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1.
Eur J Neurol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048389

RESUMO

BACKGROUND AND PURPOSE: Tirofiban administration during mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of low-dose rescue tirofiban regimen during MT for Chinese acute ischemic stroke (AIS) patients. METHODS: We derived patients from the ANGEL study, a multi-centric, prospective registry study that included AIS patients underwent MT owing to proximal large-artery occlusion from June 2015 to December 2017. The patients included were dichotomized into tirofiban and non-tirofiban group according to whether rescue tirofiban was performed during MT. Safety outcomes (symptomatic intracerebral hemorrhage [sICH], total ICH and distal embolization) and efficacy outcomes (artery recanalization and functional outcomes at three-month follow-up) were compared between groups using logistic regression analysis. RESULTS: A total of 662 patients were included in this study, wherein 230 (34.7%) were in tirofiban group. No significant differences of safety outcomes on sICH, total ICH, distal embolization and efficacy outcomes on artery recanalization, three-month functional independence were observed between tirofiban and non-tirofiban group either in the entire cohort, anterior circulation stroke (ACS) or posterior circulation stroke (PCS) patients (p>0.05 for all groups). However, low-dose rescue tirofiban was significantly correlated with three-month mortality reduction for PCS patients (adjusted hazard ratio= 0.35 [0.14-0.92], p=0.03). CONCLUSIONS: Low-dose rescue tirofiban during MT was not associated with increased risk of sICH, ICH, and distal embolization for AIS patients, and maybe correlated with three-month mortality reduction for PCS.

2.
Chem Commun (Camb) ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048636

RESUMO

It remains challenging to develop new materials exhibiting enzyme-like activities and understand the structure-property correlations and catalytic mechanisms. In this study, the characteristics, mechanisms, and applications of a light-activated mimic oxidase based on semiconducting polymer dots (Pdots) prepared from an organic conjugated polymer are demonstrated.

3.
Viruses ; 12(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023860

RESUMO

Non-human primates (NHP) are the only animal model suitable to evaluate the protection efficacy of HIV-1 vaccines. It is important to understand how and when neutralizing antibodies (nAbs) with specificities similar to those of human broadly neutralizing antibodies (bnAbs) develop in NHPs. To address these questions, we determined plasma neutralization specificities in two macaques which developed neutralization breadth after long-term simian/human immunodeficiency virus (SHIV) infection and identified neutralization escape mutations by analyzing the env sequences from longitudinal plasma samples. Neutralization activities targeting V2, CD4bs, V3 and gp120-gp41 interface only became detectable in week 350 plasma from macaques G1015R and G1020R using 25710 env mutants. When mapped with CAP45 env mutants, only V2 specificity was detected at week 217 and persisted until week 350 in G1015R. Neutralization escape mutations were found in CD4bs and V2 regions. However, all of them were different from those resistant mutations identified for human bnAbs. These results show that nAbs with specificities similar to human bnAbs are only detectable after long-term SHIV infection and that neutralization escape mutations in macaques are different from those found in HIV-1-infected individuals. These findings can have important implications in the best utilization of the NHP model to evaluate HIV-1 vaccines.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32009380

RESUMO

Many metal-organic frameworks have been designed and synthesized for biosensor due to high surface area and porosity, suitable size and good biocompatibility. Despite recent advances, however, most of them are only as the nanocarrier. In this work, a new artificial nanozyme was constructed on the metalloporphyrinic metal organic frameworks (PMOF(Fe)), which was formed by Fe porphyrin and Zr4+ ions. Then ultra-small Pt nanoparticles (Pt NPs) was loaded on the surface of PMOF(Fe) to form Pt@PMOF(Fe). Because of PMOF(Fe) with high surface area and exposed Fe activity centre, PMOF(Fe) works as the nanocarrier to hinder the Pt NPs aggregating and exhibits high peroxidase mimics activity. So, Pt NPs decorated on the surface of PMOF(Fe) possessed high stability and exhibited high activity. Due to the synergistic effect between PMOF(Fe) and Pt NPs, Pt@PMOF(Fe) exhibits superior catalase-like and peroxidase-like activity. Moreover, Pt@PMOF(Fe) possesses high electrocatalytic activity towards to the reduction of H2O2 and oxygen reduction reaction (ORR). This strategy may serve as a strong foundation to design MOF-based artificial nanozyme and develop an ideal platform for MOF and nanozymes toward artificial enzymatic catalytic systems, fuel cell and new analytical applications.

5.
BMC Med Genet ; 21(1): 27, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039712

RESUMO

BACKGROUND: Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present. METHODS: By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1. RESULTS: There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found. CONCLUSIONS: Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.

6.
Cell Signal ; : 109555, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032659

RESUMO

All-trans retinoic acid (ATRA)-based differentiation therapy has been unsuccessful in treating t(15;17) negative acute myeloid leukemia (AML) patients, motivating interest in combination therapies using ATRA plus other agents. Using the t (15, 17) negative HL-60 human myeloblastic leukemia model, we find that the cyclin-dependent kinase (CDK) inhibitor, roscovitine, augments signaling by an ATRA-induced macromolecular signalsome that propels differentiation and enhances ATRA-induced differentiation. Roscovitine co-treatment enhanced ATRA-induced expression of pS259- pS289/296/301- pS621-c-Raf, pS217/221-Mek, Src Family Kinases (SFKs) Lyn and Fgr and SFK Y416 phosphorylation, adaptor proteins c-Cbl and Slp-76, Vav, and acetylated 14-3-3 in the signalsome. Roscovitine enhanced ATRA-induced c-Raf interaction with Lyn, Vav, and c-Cbl. Consistent with signalsome hyper-activation, roscovitine co-treatment enhanced ATRA-induced G1/0 arrest and expression of differentiation markers, CD11b, ROS and p47 Phox. Because roscovitine regulated Lyn expression, activation and partnering, a stably transfected Lyn knockdown was generated from wt-parental cells to investigate its function in ATRA-induced differentiation. Lyn-knockdown enhanced ATRA-induced up-regulation of key signalsome molecules, c-Raf, pS259-c-Raf, pS289/296/301-c-Raf, Vav1, SLP-76, and Fgr, but with essentially total loss of pY416-SFK. Compared to ATRA-treated wt-parental cells, differentiation markers p47 phox, CD11b, G1/G0 arrest and ROS production were enhanced in ATRA-treated Lyn-knockdown stable transfectants, and addition of roscovitine further enhanced these ATRA-inducible markers. The Lyn-knockdown cells expressed slightly higher Raf, pS259-Raf, pS289/296/301-Raf, and Slp-76 than wt-parental cells, and this was associated with enhanced ATRA-induced upregulation of Fgr and cell differentiation, consistent with heightened signaling, suggesting that enhanced Fgr may have compensated for loss of Lyn to enhance differentiation in the Lyn-knockdown cells.

7.
J Neurointerv Surg ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034104

RESUMO

BACKGROUND AND PURPOSE: In-stent restenosis (ISR) is one of the long-term adverse outcomes of endovascular angioplasty and stenting for symptomatic intracranial arterial stenosis. In this study, we try to evaluate the safety and efficacy of endovascular treatment for intracranial ISR. METHODS: We retrospectively collected patients with intracranial ISR who underwent endovascular treatment from June 2012 to August 2019 at a high-volume stroke center. Successful recanalization was defined as ≤30% residual stenosis. Stroke, myocardial infarction, and death after stenting within 30 days were used to evaluate periprocedural safety. Recurrent stroke in the territory of the culprit vessel and re-ISR in patients with clinical and vascular imaging follow-up data were used to evaluate the long-term outcome. RESULTS: 32 patients (59.6±7.2 years old) with ISR were recruited, including 22 patients (68.8%) treated with balloon dilatation, 8 patients (25%) with stenting, and 2 patients (6.3%) with failed procedures. Successful recanalization was achieved in 71.9% (23/32) of patients. There was no stroke, myocardial infarction or death within 30 days after the procedure. Recurrent stroke was found in 10.7% (3/28) of the patients, and re-ISR was found in 42.1% (8/19) of the patients. The re-ISR rate was lower in patients with stenting than in those with balloon dilatation (0% vs 57.1%, p=0.090), and in patients with successful recanalization than in those with unsuccessful recanalization (33.3% vs 75.0%, p=0.352), but with no statistically significant difference. CONCLUSIONS: The periprocedural safety of endovascular treatment for intracranial ISR may be acceptable, but the long-term rates of recurrent stroke and re-ISR remain at high levels.

10.
Nat Commun ; 11(1): 891, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060279

RESUMO

Although perovskite light-emitting diodes (PeLEDs) have recently experienced significant progress, there are only scattered reports of PeLEDs with both high efficiency and long operational stability, calling for additional strategies to address this challenge. Here, we develop perovskite-molecule composite thin films for efficient and stable PeLEDs. The perovskite-molecule composite thin films consist of in-situ formed high-quality perovskite nanocrystals embedded in the electron-transport molecular matrix, which controls nucleation process of perovskites, leading to PeLEDs with a peak external quantum efficiency of 17.3% and half-lifetime of approximately 100 h. In addition, we find that the device degradation mechanism at high driving voltages is different from that at low driving voltages. This work provides an effective strategy and deep understanding for achieving efficient and stable PeLEDs from both material and device perspectives.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32060720

RESUMO

There were limited studies comparing the anterior (AC) and posterior (PC) circulation acute ischemic strokes (AIS). Our study aimed to evaluate distinct features of AC and PC strokes regarding clinical, vascular risk, pathogenesis and outcome factors after endovascular procedures. This multicenter prospective study registered 873 patients with acute large occlusion of anterior circulation stroke (ACS) and posterior circulation stroke (PCS). Patients who underwent endovascular procedures were included in this study. The differences in ACS and PCS regarding baseline characteristics, post-operative intracranial hemorrhage and outcomes were evaluated. A total of 741 patients were included in the data analysis. Intravenous thrombolysis (31.5%), atrial fibrillation (22.7%) and stent thrombectomy (82.4%) were more frequently observed in ACS patients. While higher NIHSS score, hypertension (67.6%) and balloon angioplasty (20.7%) were more prevalent in PCS patients. Symptomatic intracranial hemorrhage was more common in ACS (7.4% vs 2.8%). However, a 3-month follow-up outcomes were better in ACS with higher functional independence and low mortality rate than PCS (46.8% vs 30.3% and 16.4% vs 33.8%, respectively, P < 0.01). In this large prospective study, there were significant differences in the pathogenesis of stroke and treatment procedure between ACS and PCS which influence the clinical outcome. These findings could lead to a tailored clinical procedures and treatment strategies to improve the prognosis in both groups.

12.
Cells ; 9(2)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046118

RESUMO

WNT5a is a mainly "non-canonical" WNT ligand whose dysregulation is observed in lung diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and asthma. Germline deletion of Wnt5a disrupts embryonic lung development. However, the temporal-specific function of WNT5a remains unknown. In this study, we generated a conditional loss-of-function mouse model (Wnt5aCAG) and examined the specific role of Wnt5a during the saccular and alveolar phases of lung development. The lack of Wnt5a in the saccular phase blocked distal airway expansion and attenuated differentiation of endothelial and alveolar epithelial type I (AT1) cells and myofibroblasts. Postnatal Wnt5a inactivation disrupted alveologenesis, producing a phenotype resembling human bronchopulmonary dysplasia (BPD). Mutant lungs showed hypoalveolization, but endothelial and epithelial differentiation was unaffected. The major impact of Wnt5a inactivation on alveologenesis was on myofibroblast differentiation and migration, with reduced expression of key regulatory genes. These findings were validated in vitro using isolated lung fibroblasts. Conditional inactivation of the WNT5a receptors Ror1 and Ror2 in alveolar myofibroblasts recapitulated the Wnt5aCAG phenotype, demonstrating that myofibroblast defects are the major cause of arrested alveologenesis in Wnt5aCAG lungs. Finally, we show that WNT5a is reduced in human BPD lung samples, indicating the clinical relevance and potential role for WNT5a in pathogenesis of BPD.

13.
Chem Commun (Camb) ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016209

RESUMO

Small-sized semiconducting polymer dots (Pdots) provide better tissue and subcellular penetration while minimizing unspecific interactions, and make the fast clearance of Pdots from human bodies possible by urinary excretion. We employ a powerful and scalable technology, flash nanoprecipitation, to prepare Pdots with small sizes (hydrodynamic diameters ∼10 nm).

