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Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.
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Arabidopsis , Brasinoesteroides , Regulación de la Expresión Génica de las Plantas , Malus , Proteínas de Plantas , Tolerancia a la Sal , Malus/genética , Malus/metabolismo , Malus/efectos de los fármacos , Brasinoesteroides/metabolismo , Brasinoesteroides/biosíntesis , Brasinoesteroides/farmacología , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Tolerancia a la Sal/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Estrés Salino/genética , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismoRESUMEN
Abscisic acid (ABA), as a plant hormone, plays a positive role in leaf chlorosis; however, the underlying molecular mechanism is less known. Our findings provide ABA treatment reduced the chlorophyll accumulation in apple, and Malus × domestica Sucrose Non-fermenting 1-Related Protein Kinase 1.1 (MdSnRK1.1) participates in the process. MdSnRK1.1 interacts with MdGLK1, a GOLDEN2-like transcription factor that orchestrates development of the chloroplast. Furthermore, MdSnRK1.1 affects MdGLK1 protein stability through phosphorylation. We found that Ser468 of MdGLK1 is target site of MdSnRK1.1 phosphorylation. MdSnRK1.1-mediated phosphorylation was critical for MdGLK1 binding to the target gene MdHEMA1 promoters. Collectively, our results demonstrate that ABA activates MdSnRK1.1 to degrade MdGLK1 and inhibit the accumulation of chlorophyll. These findings extend our understanding on how MdSnRK1.1 balances normal growth and hormone response.
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Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2]diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC50 values of 1.7-48.5 µM. Most importantly, compound 1 decreased the viability of AGS cells in a concentration-dependent manner with an IC50 value of 1.7 µM. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway.
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Antineoplásicos , Aspergillus , Algas Comestibles , Rhodophyta , Humanos , Estructura Molecular , Aspergillus/química , Hongos/química , Alcaloides Indólicos , Antineoplásicos/farmacologíaRESUMEN
The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.
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Proteínas de Arabidopsis , Arabidopsis , Malus , Malus/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Filogenia , Sequías , Proteínas de Arabidopsis/metabolismoRESUMEN
Nitrogen (N) is an essential element that plays an important role in crop biomass accumulation and quality formation. Increased crop yield is relied on excessive application of fertilizers, which usually leads to environmental pollution and unsustainable development. Thus, identification and characterization of genes involved in promoting nitrogen use efficiency is of high priority in crop breeding. The activity of nitrate reductase (NR) plays a critical role in nitrogen metabolism. In model plant Arabidopsis, NITRATE REDUCTASE 2 (NIA2), one of the two NRs, is responsible for about 90% of the NR activity. In this study, MdNIA2 gene in apple (Malus domestica) genome was screened out and identified by using AtNIA2 as bait. Phylogenetic analysis revealed that MdNIA2 had the closest evolutionary relationship with MbNIA from Malus baccata. Ectopic expression of MdNIA2 in Arabidopsis elevated the nitrogen use efficiency and increased root hair elongation and formation, resulting in promoted plant growth. Furthermore, the overexpression of MdNIA2 improved salt and drought tolerance in transgenic Arabidopsis and improved the salt tolerance of transgenic apple callus, and MdNIA2-reagualted NO metabolism might contribute to the abiotic stress tolerance. Overall, our data indicate the critical role of MdNIA2 in regulating nitrogen utilization efficiency and abiotic stress responses.
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Arabidopsis , Malus , Arabidopsis/metabolismo , Malus/metabolismo , Nitrato-Reductasa/genética , Nitrato-Reductasa/metabolismo , Nitratos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Fitomejoramiento , Estrés Fisiológico/genética , Nitrógeno/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
With the development of artificial intelligence and Internet of Things, hand gesture recognition techniques have attracted great attention owing to their excellent applications in developing human-machine interaction (HMI). Here, the authors propose a non-contact hand gesture recognition method based on intelligent metasurface. Owing to the advantage of dynamically controlling the electromagnetic (EM) focusing in the wavefront engineering, a transmissive programmable metasurface is presented to illuminate the forearm with more focusing spots and obtain comprehensive echo data, which can be processed under the machine learning technology to reach the non-contact gesture recognition with high accuracy. Compared with the traditional passive antennas, unique variations of echo coefficients resulted from near fields perturbed by finger and wrist agonist muscles can be aquired through the programmable metasurface by switching the positions of EM focusing. The authors realize the gesture recognition using support vector machine algorithm based on five individual focusing spots data and all-five-spot data. The influences of the focusing spots on the gesture recognition are analyzed through linear discriminant analysis algorithm and Fisher score. Experimental verifications prove that the proposed metasurface-based non-contact wireless design can realize the classification of hand gesture recognition with higher accuracy than traditional passive antennas, and give an HMI solution.
