RESUMO
BACKGROUND: In previous observational studies, food-derived antioxidant vitamins have been suggested to be associated with breast cancer. However, the findings were inconsistent and the causal relationship could not be clearly elucidated. To confirm the potential causal relationship between food-derived antioxidants (retinol, carotene, vitamin C and vitamin E) and the risk of breast cancer, we conducted a two-sample Mendelian randomization (MR) study. METHODS: The instrumental variables (IVs) as proxies of genetic liability to food-derived antioxidant vitamins were obtained from the UK Biobank Database. We extracted breast cancer data (122,977 cases and 105,974 controls) from the Breast Cancer Consortium (BCAC). In addition, we studied estrogen expression status categorically, including estrogen receptor positive (ER+) breast cancer (69,501 cases and 105,974 controls) and versus estrogen receptor (ER-) negative breast cancer (21,468 cases and 105,974 controls). We performed two-sample Mendelian randomization study, and inverse variance-weighted (IVW) test was regarded as main analysis. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy. RESULTS: The results of IVW showed that among the four food-derived antioxidants, only vitamin E had protective effect on the risk of overall breast cancer (OR = 0.837, 95% CI 0.757-0.926, P = 0.001) and ER+ breast cancer (OR = 0.823, 95% CI 0.693-0.977, P = 0.026). However, we found no association between food-derived vitamin E and ER- breast cancer. CONCLUSIONS: Our study suggested food-derived vitamin E can decrease the risk of breast cancer overall and ER+ breast cancer, and the robustness of our results was confirmed by sensitivity analyses.
Assuntos
Antioxidantes , Neoplasias da Mama , Feminino , Humanos , Aditivos Alimentares , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/genética , Vitamina A , Vitamina E , Vitamina K , VitaminasRESUMO
A superior semiconductor material with efficient charge separation and easy reuse could be a promising route for efficient photocatalytic hydrogen evolution and pollutant degradation. AgVO3 is one of the best visible light active materials which has attracted much attention for several biological and environmental applications. In the aim of enhancing its stability and recyclability a novel AgVO3/rGO/CuFe2O4 heterojunction was prepared by hydrothermal method for hydrogen generation (H2) and 4-nitrophenol (4-NP) degradation as well. The composite was well characterized by XRD, SEM, HR-TEM, XPS and VSM. The morphological images suggested the rod shaped AgVO3 and irregular shaped CuFe2O4 are unevenly distributed on reduced graphene oxide (rGO) layers. The hydrogen evolution results indicated that the composite showed around 8.937 mmol g-1h-1 of H2 generation which was â¼2.3 times and â¼9.2 times higher than pure AgVO3 (3.895 mmol g-1h-1) and CuFe2O4 (0.96 mmol g-1h-1) respectively. The 4-NP degradation efficiency of the prepared composite was observed as 94.7% (k = 0.01841 min-1) which is much higher than the AgVO3 (66.3%) and CuFe2O4 (38.2%) after 4 h of irradiation. The higher efficiency could be attributed to the heterojunction formation and faster charge separation. The radical trapping results indicated that the â¢OH, O2â¢- and photogenerated h+ are the main species responsible for efficient activity. The AgVO3/rGO/CuFe2O4 heterojunction showed 49.6 emu/g of saturation magnetization and confirms that it could be easily separated with an external magnet, and showed 85.3% of degradation efficiency even after 6 recycles which indicated its higher stability and recyclability. Thus, our study provides new insight into hydrogen generation and phenol degradation using AgVO3 based recyclable composites.