14.
Mol Med ; 26(1): 14, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000660

RESUMO

BACKGROUND: Aspirin, as a non-steroidal anti-inflammatory drug, can improve the survival rate of patients with colorectal cancer, while aspirin is effective in patients with PIK3CA mutant colorectal cancer (CRC). However, the mechanism of aspirin in the treatment of PIK3CA mutated CRC patients remains unclear. METHODS: In this study, immunohistochemistry was used to detect the expression levels of PI3K and Raptor in colorectal cancer patients with PIK3CA mutation and PIK3CA wild-type patients. To demonstrate that aspirin has a better effect on the CRC of PIK3CA mutations in association with the PI3K/Akt/Raptor pathway, we used aspirin to treat PIK3CA mutant CRC cells (HCT-116 and RKO). Subsequently, the CCK8 assay and flow cytometry assay were used to detect the apoptosis of PIK3CA mutant CRC cells before and after aspirin use. Western blot was used to detect the changes of PI3K/Akt/Raptor-associated protein, autophagy protein microtubule associated protein 1 light chain 3 alpha (MAP1LC3A, LC3), beclin 1 (BECN1) and apoptosis protein BCL2-associated X protein/ BCL2 apoptosis regulator (Bax/Bcl2), Caspase 3 after treatment of CRC cells with PIK3CA mutation by aspirin. RESULTS: Phosphoinositide-3-kinase (PI3K) and regulatory associated protein of MTOR complex 1 (Raptor) protein expression levels were higher in PIK3CA-mutant patients than in IK3CA wild-type patients. The expression of Bax/Bcl2 increased after treatment indicates that aspirin can induce apoptosis of PIK3CA-mutant CRC cells. The expression level of MAP1LC3 (LC3) in cells increases with the concentration of aspirin demonstrates that aspirin can induce autophagy in CRC cells. After 48 h of treatment with aspirin, the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase B1 (S6K1) was reduced, cell proliferation has been inhibited. After treatment with aspirin, as phosphorylation of PI3K and Protein kinase B (PKB, Akt) was decreased, Raptor expression was also decreased. CONCLUSION: Aspirin can regulate the proliferation, apoptosis and autophagy of CRC cells through the PI3K/Akt/Raptor pathway, affecting PIK3CA-mutant CRC.

15.
Food Chem ; 316: 126271, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32036178

RESUMO

The current study was designed to investigate the physiochemical properties, protein and metabolite profiles of muscle exudate obtained from chicken breast fillets affected by wooden breast (WB) myopathy. Twenty-four fillets were categorized into varying degrees of WB condition including normal, moderate and severe. Results indicated that exudate loss, free hemoglobin concentration, protein and lipid oxidation were affected by WB myopathy. Electrophoresis analysis showed eight distinct protein bands of differential relative abundance in WB samples compared with the normal, and the identified proteins were mostly involved in carbohydrate metabolic process. 1H nuclear magnetic resonance-based metabolomics identified eleven metabolites including amino acids, nucleotides and organic acid as the most influential metabolites affected by WB myopathy. Overall, this study shows differential molecular profiles of myopathic chicken muscle exudate, and provides a valuable resource for further recognition of WB myopathy.

16.
J Org Chem ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039595

RESUMO

A facile access to the polycyclic fused pyrano[2,3-b]pyridines has been established under room temperature via Rh(III)-catalyzed C-H bond activation and intramolecular cascade annulation. This strategy features high efficiency, unique versatility, and generality and it can occur under mild conditions in good to excellent yields. More importantly, this strategy can be extended to the late-stage functionalization of drugs possessing CN group.

17.
Eur J Protistol ; 73: 125675, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32036251

RESUMO

Ciliated protists represent a morphologically and genetically distinct group of single-celled eukaryotes which can reproduce asexually and sexually. Morphogenesis occurs in both asexual and sexual modes of reproduction which is of interest for researchers investigating cell differentiation, regeneration, systematics and evolution. However, studies of morphogenesis have concentrated almost entirely on the asexual mode. Here we use protargol staining to investigate the morphogenetic processes during sexual reproduction in the model species Euplotes vannus (Müller). The major events include: (1) two rounds of morphogenesis occur during sexual reproduction, i.e., conjugational and postconjugational reorganization; (2) in both processes the oral primordium is generated de novo in a pouch beneath the cortex; (3) the frontoventral-transverse cirri anlagen are formed de novo and fragment in a 3:3:3:3:2 pattern; (4) the leftmost cirrus and the paroral membrane do not change during conjugational morphogenesis, but reorganize de novo during postconjugational morphogenesis; (5) marginal cirral anlagen are formed de novo in both morphogenetic processes; (6) two or three caudal cirri are formed at the ends of the rightmost two or three old dorsal kineties; (7) the dorsal kineties are retained entirely. These results can serve as reference to investigate the morphogenetic events in the different stages of sexual reproduction.

