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A simple and efficient top-down strategy, the chemical vapor etching method, is reported for synthesizing corrugated ZnO nano/micro rods (NRs). The stabilization mechanism of this unique nanostructure has been determined through a combination of aberration-corrected field emission scanning electron microscopy, high-resolution transmission electron microscopy, and first-principles calculations. The experimental data are in good agreement with the theoretical calculations, and a remarkable nonpolar-to-polar surface faceting transition is demonstrated. The corrugated-shaped structure results from the remarkable stability of the defect-induced reconstructions (O vacancy, Zn-Zn dimer), which makes the high-index polar {303[combining macron]1} and {101[combining macron]1[combining macron]} planes lower in energy compared to the nonpolar {101[combining macron]0} plane. Based on the results of first-principles surface calculations, a general formula is established to provide an accurate description of the unusual size effect of the length of the corrugated unit vs. the NR diameter, and it also offers direct explanations for certain experimental observations. The present study deepens our atomic-level understanding of the detailed structure and stability of polar surface decorated corrugated ZnO NRs, and points to a viable path towards designing polar-stable wurtzite structures.
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Multiple studies have confirmed that acid sphingomyelinase (ASM) activity is associated with depression. The discovery of direct inhibitors against ASM is of great significance for exploring antidepressants and their mechanisms of action. Herein, a series of novel phenylpyrazole analogues were rationally designed and synthesized. Among them, compound 46 exhibited potent inhibitory activity (IC50 = 0.87 µM) and good drug-like properties. In vivo studies demonstrated that compound 46 was involved in multiple antidepressant mechanisms of action, which were associated with a decline of ceramide, including increasing the Bcl-2/Bax ratio and BDNF expression, down-regulating caspase-3 and caspase-9, ameliorating oxidative stress, reducing the levels of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6, and elevating 5-HT levels in the brains of mice, respectively. These meaningful results reveal for the first time that direct inhibitors exhibit remarkable antidepressant effects in the CUMS-induced mouse model through multiple mechanisms of antidepressant action.
Asunto(s)
Antidepresivos , Pirazoles , Esfingomielina Fosfodiesterasa , Animales , Antidepresivos/farmacología , Antidepresivos/química , Antidepresivos/síntesis química , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Ratones , Esfingomielina Fosfodiesterasa/antagonistas & inhibidores , Esfingomielina Fosfodiesterasa/metabolismo , Relación Estructura-Actividad , Masculino , Depresión/tratamiento farmacológico , Depresión/metabolismo , Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Acid sphingomyelinase (ASM), which regulates sphingolipid metabolism and lipid signaling, has been considered as a new potential target for the treatment of atherosclerosis. In this study, a series of benzene-heterocyclic-based ASM inhibitors were rationally designed, synthesized, and screened for the first time. As a result, some compounds showed favorable inhibitory activity against recombinant human ASM. The detailed SARs are also discussed. Compound 4i revealed good pharmacokinetic data and in vivo inhibitory activity against ASM by reducing the level of ceramide in mice plasma and liver. Pharmacodynamic studies confirmed that 4i could lessen lipid plaques in the aortic arch and aorta and reduce plasma ceramide concentration and Ox-LDL levels. Moreover, 4i was found to significantly decrease LPS-induced and Ox-LDL-induced cell inflammation by regulating the levels of ceramide and sphingomyelin. Overall, this study preliminarily demonstrates that ASM may be an effective target against atherosclerosis for the first time.
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Aterosclerosis , Esfingomielina Fosfodiesterasa , Ratones , Humanos , Animales , Ceramidas , Aorta , Aorta TorácicaRESUMEN
Micropipe, a "killer" defect in SiC crystals, severely hampers the outstanding performance of SiC-based devices. In this paper, the etching behavior of micropipes in 4H-SiC and 6H-SiC wafers was studied using the molten KOH etching method. The spectra of 4H-SiC and 6H-SiC crystals containing micropipes were examined using Raman scattering. A new Raman peak accompanying micropipes located near -784 cm-1 was observed, which may have been induced by polymorphic transformation during the etching process in the area of micropipe etch pits. This feature may provide a new way to distinguish micropipes from other defects. In addition, the preferable etching conditions for distinguishing micropipes from threading screw dislocations (TSDs) was determined using laser confocal microscopy, scanning electron microscopy (SEM) and optical microscopy. Meanwhile, the micropipe etching pits were classified into two types based on their morphology and formation mechanism.
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We report herein high-resolution X-ray diffraction measurements of basal plane bending of homoepitaxial single-crystal diamond (SCD). We define SCD (100) as the base plane. The results revealed that growth parameters such as temperature, growth time, and basal plane bending of the substrate all affect the basal plane bending of SCD. First, the basal plane bending of SCD depends mainly on the substrate and becomes severe with increasing basal plane bending of the substrate. The SCD growth experiments show that the basal plane bending increases with elevated growth temperature and increased growth time. Finally, to understand the mechanism, we investigated the substrate-surface temperature distribution as a function of basal plane bending of SCD fabricated by chemical vapor deposition (CVD). This allowed us to propose a model and understand the origin of basal plane bending. The results indicate that an uneven temperature distribution on the substrate surface is the main cause of the base-plane bending of CVD diamond.
RESUMEN
Recent studies on sphingolipids suggest that acid sphingomyelinase (ASM), which plays a central role in the pathogenesis of major depression, is emerging to be a novel target for developing antidepressants. Herein we first described the design, synthesis, and biological evaluation of hydroxamic acid-based direct inhibitors of ASM with the effort of validating their antidepressant effects in vivo. As a result, a series of novel ASM inhibitors were developed using a structure-based approach. Our studies demonstrated that the administration of 21b improved depression-like behaviors of rats. Importantly, this positive result was relevant to the inhibition of ASM and the increasing neurogenesis in hippocampus. To the best of our knowledge, this is the first time that direct inhibitors of ASM were developed to support the possibility of ASM as a potential therapeutic target for depression.
