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These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Magnetic brain stimulation has greatly contributed to the advancement of neuroscience.With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease.
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However, challenges remain in the power of penetration and precision of magnetic stimulation, especially in small animals. Here, a novel combined magnetic stimulation system (c-MSS) was established for brain stimulation in mice. The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide (SPIO) nanodrugs to elevate local cortical susceptibility. After imaging of the SPIO nanoparticles in the left prelimbic (PrL) cortex in mice, we determined their safety and physical characteristics. Depressive-like behavior was established in mice using a chronic unpredictable mild stress (CUMS) model. SPIO nanodrugs were then delivered precisely to the left PrL cortex using in situ injection. A 0.1 T magnetic field (adjustable frequency) was used for magnetic stimulation (5 min/session, two sessions daily). Biomarkers representing therapeutic effects were measured before and after c-MSS intervention. Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d, combined with increased brain-derived neurotrophic factor (BDNF) and inactivation of hypothalamic-pituitary-adrenal (HPA) axis function, which enhanced neuronal activity due to SPIO nanoparticle-mediated effects. The c-MSS was safe and effective, representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals, playing a bioelectric role in neural circuit regulation, including antidepressant effects in CUMS mice.
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#Authors contributed equally to this work This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application. Treatment of CUMS mice and confirmation of effects of c-MSS through behavioral experimentsĪ : Experimental procedures for selection of optimal field frequency and duration of treatment. before CUMS modelling (control mice) (paired Student’s t-test). D : Monitoring of body weight of mice compared with age-matched control mice. E, F : SPT and FST results in CUMS mice after c-MSS treatment using different frequencies of magnetic field.
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G, H : SPT and FST results in CUMS mice after treatment with a 10 Hz c-MSS for a variety of durations.