Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 350
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chem Commun (Camb) ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32195505

RESUMO

Sortase is one of the most widely used enzymes for covalent protein conjugation that links protein and protein/small molecules together in a site-specific way. It typically recognizes the "GGG" and "LPXTG" peptide sequences and conjugates them into an "LPXTGGG" linker. As a non-natural linker with several flexible glycine residues, it is unknown whether it affects the properties of the conjugated protein. To verify the use of sortase for protein-protein conjugation, we combined single-molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulations to characterize sortase-conjugated polyprotein I27 with three different linkers. We found that the I27 with classic linkers "LPETGGG" and "LPETG" from sortase ligation were of normal stability. However, a protein with a longer artificial linker "LPETGGGG" showed a 15% lower unfolding force. MD simulations revealed that the 4G linker showed a high probability of a closed conformation, in which the adjacent monomer has transient protein-protein interaction. Thus, we verify the use of sortase for protein conjugation, and a longer linker with a higher glycine content should be used with caution.

2.
Theriogenology ; 148: 8-17, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32126395

RESUMO

To determine the role of 3, 3', 5-triiodo-L thyroxine (T3) in the differentiation of Sertoli cells (SCs) and the factors influencing maturity via the Wilms' tumor 1 (WT1)/non-canonical Wnt signaling pathway, high purity SCs were isolated from newborn calves' testes and cultured in vitro. The SCs were stimulated with T3, and co-treated with short interference (si) RNA to knockdown endogenous WT1 and non-canonical Wnt signalling inhibitor Wnt-c59. Our results suggested that the addition of different concentrations (0, 25, 50, and 100 nM) of T3 in the culture medium changed the expression of KRT-18 (SCs immature marker) and accelerated the differentiation of SCs. T3 (100 nM) treatment induced up-regulated expression of WT1 over time (p < 0.05), while the expression of polarity proteins (Par3, Par6b, and E-cadherin) and Wnt4 were affected to varying degrees (p < 0.05). SCs were treated simultaneously with T3 + Wnt-c59 and T3 + WT1 siRNA, and the results showed that T3 could affect the expression of polarity proteins via WT1/non-canonical Wnt signaling pathway. These data put together indicate that T3 plays a dependent role in the induction of bovine SCs differentiation via WT1/non-canonical Wnt signaling pathway in vitro. This study proposes for the first time that WT1 is a major target for T3.

3.
Lipids Health Dis ; 19(1): 37, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164735

RESUMO

BACKGROUND: The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms. METHODS: Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients. RESULTS: A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3. CONCLUSIONS: The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.

4.
Transl Psychiatry ; 10(1): 95, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179735

RESUMO

Major depressive disorder (MDD) is a prevalent and debilitating psychiatric mood disorder that lacks objective laboratory-based tests to support its diagnosis. A class of microRNAs (miRNAs) has been found to be centrally involved in regulating many molecular processes fundamental to central nervous system function. Among these miRNAs, miRNA-134 (miR-134) has been reported to be related to neurogenesis and synaptic plasticity. In this study, the hypothesis that plasma miR-134 can be used to diagnose MDD was tested. Perturbation of peripheral and central miR-134 in a depressive-like rat model was also examined. By reverse-transcription quantitative PCR, miR-134 was comparatively measured in a small set of plasma samples from MDD and healthy control (HC) subjects. To determine its diagnostic efficacy, plasma miR-134 levels were assessed in 100 MDD, 50 bipolar disorder (BD), 50 schizophrenic (SCZ), and 100 HC subjects. A chronic unpredictable mild stress (CUMS) rat model was also developed to evaluate miR-134 expression in plasma, hippocampus (HIP), prefrontal cortex (PFC), and olfactory bulb. We found that plasma miR-134 was significantly downregulated in MDD subjects. Diagnostically, plasma miR-134 levels could effectively distinguish MDD from HC with 79% sensitivity and 84% specificity, while distinguishing MDD from HC, BD, and SCZ subjects with 79% sensitivity and 76.5% specificity. Congruent with these clinical findings, CUMS significantly reduced miR-134 levels in the rat plasma, HIP, and PFC. Although limited by the relatively small sample size, these results demonstrated that plasma miR-134 displays potential ability as a biomarker for MDD.

