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Three new quaternary Zintl phases with the "9-4-9" formula, Ae9Mn4-xAlxSb9 (Ae = Ca, Yb, Eu), have been synthesized using Pb as the metal flux, and their crystal structures have been established by single-crystal X-ray diffraction. Both Ca9Mn2.91(4)Al1.09Sb9 and Yb9Mn3.59(6)Al0.41Sb9 are isostructural with Ca9Mn4Bi9, and they crystallize in the orthorhombic space group Pbam with unit cell dimensions of a = 12.4571(8), 12.2884(16) Å, b = 22.1352(16), 22.024(3) Å, and c = 4.6012(3), 4.6187(6) Å, respectively. Their anionic structures can be viewed as infinite ribbons based on corner-shared tetrahedrons. Also, Eu9Mn2.87(4)Al1.13Sb9 has the space group Cmca and a = 9.4883(7) Å, b = 23.6895(18) Å, and c = 24.4845(19) Å. The structural relationships between Ca9Mn2.91(4)Al1.09Sb9 and Eu9Mn2.87(4)Al1.13Sb9 are compared and discussed as well. The successful Al3+ substitution provides additional electrons to the compounds to achieve structural stability. Magnetic susceptibility and electrical resistivity measurements, performed on single crystals of Eu9Mn2.87(4)Al1.13Sb9, indicate complex magnetic properties and semiconductor behavior. The physical properties of Yb9Mn3.59(6)Al0.41Sb9 are similar to those observed for Yb9Mn4.18(2)Sb9.
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MYB proteins play important roles in the regulation of plant growth, development, and stress responses. Overexpression of BplMYB46 from Betula platyphylla improved plant salt and osmotic tolerances. In the present study, the interaction of eight avian myeloblastosis viral oncogene homolog (MYB) transcription factors with BplMYB46 was investigated using the yeast two-hybrid system, which showed that BplMYB46 could form homodimers and heterodimers with BplMYB6, BplMYB8, BplMYB11, BplMYB12, and BplMYB13. Relative beta-glucuronidase activity and chromatin immunoprecipitation assays showed that the interaction between BplMYB46 and the five MYBs increased the binding of BplMYB46 to the MYBCORE motif. A subcellular localization study showed that these MYBs were all located in the nucleus. Real-time fluorescence quantitative PCR results indicated that the expressions of BplMYB46 and the five MYB genes could be induced by salt and osmotic stress, and the BplMYB46 and BplMYB13 exhibited the most similar expression patterns. BplMYB46 and BplMYB13 co-overexpression in tobacco using transient transformation technology improved tobacco's tolerance to salt and osmotic stresses compared with overexpressing BplMYB13 or BplMYB46 alone. Taken together, these results demonstrated that BplMYB46 could interact with five other MYBs to form heterodimers that activate the transcription of target genes via an enhanced binding ability to the MYBCORE motif to mediate reactive oxygen species scavenging in response to salt and osmotic stresses.
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Betula/crescimento & desenvolvimento , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Motivos de Aminoácidos , Betula/química , Betula/genética , Betula/metabolismo , Sítios de Ligação , Núcleo Celular/metabolismo , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Pressão Osmótica , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligação Proteica , Multimerização Proteica , Estresse Salino , Técnicas do Sistema de Duplo-HíbridoRESUMO
BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.
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Neoplasias Encefálicas/patologia , Caderinas/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Glioma/patologia , Idoso , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/genética , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Mitocondriais , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , TemozolomidaRESUMO
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. METHODS: The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. RESULTS: G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 µmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 µmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation. CONCLUSION: The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.
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Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glutationa/sangue , Triagem Neonatal/métodos , Espectrometria de Massas em Tandem , Biomarcadores/sangue , Estudos de Casos e Controles , Teste em Amostras de Sangue Seco , Deficiência de Glucosefosfato Desidrogenase/sangue , Dissulfeto de Glutationa/sangue , Humanos , Recém-NascidoRESUMO
A new polyhydroxycholestane sulfate ester, 3α,12ß,25,26-tetrahydroxy-7-oxo-5ß-cholestane 26-O-sulfate (1), was isolated from dried skin of Bufo bufo gargarizans Cantor and its structure was elucidated on the basis of extensive 1D and 2D NMR as well as HR-ESI-MS analysis. A comparison of steroidal metabolite profiles, based on HPLC and LC-MS analyses, indicates that the chemical compositions of the various parts of toads, such as venom, skin and stratum corneum, are significantly different.