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Inteligencia Artificial , Miembros Artificiales , Algoritmos , Fenómenos Electromagnéticos , Gestos , HumanosRESUMEN
Low-dimensional organic-inorganic hybrid metal halide materials have been extensively studied due to their excellent optoelectronic performances. Herein, by using the facile wet-chemistry method, we designed one new hybrid cadmium bromide of (H3AEP)2CdBr6·2Br based on discrete octahedral [CdBr6]4- units. Remarkably, the bulk crystal of (H3AEP)2CdBr6·2Br exhibits strong broadband orange-red light emission from the radiative recombination of self-trapped excitons (STEs) with a high photoluminescence quantum yield (PLQY) of 9%. Benefiting from the highly efficient luminescent performance, this 0D cadmium perovskite can be utilized as an excellent down-conversion red phosphor to assemble a white light-emitting diode, and a high color rendering index (CRI) of 93 is realized. As far as we know, this is the first orange-red light-emitting hybrid cadmium perovskite which promotes the full-color display in this system.
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Phenolic bisabolane-type sesquiterpenoids (PBS) represent a rare class of natural products with diverse biological activities. In this study, chemical investigations of the fungus Aspergillus flavipes 297 resulted in the isolation and identification of seven PBS, including a pair of new enantiomers (+)-1a and (-)-1b, a new derivative 2, and five previously reported ones 3-7. The chemical structures of the isolated PBS were determined by extensive NMR and HRESIMS spectroscopic analysis. The absolute configurations of the separated enantiomers (+)-1a and (-)-1b were solved by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra. The new compounds 1 and 2 represent rare cases of PBS bearing a methylsulfinyl group, which was distinct from the commonly-observed PBS structurally. All the isolated compounds 1-7 were evaluated their antimicrobial and cytotoxic activities. As a result, the tested compounds showed selective antimicrobial activity against several pathogenic bacteria and fungi with the MIC (minimum inhibiting concentrations) values ranging from 2 to 64 µg/mL. Moreover, enantiomers (+)-1a and (-)-1b, together with compound 2, exhibited promising cytotoxicity against MKN-45 and HepG2 cell lines, respectively, indicating that the methylsulfinyl substituent enhanced cytotoxicity to a certain degree.
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Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Aspergillus/química , Sesquiterpenos Monocíclicos/farmacología , Fenoles/farmacología , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Línea Celular Tumoral , China , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Sesquiterpenos Monocíclicos/aislamiento & purificación , Fenoles/aislamiento & purificación , Agua de Mar/microbiologíaRESUMEN
The landfill with low economic cost and technical barrier has become a popular option for municipal solid waste treatment, but it is likely to seriously pollute groundwater by solute leaching. In this study, the pollutants concentration model, leakage rate model, and the solute transport model were coupled to investigate the effect of municipal solid waste landfill on groundwater quality. Major results obtained are, (1) the leakage rate of leachate differs significantly among the landfilling stage, covering stage and completely covered stage as the leachate depth varies with the infiltration rainfall. The contact condition between HDPE and CCL was found to be a key factor in determining the leakage rate of leachate. Ensuring good connection between HPDE and CCL is thus critical in protecting groundwater from being polluted by landfill. (2) The NH3-N as a proxy for organic pollutants was generated via the degradation process, and Cl- as a proxy for inorganic pollutants is a leachable fraction of mobilized substances. The concentration of Cl- is higher than that of NH3-N before 7600 days, then the concentration of NH3-N becomes roughly stable while that of Cl- continues to decrease. (3) The load of NH3-N as a proxy for organic pollutants declines linearly downwards before the completely covering stage. The load of Cl- as a proxy for inorganic pollutants increased during the first five years, and then declined. (4) In the case study, the path of maximum pollutants concentration is perpendicular to the groundwater contour, and the maximum pollutants concentration has two peaks, occurring on 7106 days and 11,554 days, respectively. The change laws of maximum pollutants concentration are similar for different connections between HPDE and CCL.
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Agua Subterránea , Eliminación de Residuos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Residuos Sólidos/análisis , Instalaciones de Eliminación de Residuos , Contaminantes Químicos del Agua/análisisRESUMEN
The degree of early brain injury (EBI) is a significant factor that affects the prognosis of patients with subarachnoid hemorrhage (SAH). Evidence has shown that fibroblast growth factor-2 (FGF-2) may alleviate the serious consequences of EBI after SAH. The objective of the current study was to investigate the underlying mechanism that mediates the neuroprotective effects of FGF-2 in the SAH rat model. Sprague-Dawley (SD) rats that underwent different treatments were divided into various groups. FGF-2 was administered intranasally to rats in the treatment group within 30 min after modeling. Rapamycin (an autophagy activator) or LY294002 (a PI3K/Akt pathway inhibitor) was administered intracerebroventricularly (i.c.v.) 30 min before modeling. Neurological scale and brain water content were measured in the brain tissue of the rats. TUNEL staining, Western blot, and immunofluorescence staining were performed to examine and compare the diverse effects of FGF-2 treatment, activated autophagy, and inhibited the PI3K/Akt pathway. We found that FGF-2 treatment effectively reduced the number of TUNEL-positive cells, decreased the brain water content, and improved the neurological function of rats after SAH. Additionally, the expression levels of autophagy-related proteins (LC3 and Beclin-1) were obviously decreased in the FGF-2 treatment group compared with the SAH + vehicle group. The therapeutic effects of FGF-2 in the SAH + FGF-2+rapamycin group were weakened compared with that in the SAH + FGF-2+DMSO group. In the event of the PI3K/Akt pathway inhibition, the expression levels of LC3 and Beclin-1 were enhanced, and the therapeutic effects of FGF-2 were compromised. In summary, our data collectively demonstrated that FGF-2 may suppress autophagy levels to play a neuroprotective role, at least partially by activating the PI3K/Akt pathway. These results highlight FGF-2 as a promising solution to the clinical intervention of SAH.
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Autofagia/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Transducción de Señal/efectos de los fármacos , Hemorragia Subaracnoidea/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Masculino , Neuronas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Traumatic brain injury (TBI) is a common injury caused by external forces that lead to damaged brain function or pathological changes in the brain tissue. To explore the molecular mechanism and the hub genes of TBI, we downloaded gene expression profiles of the TBI model of rat and the sham control for the subsequent gene set enrichment analysis, pathway analysis and protein-protein interactions analysis. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that multiple biological pathways, including immune response, inflammatory response and cellular response to interleukin-1, as well as signaling pathways, such as tumor necrosis factor signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and nuclear factor kappa B signaling pathway were implicated in the TBI. In conclusion, this study provides insights into the molecular mechanism of TBI by screening the differentially expressed genes and hub genes that can be used as biomarkers and therapeutic targets.
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Lesiones Traumáticas del Encéfalo/genética , Regulación de la Expresión Génica/genética , Interleucina-1/genética , Factor de Necrosis Tumoral alfa/genética , Animales , Biomarcadores , Lesiones Traumáticas del Encéfalo/patología , Biología Computacional , Modelos Animales de Enfermedad , Redes Reguladoras de Genes/genética , Humanos , Mapas de Interacción de Proteínas/genética , Ratas , Transducción de Señal/genética , Receptores Toll-Like/genéticaRESUMEN
Recently, low-dimensional organic-inorganic hybrid metal halide perovskites acting as single-component white-light emitting materials have attracted extensive attention, but most studies concentrate on hybrid lead perovskites. Herein, we present two isomorphic zero-dimensional (0D) hybrid cadmium perovskites, (HMEDA)CdX4 (HMEDA=hexamethylenediamine, X=Cl (1), Br (2)), which contain isolated [CdX4 ]2- anions separated by [HMEDA]2+ cations. Under UV light excitation, both compounds display broadband bluish white-light emission (515â nm for 1 and 445â nm for 2) covering the entire visible light spectrum with sufficient photophysical stabilities. Remarkably, compound 2 shows a high color rendering index (CRI) of 83 enabling it as a promising candidate for single-component WLED applications. Based on the temperature-dependent, powder-dependent and time-resolved PL measurements as well as other detailed studies, the broadband light emissions are attributed to self-trapped excitons stemming from the strong electron-phonon coupling.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.
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Osteoporosis is a skeleton disease affecting 55% of people over age 60, and the number is still increasing due to an ageing population. One method to prevent osteoporosis is to increase the formation of new bone while preventing the resorption of older bone. Thus, osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of osteoporosis. On the other hand, glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders, but long-term exposure to GCs can induce osteoporosis. In present study, we treated BMSCs with dexamethasone (DEX) to simulate GC-induced osteoporosis. MTT assay, ALP activity, and Alizarin Red were used to evaluate the role miRNA-291a-3p in the DEX-induced osteogenic differentiation suppression. Further, we used qPCR and western blot to investigate the mechanisms of miRNA-291a-3p affecting BMSCs differentiation. The results showed that miRNA-291a-3p could improve the cell viability, osteogenic differentiation, and ALP activity, which are suppressed by DEX in BMSCs. Furthermore, we found that the osteogenesis genes Runx2, DMP1, and ALP were upregulated whereas the lipogenic genes C/EBPα and PPARγ were downregulated when miRNA-291a-3p mimics were transfected. Additionally, we demonstrated that miRNA-291a-3p promoted BMSCs' osteogenic differentiation by directly suppressing DKK1 mRNA and protein expression and subsequently activating Wnt/ß-catenin signaling pathway. Our study suggests that miR-291a-3p plays an important role in preventing osteoporosis and may serve as a potential miRNA osteoporosis biomarker.
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Dexametasona/toxicidad , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , MicroARNs/metabolismo , Osteoporosis/inducido químicamente , Osteoporosis/metabolismo , Animales , Western Blotting , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , MicroARNs/genética , Osteogénesis/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Based on analysis of hydrogen and oxygen isotopes in 113 rainfall samples collected from September 2016 to October 2017 in Chengdu, which is a typical representative of humid areas affected by multiple moisture sources, the compositional characteristics of hydrogen and oxygen isotopes (2H, 18O, and 17O) and the water vapor sources of precipitation were analyzed. It was found that δD, δ18O, δ17O, d-excess, and 17O-excess in atmospheric event-based precipitation have significant seasonal variation. In the dry season they are high and in the wet season are low, reflecting the different moisture sources during two seasons (dry and wet). The slope and intercept of the Local Meteoric Water Line were small, indicating that the precipitation originated from sources with various stable isotope ratios and that raindrops were subject to secondary evaporation during their landing process. The Local Meteoric Water Line slope for the triple oxygen isotopes (δ'17O=0.5289δ'18O+0.0075) ranged between the slopes for seawater vapor and dry air, and the value of 17O-excess was far larger than that of seawater. This indicates that the Chengdu area lies in the path of marine air masses moving toward inland regions. The atmospheric precipitation mainly came from these marine air masses and the isotope had undergone serious enrichment in the process of reaching the area. The d values were close to the global average, and the extremely low value of d-excess in the dry season may be affected by artificial rainfall operations. In addition to the relative humidity of the water vapor source, 17O-excess is also affected by the upstream air mass convection; moreover, the 17O-excess of the precipitation was not affected by the meteorological factors over the whole study period, so the 17O-excess could be considered tracers of evaporative conditions at the vapor source in Chengdu. The precipitation 17O-excess in different seasons provides additional information to better understand the precipitation formation processes in Chengdu.
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Inflammation has been implicated in the pathogenesis of type 2 diabetes (T2D), which is a progressive disease characterized by pancreatic ßcell dysfunction and apoptosis with consequential insufficient insulin secretion. Autophagy is necessary to maintain the structure, mass and function of pancreatic ßcells. The present study investigated the crosstalk between autophagy and inflammasome activation in T2D. INS1 cells were stimulated with lipopolysaccharide. Apoptosis and reactive oxygen species (ROS) formation were measured using flow cytometry, and cell proliferation was measured using Cell Counting Kit8 solution. Autophagy was assayed using western blotting and transmission electron microscopy. The expression levels of interleukin1ß (IL1ß) and caspase1 were detected by western blotting. The results demonstrated that inhibiting autophagy using 3methyladenine (3MA) promoted INS1 cell apoptosis. This response was correlated with an increase in ROS production and the inflammatory response, including IL1ß maturation and caspase1 activation. Furthermore, when ROS were inhibited using NacetylLcysteine, inflammation was decreased. These results demonstrated that inhibition of autophagy enhanced inflammatory injury via the ROSmediated activation of the Nodlike receptor pyrin domaincontaining protein 3 inflammasome. Autophagy may have a protective effect by mitigating inflammation in T2D, which may provide a novel approach for T2D treatment.
