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1.
Nat Immunol ; 16(11): 1195-203, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26390157

RESUMO

Sumoylation regulates many cellular processes, but its role in signaling via the T cell antigen receptor (TCR) remains unknown. We found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the TCR plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. We identified the SUMO E3 ligase PIASxß as a ligase for PKC-θ. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-θ but inhibited the association of CD28 with PKC-θ and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-θ and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-θ is essential for the formation of a mature immunological synapse and T cell activation.


Assuntos
Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/enzimologia , Linfócitos T/imunologia , Animais , Sítios de Ligação , Antígenos CD28/metabolismo , Diferenciação Celular , Células Cultivadas , Filaminas/metabolismo , Células HEK293 , Humanos , Sinapses Imunológicas/metabolismo , Isoenzimas/química , Isoenzimas/deficiência , Isoenzimas/genética , Células Jurkat , Ativação Linfocitária , Lisina/química , Camundongos , Camundongos Knockout , Mutagênese Sítio-Dirigida , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteína Quinase C/química , Proteína Quinase C/deficiência , Proteína Quinase C/genética , Proteína Quinase C-theta , Transdução de Sinais , Sumoilação , Linfócitos T/citologia , Células Th2/citologia , Células Th2/enzimologia , Células Th2/imunologia
2.
Proc Natl Acad Sci U S A ; 120(45): e2304179120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903265

RESUMO

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.

3.
J Sep Sci ; 47(12): e2400223, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39031838

RESUMO

Much more attention has been paid to the contamination of Alternaria toxins because of food contamination and the threat to human health. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous detection of the prototypical alternariol, alternariol monomethylether, and the metabolites 4-oxhydryl alternariol, and alternariol monomethylether 3-sulfate ammonium salt of Alternaria toxins. The positive samples were used as matrix samples to optimize the different experimental conditions. 0.01% formic acid solution and acetonitrile were used as the mobile phase, and analytes were scanned in negative electron spray ionization under multiple reaction monitoring, and quantitative determination by isotope internal standard method. Application of this method to samples of human plasma and urine showed the detection of the above analytes. The results showed that the recoveries were from 80.40% to 116.4%, intra-day accuracy was between 0.6% and 8.0%, and inter-day accuracy was between 1.1% and 12.1%. The limit of detection of the four analytes ranged from 0.02 to 0.6 µg/L in urine, and 0.02 to 0.5 µg/L in plasma, respectively. Thus, the developed method was rapid and accurate for the simultaneous detection of analytes and provided a theoretical basis for the risk assessment of Alternaria toxins for human exposure.


Assuntos
Alternaria , Micotoxinas , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Alternaria/metabolismo , Alternaria/química , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Micotoxinas/urina , Micotoxinas/sangue , Micotoxinas/análise , Lactonas/urina , Lactonas/sangue
4.
Molecules ; 29(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38398624

RESUMO

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.


Assuntos
Apoptose , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Camundongos Nus , Linhagem Celular Tumoral , Proteômica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Chá , Autofagia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proliferação de Células
5.
Chem Biodivers ; 20(2): e202200899, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36631282

RESUMO

BACKGROUND: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti-inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields. OBJECTIVE: In this study, we aimed to synthesize bioactive flavonoids and flavonoid glycosides from hesperetin and evaluate the antitumor and anti-inflammatory activities of these compounds. METHODS: A series of flavonoids and their derivatives were synthesized by methoxylation, oxidative dehydrogenation, benzylation, debenzylation, and deacetylation as well as using a modified peroxyacetone method and a glycoside condensation reaction. Their anti-inflammatory activities were evaluated for their inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) production in LPS-induced RAW264.7 mouse macrophages. Their structures were characterized by HRMS, 1 H-NMR, and 13 C-NMR, and their cytotoxicity on the human triple-negative breast cancer cell (TNBC) line, SUM 149, was tested by using the MST assay. RESULTS: Most of the compounds markedly reduced NO production in LPS-stimulated murine macrophages at the tested concentrations in a dose-dependent manner. Among these, compounds 1, 7, 9, and 17 showed significant anti-inflammatory activities against NO production in LPS-induced RAW264.7 mouse macrophages. In addition, they could also reduce the release of TNF-α and IL-6 in a concentration-dependent manner. Most of the tested compounds showed remarkable anti-human TNBC activities. Compounds 1b-1m, 1, and 3 showed a certain degree of growth inhibition effect on the human TNBC cell lines and their IC50 values were all below 16.61 µM. In addition, compound 1l was the most cytotoxic with IC50 values of 1.38±0.31 µM, while the other compounds were inactive with inhibition rates <50 % at the highest concentration tested (20 µM). CONCLUSIONS: A novel series of flavonoids were synthesized from the natural flavonoid, hesperetin, including 17 new compounds. Screening tests indicated that most of these compounds reduced NO production in LPS-stimulated murine macrophages at concentrations of 15 to 60 µM, and the inhibition generally increased in a dose-dependent manner. Some compounds showed different degrees of cytotoxicity on the human TBNC cell lines, SUM 149.


Assuntos
Flavonoides , Neoplasias de Mama Triplo Negativas , Camundongos , Animais , Humanos , Flavonoides/química , Glicosídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Óxido Nítrico
6.
Int J Mol Sci ; 24(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37833979

RESUMO

Oral squamous cell carcinoma (OSCC) poses a significant obstacle to the worldwide healthcare system. Discovering efficient and non-toxic medications is crucial for managing OSCC. Nuciferine, an alkaloid with an aromatic ring, is present in the leaves of Nelumbo nucifera. It has been proven to play a role in multiple biological processes, including the inhibition of inflammation, regulation of the immune system, formation of osteoclasts, and suppression of tumors. Despite the demonstrated inhibitory effects of nuciferine on different types of cancer, there is still a need for further investigation into the therapeutic effects and potential mechanisms of nuciferine in OSCC. Through a series of in vitro experiments, it was confirmed that nuciferine hindered the growth, movement, and infiltration, while enhancing the programmed cell death of OSCC cells. Furthermore, the administration of nuciferine significantly suppressed the signal transducer and activator of transcription 3 (STAT3) signaling pathway in comparison to other signaling pathways. Moreover, the activation of the STAT3 signaling pathway by colivelin resulted in the reversal of nuciferine-suppressed OSCC behaviors. In vivo, we also showed the anti-OSCC impact of nuciferine using the cell-based xenograft (CDX) model in nude mice. Nonetheless, colivelin diminished the tumor-inhibiting impact of nuciferine, suggesting that nuciferine might partially impede the advancement of OSCC by suppressing the STAT3 signaling pathway. Overall, this research could offer a fresh alternative for the pharmaceutical management of OSCC.


Assuntos
Aporfinas , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Nus , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Aporfinas/uso terapêutico
7.
Hell J Nucl Med ; 26(3): 201-206, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149774

RESUMO

OBJECTIVE: To investigate the automatic synthesis of ß-amyloid (Aß) positron emission tomography (PET) imaging agent (E) -4- (2- (6- (2- (2-18F fluoroethoxy) ethoxy) ethoxy) pyridine-3-yl) vinyl) - N-methylaniline (18F-AV-45) for the diagnosis of Alzheimer's disease (AD) and its clinical application in AD patients. MATERIALS AND METHODS: Fluorine-18-AV-45 was synthesized with AV-105 as the precursor, and the factors affecting the synthesis efficiency, such as the amount of precursor, nucleophilic reaction temperature were studied. At the same time, 18F-AV-45 PET/computed tomography (CT) brain scanning was performed in 15 patients with dementia to determine whether AD was the cause of the dementia. RESULTS: After optimizing the parameters, it was discovered that the highest synthesis efficiency was achieved with a AV-105 dosage of 2mg, a reaction temperature of 130oC, and 1mL of DMSO. The radiochemical yield (RCP) was greater than 98, and the uncorrected synthesis efficiency was about 31.0%±2.8%. Ten of the 15 patients with dementia showed positive Aß protein deposition, and the main deposition site of the imaging agent was the gray matter area of the brain, which was consistent with AD diagnosis, while the other 5 patients showed negative Aß protein deposition, suggesting non-AD dementia. CONCLUSION: ß-amyloid protein 18F-AV-45 imaging agent can be easily and quickly prepared by the All in One radiochemical synthesis module. Our preliminary results offer hope that it can effectively detect ß-amyloid deposition in the brain of AD patients in order to determine the etiology of dementia.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Compostos Radiofarmacêuticos/metabolismo
8.
Wei Sheng Yan Jiu ; 52(6): 907-911, 2023 Nov.
Artigo em Zh | MEDLINE | ID: mdl-38115654

RESUMO

OBJECTIVE: Comparative analysis of two method for determining fat and analysis of fatty acid content in tea samples. METHODS: The content of freefatand total fat in tea was determined by Soxhlet extraction method and acid hydrolysis method, and the content of fatty acids were determined by gas chromatography. The composition and content of fatty acids in 21 tea samples from 5 regions were analyzed. RESULTS: The freefat content of tea determined by Soxhlet extraction method was significantly lower than that determined by acid hydrolysis method. The totalfat content in tea determined by acid hydrolysis method was consistent with the total amount of fatty acids determined by gas chromatography, and their content conformed to the logical relationshipsimultaneously. The totalfat content in tea ranged from 0.6 to 4.1 g/100 g, which in green tea, white tea, yellow tea, and black tea were 2.2, 1.8, 1.6 and 0.6 g/100 g, respectively. The content of free fat in tea was less than 58%, with 42%-80% of the fat existing in a bound form. The fatty acids in tea were mainly unsaturated fatty acids, accounting for 67.52%-99.03% of the total fatty acids. There were differences in the composition of fatty acids in different types of tea, with the proportion of unsaturated fatty acids in yellow tea accounting for 98.84% of the total fatty acids, which was significantly higher than that of green tea, white tea, and black tea. The fatty acids with high content in green tea(except Tang chi xiaolan tea, Bawangjian green tea and Liuxi yuye tea)were α-linoleic acid, linoleic acid, and palmitic acid. CONCLUSION: Theacid hydrolysis method is more suitable for the determination of fat in tea samples. The composition and content of fat and fatty acids in tea vary depending onfactors such as the type of tea and the degree of fermentation.


Assuntos
Ácidos Graxos Insaturados , Ácidos Graxos , Ácidos Graxos/análise , Ácidos Graxos Insaturados/análise , Chá/química , Ácidos Linoleicos
9.
Proc Natl Acad Sci U S A ; 115(2): 266-271, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29284755

RESUMO

We discover a population of short-period, Neptune-size planets sharing key similarities with hot Jupiters: both populations are preferentially hosted by metal-rich stars, and both are preferentially found in Kepler systems with single-transiting planets. We use accurate Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Data Release 4 (DR4) stellar parameters for main-sequence stars to study the distributions of short-period [Formula: see text] Kepler planets as a function of host star metallicity. The radius distribution of planets around metal-rich stars is more "puffed up" compared with that around metal-poor hosts. In two period-radius regimes, planets preferentially reside around metal-rich stars, while there are hardly any planets around metal-poor stars. One is the well-known hot Jupiters, and the other one is a population of Neptune-size planets ([Formula: see text]), dubbed "Hoptunes." Also like hot Jupiters, Hoptunes occur more frequently in systems with single-transiting planets although the fraction of Hoptunes occurring in multiples is larger than that of hot Jupiters. About [Formula: see text] of solar-type stars host Hoptunes, and the frequencies of Hoptunes and hot Jupiters increase with consistent trends as a function of [Fe/H]. In the planet radius distribution, hot Jupiters and Hoptunes are separated by a "valley" at approximately Saturn size (in the range of [Formula: see text]), and this "hot-Saturn valley" represents approximately an order-of-magnitude decrease in planet frequency compared with hot Jupiters and Hoptunes. The empirical "kinship" between Hoptunes and hot Jupiters suggests likely common processes (migration and/or formation) responsible for their existence.

10.
J Cell Mol Med ; 24(18): 11012-11017, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32744427

RESUMO

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.


Assuntos
Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Crescimento Neuronal/fisiologia , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Fenantrenos/farmacologia , Lectinas de Plantas/análise , Neuropatia Ciática/fisiopatologia , Células Receptoras Sensoriais/metabolismo , Animais , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Gânglios Espinais/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Knockout , Regeneração Nervosa/efeitos dos fármacos , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Crescimento Neuronal/efeitos dos fármacos , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Células Receptoras Sensoriais/química , Células Receptoras Sensoriais/classificação , Células Receptoras Sensoriais/efeitos dos fármacos
11.
Cell Commun Signal ; 18(1): 46, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183816

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) has been described as an attractive target for antiangiogenic therapy. Exosomes are small extracellular vesicles secreted by most cell types and contribute to cell-to-cell communication by delivering functional cargo to recipient cells. The expression of ANGPT2 in tumor-derived exosomes remains unknown. METHODS: We detected the ANGPT2 expression in HCC-derived exosomes by immunoblotting, enzyme-linked immunosorbent assay and immunogold labeling, then observed exosomal ANGPT2 internalization and recycling by confocal laser scanning microscopy, co-immunoprecipitation and immunoblotting. We used two HCC cell lines (Hep3B and MHCC97H) to overexpress ANGPT2 by lentivirus infection or knockdown ANGPT2 by the CRISPR/Cas system, then isolated exosomes to coculture with human umbilical vein endothelial cells (HUVECs) and observed the angiogenesis by Matrigel microtubule formation assay, transwell migration assay, wound healing assay, cell counting kit-8 assay, immunoblotting and in vivo tumorigenesis assay. RESULTS: We found that HCC-derived exosomes carried ANGPT2 and delivered it into HUVECs by exosome endocytosis, this delivery led to a notable increase in angiogenesis by a Tie2-independent pathway. Concomitantly, we observed that HCC cell-secreted exosomal ANGPT2 was recycled by recipient HUVECs and might be reused. In addition, the CRISPR-Cas systems to knock down ANGPT2 significantly inhibited the angiogenesis induced by HCC cell-secreted exosomal ANGPT2, and obviously suppressed the epithelial-mesenchymal transition activation in HCC. CONCLUSIONS: Taken together, these results reveal a novel pathway of tumor angiogenesis induced by HCC cell-secreted exosomal ANGPT2 that is different from the classic ANGPT2/Tie2 pathway. This way may be a potential therapeutic target for antiangiogenic therapy. Video Abstract.


Assuntos
Angiopoietina-2/fisiologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica
12.
Biol Pharm Bull ; 43(1): 145-152, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31666439

RESUMO

Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Lignanas/farmacologia , Compostos Policíclicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Ciclo-Octanos/isolamento & purificação , Ciclo-Octanos/farmacologia , Relação Dose-Resposta a Droga , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/genética , Hepatócitos/metabolismo , Humanos , Lignanas/isolamento & purificação , Compostos Policíclicos/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Schisandra/química
13.
Proc Natl Acad Sci U S A ; 113(41): 11431-11435, 2016 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-27671635

RESUMO

The nearly circular (mean eccentricity [Formula: see text]) and coplanar (mean mutual inclination [Formula: see text]) orbits of the solar system planets motivated Kant and Laplace to hypothesize that planets are formed in disks, which has developed into the widely accepted theory of planet formation. The first several hundred extrasolar planets (mostly Jovian) discovered using the radial velocity (RV) technique are commonly on eccentric orbits ([Formula: see text]). This raises a fundamental question: Are the solar system and its formation special? The Kepler mission has found thousands of transiting planets dominated by sub-Neptunes, but most of their orbital eccentricities remain unknown. By using the precise spectroscopic host star parameters from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) observations, we measure the eccentricity distributions for a large (698) and homogeneous Kepler planet sample with transit duration statistics. Nearly half of the planets are in systems with single transiting planets (singles), whereas the other half are multiple transiting planets (multiples). We find an eccentricity dichotomy: on average, Kepler singles are on eccentric orbits with [Formula: see text] 0.3, whereas the multiples are on nearly circular [Formula: see text] and coplanar [Formula: see text] degree) orbits similar to those of the solar system planets. Our results are consistent with previous studies of smaller samples and individual systems. We also show that Kepler multiples and solar system objects follow a common relation [[Formula: see text](1-2)[Formula: see text]] between mean eccentricities and mutual inclinations. The prevalence of circular orbits and the common relation may imply that the solar system is not so atypical in the galaxy after all.

14.
Chemistry ; 23(28): 6752-6756, 2017 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-28346763

RESUMO

HOMO-raising noncovalent activation of α-aryl α,ß-unsaturated aldehydes using a bifunctional Brønsted base catalyst is achieved. The catalytically generated dienolate intermediate undergoes all-carbon [4+2] cyclizations with nitroolefins, leading to chiral cyclohexenes with four contiguous stereocenters in high yields and with excellent enantioseletivity. Furthermore, the diastereodivergent synthesis of the products is realized by introducing a second steric control to the bifunctional catalyst; 4 isomers out of 16 possible stereoisomers of the products were selectively produced by simple use of two catalysts and their (pseudo)enantiomers. The results presented here provide new insights into the remote activation of the carbonyl functionality as well as the stereodivergent synthesis of complex chiral molecules with multiple stereocenters.