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Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Esfingomielina Fosfodiesterasa/antagonistas & inhibidores , Animales , Antidepresivos/síntesis química , Antidepresivos/metabolismo , Línea Celular Tumoral , Corteza Cerebral/metabolismo , Depresión/inducido químicamente , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/metabolismo , Femenino , Hipocampo/metabolismo , Humanos , Ácidos Hidroxámicos/síntesis química , Ácidos Hidroxámicos/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Neurogénesis/efectos de los fármacos , Unión Proteica , Ratas Sprague-Dawley , Reserpina , Esfingomielina Fosfodiesterasa/metabolismo , Relación Estructura-ActividadRESUMEN
Nucleus pulposus (NP) cell apoptosis is a classical cellular character during intervertebral disc degeneration (IDD). Previous studies have shown that inflammatory cytokine-induced NP cell apoptosis plays an important role in disc degeneration. The present study was aimed to investigate whether resveratrol can suppress IL-1ß-mediated NP cell apoptosis and the potential signal transduction pathway. Experimental rat NP cells were treated with culture medium containing IL-1ß (20 ng/ml) for 7 days. Control NP cells were cultured in the baseline medium. Resveratrol was added along with culture medium to investigate its effects. The inhibitor LY294002 was used to study the role of the PI3K/Akt pathway. NP cell apoptosis was reflected by the caspase-3 activity, cell apoptosis ratio, and expression of apoptosis-related molecules (Bcl-2, Bax, caspase-3, cleaved caspase-3, and cleaved PARP). Compared with the control NP cells, IL-1ß significantly increased caspase-3 activity, NP cell apoptosis ratio and mRNA/protein expression of Bax, caspase-3, cleaved caspase-3 and cleaved PARP, but decreased mRNA expression of Bcl-2. However, resveratrol partly suppressed the effects of IL-1ß on those cell apoptosis-related parameters. Further analysis showed that IL-1ß significantly decreased activity of the PI3K/Akt pathway whereas resveratrol partly increased activity of the PI3K/Akt pathway in NP cells treated with IL-1ß. Additionally, when the inhibitor LY294002 was added along with the resveratrol, its protective effects against IL-1ß-induced NP cell apoptosis were attenuated. In conclusion, resveratrol suppresses IL-1ß-mediated NP cell apoptosis through activating the PI3K/Akt pathway. Resveratrol may be an effective drug to attenuate inflammatory cytokine-induced disc degenerative changes.
Asunto(s)
Apoptosis/efectos de los fármacos , Interleucina-1beta/farmacología , Núcleo Pulposo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Resveratrol/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antioxidantes/farmacología , Apoptosis/genética , Caspasa 3/genética , Caspasa 3/metabolismo , Células Cultivadas , Femenino , Masculino , Núcleo Pulposo/citología , Núcleo Pulposo/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas Sprague-DawleyRESUMEN
Using the hybrid exchange-correlation functional within the density-functional theory, we have systematically investigated the structural and electronic properties of MO (M = Be, Mg, Ca, Sr, Ba, Zn, Cd) in binary rock salt (B1), zinc-blende (B3) and wurtzite (B4) phases, including the structural parameters, bulk moduli, band gaps and deformation potentials. Our results agree well with the experimental data and other theoretical results, and give a better understanding of the relationship between the geometric and electronic structure. After calculating the band alignment, we find that in both the B1 and B3 structures, the valence band maximum (VBM) has an obvious decrease from BeO to MgO to CaO, then it goes up from SrO to BaO to ZnO to CdO. Moreover, the properties of the ternary alloys M x Zn1-x O were studied through the application of the special quasi-random structure method. The critical value of the ZnO composition for the transition from the B3 structure to the B1 structure gradually increases from (Ca, Zn)O to (Mg, Zn)O to (Sr, Zn)O to (Ba, Zn)O to (Cd, Zn)O, indicating that (Ca, Zn)O can exist in the B3 structure with the lowest ZnO composition. These results provide a good guideline for the accessible phase space in these alloy systems.
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Dislocations are always observed during crystal growth, and it is usually desirable to reduce the dislocation density in high-quality crystals. Here, the annihilation process of the 30° Shockley partial dislocation pairs in CdTe is studied by first-principles calculations. We found that the dislocations can glide relatively easily due to the weak local bonding. Our systematic study of the slipping mechanism of the dislocations suggests that the energy barrier for the annihilation process is low. Band structure calculations reveal that the band bending caused by the charge transfer between the two dislocation cores depends on the core-core distance. A simple linear model is proposed to describe the mechanism of formation of the dislocation pair. More importantly, we demonstrate that hole injection can affect the core structure, increase the mobility, and eventually trigger a spontaneous mutual annihilation, which could be employed as a possible facile way to reduce the dislocation density.
RESUMEN
Eu(2+) singly and Eu(2+), Mn(2+) co-doped Sr(2)Mg(3)P(4)O(15) exhibit not only the well known blue emission band of Eu(2+) peaking at 448 nm but also a new band at 399 nm in violet. They are attributed to Eu(2+) on different Sr(2+) sites. The Eu(2+) for the violet band can transfer energy to the red emitting Mn(2+) more efficiently than Eu(2+) for the blue band. The new Eu(2+) band could enable Sr(2)Mg(3)P(4)O(15):Mn(2+), Eu(2+) to be a promising phosphor for enriching the red component of white LEDs.