5.
Psychoneuroendocrinology ; 114: 104594, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32007669

RESUMO

Second generation antipsychotics, particularly olanzapine, induce severe obesity, which is associated with their antagonistic effect on the histamine H1 receptor (H1R). We have previously demonstrated that oral administration of olanzapine increases the concentration of neuropeptide Y (NPY) in the hypothalamus of rats, accompanied by hyperphagia and weight gain. However, it is unclear if the increased NPY after olanzapine administration is due to its direct effect on hypothalamic neurons and its H1R antagonistic property. In the present study, we showed that with an inverted U-shape dose-response curve, olanzapine increased NPY expression in the NPY-GFP hypothalamic neurons; however, this was not the case in the hypothalamic neurons of H1R knockout mice. Olanzapine inhibited the interaction of H1R and GHSR1a (ghrelin receptor) in the primary mouse hypothalamic neurons and NPY-GFP neurons examined by confocal fluorescence resonance energy transfer (FRET) technology. Furthermore, an H1R agonist, FMPH inhibited olanzapine activation of GHSR1a downstream signaling pAMPK and transcription factors of NPY (pFOXO1 and pCREB) in the hypothalamic NPY-GFP cell. However, an olanzapine analogue (E-Olan) with lower affinity to H1R presented negligible enhancement of pCREB within the nucleus of NPY neurons. These findings suggest that the H1R antagonist property of olanzapine inhibits the interaction of H1R and GHSR1a, activates GHSR1a downstream signaling pAMPK-FOXO1/pCREB and increases hypothalamic NPY: this could be one of the important molecular mechanisms of H1R antagonism of olanzapine-induced obesity in antipsychotic management of psychiatric disorders.

6.
Reprod Fertil Dev ; 32(5): 522-530, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32023428

RESUMO

The gap junction protein connexin (Cx) 43 between adjacent Sertoli cells (SCs) is the main testicular factor regulating the growth and development of SCs, and plays a vital role in controlling cell differentiation and maturation. However, the endogenous testicular factors that regulate Cx43 and the downstream signalling pathways that mediate Cx43-dependent SC differentiation are unclear. In this study, high-purity SCs were isolated from newborn calves' testes by differential adherence. The SCs were then cultured invitro and treated with short interference RNA to knockdown endogenous Wilms' tumour 1 (WT1). In WT1-knockdown SCs, Cx43 expression was upregulated. To elucidate the intracellular signalling mechanism of Cx43 in the differentiation and maturation of immature SCs, SCs were treated simultaneously with non-canonical Wnt signalling inhibitors CCG-1423 and GO-6983; in these SCs, Cx43 expression was upregulated. Together, these data indicate that WT1 negatively regulates the expression of Cx43 produced from SCs via a non-canonical Wnt signalling pathway in cultured bovine SCs.

7.
J Phys Chem Lett ; : 1947-1953, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32079400

RESUMO

Plasmonic optical antennas (POAs), often constructed from gold or silver nanostructures, can enhance the radiation efficiency of emitters coupled to POAs and are applied in surface-enhanced Raman spectroscopy (SERS) and light-emitting devices. Over the past four decades, radiation enhancement factors (REFs) of POA-emitter systems were considered to be difficult to calculate directly and have been predicted indirectly and approximately, assuming POAs are illuminated by electromagnetic plane waves without emitters. The validity of this approximation remains a significant open problem in SERS theory. Herein, we develop a method based on the rigorous optical reciprocity theorem for accurately calculating the REFs of emitters in nanoparticle-substrate nanogaps for single-molecule SERS and scanning probe-substrate nanogaps for tip-enhanced Raman spectroscopy. We show that the validity of the plane wave approximation breaks down if high-order plasmonic modes are excited. The as-developed method paves the way toward designing high-REF POA nanostructures for luminescence-related devices.

8.
Inhal Toxicol ; 32(1): 24-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32028803

RESUMO

Objective: In this study, we compared in vitro and in vivo bioactivity of nitrogen-doped multi-walled carbon nanotubes (NDMWCNT) to MWCNT to test the hypothesis that nitrogen doping would alter bioactivity.Materials and Methods: High-resolution transmission electron microscopy (TEM) confirmed the multilayer structure of MWCNT with an average layer distance of 0.36 nm, which was not altered by nitrogen doping: the nanomaterials had similar widths and lengths. In vitro studies with THP-1 cells and alveolar macrophages from C57BL/6 mice demonstrated that NDMWCNT were less cytotoxic and stimulated less IL-1ß release compared to MWCNT. For in vivo studies, male C57BL/6J mice received a single dose of dispersion medium (DM), 2.5, 10 or 40 µg/mouse of NDMWCNT, or 40 µg/mouse of MWCNT by oropharyngeal aspiration. Animals were euthanized between 1 and 7 days post-exposure for whole lung lavage (WLL) studies.Results and Discussion: NDMWCNT caused time- and dose-dependent pulmonary inflammation. However, it was less than that caused by MWCNT. Activation of the NLRP3 inflammasome was assessed in particle-exposed mice by determining cytokine production in WLL fluid at 1 day post-exposure. Compared to DM-exposed mice, IL-1ß and IL-18 were significantly increased in MWCNT- and NDMWCNT-exposed mice, but the increase caused by NDMWCNT was less than MWCNT. At 56 days post-exposure, histopathology determined lung fibrosis in MWCNT-exposed mice was greater than NDMWCNT-exposed mice.Conclusions: These data indicate nitrogen doping of MWCNT decreases their bioactivity, as reflected with lower in vitro and in vivo toxicity inflammation and lung disease. The lower activation of the NLRP3 inflammasome may be responsible. Abbreviations: NDMWCNT: nitrogen-doped multi-walled carbon nanotubes; MWCNT: multi-walled carbon nanotubes; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; IL-1ß: interleukin-1ß; DM: dispersion medium; WLL: whole lung lavage; IL-18: interleukin-18; GSD: geometric standard deviation; XPS: X-ray photoelectron spectroscopy; SEM: standard error of the mean; PMA: phorbol 12-myristate 13-acetate; LPS: lipopolysacharride; LDH: lactate dehydrogenase; AM: alveolar macrophage; PMN: polymorphonuclear leukocyte.

9.
J Vis Exp ; (156)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32091003

RESUMO

Chemical and bio-conjugation techniques have been developed rapidly in recent years and allow the building of protein polymers. However, a controlled protein polymerization process is always a challenge. Here, we have developed an enzymatic methodology for constructing polymerized protein step by step in a rationally-controlled sequence. In this method, the C-terminus of a protein monomer is NGL for protein conjugation using OaAEP1 (Oldenlandia affinis asparaginyl endopeptidases) 1) while the N-terminus was a cleavable TEV (tobacco etch virus) cleavage site plus an L (ENLYFQ/GL) for temporary N-terminal protecting. Consequently, OaAEP1 was able to add only one protein monomer at a time, and then the TEV protease cleaved the N-terminus between Q and G to expose the NH2-Gly-Leu. Then the unit is ready for next OaAEP1 ligation. The engineered polyprotein is examined by unfolding individual protein domain using atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS). Therefore, this study provides a useful strategy for polyprotein engineering and immobilization.

10.
Mol Psychiatry ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959849

RESUMO

Major depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of L-acetylcarnitine, creatinine, L-asparagine, L-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, L-serine, oleic acid, myo-inositol, dodecanoic acid, L-methionine, hypoxanthine, palmitic acid, L-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. L-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of L-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan-kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased L-tryptophan and kynurenic acid levels, and alterations in the tryptophan-kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.

11.
Int J Oncol ; 56(3): 783-793, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922213

RESUMO

The effective antitumor drug evodiamine (EVO) is attracting increased attention. Therefore, the present study aimed to investigate the effects of EVO on the proliferation, apoptosis and autophagy of human pancreatic cancer (PC) cell lines in vitro and in vivo. Human PANC­1 and SW1990 PC cell lines were treated with different concentrations of EVO and proliferation was detected using a Cell Counting Kit (CCK)­8 assay. Colony formation and wound­healing assays showed that EVO inhibited PC cell viability and migration, and apoptosis was detected using flow cytometry. Western blotting and immunofluorescence detected the expression of proteins in PANC­1 and SW1990 cells. The PANC­1 cells were used to establish an orthotopic pancreatic tumor model in nude mice. Tumor­bearing nude mice were administered with different concentrations of EVO, and growth was monitored. High­resolution positron emission tomography and fluorine­18­labeled fluorodeoxyglucose were used to monitor the tumor/non­tumor (T/NT) ratio and standard uptake value (SUV) of the mice, which were subsequently sacrificed to measure the transplanted tumor weight. Apoptosis increased with increasing EVO concentration. The EVO­treated PC cells exhibited significantly higher expression of LC3II than the controls cells. EVO decreased LC3II, enhanced P62 and inhibited the expression of Akt, extracellular­signal­regulated protein kinase (ERK)1/2 and p38. Compared with the control group, the T/NT ratio, SUV and tumor weight decreased more markedly in the EVO­treated group. The tumor expression of phosphorylated AKT, detected using immunohistochemistry, decreased with increasing EVO doses in vivo. EVO induced PC cell apoptosis by inhibiting phosphoinositide 3­kinase/AKT and mitogen­activated protein kinase/ERK and inhibiting the phosphorylation of signal transducer and activator of transcription activator 3 in PC cells to inhibit autophagy, suggesting that EVO may be considered as a novel PC treatment.