15.
J Org Chem ; 81(21): 10532-10537, 2016 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-27649297

RESUMO

A highly regioselective DBU-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman carbonates with isothiocyanates was developed. This method allows rapid and efficient synthesis of spirocyclic oxindole dihydrothiophene products in moderate to high yields with excellent regioselectivities under simple conditions. A plausible reaction mechanism is also proposed.

16.
Sensors (Basel) ; 16(12)2016 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-27941702

RESUMO

In this research, the novel concept of a resonance-based reflector (RBR) was proposed, and a ring-shaped RBR was utilized to design a unidirectional antenna with low-profile and broadband characteristics. Research found the ring operates as two half-wavelength (λ/2) resonators. Then, the resonance effect transforms the reflection phase of the ring RBR, and achieves a reflection phase of 0° < ϕ < 180° in a wide frequency range above the resonance. Then, the in-phase reflection characteristic (-90° < ϕ < 90°) can be obtained in the wide frequency band by placing an antenna above the RBR with a distance smaller than λ/4. Two unidirectional antennas, named Case 1 and Case 2, were designed with the ring-shaped RBRs and bowtie antennas (RBR-BAs). The impedance bandwidths of Case 1 and the Case 2 are 2.04-5.12 GHz (86.3%) and 1.97-5.01 GHz (87.1%), respectively. The front-to-back ratio (FBR, an important parameter to measure the unidirectional radiation) of Case 1 ranges from 5-9.9 dB for frequencies 2.04-2.42 GHz, and the FBR of Case 2 ranges from 5-16 dB for frequencies 2.16-3.15 GHz. The proposed concept of RBR is desirable in wideband unidirectional antenna design, and the designing antennas can be used at the front end of wireless systems-such as indoors communication, remote sensing, and wireless sensor systems-for signal receiving or transmitting.

17.
Yao Xue Xue Bao ; 51(6): 961-4, 2016 06.
Artigo em Zh | MEDLINE | ID: mdl-29883073

RESUMO

Two new flavonoid glycosides were isolated from the aerial parts of Nervilia fordii by various chromatographies such as D101 macroporous resin, ODS and preparative HPLC chromatographic techniques. Their structures were elucidated as rhamnocitrin-3-O-ß-glucopyranosyl-4'-O-ß-galactosyl-(1→3)-glucopyranoside(1) and 7,3'-di-O-methylquercetin-4'-O-[ß-galactosyl-(1→3)-ß-glucopyranosyl]-3-O-ß-glucopyranoside(2) on the basis of extensive spectroscopic analyses, including 1D-, 2D-NMR, HR-ESI-MS and analytical hydrolysis.


Assuntos
Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Orchidaceae/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Hidrólise , Estrutura Molecular
18.
J Immunol ; 190(8): 4027-36, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23514740

RESUMO

TNFR-associated factor (TRAF)6 is an essential ubiquitin E3 ligase in immune responses, but its function in adaptive immunity is not well understood. In this study, we show that TRAF6 is recruited to the peripheral ring of the T cell immunological synapse in Jurkat T cells or human primary CD4(+) T cells conjugated with staphylococcal enterotoxin E-pulsed B cells. This recruitment depends on TRAF6 interacting with linker for activation of T cells (LAT) via its TRAF domain. Although LAT was indispensable for TCR/CD28-induced TRAF6 ubiquitination and its ligase activity, RNA interference-induced TRAF6 knockdown in T cells decreased TCR/CD28-induced LAT ubiquitination, tyrosine phosphorylation, and association with tyrosine kinase ZAP70. Overexpression of TRAF6 or its catalytically inactive form C70A promoted and decreased, respectively, LAT tyrosine phosphorylation upon stimulation. Moreover, LAT was ubiquitinated at Lys(88) by TRAF6 via K63-linked chain. In addition, TRAF6 was required for and synergized with LAT to promote the TCR/CD28-induced activation of NFAT. These results reveal a novel function and mechanism of TRAF6 action in the TCR-LAT signaling pathway distinct from its role in TCR-induced NF-κB activation, indicating that LAT also plays an adapter role in TCR/CD28-induced activation of TRAF6.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Membrana/metabolismo , Mapeamento de Interação de Proteínas/métodos , Receptores de Antígenos de Linfócitos T/fisiologia , Transdução de Sinais/imunologia , Fator 6 Associado a Receptor de TNF/fisiologia , Antígenos CD28/fisiologia , Células HEK293 , Humanos , Células Jurkat , Fosforilação/imunologia , Cultura Primária de Células , Fator 6 Associado a Receptor de TNF/deficiência , Fator 6 Associado a Receptor de TNF/metabolismo , Ubiquitinação/imunologia
19.
Chin Med Sci J ; 30(1): 28-33, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25837357

RESUMO

OBJECTIVE: To analyze the short-term outcomes of redo coronary artery bypass grafting (CABG) using on-pump and off-pump CABG techniques. METHODS: From January 2003 to August 2013, non-randomized 80 patients were treated with redo CABG in the Department of Cardiac Surgery, Peking University Third Hospital. Among these patients, 40 underwent on-pump CABG technique (redo-ONCAB group) and 40 underwent off-pump CABG technique (redo-OPCAB group). Furthermore, transmyocardial laser revascularization was performed in high-risk patients who were not suitable to conventional grafting. Clinical data of the two groups were recorded and analyzed including operation time, coronary grafts, incomplete revascularization, postoperative ventilation, perioperative stroke, and low output syndrome, etc. RESULTS: There were no significantly differences in age, gender distribution, incidences of hypertension, stroke, and other clinical characteristics between redo-OPCAB group and redo-ONCAB group (all P>0.05), except for incidences of renal dysfunction and pulmonary disease (all P<0.05). The number of grafting vessels in the redo-ONCAB and redo-OPCAB groups was 2.1 ± 0.74 and 1.4 ±0.52 respectively. There was significant difference between the two groups (P=0.0243). Compared with the redo-ONCAB group, there was shorter operation time (P=0.0045), postoperative ventilation (P=0.0211) and intensive care unit stay (P=0.0400), as well as fewer use of platelet (P=0.0338) and blood transfusion (P=0.0034) in the redo-OPCAB group. The incidence of incomplete revascularization (P=0.0253) and the use of transmyocardial laser revascularization (P=0.0052) were higher in the redo-OPCAB group than those in the redo-ONCAB group (all P<0.05). However, no significant differences were showed for the incidence of the use of intra aortic balloon pump and continuous renal replacement therapy, perioperative stroke, low output syndrome, and in-hospital mortality between the two groups (all P>0.05). CONCLUSION: Redo CABG is the safety and efficacy surgical procedure, and redo-OPCAB technique with better outcomes is commended especially in high-risk patients.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Reoperação , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(5): 769-73, 2015 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-26474613

RESUMO

OBJECTIVE: To investigate the predicting value of European system for cardiac operative risk evaluation (EuroSCORE) and sino system for coronary operative risk evaluation (SinoSCORE) in early quality of life of patients after coronary artery bypass surgery (CABG). METHODS: A total of 218 consecutive patients who underwent CABG from March 2010 to January 2013 were evaluated with both systems before operation. Health related quality of life (QoL) was estimated by using 36-item short form health survey (SF-36) preoperatively and postoperatively in order to evaluate the predicting value of the two systems in early post-operative QoL. Calibration was evaluated by Hosmer-l,emeshow goodness-of-fit test.Discrimination was tested by determining the area under the receiver operating characteristic (ROC) curve. RESULTS: There was no significant difference between the accumulation of the EuroSCORE and SinoSCORE in the all patients (t=-0.904, P=0.368), When using Wilcoxon test on life quality in the preoperative and postoperative patients respectively,the data showed that the quality of life improved significantly in various dimensions of the postoperative patients (Z=-2.886, P<0.001).Except for bodily pain (BP) and mental health (MH), statistically significant correlation was found between the preoperative risk evaluation scores and the postoperative QoL scores (r:-0.203 to -0.493, P<0.05). Logistic regression analyses indicated that both the scores emerged as the independent predictor for a relatively worse QoL (OR>1, P<0.05). Furthermore, the EuroSCORE predicted the outcome with a higher OR. For SinoSCORE the Hosmer-Lemeshow test was significant (P=0.628) and the area under ROC curve was 0.754.For the EuroSCORE the Hosmer-Lemeshow test was significant (P=0.538) and the area under ROC curve was 0.854. CONCLUSION: Both EuroSCORE and SinoSCORE could be viewed as a predictor for several aspects of postoperative QoL, while EuroSCORE might have a greater predicting value.


Assuntos
Ponte de Artéria Coronária , Mortalidade Hospitalar , Qualidade de Vida , Humanos , Período Pós-Operatório , Valor Preditivo dos Testes , Curva ROC , Medição de Risco
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