18.
Biomater Sci ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064471

RESUMO

The development of magnetic resonance imaging (MRI) contrast agents with high sensitivity and good biocompatibility is of great value for the diagnosis of primary hepatocellular carcinoma (HCC). Here, a novel MRI contrast agent based on calcium phosphate (CaP) nanoparticles modified with a liver cancer cell targeting peptide A54 (A54-CaP) was fabricated. The T1-positive contrast agent Gd-DTPA was encapsulated inside the nanoparticles (A54-CaPNPs), with a mean diameter of 30 nm and a high encapsulation efficiency of 92.73%. The A54-CaPNP solution exhibited higher longitudinal relaxivity (6.07 mM-1 s-1) than that of the clinically used MRI contrast agent Gd-DTPA (3.56 mM-1 s-1). A much higher accumulation of the nanoparticles in the liver cells was observed, which was directed by the A54 targeting peptide. Furthermore, the MRI diagnostic efficiency of A54-CaPNPs was systematically investigated in an orthotopic liver cancer model and primary HCC model. In vivo MRI experiments showed that A54-CaPNPs had higher sensitivity in the BEL-7402 orthotopic liver cancer model with a more remarkable contrast enhancement and a longer imaging time compared to those without A54 modification. Moreover, the experiments on primary HCC models suggested that A54-CaPNPs showed greatly enhanced MR imaging performance in comparison with Gd-DTPA. These results suggest that A54-CaPNPs possess great potential to enable the non-invasive early diagnosis of primary HCC for timely surgical resection.

19.
Brief Bioinform ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065216

RESUMO

Pan-genome analysis is widely used to study the evolution and genetic diversity of species, particularly in bacteria. However, the impact of strain selection on the outcome of pan-genome analysis is poorly understood. Furthermore, a standard protocol to ensure high-quality pan-genome results is lacking. In this study, we carried out a series of pan-genome analyses of different strain sets of Bacillus subtilis to understand the impact of various strains on the performance and output quality of pan-genome analyses. Consequently, we found that the results obtained by pan-genome analyses of B. subtilis can be influenced by the inclusion of incorrectly classified Bacillus subspecies strains, phylogenetically distinct strains, engineered genome-reduced strains, chimeric strains, strains with a large number of unique genes or a large proportion of pseudogenes, and multiple clonal strains. Since the presence of these confounding strains can seriously affect the quality and true landscape of the pan-genome, we should remove these deviations in the process of pan-genome analyses. Our study provides new insights into the removal of biases from confounding strains in pan-genome analyses at the beginning of data processing, which enables the achievement of a closer representation of a high-quality pan-genome landscape of B. subtilis that better reflects the performance and credibility of the B. subtilis pan-genome. This procedure could be added as an important quality control step in pan-genome analyses for improving the efficiency of analyses, and ultimately contributing to a better understanding of genome function, evolution and genome-reduction strategies for B. subtilis in the future.

20.
Adv Mater ; : e1906763, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31975446

RESUMO

Organic solar cells are currently experiencing a second golden age thanks to the development of novel non-fullerene acceptors (NFAs). Surprisingly, some of these blends exhibit high efficiencies despite a low energy offset at the heterojunction. Herein, free charge generation in the high-performance blend of the donor polymer PM6 with the NFA Y6 is thoroughly investigated as a function of internal field, temperature and excitation energy. Results show that photocurrent generation is essentially barrierless with near-unity efficiency, regardless of excitation energy. Efficient charge separation is maintained over a wide temperature range, down to 100 K, despite the small driving force for charge generation. Studies on a blend with a low concentration of the NFA, measurements of the energetic disorder, and theoretical modeling suggest that CT state dissociation is assisted by the electrostatic interfacial field which for Y6 is large enough to compensate the Coulomb dissociation barrier.

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