Assuntos
Grafite , Hidrogênio , Luz , CatáliseRESUMO
Exploration of highly efficient and robust catalyst is pivotal for electrocatalytic degradation of dye wastewater, but it still is a challenge. Here, we develop a three-dimensional self-supported SnO2-Mn2O3 hybrid nanosheets grown on carbon cloth (noted by SnO2-Mn2O3@CC) electrode via a simple hydrothermal method and annealing treatment. Benefitting from the interlaced nanosheets architecture that enlarges the surface area and the synergetic component effect that accelerates the interfacial electronic transfer, SnO2-Mn2O3@CC electrode exhibits a superior electrocatalytic degradation efficiency for cationic blue X-GRRL dye in comparison with the single metal oxide electrode containing SnO2@CC and Mn2O3@CC. The degradation efficiency of cationic blue X-GRRL on SnO2-Mn2O3@CC electrode can reach up to 97.55% within 50 min. Furthermore, self-supported architecture of nanosheets on carbon cloth framework contributes to a robust stability compared with the traditional electrode via the multiple dip/brush coating accompanied by the thermal decomposition method. SnO2-Mn2O3@CC electrode exhibits excellent recyclability, which can still retain a degradation efficiency of 94.12% after six cycles. This work may provide a new pathway for the design and exploration of highly efficient and robust electrooxidation catalysts for dye degradation.
RESUMO
The proliferation, migration and apoptotic resistance of pulmonary artery smooth muscle cells (PASMCs) are central to the progression of pulmonary arterial hypertension (PAH). Our previous study identified that fibroblast growth factor 21 (FGF21) regulates signalling pathway molecules, such as peroxisome proliferator-activated receptor gamma (PPARγ), to play an important role in PAH treatment. However, the biological roles of miRNAs in these effects are not yet clear. In this study, using miRNA sequencing and real-time PCR, we found that FGF21 treatment inhibited miR-130 elevation in hypoxia-induced PAH in vitro and in vivo. Dual luciferase reporter gene assays showed that miR-130 directly negatively regulates PPARγ expression. Inhibition of miR-130 expression suppressed abnormal proliferation, migration and apoptotic resistance in hypoxic PASMCs, and this effect was corrected upon PPARγ knockdown. Both the ameliorative effect of FGF21 on pulmonary vascular remodelling and the inhibitory effect on proliferation, migration and apoptotic resistance in PASMCs were observed following exogenous administration of miR-130 agomir. In conclusion, this study revealed the protective effect and mechanism of FGF21 on PAH through regulation of the miR-130/PPARγ axis, providing new ideas for the development of potential drugs for PAH based on FGF21.
Assuntos
MicroRNAs , Hipertensão Arterial Pulmonar , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo/genética , Fatores de Crescimento de Fibroblastos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos de Músculo Liso/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Artéria Pulmonar/metabolismoRESUMO
Long non-coding RNAs (lncRNAs) play a significant role in pulmonary hypertension (PH). Our preliminary data showed that hypoxia-induced PH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the regulatory role of long non-coding RNAs in PH treated with FGF21. RNA sequencing analysis and real-time PCR identified a significantly up-regulation of the H19 after FGF21 administration. Moreover, gain- and loss-of-function assays demonstrated that FGF21 suppressed hypoxia-induced proliferation of pulmonary artery smooth muscle cells partially through upregulation of H19. In addition, FGF21 deficiency markedly exacerbated hypoxia-induced increases of pulmonary artery pressure and pulmonary vascular remodelling. In addition, AAV-mediated H19 overexpression reversed the malignant phenotype of FGF21 knockout mice under hypoxia expose. Further investigation uncovered that H19 also acted as an orchestra conductor that inhibited the function of mechanistic target of rapamycin complex 1 (mTORC1) by disrupting the interaction of mTORC1 with eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1). Our work highlights the important role of H19 in PH treated with FGF21 and suggests a mechanism involving mTORC1/EIF4EBP1 inhibition, which may provide a fundamental for clinical application of FGF21 in PH.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ciclo Celular , Fatores de Crescimento de Fibroblastos , Hipertensão Pulmonar , Alvo Mecanístico do Complexo 1 de Rapamicina , RNA Longo não Codificante , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Fatores de Crescimento de Fibroblastos/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , RNA Longo não Codificante/metabolismoRESUMO
