RESUMEN
Activin A, a member of the transforming growth factor-ß superfamily, provides pleiotropic regulation of fibrosis and inflammation. We aimed at determining whether selective inhibition of activin A would provide a regenerative benefit. The introduction of activin A into normal muscle increased the expression of inflammatory and muscle atrophy genes Tnf, Tnfrsf12a, Trim63, and Fbxo32 by 3.5-, 10-, 2-, and 4-fold, respectively. The data indicate a sensitive response of muscle to activin A. Two hours after cardiotoxin-induced muscle damage, local activin A protein expression increased by threefold to ninefold. Neutralization of activin A with a specific monoclonal antibody in this muscle injury model decreased the muscle protein levels of lymphotoxin α and Il17a by 32% and 42%, respectively. Muscle histopathological features showed that activin A antibody-treated mice displayed an increase in muscle degradation, with the concomitant 9.2-fold elevation in F4/80-positive cells 3 days after injury. At the same time, the number of Pax7/Myod1-positive cells also increased, indicative of potentiated muscle precursor activation. Ultimately, activin A inhibition resulted in rapid recovery of muscle contractile properties indicated by a restoration of maximum and specific force. In summary, selective inhibition of activin A with a monoclonal antibody in muscle injury leads to the early onset of tissue degradation and subsequent enhanced myogenesis, thereby accelerating muscle repair and functional recovery.
Asunto(s)
Activinas/antagonistas & inhibidores , Contracción Muscular/fisiología , Músculo Esquelético/lesiones , Músculo Esquelético/metabolismo , Animales , Electroporación , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunohistoquímica , Ratones Endogámicos C57BL , Regeneración/fisiología , TranscriptomaRESUMEN
The development of hippocampal circuitry depends on the proper assembly of correctly specified and fully differentiated hippocampal neurons. Little is known about factors that control the hippocampal specification. Here, we show that zinc finger protein Zbtb20 is essential for the specification of hippocampal CA1 field identity. We found that Zbtb20 expression was initially activated in the hippocampal anlage at the onset of corticogenesis, and persisted in immature hippocampal neurons. Targeted deletion of Zbtb20 in mice did not compromise the progenitor proliferation in the hippocampal and adjacent transitional ventricular zone, but led to the transformation of the hippocampal CA1 field into a transitional neocortex-like structure, as evidenced by cytoarchitectural, neuronal migration, and gene expression phenotypes. Correspondingly, the subiculum was ectopically located adjacent to the CA3 in mutant. Although the field identities of the mutant CA3 and dentate gyrus (DG) were largely maintained, their projections were severely impaired. The hippocampus of Zbtb20 null mice was reduced in size, and exhibited increased apoptotic cell death during postnatal development. Our data establish an essential role of Zbtb20 in the specification of CA1 field identity by repressing adjacent transitional neocortex-specific fate determination.
Asunto(s)
Región CA1 Hipocampal/embriología , Región CA1 Hipocampal/metabolismo , Factores de Transcripción/metabolismo , Animales , Apoptosis , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/crecimiento & desarrollo , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Noqueados , Factores de Transcripción/deficiencia , Factores de Transcripción/genéticaRESUMEN
A series of O3-phase NaFe(x)(Ni0.5Mn0.5)(1-x)O2 (x = 0, 0.1, 0.2, 0.3, 0.4, and 1) samples with different Fe contents was prepared and investigated as high-capacity cathodic hosts of Na-ion batteries. The partial substitution of Ni and Mn with Fe in the O3-phase lattice can greatly improve the electrochemical performance and the structural stability. A NaFe0.2Mn0.4Ni0.4O2 cathode with an optimized Fe content of x = 0.2 can deliver an initial reversible capacity of 131 mAh g(-1), a reversible capacity greater than 95% over 30 cycles, and a high rate capacity of 86 mAh g(-1) at 10 C in a voltage range of 2.0-4.0 V. The structural characterizations reveal that pristine NaMn0.5Ni0.5O2 and Fe-substituted NaFe0.2Mn0.4Ni0.4O2 lattices underwent different phase transformations from P3 to P3â³ and from P3 to OP2 phases, respectively, at high voltage interval. The as-resulted OP2 phase by Fe substitution has smaller interslab distance (5.13 Å) than the P3â³ phase (5.72 Å), which suppresses the co-insertion of the solvent molecules, the electrolyte anions, or both and therefore enhances the cycling stability in the high voltage charge. This finding suggests a new strategy for creating cycle-stable transition-metal oxide cathodes for high-performance Na-ion batteries.
RESUMEN
Mg-doped Li[Li0.2-2xMgxCo0.13Ni0.13Mn0.54]O2 is synthesized by introducing Mg ions into the transition-metal (TM) layer of this layered compound for substituting Li ions through a simple polymer-pyrolysis method. The structural and morphological characterization reveals that the doped Mg ions are uniformly distributed in the bulk lattice, showing an insignificant impact on the layered structure. Electrochemical experiments reveal that, at a Mg doping of 4%, the Li[Li0.16Mg0.04Co0.13Ni0.13Mn0.54]O2 electrode can deliver a larger initial reversible capacity of 272 mAh g(-1), an improved rate capability with 114 mAh g(-1) at 8 C, and an excellent cycling stability with 93.3% capacity retention after 300 cycles. The superior electrochemical performances of the Mg-doped material are possibly due to the enhancement of the structural stability by substitution of Li by Mg in the TM layer, which effectively suppresses the cation mixing arrangement, leading to the alleviation of the phase change during lithium-ion insertion and extraction.