Cancer is a devastating disease that takes the lives of hundreds of thousands of people every year. Due to disease heterogeneity, standard treatments, such as chemotherapy or radiation, are effective in only a subset of the patient population. Tumors can have different underlying genetic causes and may express different proteins in one patient versus another. This inherent variability of cancer lends itself to the growing field of precision and personalized medicine (PPM). There are many ongoing efforts to acquire PPM data in order to characterize molecular differences between tumors. Some PPM products are already available to link these differences to an effective drug. It is clear that PPM cancer treatments can result in immense patient benefits, and companies and regulatory agencies have begun to recognize this. However, broader changes to the healthcare and insurance systems must be addressed if PPM is to become part of standard cancer care.
Stem cell transplantation, as a promising treatment for central nervous system (CNS) diseases, has been hampered by crucial issues such as a low cell survival rate, incomplete differentiation, and limited neurite outgrowth in vivo. Addressing these hurdles, scientists have designed bioscaffolds that mimic the natural tissue microenvironment to deliver physical and soluble cues. However, several significant obstacles including burst release of drugs, insufficient cellular adhesion support, and slow scaffold degradation rate remain to be overcome before the full potential of bioscaffold–based stem-cell therapies can be realized. To this end, we developed a biodegradable nanoscaffold-based method for enhanced stem cell transplantation, differentiation, and drug delivery. These findings collectively support the therapeutic potential of our biodegradable hybrid inorganic (BHI) nanoscaffolds for advanced stem cell transplantation and neural tissue engineering.
Promoting residential cells, particularly endogenous neural stem and progenitor cells (NSPCs), for tissue regeneration represents a potential strategy for the treatment of spinal cord injury (SCI). However, adult NSPCs differentiate mainly into glial cells and contribute to glial scar formation at the site of injury. Gsx1 is known to regulate the generation of excitatory and inhibitory interneurons during embryonic development of the spinal cord. In this study, we show that lentivirus-mediated expression of Gsx1 increases the number of NSPCs in a mouse model of lateral hemisection SCI during the acute stage. Subsequently, Gsx1 expression increases the generation of glutamatergic and cholinergic interneurons and decreases the generation of GABAergic interneurons in the chronic stage of SCI. Importantly, Gsx1 reduces reactive astrogliosis and glial scar formation, promotes serotonin (5-HT) neuronal activity, and improves the locomotor function of the injured mice. Moreover, RNA sequencing (RNA-seq) analysis reveals that Gsx1induced transcriptome regulation correlates with NSPC signaling, NSPC activation, neuronal differentiation, and inhibition of astrogliosis and scar formation. Collectively, our study provides molecular insights for Gsx1-mediated functional recovery and identifies the potential of Gsx1 gene therapy for injuries in the spinal cord and possibly other parts of the central nervous system.
An important determinant of the quality factor Q of a quartz resonator is the loss of energy from the electrode area to the base via the mountings. The acoustical characteristics of the plate resonator are changed when the plate is mounted onto a base substrate. The base substrate affects the frequency spectra of the plate resonator.A resonator with a high Q may not have a similarly high Q when mounted on a base. Hence, the base is an energy sink and the Q will be affected by the shape and size of this base. A lower bound Q will be obtained if the base is a semi-infinite base since it will absorb all acoustical energies radiated from the resonator. A scaled boundary finite element method is employed to model a semi-infinite base. The frequency spectra of the quartz resonator with and without the base are presented. In addition to the loss of energy via the base, there are other factors which affect the resonator Q, such as, for example, material dissipation, and damping at the interfaces of quartz and electrodes. The energy dissipation due to material damping increases with the resonant frequency and the reduction of resonator size; hence material damping becomes important in the current and future miniaturized resonators operating at very high frequencies. An energy sink model along with material dissipation would provide realistic Q, motional capacitance, motional resistance, and other figures of merit useful for designing resonators. The model could be used for evaluating resonator and mountings designs of microelectromechanical systems and miniaturized devices. The effect of the mountings, and plate and electrode geometries on the resonator Q and other electrical parameters are presented for AT-cut quartz resonators. Model results from the energy sink method were compared with experimental results and were found to be good.
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