Haze pollution has drawn lots of public concern due to its potential damages to human health. Strategic interaction of environmental regulation among local governments may lead to a race to the bottom and hinder air quality improvement. Still, current empirical evidence is scarce, especially from developing countries. Based on province-level panel data from 2004 to 2015, the paper employs a dynamic fixed effect spatial Durbin model to identify interactive patterns of environmental regulation and then investigate its environmental impact. Empirical results indicate that regional differences are observed in environmental regulation and haze pollution, and high-high and low-low clusters dominate the spatial pattern. Interactive patterns of economically similar provinces are dominated by strategic substitution, whereas provinces sharing common borders or belonging to the same region are dominated by strategic complementation. Further, both race to the bottom and race to the top effect are discovered in the asymmetric test. The reaction coefficient values are much more extensive when competitors implement laxer policies, indicating a more significant racing trend to the bottom. Overall, after controlling for the spillover effect and hysteresis effect of haze pollution, the strategic interaction of environmental regulation among provinces is not conducive to improve air quality. The consequence might be correlated with low environmental standards, weak regulation enforcement, and the "free-ride" motive in China. These findings will be of great significance for optimizing local government behavior and improving air quality.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Poluição Ambiental , HumanosRESUMO
Cymbidium geringii has high ornamental and economic importance. Its traits, including flower shape, size, and color, are highly sought by orchid breeders. Gaining insights into the molecular basis of C. geringi flower development would accelerate genetic improvement of other orchids. Methods and Results: Here, C. goeringii RNA was purified from normal and peloric mutant flowers, and cDNA libraries constructed for Illumina sequencing. We generated 329,156,782 clean reads, integrated them, and then assembled into 236,811 unigenes averaging 595 bp long. A total of 11,992 differentially expressed genes s, of which 6119 were upregulated and 5873 downregulated, were uncovered in peloric mutant flower buds relative to normal flower buds. Kyoto Encyclopedia of Genes and Genomes enrichment assessments posited that these differentially expressed genes are associated with "Photosynthesis", "Linoleic acid metabolism", as well as "Plant hormone signal transduction" cascades. The DEGs were designated to 12 remarkably enriched GO terms, and 16 cell wall associated GO terms. The expression level of 16 determined genes were verified using RT-qPCR. Conclusions: Our gene expression data may be used to study the regulatory mechanism of flower organ development in C. geringi.
Assuntos
Flores/crescimento & desenvolvimento , Flores/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Orchidaceae/crescimento & desenvolvimento , Orchidaceae/genética , Flores/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ontologia Genética , Anotação de Sequência Molecular , Orchidaceae/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análise de Sequência de RNARESUMO
INTRODUCTION: Microvascular decompression (MVD) is the preferred surgical method for hemifacial spasm (HFS). The purpose of this study was to analyze the effectiveness and safety of fully endoscopic MVD for HFS relative to microscopic MVD. MATERIAL AND METHODS: The retrospective study was conducted on HFS patients who underwent microscopic or fully endoscopic MVD from January 2018 to March 2019. All patients were treated at a single institution and by a single surgeon. Patients were divided into two groups based on the surgical method, and clinical data were then compared between groups. RESULTS: A total of 116 patients, including 54 cases who received fully endoscopic MVD (E group) and 62 cases who received microscopic MVD (M group), were included in this study. Follow-up efficacy did not differ significantly between groups, with total effective rates of 88.9% in the E group and 90.3% in the M group. When postoperative complications were compared individually, there were no statistically significant differences between the two groups; however, the E group had a higher total incidence of complications than the M group (48.1% vs. 29.0%, P = 0.034). CONCLUSION: Although both fully endoscopic and microscopic MVD for HFS achieved good efficacy, the former method had a higher total incidence of complications. Based on the results of this study, there is no evidence that a microscope can be replaced by a full endoscope in MVD for HFS.
Assuntos
Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Descompressão , Endoscopia , Espasmo Hemifacial/cirurgia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Asiaticoside (AS) has been reported to have protective effect on pulmonary fibrosis (PF). In this study, we aimed to explore the potential mechanism of the therapeutic role of AS and its relationship with A2AR in PF. Adenosine 2A receptor gene knockout (A2AR-/- ) mice and wild-type (WT) mice were used to establish bleomycin (BLM)-induced PF models and were then treated with AS (50 mg/kg/d). Pulmonary inflammation and fibrosis were observed in the PF model with much higher severity in A2AR-/- mice than that in WT mice and AS significantly alleviated lung inflammation and fibrosis; however, it was less effective in A2AR-/- mice than in WT mice via histopathological analysis. Using RNA sequencing analysis, we found up-regulated differentially expressed genes (DEGs) in BLM group were enriched in immune and inflammation-associated pathways compared with control group. There were 242 common DEGs between down-regulated in BLM vs control group and up-regulated in BLM + AS vs BLM group, which were enriched in cAMP and Rap1 signalling pathways. Furthermore, the expression of five key factors of these two pathways including adenylate cyclase (ADCY1, ADCY5, ADCY8, cAMP and Rap1) were confirmed up-regulated by AS with the presence of A2AR. Therefore, AS might attenuate BLM-induced PF by activating cAMP and Rap1 signalling pathways which is assisted by A2AR, making it a promising therapeutic optional for PF.
Assuntos
AMP Cíclico/metabolismo , Substâncias Protetoras/farmacologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Proteínas rap1 de Ligação ao GTP/metabolismo , Animais , Bleomicina/efeitos adversos , Biologia Computacional/métodos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Imuno-Histoquímica , Imunomodulação/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , TranscriptomaRESUMO
BACKGROUND: Walnut (Juglans regia L.) is one of the most widely cultivated nuts. Walnut milk beverage is very popular in China due to its nutritional value. However, adulterated walnut milk ingredients have been detected in the Chinese market. Peanut and soybean are sold at much lower prices than walnut and are reported to be commonly used for adulteration in the industrial chain of walnut milk production. The purpose of this study is therefore to develop an accurate and efficient method for detecting the authenticity of the raw materials used in walnut milk beverage. RESULTS: DNA barcoding and high-resolution melting (HRM) analyses were used to identify common adulterated raw ingredients such as peanut and soybean in commercial walnut milk beverage samples. The chloroplast psbA-trnH gene was used for sequencing, and HRM analysis was performed. We also prepared experimental mixtures, in the laboratory, with different quantities of walnut, peanut, and soybean. High-resolution melting analysis of the experimental mixtures clearly distinguished all of them. The results revealed that most of the walnut milk beverage samples fell in the same cluster of walnut species. Several samples fell in the peanut cluster, confirming that they were adulterated products. CONCLUSION: The results revealed that HRM analysis based on the psbA-trnH barcode sequence can be used to identify raw ingredients in walnut milk beverages. © 2020 Society of Chemical Industry.
Assuntos
Bebidas/análise , Código de Barras de DNA Taxonômico/métodos , Juglans/química , Juglans/genética , Arachis/química , Arachis/genética , China , Cloroplastos/genética , DNA de Plantas/genética , Contaminação de Alimentos/análise , Nozes/química , Glycine max/química , Glycine max/genéticaRESUMO
BACKGROUND: Salinization seriously threatens land use efficiency and crop yields across the world. Understanding the mechanisms plants use to protect against salt stress will help breeders develop salt-tolerant vegetable crops. Okra (Abelmoschus esculentus L.) is an important vegetable crop of the mallow family, which is now cultivated in warm regions worldwide. To understand the effects of salt stress on the protein level of okra, a comparative proteomic analysis of okra seedlings grown in the presence of 0 or 300 mmol L- 1 NaCl treatment was performed using an integrated approach of Tandem Mass Tag labeling and LC-MS/MS integrated approach. RESULTS: A total of 7179 proteins were identified in this study, for which quantitative information was available for 5774 proteins. In the NaCl/control comparison group, there were 317 differentially expressed proteins (DEPs), of which 165 proteins were upregulated and 152 proteins downregulated in the presence of NaCl. Based on the above data, we carried out a systematic bioinformatics analysis of proteins with information, including protein annotation, domain characteristics, functional classification, and pathway enrichment. Enriched gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEPs were most strongly associated with "response to stress" and "protein processing in endoplasmic reticulum". Furthermore, several heat shock proteins were identified as DEPs. CONCLUSIONS: This information provides a reference direction for further research on the okra proteome in the downstream of the salt stress response, with our data revealing that the responses of okra to salt stress involves by various pathways.
Assuntos
Abelmoschus/metabolismo , Biologia Computacional/métodos , Proteínas de Plantas/metabolismo , Proteômica/métodos , Estresse Salino , Plântula/metabolismo , Abelmoschus/crescimento & desenvolvimento , Mapas de Interação de Proteínas , Plântula/crescimento & desenvolvimentoRESUMO
MicroRNAs (miRNAs) are 20- to 24-nucleotide small noncoding RNAs that regulate gene expression in eukaryotic organisms. Several plant miRNAs, such as miR166, have vital roles in plant growth, development and responses to environmental stresses. One such environmental stress encountered by crop plants is exposure to cadmium (Cd), an element highly toxic to most organisms, including humans and plants. In this study, we analyzed the role of miR166 in Cd accumulation and tolerance in rice (Oryza sativa). The expression levels of miR166 in both root and leaf tissues were significantly higher in the reproductive stage than in the seedling stage in rice. The expression of miR166 in the roots of rice seedlings was reduced after Cd treatment. Overexpression of miR166 in rice improved Cd tolerance, a result associated with the reduction of Cd-induced oxidative stress in transgenic rice plants. Furthermore, overexpression of miR166 reduced both Cd translocation from roots to shoots and Cd accumulation in the grains. miR166 targets genes encoding the class-III homeodomain-Leu zipper (HD-Zip) family proteins in plants. In rice, HOMEODOMAIN CONTAINING PROTEIN4 (OsHB4) gene (Os03g43930), which encodes an HD-Zip protein, was up-regulated by Cd treatment but down-regulated by overexpression of miR166 in transgenic rice plants. Overexpression of OsHB4 increased Cd sensitivity and Cd accumulation in the leaves and grains of transgenic rice plants. By contrast, silencing OsHB4 by RNA interference enhanced Cd tolerance in transgenic rice plants. These results indicate a critical role for miR166 in Cd accumulation and tolerance through regulation of its target gene, OsHB4, in rice.
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Cádmio/farmacocinética , MicroRNAs/genética , Oryza/efeitos dos fármacos , Oryza/genética , Cádmio/toxicidade , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oryza/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Interferência de RNARESUMO
Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function. Specifically, we observed restoration of rod-and-cone-driven electroretinograms in about 25% of injected eyes, restoration of pupillary light responses in the majority of treated eyes, an â¼20-fold decrease in target luminance necessary for visually guided behavior, and improved retinal architecture following gene transfer. Using LCA5 patient-derived iPSC-RPEs, we show that delivery of the LCA5 cDNA restores lebercilin protein and rescues cilia quantity. The results presented in this study support a path forward aiming to develop safety and efficacy trials for gene augmentation therapy in human subjects with LCA5 mutations. They also provide the framework for measuring the effects of intervention in ciliopathies and other severe, early-onset blinding conditions.
Assuntos
Cegueira/metabolismo , Cegueira/terapia , Dependovirus/genética , Terapia Genética/métodos , Animais , Eletrorretinografia , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Feminino , Humanos , Amaurose Congênita de Leber/metabolismo , Amaurose Congênita de Leber/terapia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismoRESUMO
Soil salinization is a major environmental stresses that seriously threatens land use efficiency and crop yields worldwide. Although the overall response of plants to NaCl has been well studied, the contribution of protein phosphorylation to the detoxification and tolerance of NaCl in okra (Abelmoschus esculentus L.) seedlings is unclear. The molecular bases of okra seedlings' responses to 300 mM NaCl stress are discussed in this study. Using a combination of affinity enrichment, tandem mass tag (TMT) labeling and high-performance liquid chromatographyâ»tandem mass spectrometry analysis, a large-scale phosphoproteome analysis was performed in okra. A total of 4341 phosphorylation sites were identified on 2550 proteins, of which 3453 sites of 2268 proteins provided quantitative information. We found that 91 sites were upregulated and 307 sites were downregulated in the NaCl/control comparison group. Subsequently, we performed a systematic bioinformatics analysis including gene ontology annotation, domain annotation, subcellular localization, and Kyoto Encyclopedia of Genes and Genomes pathway annotation. The latter revealed that the differentially expressed proteins were most strongly associated with 'photosynthesis antenna proteins' and 'RNA degradation'. These differentially expressed proteins probably play important roles in salt stress responses in okra. The results should help to increase our understanding of the molecular mechanisms of plant post-translational modifications in response to salt stress.
