays, especially when input material was limited. Missed mutations (false-negatives) were more common than erroneous candidates (false-positives), indicating that the reliable sampling of rare ctDNA fragments is the key challenge for ctDNA assays. This comprehensive evaluation of the analytical performance of ctDNA assays serves to inform best-practice guidelines and provides a resource for precision oncology.
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Understanding the fundamental insights of oxygen activation and reaction at metal−oxide interfaces is of significant importance yet remains a major challenge due to the difficulty in in situ characterization of active oxygen species. Herein, the activation and reaction of molecular oxygen during CO oxidation at platinum−ceria interfaces has been in situ explored using surface-enhanced Raman spectroscopy (SERS) via a borrowing strategy, and different active oxygen species and their evolution during CO oxidation at platinum− ceria interfaces have been directly observed. In situ Raman spectroscopic evidence with isotopic exchange experiments demonstrate that oxygen is efficiently dissociated to chemisorbed O on Pt and lattice Ce−O species simultaneously at interfacial Ce 3+ defect sites under CO oxidation, leading to a much higher activity at platinum−ceria interfaces compared to that at Pt alone. Further in situ time-resolved SERS studies and density functional theory simulations reveal a more efficient molecular pathway through the reaction between adsorbed CO and chemisorbed Pt−O species transferred from the interfaces. This work deepens the fundamental understandings on oxygen activation and CO oxidation at metal−oxide interfaces and offers a sensitive technique for the in situ characterization of oxygen species under working conditions.
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