Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL-and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.
Motor imagery classification is an important topic in brain-computer interface (BCI) research that enables the recognition of a subject's intension to, e.g., implement prosthesis control. The brain dynamics of motor imagery are usually measured by electroencephalography (EEG) as nonstationary time series of low signal-to-noise ratio. Although a variety of methods have been previously developed to learn EEG signal features, the deep learning idea has rarely been explored to generate new representation of EEG features and achieve further performance improvement for motor imagery classification. In this study, a novel deep learning scheme based on restricted Boltzmann machine (RBM) is proposed. Specifically, frequency domain representations of EEG signals obtained via fast Fourier transform (FFT) and wavelet package decomposition (WPD) are obtained to train three RBMs. These RBMs are then stacked up with an extra output layer to form a four-layer neural network, which is named the frequential deep belief network (FDBN). The output layer employs the softmax regression to accomplish the classification task. Also, the conjugate gradient method and backpropagation are used to fine tune the FDBN. Extensive and systematic experiments have been performed on public benchmark datasets, and the results show that the performance improvement of FDBN over other selected state-of-the-art methods is statistically significant. Also, several findings that may be of significant interest to the BCI community are presented in this article.
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