Assuntos
Abelmoschus/metabolismo , Fosforilação/fisiologia , Proteoma/metabolismo , Estresse Salino/fisiologia , Plântula/metabolismo , Abelmoschus/genética , Biologia Computacional/métodos , Regulação para Baixo/genética , Regulação para Baixo/fisiologia , Ontologia Genética , Genes de Plantas/genética , Genes de Plantas/fisiologia , Genoma de Planta/genética , Genoma de Planta/fisiologia , Fosforilação/genética , Processamento de Proteína Pós-Traducional/genética , Processamento de Proteína Pós-Traducional/fisiologia , Proteoma/genética , Proteômica/métodos , Estresse Salino/genética , Plântula/genética , Regulação para Cima/genética , Regulação para Cima/fisiologiaRESUMO
BACKGROUND/AIMS: Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects the tenderness, juiciness, and favor of chicken. An increasing number of studies are focusing on the functions of microRNAs (miRNAs) during the adipogenic process. However, little is known about miRNAs associated with poultry IMF deposition, especially intramuscular adipocyte differentiation. METHODS: The IMF content of two physiological stages was measured, and miRNA-Seq and RNA-Seq data were integrated and analyzed. A chicken intramuscular adipocyte cell differentiation model was constructed. A luciferase reporter assay, miRNA overexpression, and Oil Red O staining were used to confirm the targets of gga-miR-140-5p. RESULTS: Our results showed that late-laying-period hens, which had a higher IMF content, exhibited lower global expression levels of miRNAs than juvenile hens. A total of 104 differentially expressed (DE) miRNAs were identified between the two groups. Integrated analysis of differentially expressed genes and DE miRNAs identified a total of 378 miRNA-mRNA pairs. Functional enrichment analysis revealed that these intersecting genes are involved in ubiquitin-mediated proteolysis, the peroxisome proliferator-activated receptor signaling pathway, glycerophospholipid metabolism, and fatty acid elongation and degradation pathways. Furthermore, we demonstrated that gga-miR-140-5p promoted intramuscular adipocyte differentiation via targeting retinoid X receptor gamma. CONCLUSION: Our findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.
Assuntos
Adipogenia , Galinhas/genética , Carne , MicroRNAs/genética , Transcriptoma , Animais , Galinhas/metabolismo , Feminino , Qualidade dos Alimentos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Carne/análise , Redes e Vias Metabólicas , Músculos/metabolismo , RNA Mensageiro/genéticaRESUMO
Navigational assistance aims to help visually-impaired people to ambulate the environment safely and independently. This topic becomes challenging as it requires detecting a wide variety of scenes to provide higher level assistive awareness. Vision-based technologies with monocular detectors or depth sensors have sprung up within several years of research. These separate approaches have achieved remarkable results with relatively low processing time and have improved the mobility of impaired people to a large extent. However, running all detectors jointly increases the latency and burdens the computational resources. In this paper, we put forward seizing pixel-wise semantic segmentation to cover navigation-related perception needs in a unified way. This is critical not only for the terrain awareness regarding traversable areas, sidewalks, stairs and water hazards, but also for the avoidance of short-range obstacles, fast-approaching pedestrians and vehicles. The core of our unification proposal is a deep architecture, aimed at attaining efficient semantic understanding. We have integrated the approach in a wearable navigation system by incorporating robust depth segmentation. A comprehensive set of experiments prove the qualified accuracy over state-of-the-art methods while maintaining real-time speed. We also present a closed-loop field test involving real visually-impaired users, demonstrating the effectivity and versatility of the assistive framework.