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Autofagia/efectos de los fármacos , Lipopolisacáridos/farmacología , Acetilcisteína/farmacología , Adenina/análogos & derivados , Adenina/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 1/metabolismo , Línea Celular , Inflamasomas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR). In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs. The relationship between O-GlcNAcylation and STAT3 was further delineated by immunoprecipitation and Western blot analysis. Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot. RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions. In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose. While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes. Immunoprecipitation revealed that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously. Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway. CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
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Retinopatía Diabética/patología , Factor de Transcripción STAT3/metabolismo , Animales , Caspasa 3/metabolismo , Bovinos , Hipoxia de la Célula , Células Cultivadas , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Glucosa/farmacología , Glicosilación/efectos de los fármacos , Humanos , Janus Quinasa 2/metabolismo , N-Acetilglucosaminiltransferasas/antagonistas & inhibidores , N-Acetilglucosaminiltransferasas/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Retina/citología , Retina/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Triterpenos/farmacologíaRESUMEN
BACKGROUND: Bone cement leakage in patients with vertebral fracture limits the use of percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Finding a method to reduce bone cement leakage is clinically rather important. OBJECTIVE: To compare the efficacy and safety of bone-filling mesh containers (BFMCS) and simple percutaneous balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures. STUDY DESIGN: A randomized controlled clinical study discussing the effect of 3 methods in the treatment of vertebral fractures. METHODS: From October 2014 to August 2015, 80 patients with single osteoporotic vertebral compression fractures were admitted in our hospital, including 31 men and 49 women with an average age of 76.2 years (range, 63-82 years). Patients were divided into a percutaneous balloon kyphoplasty group (Group A) and a PVP with dilated balloon placement group (Group B), with 40 cases in each group. The visual analog scale (VAS), Oswestry disability index (ODI), height of the vertebral body and Cobb's angle of the injured vertebrae were observed before operation and at 1 day, 1 month, and 6 months after the operation. Bone cement leakage and postoperative complications were also observed. RESULTS: Operations were successfully completed in all 80 patients without pulmonary embolism and without spinal cord or nerve root injury. The operation time was (32.6 ± 6.1) minutes in Group A and (31.8 ± 5.8) minutes in Group B. Operation time did not significantly differ between the 2 groups (P > 0.05). Both groups differed significantly when comparing the results with those measured before treatment. In Group A, the ODIs before operation and at 1 day, 1 month, and 6 months after the operation were 84.125 ± 8.821, 29.300 ± 8.951, 16.175 ± 6.748, and 11.400 ± 6.164, respectively, and those in Group B were 84.300 ± 8.768, 29.200 ± 9.121, 15.975 ± 6.811, and 11.575 ± 6.460, respectively. Cobb's angle values in Group A before and after treatment were (19.225 ± 5.881)° and (13.900 ± 3.720)°, respectively, and those in Group B were (19.275 ± 6.210)° and (14.225 ± 4.016)°, respectively. CONCLUSION: Both bone-filling mesh bag and simple percutaneous balloon kyphoplasty for treating osteoporotic vertebral compression fractures can relieve pain effectively and correct the Cobb angle. The bone-filling mesh container can effectively prevent bone cement leakage and reduce the incidence of bone cement leakage. LIMITATIONS: The study has limitations due to the small number of cases and short period of follow-up time. Further studies are needed to determine whether the mesh bag can limit the distribution of bone cement within the vertebral body. KEY WORDS: Bone-filling mesh container, kyphoplasty, osteoporosis, vertebral compression fracture.
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Cementos para Huesos/uso terapéutico , Extravasación de Materiales Terapéuticos y Diagnósticos/prevención & control , Fracturas por Compresión/cirugía , Cifoplastia/métodos , Fracturas Osteoporóticas/cirugía , Fracturas de la Columna Vertebral/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
Highly efficient electrocatalysts for hydrogen evolution reactions (HER) are crucial for electrochemical water splitting, where high-cost and low-abundance Pt-based materials are the benchmark catalysts for HER. Herein, we report the fabrication of MoP nanoparticles confined in P-doped porous carbon (MoP@PC) via a metal-organic framework-assisted route for the first time. Remarkably, due to the synergistic effects of MoP nanocrystals, P dopant, and porous carbon, the resulting MoP@PC composite exhibits superior HER catalytic activity with an onset overpotential of 97 mV, a Tafel slope of 59.3 mV dec-1, and good long-term durability, which compares to those of most reported MoP-based HER catalysts. Most importantly, the work opens a new route in the development of high-performance nonprecious HER electrocatalysts derived from MOFs.