Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.
Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.
Nuclear family structures are often thought to be essential for the well-being of children. Divorce, the loss of either biological parent, the presence of step-parents, and the practice of polygynous marriage have all been claimed to negatively impact child well-being. However, empirical research on these topics has been limited by the routine use of cross-regional and cross-sectional databases.
View Article and Find Full Text PDFOxide superlattices reveal a rich array of emergent properties derived from the composition modulation and the resulting lattice distortion, charge transfer, and symmetry reduction that occur at the interfaces between the layers. The great majority of studies have focused on perovskite oxide superlattices, revealing, for example, the appearance of an interfacial 2D electron gas, magnetic moment, or improper ferroelectric polarization that is not present in the parent phases. Garnets possess greater structural complexity than perovskites: the cubic garnet unit cell contains 160 atoms with the cations distributed between three different coordination sites, and garnets exhibit a wide range of useful properties, including ferrimagnetism and ion transport.
View Article and Find Full Text PDFBackground: To demonstrate the safety and performance of the Arrow EZ-IO Intraosseous Vascular Access System, particularly in the pediatric patient population, a retrospective observational study was conducted in 2021 and 2022.
Methods: Following study design, IRB approval, and investigator selection, data were collected for all patients needing intraosseous access-adult and pediatric. The primary endpoint was the success rate for achieving intraosseous access; the secondary endpoint was the rate of adverse events.