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Auxiliares Sensoriais , Pessoas com Deficiência Visual/reabilitação , Dispositivos Eletrônicos Vestíveis , Percepção de Profundidade , Humanos , Interpretação de Imagem Assistida por Computador , Reconhecimento Automatizado de Padrão , CaminhadaRESUMO
BACKGROUND: Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study. METHODS: In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5â×â10(11) vector genomes) in a total volume of 300 µL was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389. FINDINGS: No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline). INTERPRETATION: To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease. FUNDING: Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders.
Assuntos
Cegueira/genética , Cegueira/terapia , Dependovirus , Terapia Genética/métodos , Mutação , Lobo Occipital/fisiopatologia , Visão Ocular , cis-trans-Isomerases/genética , Administração Oftálmica , Adolescente , Adulto , Idade de Início , Cegueira/patologia , Cegueira/fisiopatologia , Criança , Medicina Baseada em Evidências , Feminino , Seguimentos , Terapia Genética/efeitos adversos , Vetores Genéticos , Humanos , Injeções Intraoculares , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/patologia , RetratamentoRESUMO
KEY MESSAGE: We review and introduce recent studies on RLK s involved in the abiotic stress response and provide insights into potential regulatory mechanisms for alleviating abiotic stress. Abiotic stresses are important factors affecting plant growth and development, resulting in crop production reduction and even plant death. To survive, plants utilize different mechanisms to respond and adapt to continuously changing environmental factors. Understanding of the molecular mechanisms of plant response to various stresses will aid in improving tolerance of plants to abiotic stress through genetic engineering, which would greatly promote the development of modern agriculture. RLKs, the largest gene family in plants, play critical roles in the regulation of plant developmental processes, signaling networks and disease resistance. Many RLKs have been shown to be involved in abiotic stress responses, including the abscisic acid response, calcium signaling and antioxidant defense. This review summarizes recent studies on RLKs involved in plant responses to abiotic stress, including drought, salt, cold, toxic metals/metalloids and other stresses, and emphasizes the upstream and downstream factors in RLK signal transduction pathways under abiotic stress.
Assuntos
Plantas/enzimologia , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Secas , Cloreto de Sódio/farmacologia , Estresse Fisiológico/genéticaRESUMO
BACKGROUND: There is an increasing frequency of pancreaticoduodenectomy (PD) and PD with superior mesenteric-portal vein (SMPV) resection in elderly cancer patients. The study aimed to investigate the safety and the survival benefits of PD and PD with SMPV resection in patients under or over 70 years of age. METHODS: We divided 296 patients who had undergone PD and PD with SMPV resection into two groups according to their ages: under or over 70 years old. The clinical data were compared between the two groups. RESULTS: Preoperative comorbidity rate was higher in elder patients than in younger patients (P=0.001). The elder patients were more likely to have postoperative complications (P=0.003). Specifically, complications above grade III were more likely to occur in the elderly patients (P=0.030). Multivariable analysis showed that age (adjusted OR=2.557, P=0.015) and hypertension (adjusted OR=2.443, P=0.019) were independent predictors of postoperative complications. There was no significant difference in the mortality rates between the two groups (P=0.885). In the PD with SMPV resection series, elderly patients were more likely to have postoperative complications (P=0.063), but this difference was not statistically significant. There was no difference in the survival rate of patients with pancreatic ductal adenocarcinoma between the two groups. Operation type (PD vs PD with SMPV resection) did not affect the survival of patients. CONCLUSIONS: Age affects postoperative complication in patients undergoing either PD or PD with SMPV resection. However, extensive experience and advanced perioperative management lower the complication rate to an acceptable limit. Hence it is safe and worthwhile to perform PD for elderly patients. Because of low numbers in the SMPV subset, we could not conclude whether PD with SMPV resection is feasible in elderly patients.
Assuntos
Neoplasias do Sistema Digestório/cirurgia , Veias Mesentéricas/cirurgia , Pancreaticoduodenectomia , Veia Porta/cirurgia , Procedimentos Cirúrgicos Vasculares , Fatores Etários , Idoso , Comorbidade , Neoplasias do Sistema Digestório/mortalidade , Neoplasias do Sistema Digestório/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/efeitos adversos , Seleção de Pacientes , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, Nω-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation.