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BACKGROUND: Pyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection in several neurological diseases. Herein, we have investigated the role of NK1R receptor inhibition using Aprepitant to attenuate NLRC4-dependent neuronal pyroptosis after intracerebral hemorrhage (ICH), as well as the underlying mechanism. METHODS: A total of 182 CD-1 mice were used. ICH was induced by injection of autologous blood into the right basal ganglia. Aprepitant, a selective antagonist of NK1R, was injected intraperitoneally at 1 h after ICH. To explore the underlying mechanism, NK1R agonist, GR73632, and protein kinase C delta (PKCδ) agonist, phorbol 12-myristate 13-acetate (PMA), were injected intracerebroventricularly at 1 h after ICH induction, and small interfering ribonucleic acid (siRNA) for NLRC4 was administered via intracerebroventricular injection at 48 h before ICH induction, respectively. Neurobehavioral tests, western blot, and immunofluorescence staining were performed. RESULTS: The expression of endogenous NK1R and NLRC 4 were gradually increased after ICH. NK1R was expressed on neurons. Aprepitant significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased neuronal pyroptosis, as well as decreased expression of NLRC4, Cleaved-caspase-1, GSDMD (gasdermin D), IL-1ß, and IL-18. Activation of NK1R or PKCδ abolished these neuroprotective effects of Aprepitant after ICH. Similarly, knocking down NLRC4 using siRNA produced similar neuroprotective effects. CONCLUSION: Aprepitant suppressed NLRC4-dependent neuronal pyroptosis and improved neurological function, possibly mediated by inhibition of NK1R/PKCδ signaling pathways after ICH. The NK1R may be a promising therapeutic target for the treatment of ICH.
Assuntos
Fármacos Neuroprotetores , Piroptose , Animais , Aprepitanto/uso terapêutico , Hemorragia Cerebral/metabolismo , Modelos Animais de Doenças , Camundongos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , RNA Interferente Pequeno/uso terapêuticoRESUMO
Topological defects such as dislocations in crystalline materials usually have major impacts on materials' mechanical, chemical and physical properties. Detailed knowledge of dislocation core structures is essential to understand their impacts on materials' properties. However, compared with imaging of core structures of edge dislocations, direct imaging of a screw dislocation core is challenging from the traditional edge-on direction because the atomic displacements are parallel to the screw dislocation line. Here, a screw dislocation with a Burgers vector 1/2[110] in orthorhombic CsPbBr3 nanocrystals is directly imaged at the atomic scale with the incident electron beam perpendicular to the dislocation line using aberration-corrected scanning transmission electron microscopy (STEM). The dislocation core is characterized by helical atomic planes along the dislocation line. Quantitative assessments of the change rate of the screw displacements reveal the dislocation line locate at a plane containing Cs and Br atoms. This study reveals the atomic structure of screw dislocation cores in CsPbBr3 and provides useful information for the understanding of structure-property relations of halide perovskites.
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Growing high-quality core-shell heterostructure nanowires is still challenging due to the lattice mismatch issue at the radial interface. Herein, a versatile strategy is exploited for the lattice-mismatch-free construction of III-V/chalcogenide core-shell heterostructure nanowires by simply utilizing the surfactant and amorphous natures of chalcogenide semiconductors. Specifically, a variety of III-V/chalcogenide core-shell heterostructure nanowires are successfully constructed with controlled shell thicknesses, compositions, and smooth surfaces. Due to the conformal properties of obtained heterostructure nanowires, the wavelength-dependent bi-directional photoresponse and visible light-assisted infrared photodetection are realized in the type-I GaSb/GeS core-shell heterostructure nanowires. Also, the enhanced infrared photodetection is found in the type-II InGaAs/GeS core-shell heterostructure nanowires compared with the pristine InGaAs nanowires, in which both responsivity and detectivity are improved by more than 2 orders of magnitude. Evidently, this work paves the way for the lattice-mismatch-free construction of core-shell heterostructure nanowires by chemical vapor deposition for next-generation high-performance nanowire optoelectronics.
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Ultrastable CsPbBr3 nanoplates against electron beam irradiations are fabricated and nanodomains with anomalous high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) contrasts are observed within CsPbBr3 nanoplates. Atomic resolution energy dispersive X-ray spectroscopy (EDS) mapping, which requires even higher beam currents and may cause significant damages on electron beam sensitive materials, are obtained without any detectable damages or decomposition. Combining HAADF-STEM images, atomic resolution EDS mapping, and image simulations has revealed detailed structure and chemistry of the nanodomains to be induced by Ruddlesden-Popper faults (RP faults) rather than any chemical intermixing or formation of new phases. A formation mechanism is also proposed on the basis of the atomic structure of the nanodomains. This result promotes an atomic-level understanding of inorganic lead halide perovskites and may help to reveal their structure-property relationship.
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Grain boundaries (GBs) have a profound impact on mechanical, chemical, and physical properties of polycrystalline materials. Comprehension of atomic and electronic structures of different GBs in materials can help to understand their impact on materials' properties. Here, with aberration-corrected scanning transmission electron microscopy (STEM), the atomic structure of a 90° twist GB s in CsPbBr3 is determined, and its impact on electron-hole pair separation is predicted. The 90° twist GB has a coherent interface and the same chemical composition as the bulk except for the lattice twist. Density functional theory (DFT) calculation results indicate that the twist GB has an electronic structure similar to that of the bulk CsPbBr3. An electronic potential at the GBs enhances the separation of photogenerated carriers and promotes the motion of electrons across the GBs. These results extend the understanding of atomic and electronic structure of GBs in halide perovskites and propose a potential strategy to eliminate the influence of GBs by GB engineering.
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Background: Oxidative stress and neuronal apoptosis have important roles in the pathogenesis after intracerebral hemorrhage (ICH). Previous studies have reported that low-density lipoprotein receptor-related protein 6 (LRP6) exerts neuroprotection in several neurological diseases. Herein, we investigate the role of LRP6 receptor activation with HLY78 to attenuate oxidative stress and neuronal apoptosis after ICH, as well as the underlying mechanism. Methods: A total of 199 CD1 mice were used. ICH was induced via injection of autologous blood into the right basal ganglia. HLY78 was administered via intranasal injection at 1 h after ICH. To explore the underlying mechanism, LRP6 siRNA and selisistat, a Sirt1 selective antagonist, were injected intracerebroventricularly at 48 h before ICH induction. Neurobehavioral tests, Western blot, and immunofluorescence staining were performed. Results: The expression of endogenous p-LRP6 was gradually increased and expressed on neurons after ICH. HLY78 significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased oxidative stress and neuronal apoptosis, as well as increased expression of p-GSK3ß, Sirt1, and PGC-1α, as well as downregulation of Romo-1 and C-Caspase-3. LRP6 knockdown or Sirt1 inhibition abolished these effects of HLY78 after ICH. Conclusion: Our results suggest that administration of HLY78 attenuated oxidative stress, neuronal apoptosis, and neurobehavioral impairments through the LRP6/GSK3ß/Sirt1/PGC-1α signaling pathway after ICH.
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Hemorragia Cerebral , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Estresse Oxidativo , Sirtuína 1 , Animais , Apoptose , Benzodioxóis , Hemorragia Cerebral/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fenantridinas , Sirtuína 1/metabolismoRESUMO
Adjusting the microstructure through the deformation process is one of the ways to improve the properties of Mg alloys. Most studies have focused on the influence of the microstructure after deformation treatment on the mechanical properties of Mg alloys. In this paper, extruded and forged Mg-Gd-Y-Nd-Zr alloys were selected to investigate the corrosion performance of two deformed magnesium alloys immersed in 0.6 M NaCl solution using a hydrogen evolution test, a weight loss test, an immersion experiment, and an electrochemical test. The results showed that WE43 alloys undergoing different deformation treatments presented different microstructures, which led to different corrosion behaviors and corrosion resistance. The extruded WE43 alloy showed uniform corrosion, while the forged WE43 alloy suffered severe local galvanic corrosion. Meanwhile, the corrosion rate of the forged WE43 alloy was about four times faster than that of the extruded WE43 alloy.
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Source localization and functional brain network modeling are methods of identifying critical regions during cognitive tasks. The first activity estimates the relative differences of the signal amplitudes in regions of interest (ROI) and the second activity measures the statistical dependence among signal fluctuations. We hypothesized that the source amplitude-functional connectivity relationship decouples or reverses in persons having brain impairments. Five Broca's aphasics with five matched cognitively healthy controls underwent overt picture-naming magnetoencephalography scans. The gamma-band (30-45 Hz) phase-locking values were calculated as connections among the ROIs. We calculated the partial correlation coefficients between the amplitudes and network measures and detected four node types, including hothubs with high amplitude and high connectivity, coldhubs with high connectivity but lower amplitude, non-hub hotspots, and non-hub coldspots. The results indicate that the high-amplitude regions are not necessarily highly connected hubs. Furthermore, the Broca aphasics utilized different hothub sets for the naming task. Both groups had dark functional networks composed of coldhubs. Thus, source amplitude-functional connectivity relationships could help reveal functional reorganizations in patients. The amplitude-connectivity combination provides a new perspective for pathological studies of the brain's dark functional networks.