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Bufanolídeos/isolamento & purificação , Bufo bufo , Colestanóis/isolamento & purificação , Animais , Bufanolídeos/química , China , Colestanóis/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pele/química , PeçonhasRESUMO
The invasive Mediterranean Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) has emerged as one of the most common agricultural pests in the world. In the present study, we examined the cross-tolerance, fitness costs, and benefits of thermal tolerance and the variation in the responses of life history traits after heat-shock selection. The results showed that survival and longevity of Mediterranean B. tabaci were decreased significantly after direct or cross temperature stress and that the number of eggs per female was not reduced significantly. Furthermore, heat-shock selection dramatically increased the survival of Mediterranean B. tabaci within two generations, and it did not significantly affect the egg number per female within five generations. These results indicated that there was a trade-off between survival, longevity, and reproduction in Mediterranean B. tabaci after temperature stress. The improvement in reproduction was costly in terms of decreased survival and longevity, and there was a fitness consequence to temperature stress. In addition, heat tolerance in Mediterranean B. tabaci increased substantially after selection by heat shock, indicating a considerable variation for survival tolerance in this species. This information could help us better understand the thermal biology of Mediterranean B. tabaci within the context of climate change.
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Hemípteros/fisiologia , Temperatura , Animais , Feminino , Fertilidade , Longevidade/fisiologia , Solanum lycopersicum/parasitologia , Masculino , Reprodução/fisiologia , Estresse FisiológicoRESUMO
Lonicera japonica flos is widely used as a pharmaceutical resource and a commonly-employed ingredient in healthy food, soft beverages and cosmetics in China. Sometimes, sulfur fumigation is used during post-harvest handling. In this study, a comprehensive comparison of the chemical profile between sun-dried and sulfur-fumigated samples was conducted by HPLC fingerprints and simultaneous quantification of nine constituents, including secologanic acid, along with another eight usually-analyzed markers. Secologanic acid was destroyed, and its sulfonates were generated, whereas caffeoylquinic acids were protected from being oxidized. The residual sulfur dioxide in sulfur-fumigated samples was significantly higher than that in sun-dried samples, which might increase the potential incidence of toxicity to humans. Meanwhile, compared with sun-dried samples, sulfur-fumigated samples have significantly stronger antioxidant activity, which could be attributed to the joint effect of protected phenolic acids and flavonoids, as well as newly-generated iridoid sulfonates.
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Antioxidantes/farmacologia , Lonicera/química , Extratos Vegetais/farmacologia , Ácido Quínico/análogos & derivados , Enxofre/farmacologia , China , Cromatografia Líquida de Alta Pressão , Flavonoides/farmacologia , Fumigação/métodos , Glicosídeos Iridoides/farmacologia , Lonicera/efeitos dos fármacos , Extratos Vegetais/química , Ácido Quínico/química , Ácido Quínico/farmacologia , Dióxido de Enxofre/químicaRESUMO