12.
ChemSusChem ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31994308

RESUMO

Owing to its large capacity and high average potential, the structure and reversible O-redox compensation mechanism of Na2 Mn3 O7 have recently been analyzed. However, capacity fade and low coulombic efficiency over multiple cycles have also been found to be a problem, which result from oxygen evolution at high charge voltages. Herein, a Na0.44 MnO2 ⋅Na2 Mn3 O7 heterojunction of primary nanosheets was prepared by a sol-gel-assisted high-temperature sintering method. In the nanodomain regions, the close contact of Na0.44 MnO2 not only supplies multidimensional channels to improve the rate performance of the composite, but also plays the role of pillars for enhancing the cycling stability and coulombic efficiency; this is accomplished by suppressing oxygen evolution, which is confirmed by high-resolution (HR)TEM, cyclic voltammetry, and charge/discharge curves. As the cathode of a Na-ion battery, at 200 mA g-1 after 100 cycles, the Na0.44 MnO2 ⋅Na2 Mn3 O7 heterojunction retains an 88 % capacity and the coulombic efficiency approaches 100 % during the cycles. At 1000 mA g-1 , the Na0.44 MnO2 ⋅Na2 Mn3 O7 heterojunction has a discharge capacity of 72 mAh g-1 . In addition, the average potential is as high as 2.7 V in the range 1.5-4.6 V. The above good performances indicate that heterojunctions are an effective strategy for addressing oxygen evolution by disturbing the long-range order distribution of manganese vacancies in the Mn-O layer.

13.
Nucl Med Commun ; 41(3): 219-227, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31895760

RESUMO

BACKGROUND: To compare the accuracy of various equations for estimating glomerular filtration rate. METHODS: Chronic kidney disease was classified by Tc-DTPA scintigraphy (reference glomerular filtration rate), estimating glomerular filtration rate was estimated using various formulas. The similarity to reference glomerular filtration rate decide the accuracy of estimating glomerular filtration rate. RESULTS: Overall, the Fengscr-cys equation had significantly higher accuracy and correct proportion in chronic kidney disease stage classification than other equations. The subgroup analysis showed that Fengscr-cys equation was slightly more precise than other equations both in the male and female patients. Moreover, in patients older than 60 years or whose reference glomerular filtration rate was above 60 ml/min, Fengscr-cys equation also showed better accuracy. CONCLUSION: Our data suggest that estimating glomerular filtration rate equations evaluated by serum cystatin C were better than serum creatinine-based equations, estimating glomerular filtration rate equations evaluated by both serum creatinine and cystatin C were better than those evaluated by serum creatinine or cystatin C alone. Among all enrolled equations, Fengscr-cys equation might be the best one to evaluate glomerular filtration rate in general Chinese paticipants.