The genus Scilla consists of 90 species widely distributed in Europe, Asia and Africa, one and its variant of which can be found in China Some species of the genus have been used in traditional medicine to treat various diseases related to inflammation and pain. Phytochemical studies have demonstrated the presence of triterpene and tritepenoid saponins derived from eucosterol, bufadienolides, alkaloids, stilbenoids and lignan in the plants of this genus. Various bioactivities such as antimicrobial, anti-inflammatory, antioxidant, anti-tumor and glycosidase inhibitory activities, have been reported. In this review, the advance of chemical constituents and pharmacological activities of the Scilla species are summarized for further development and utilization of the resource.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Scilla/química , Animais , HumanosRESUMO
Mian-Zao-Er was collected from the bulbs of Scilla scilloides (Lindl. ) Druce, belonging to the Hyacinthaceae family. 17 compounds were obtained using various column chromatographies on macroporus resin (HPD100), silica gel, Sephadex LH-20 and ODS, as well as semi-preparative HPLC. Their structures were elucidated on the basis of physicochemical properties and spectral data as 2-hydroxy-7-methoxyscillascillin (1), scillascillin (2), 5,7-dihydroxy-3',4'-dimethoxyspiro 2H-1-benzopyran-7'-bicyclo[4.2.0 ] octa [1,3,5 ] -trien } -4-one (3), socialinone (4), 4-methylresveratrol (5), (E)-resveratrol (6), scillavoneA (7), 3,9-di- hydroeucomnalin (8), 3-(3-hydroxy-4-methoxybenzyl) -5,7-dihydroxychroman-4-one (9), (3R)-5,7,3'-trihydroxy-4'-methoxyspiro (2H-1-benzopyran-7'-bicyclo[4, 2, 0] octa [1, 3, 5]-trien} -4-one (10), scillabene A (11), 2-hydroxyscillascillin (12), 3-(4-hydroxybenzyl) -5,7-dihydroxychroman-4-one (13), 3-( 4-hydroxybenzylidene) -5, 7-dihydroxychroman-4-one (14), 3-( 4-hydroxybenzyl) -5-hydroxy-7,8-dimethoxychroman-4-one (15), 3-(4-hydroxybenzyl) -5-hydroxy-6, 7-dimethoxychroman-4-one (16), and 3-(4-hydroxybenzyl)-5,8-hydroxy-7-methoxychroman-4-one (17). Among them, compounds 3, 4, 6, 9, 13 and 15-17 were isolated from this plant for the first time.
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Medicamentos de Ervas Chinesas/química , Flores/química , Isoflavonas/química , Scilla/química , Estilbenos/química , Espectrometria de Massas , Estrutura MolecularRESUMO
BACKGROUND: It is possible that this condition will lead to urosepsis and progressive deterioration of renal function in the absence of surgical intervention. Several recent clinical studies have shown that multi-tract percutaneous nephrolithotomy (M-PCNL) has a similar stone free rate (SFR) as standard percutaneous nephrolithotomy (S-PCNL). As a result, M-PCNL was also recommended as a treatment option for staghorn calculi. AIM: To examine the perioperative and long-term results of ultrasonography-guided single- and M-PCNL. METHODS: This was a retrospective cohort study. Between March 2021 and January 2022, the urology department of our hospital selected patients for the treatment of staghorn calculi using percutaneous nephrolithotomy. The primary outcomes were complication rate and SFR, and the characteristics of patients, operative parameters, laboratory measurements were also collected. RESULTS: In total, 345 patients were enrolled in the study (186 in the S-PCNL group and 159 in the M-PCNL group). The SFR in the M-PCNL group was significantly higher than that in the S-PCNL group (P = 0.033). Moreover, the incidence rates of hydrothorax (P = 0.03) and postoperative infection (P = 0.012) were higher in the M-PCNL group than in the S-PCNL group. Logistic regression analysis demonstrated that post-operative white blood cell count (OR = 2.57, 95%CI: 1.90-3.47, P < 0.001) and stone size (OR = 1.59, 95%CI: 1.27-2.00, P < 0.001) were associated with a higher overall complication rate in the S-PCNL group. Body mass index (OR = 1.22, 95%CI: 1.06-1.40, P = 0.004) and stone size (OR = 1.70, 95%CI: 1.35-2.15, P < 0.001) were associated with increased overall complications in the M-PCNL group. CONCLUSION: Multiple access tracts can facilitate higher SFR while slightly increasing the incidence of acceptable complications.
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INTRODUCTION: Methylmalonic acidemia (MMA) is a disorder of autosomal recessive inheritance, with an estimated prevalence of 1:50,000. First-tier clinical diagnostic tests often return many false positives [five false positive (FP): one true positive (TP)]. In this work, our goal was to refine a classification model that can minimize the number of false positives, currently an unmet need in the upstream diagnostics of MMA. METHODS: We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction. We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients, followed by additional ratio feature construction. Feature selection strategies (selection by filter, recursive feature elimination, and learned vector quantization) were used to determine the input set for evaluating the performance of 14 classification models to identify a candidate model set for an ensemble model development. RESULTS: Our work identified computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity. The best results [area under the receiver operating characteristic curve (AUROC) of 97%, sensitivity of 92%, and specificity of 95%] were obtained utilizing an ensemble of the algorithms random forest, C5.0, sparse linear discriminant analysis, and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor. The model achieved a good performance trade-off for a screening application with 6% false-positive rate (FPR) at 95% sensitivity, 35% FPR at 99% sensitivity, and 39% FPR at 100% sensitivity. CONCLUSIONS: The classification results and approach of this research can be utilized by clinicians globally, to improve the overall discovery of MMA in pediatric patients. The improved method, when adjusted to 100% precision, can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families.
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Erros Inatos do Metabolismo dos Aminoácidos , Aprendizado de Máquina , Humanos , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Recém-Nascido , Feminino , Masculino , Triagem Neonatal/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To explore the expression of Foxa2 in different pathological types of gastric polyps and examine the correlation with cancerous risk. METHODS: According to computerize random number, a total of 2000 patients were selected to receive endoscopic biopsy during November 2011 to October 2012. Tissues were harvested from 170 with gastric polyps and suspicious cancerous lesions and their histological types detected. There were hyperplastic polyps(n = 35), adenomatous polyps(n = 31), fundic gland polyps(n = 42), advanced gastric cancer tissues (n = 32)and normal gastric mucosa tissues (n = 30). ABC immunohistochemical staining and reverse transcription(RT)-PCR were employed to detect the expression of Foxa2 in these different types of tissues. Imagepro plus was used for quantitative and statistical analyses. RESULTS: A low-level expression of Foxa2 was 3.6% ± 1.3% in normal gastric mucosa group. And its expreesion gradually higher in proliferative inflammatory polyp group(33.1% ± 8.0%), adenomatous polyp group (71.4% ± 1.7%) and gastric cancer group(96.3% ± 0.9%, all P < 0.05). Its expression was 35.6% ± 5.6% in fundic gland polyps, similar to that of proliferative inflammatory polyp group (P > 0.05), it was markedly lower than the gastric cancer group (P < 0.05) and higher than the normal gastric mucosa group (P < 0.05). Correlation analyses of clinicopathological parameters showed that no significant correlation existed between its expression and patient gender, age, predilection, Helicobacter. pylori infection or proton pump inhibitor used (all P > 0.05). However, the size of polyps was correlated with Foxa2 (rs = 0.69, P < 0.05). CONCLUSION: The expression level of Foxa2 in different types of gastric polyps may be used as a clinical predicator of polyps risk.
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Pólipos Adenomatosos/metabolismo , Pólipos Adenomatosos/patologia , Fator 3-beta Nuclear de Hepatócito/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/metabolismoRESUMO
OBJECTIVE: To develop dataset for basic medical information system. METHODS: All items of basic medical information system dataset were drafted by literature review, brain storm and group discussion. A Delphi study was conducted to evaluate and adjust the candidate items; then items were finalized based on comprehensive scores. RESULTS: The final dataset developed through two-round Delphi study contained 20 first-level items, 102 second-level items, 40 third-level items and 88 fourth-level items. The response rates were 71.79% and 92.86% in round 1 and 2, respectively. The authority coefficient was both 0.77 and the coordination coefficient of the specialists' opinion was 0.239 and 0.516, respectively. CONCLUSION: The dataset for basic medical information system determined from Delphi study is credible and can be used for development of related software.
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Sistemas de Informação , Design de Software , Técnica DelphiRESUMO
Taking coal under hydro-mechanical coupling as the research object, the discrete element software PFC3D (particle flow code) was used to analyze the relationships among the force, acoustic emission (AE), and energy during coal fracture. Based on the moment tensor (MT) inversion, we revealed the AE event distribution and source type during crack initiation and propagation until the final failure of coal. Meanwhile, we examined the relationships among the stress, number and type of cracks, magnitude, KE, and b value of AE under different water and confining pressures. The results show that the numerical simulation can effectively determine the microscopic damage mechanism of coal under different conditions. Moreover, the rupture type of the numerical simulation is consistent with the field investigations, which verifies the rationality of the simulation. These research results can provide reference for safety production evaluation of water inrush mines.
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OBJECTIVE: To evaluate and compare mail and meeting forms in evaluation of Delphi study. METHODS: Delphi study by mail and meeting approaches was used to determine the health information dataset. Experts were required to grade the listed items through three indexes: importance, necessity and availability. Study duration, coefficient of variation of items, authority coefficient and coordination coefficient of the experts' opinion of two forms of study were calculated and compared. RESULT: The study duration was four months through mail form and 2 days through meeting. Compared with the first round, the coefficient of variation decreased (P<0.001, all of the three indexes by two forms), and the cooperation index increased (P<0.005) in the second round. The experts' opinions were easier to be consistent through meeting than through mail(P<0.033). And the authority coefficient by meeting consultation (0.83 ± 0.05) was higher than that by mail (0.77 ± 0.03) (P=0.001). CONCLUSION: Both mail and meeting forms of Delphi study can determine the health information dataset,but meeting consultation is better and requires shorter study duration.
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Meios de Comunicação , Técnica Delphi , Serviços Postais , RegistrosRESUMO
Low temperature is a major stress that severely affects plant growth and development. Inducer of CBF expression 1 (ICE1) plays a key role in plant cold tolerance by regulating the expression of cold stress-responsive genes. In the present study, we characterized the function and underlying regulatory mechanism of PsnICE1 from Xiaohei poplar (Populus simonii × Populus nigra). PsnICE1 was significantly induced in response to cold stress in the roots, stems and leaves. PsnICE1 proteins were found to localize to the nucleus and exert transactivation activity via their N-terminal transactivation domain. Compared with non-transgenic poplar, transgenic poplar overexpressing PsnICE1 showed substantially enhanced tolerance to cold stress, with higher survival rates and antioxidant enzyme activity levels and reduced reactive oxygen species (ROS) accumulation. In contrast, plants with RNA inhibition-mediated silencing of PsnICE1 showed the opposite phenotype. PsnICE1 can bind to H-box element and abscisic acid-responsive element (ABRE), and more importantly, it mainly binds to IBS1 (a newly discovered cis-acting element) and E-box elements to regulate stress-related genes involved in ROS scavenging. Overall, these results indicated that PsnICE1 functions as a positive regulator of cold tolerance and serves as a potential candidate gene for plant cold tolerance improvement via molecular breeding.
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Populus , Temperatura Baixa , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tolerância ao Sal/genética , Estresse Fisiológico/genéticaRESUMO
Glycogen synthase kinase-3beta (GSK-3beta) is thought to mediate morphological responses to a variety of extracellular signals. Surprisingly, we found no gross morphological deficits in nervous system development in GSK-3beta null mice. We therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown of both GSK-3alpha and beta markedly reduced axon growth in dissociated cultures and slice preparations. We then assessed the role of different GSK-3 substrates in regulating axon morphology. Elimination of activity toward primed substrates only using the GSK-3 R96A mutant was associated with a defect in axon polarity (axon branching) compared to an overall reduction in axon growth induced by a kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3 activity by pharmacological inhibitors induced axon branching and was associated primarily with effects on primed substrates. Our results suggest that GSK-3 is a downstream convergent point for many axon growth regulatory pathways and that differential regulation of primed versus all GSK-3 substrates is associated with a specific morphological outcome.
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Axônios/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/fisiologia , Hipocampo/citologia , Fator de Crescimento Neural/farmacologia , Neurônios/citologia , Animais , Axônios/fisiologia , Western Blotting , Contagem de Células/métodos , Células Cultivadas , Relação Dose-Resposta a Droga , Interações Medicamentosas , Embrião de Mamíferos , Imunofluorescência/métodos , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Técnicas In Vitro , Indóis/farmacologia , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/fisiologia , Modelos Biológicos , Mutação/fisiologia , Neocórtex/citologia , Neocórtex/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Oximas/farmacologia , Transfecção/métodosRESUMO
BACKGROUND: Elevated blood C24:0- and C26:0-carnitines and lysophosphatidylcholines (LPCs) were reported as diagnostic biomarkers for X-linked adrenoleukodystrophy (X-ALD). Our aim was to establish the reference intervals of very long-chain (VLC) acylcarnitines (C20-C26) and LPCs in Chinese population, and evaluate valuable biomarkers and develop panel for screening X-ALD in China. METHODS: The method of FIA-MS/MS-based quantification of VLC acylcarnitines and LPCs was validated in order to determine their concentrations in dried blood spots from 7 X-ALD boys, 396 age-matched healthy controls, and 3078 putative normal newborns. Screening performance of these metabolites for X-ALD was clinically evaluated. RESULTS: The reference intervals of VLC acylcarnitines, LPCs and their ratios were established in Chinese population, and for some metabolites like C26 and C26:0-LPC, the reference intervals were found to be significantly different between children and newborns. C24 and C26, C26:0-LPC, C24/C22 and C26/C22 ratios were found to have better performance than other analytes to identify X-ALD boys from normal children. CONCLUSION: C26:0-LPC, C24 and C26 are three most valuable biomarkers for screening of X-ALD in children group. The information of age-related variations in concentration of some biomarkers is helpful for accurate screening of X-ALD.
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Adrenoleucodistrofia/diagnóstico , Carnitina/análogos & derivados , Lisofosfatidilcolinas/análise , Programas de Rastreamento/métodos , Adrenoleucodistrofia/sangue , Fatores Etários , Biomarcadores/sangue , Carnitina/análise , Estudos de Casos e Controles , Criança , Teste em Amostras de Sangue Seco , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Recém-Nascido , Masculino , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To promote stem cells differentiation into neurons and enhance neuromotor function after brain injury through brain-derived neurotrophic factor (BDNF) induction. METHODS: Recombinant adenovirus vector was applied to the transfection of BDNF into human-derived umbilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to determine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively. RESULTS: The BDNF expression achieved its stabilization at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly. CONCLUSION: BDNF gene can promote the differentiation of the stem cells into neurons rather than glial cells, and enhance neuromotor function after brain injury.
Assuntos
Lesões Encefálicas/terapia , Fator Neurotrófico Derivado do Encéfalo/genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Neurônios/citologia , Adenoviridae/genética , Animais , Apoptose , Lesões Encefálicas/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/análise , Diferenciação Celular , Proteína Glial Fibrilar Ácida , Humanos , Camundongos , Proteínas do Tecido Nervoso/análise , Fosfopiruvato Hidratase/análise , TransfecçãoRESUMO
BACKGROUND: This study intends to explore whether lncRNA ANRIL has an influence on type 2 diabetes mellitus (T2DM) complicated with acute myocardial infarction (MI) and to further investigate the underlying mechanism. METHODS: The ANRIL level in peripheral blood from patients was detected by qRT-PCR. A T2DM mouse model was established by intraperitoneal injection of streptozocin (STZ). MI was induced by ligation of the left anterior descending coronary artery. Cardiac function parameters were measured using echocardiography. Triphenyltetrazolium chloride (TTC) staining was performed to determine the infarct size, and Masson staining was conducted to delineate the area of fibrosis in the myocardium. TUNEL staining was used to detect myocardial cell apoptosis. The expression of the myocardial fibrosis-related proteins TGF-ß1, collagen I and collagen III was analysed using Western blot. RESULTS: ANRIL was upregulated in peripheral venous blood from patients with T2DM-MI and in myocardial tissues from the established T2DM-MI model mice. Furthermore, ANRIL overexpression caused cardiac dysfunction and increased the heart/body weight rate and infarct size in the T2DM-MI mice. Moreover, ANRIL overexpression caused myocardial fibrosis and myocardial cell apoptosis, and it increased the expression of the myocardial fibrosis-related proteins TGF-ß1, collagen I and collagen III in the T2DM-MI mice. However, ANRIL knockdown exerted the opposite effects. CONCLUSION: ANRIL may be involved in the progression and development of T2DM-MI, which might provide novel ideas for the prevention and treatment of cardiovascular diseases.