14.
Oncol Rep ; 43(1): 41-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31661139

RESUMO

Several proteins in the iRhom family function as oncogenic regulators in certain cancers. However, the function of these proteins in cervical cancer (CC) is unknown. The relationship of iRhom1 and iRhom2 expression with the clinicopathological features and prognosis of patients with CC was investigated, and their possible molecular mechanisms were examined using in vitro experiments. The expression of iRhom1 and iRhom2 in CC samples of 83 patients was determined by immunohistochemistry (IHC), and the associations of their expression with the clinicopathological features of patients were determined. The relationship of iRhom1, iRhom2, and Ki­67 expression with survival rates was determined using Kaplan­Meier analysis and Cox regression analyses. HeLa cells were analyzed using MTT assays, cell cycle analysis, and apoptosis assays. The results revealed that CC tissues had higher levels of iRhom1 and iRhom2 than adjacent normal tissues. Increased expression of iRhom1, iRhom2, and K­i67 was significantly associated with tumor stage, size, and parametrium invasion. High expression of iRhom1, iRhom2 and Ki­67 was correlated with poor outcomes. Cancer stage and iRhom2 expression were independent prognostic indicators of CC. Knockdown of iRhom1 and iRhom2 in HeLa cells inhibited cell proliferation, promoted the G1 phase and relieved S­phase arrest, and induced apoptosis. Genomic microarray analysis indicated that iRhom2 knockdown altered several pathways with roles in oncogenesis, including the expression of five genes in the Wnt/ß­catenin pathway. Western blotting in HeLa cells revealed that iRhom1 knockdown significantly suppressed the expression of ß­catenin, Myc, p­EGFR and TGFBR2, and increased the expression of FAS; iRhom2 knockdown significantly suppressed the expression of ß­catenin, GSK3ß, p­EGFR and Myc. These results were consistent with the genomic microarray data. Collectively, the results indicated that iRhom1 and iRhom2 may function as oncogenes in CC and are potential therapeutic targets.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31676463

RESUMO

Pigment epithelium-derived factor (PEDF, also known as SERPINF1) is a secreted glycoprotein with neuroprotective effects. However, the potential role of PEDF in major depressive disorder (MDD) remains largely unknown. Here, applying two-dimensional gel electrophoresis (2-DE) proteomics, we found that PEDF levels were significantly decreased in the plasma of 12 first-episode treatment-naïve MDD patients (FETND) compared to the levels in 12 healthy controls (HCs). PEDF levels were especially lower in MDD patients than in HCs and patients with bipolar disorder (BD) and schizophrenia (SCZ), and elevated PEDF were consistent with decreased HAM-D scores in patients given antidepressant therapy (ADT). Animal research indicated that PEDF was decreased in the periphery and hippocampus of two well-known depression rodent models (the chronic unpredictable mild stress (CUMS) rat model and chronic social defeat stress (CSDS) mouse model). Decreased PEDF levels in the hippocampus led to depressive-like behaviors, synaptic impairments and aberrant Wnt signaling in C57BL mice, while increased PEDF resulted in the opposite results. Mechanistic studies indicated that PEDF contributes to dendritic growth and Wnt signaling activation in the hippocampus of adult mice. Taken together, the results of our study demonstrate the involvement of PEDF and its related mechanism in depression, thus providing translational evidence suggesting that PEDF may be a novel therapeutic target for depression.

16.
J Chem Inf Model ; 60(2): 653-660, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31790241

RESUMO

Iron-sulfur (FeS) clusters are essential metal cofactors involved in a wide variety of biological functions. Their catalytic efficiency, biosynthesis, and regulation depend on FeS stability in aqueous solution. Here, molecular modeling is used to investigate the hydrolysis of an oxidized (ferric) mononuclear FeS cluster by bare dissociation and water substitution mechanisms in neutral and acidic solution. First, approximate electronic structure descriptions of FeS reactions by density functional theory are validated against high-level wave function CCSD(T) calculations. Solvation contributions are included by an all-atom model with hybrid quantum chemical/molecular mechanical (QM/MM) potentials and enhanced sampling molecular dynamics simulations. The free energy profile obtained for FeS cluster hydrolysis indicates that the hybrid functional M06 together with an implicit solvent correction capture the most important aspects of FeS cluster reactivity in aqueous solution. Then, 20 reaction channels leading to two consecutive Fe-S bond ruptures were explored with this calibrated model. For all protonation states, nucleophilic substitution with concerted bond breaking and forming to iron is the preferred mechanism, both kinetic and thermodynamically. In neutral solution, proton transfer from water to the sulfur leaving group is also concerted. Dissociative reactions show higher barriers and will not be relevant for FeS reactivity when exposed to solvent. These hydrolysis mechanisms may help to explain the stability and catalytic mechanisms of FeS clusters of multiple sizes and proteins.

17.
J Stroke Cerebrovasc Dis ; 29(2): 104512, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786044

RESUMO

BACKGROUND: Extracranial carotid artery (ECA) tortuosity may influences successful recanalization rates of mechanical thrombectomy in acute ischemic stroke (AIS), yet the relationship between ECA tortuosity and the prognosis of patients with anterior circulation AIS who cannot undergo endovascular treatment remains uncertain. We hypothesized that increased tortuosity of the ECA leads to unfavorable outcomes in such patients. METHODS: Patients with anterior circulation AIS who underwent computed tomography angiography of the head and neck in our hospital between March 2018 and November 2018 were retrospectively analyzed. The tortuosity of the bilateral ECA was measured, and functional outcomes were evaluated by a modified Rankin Scale (mRS) at 90 days. Multivariate logistic regression models were used to determine the association between ECA tortuosity and outcomes of patients. RESULTS: A total of 203 patients were enrolled in our study, including 140 patients (68.97%) with favorable outcomes (mRS, 0-2) and 63 patients (31.03%) with unfavorable outcomes (mRS, 3-6). After adjusting for age, atrial fibrillation, stroke territory, and posthospital antithrombotics/statins therapy in multivariate logistic regression model I, ECA tortuosity (odds ratio, 1.052; 95% confidence interval, 1.010-1.096; P = .015) was an independent risk of unfavorable outcomes in enrolled patients. In the other 2 models (II and III) which adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, and with or without posthospital medication, ECA tortuosity was also showed independent relationship to unfavorable outcomes. The optimal cutoff was 12.5 to predict the unfavorable outcomes in a receiver operating characteristic curve. CONCLUSIONS: Our study demonstrated that the ECA tortuosity is an independent predictor of unfavorable outcomes for anterior circulation AIS patients who without undergoing endovascular treatment after hospital admission. ECA tortuosity values greater than 12.5 may indicate an unfavorable outcome.


Assuntos
Isquemia Encefálica/terapia , Artérias Carótidas/diagnóstico por imagem , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Artérias Carótidas/fisiopatologia , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
18.
J Plant Physiol ; 244: 153089, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812904

RESUMO

Inorganic phosphate (Pi) starvation severely affects the normal growth and development of plants. Here, a Pi-responsive gene, named MdMYB2 (MDP0000823458), was cloned and functionally identified in apple. Overexpression of MdMYB2 regulated the expression of Pi starvation-induced (PSI) genes and then promoted phosphate assimilation and utilization. The ectopic expression of MdMYB2 in Arabidopsis influenced plant growth and flowering, which was partially rescued by application of exogenous gibberellin (GA). These results indicated that MdMYB2 may be an essential regulator in phosphate utilization and GA-regulated plant growth and development.

19.
Nanoscale ; 12(2): 832-842, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31830188

RESUMO

Spectrally rich but geometrically simple plasmonic metallic nanoparticles are highly favored in nanophotonics. However, they remain elusive owing to the symmetry-induced mode degeneracy and interband transition-induced plasmonic damping. Hence, most nanoparticles exhibit a single major extinction peak originating from the lowest-order dipole resonance. In this study, we uncover that even a simple tetrahedral nanoparticle supports rich spectral features due to symmetry breaking. This discovery runs counter to the reported gold tetrahedral nanoparticles, where only a single extinction peak was observed. We find that, in the case of a tetrahedral nanoparticle, the plasmonic quadrupole vertex mode becomes a bright mode and hybridizes with the dipole vertex mode, which splits the extinction peak and contributes to spectral diversity and tunability. The peak splitting is also found to be sensitively dependent on the roundness of vertices and edges. Furthermore, the tetrahedral depolarization factors are determined using the previously generalized absorption coefficient. We envision that this work will not only help fill the gap in understanding the optical properties enriched by symmetry breaking but also guide the superior probe design by combining spectral tunability with geometric simplicity of the nanoparticle.

20.
Org Lett ; 22(1): 300-304, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31841342

RESUMO

A selective C-O cross-coupling reaction between porphyrins and phenols has been developed through 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ)/Sc(OTf)3 oxidation, efficiently delivering meso-etherified porphyrins in good yields (≤93%). The radical complex process was proposed and calculated as the rationalized mechanism to block the homocoupling process. In addition, the switchable selective C-C cross-coupling reaction was achieved by using bulky electron-rich phenols and naphthols under DDQ oxidation conditions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA