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1.
J Cell Physiol ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595984

RESUMO

Osteosarcoma (OS) is the most common bone tumor that occurs predominantly in children and teenagers. Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt/ß-catenin signaling pathway is frequently observed in OS. We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt-related transcription factor 2 via the AKT/GSK-3ß/ß-catenin signaling pathway in OS. However, the precise role of T cell factors/lymphoid enhancer-binding factor (TCFs/LEF) family members, which are the major binding complex of ß-catenin, in OS is poorly understood. In the present study, we first demonstrated that TCF-1 is overexpressed in OS compared with other bone tumors. Knockdown of TCF-1 significantly induced cell cycle arrest, severe DNA damage, and subsequent caspase-3-dependent apoptosis. Interestingly, coexpression of HSP90 and TCF-1 was observed in OS, and mechanistically, we demonstrated that TCF-1 expression is regulated by HSP90 either through a ß-catenin-dependent mechanism or a direct degradation of the proteasome. We also found that overexpression of TCF-1 partially abolishes the apoptosis induced by HSP90 inhibition. Furthermore, we provided evidence that p53, but not miR-34a, plays a crucial role in the HSP90-regulated TCF-1 expression and subsequent apoptosis. Given the diverse combination regimens of HSP90 inhibition with some other treatments, we propose that the p53 status and the expression level of TCF-1 should be taken into consideration to enhance the therapeutic efficacy of HSP90 inhibition.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31602595

RESUMO

BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work investigated its excretion, metabolism, and cytochrome P450-based drug-drug interactions (DDIs). METHODS: After intragastric administration of MDHB, the parent drug was assayed in the urine and faeces of mice. Metabolites of MDHB in the urine, faeces, brain, plasma and liver were detected by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A cocktail approach was used to evaluate the inhibition of cytochrome P450 isoforms by MDHB. RESULTS: The cumulative excretion permille of MDHB in the urine and faeces were found to be 0.67 ± 0.31 and 0.49 ± 0.44‰, respectively. A total of 96 metabolites of MDHB were identified, and all IC50 (half-maximal inhibitory concentration) values of MDHB towards cytochrome P450 isoforms were > 100 µM. CONCLUSIONS: The results suggest that MDHB has a low parent drug cumulative excretion percentage and that MDHB has multiple metabolites and is mainly metabolized through the loss of -CH2 and -CO2, the loss of -CH2O, ester bond hydrolysis, the loss of -O and -CO2, isomerization, methylation, sulfate conjugation, the loss of -CH2O and -O and glycine conjugation, glycine conjugation, the loss of two -O groups and alanine conjugation, the loss of -CH2O and -O and glucose conjugation, glucuronidation, glucose conjugation, etc., in vivo. Finally, MDHB has a low probability of cytochrome P450-based DDIs.

4.
Neuroimage ; : 116227, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568871

RESUMO

The individual heterogeneity is a challenge to the prosperous promises of cutting-edge neuroimaging techniques for better diagnosis and early detection of psychiatric disorders. Individuals with similar clinical manifestations may result from very different pathophysiology. Conventional approaches based on comparing group-averages provide insufficient information to support the individualized diagnosis. Here we present an individualized imaging methodology that combines naturalistic imaging and the normative model. This paradigm adopts video clips with rich cognitive, social, and emotional contents to evoke synchronized brain dynamics of healthy participants and builds a spatiotemporal response norm. By comparing individual brain responses with the response norm, we could recognize patients using machine learning techniques. We applied this methodology to recognize first-episode drug-naïve schizophrenia patients in a dataset containing 72 patients and 54 healthy controls. Some segments of the video evoked more synchronized brain activity in the healthy controls than in the schizophrenia patients. We built a spatiotemporal response norm by averaging the brain responses of the healthy controls in a training set, and trained a classifier to recognize patients based on the differences between individual brain responses and the norm. The performance of the classifier was then evaluated using an independent test set. The mean accuracies from a 5-fold cross-validation were 0.71-0.78 depending on the parameters such as the number of features and the width of the sliding windows. These findings reflected the potential of this methodology towards a clinical tool for individualized diagnosis.

5.
J Am Heart Assoc ; 8(19): e013543, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31567003

RESUMO

Background Whether marine omega-3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial. Methods and Results This meta-analysis included study-level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed-effect meta-analysis. A meta-regression was conducted to estimate the dose-response relationship between marine omega-3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), marine omega-3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE-IT while introducing statistically significant heterogeneity. Statistically significant linear dose-response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE-IT. Conclusions Marine omega-3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE-IT. Risk reductions appeared to be linearly related to marine omega-3 dose.

6.
Environ Res ; 179(Pt A): 108775, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31593837

RESUMO

BACKGROUND: Recent studies suggested an inverse association between exposures to perfluoroalkyl substances (PFASs) and bone mineral density (BMD). Whether exposures to PFASs are also associated with changes in BMD has not been examined. METHODS: Five major PFASs (perfluorooctanesulfonic acid, PFOS; perfluorooctanoic acid, PFOA; perfluorohexanesulfonic acid, PFHxS; perfluorononanoic acid, PFNA; perfluorodecanoic acid, PFDA) and BMD (g/cm2) at six bone sites (spine, total hip, femoral neck, hip intertrochanteric area, hip trochanter, and hip Ward's triangle area) were measured at baseline among 294 participants in the POUNDS-LOST study, a weight-loss trial, of whom a total of 175 participants had BMD measured at both baseline and year 2. Linear regression was used to model the differences or changes in BMD for each SD increment of PFAS concentrations. In a secondary analysis, interactions between PFASs and baseline body mass index (BMI), as well as a BMI-related genetic risk score (GRS) derived from 97 BMI-predicting SNPs were examined in relation to changes in BMD. RESULTS: At baseline, both PFOS and PFOA were significantly associated with lower BMD at several sites. For each SD increase of PFOS, the ßs (95% CIs) for BMD were -0.020(-0.037, -0.003) for spine, -0.013(-0.026, 0.001) for total hip, -0.014(-0.028, 0.000) for femoral neck, and -0.013(-0.026, 0.000) for hip trochanter. For PFOA, the corresponding figures were -0.021(-0.038, -0.004) for spine, -0.015(-0.029, -0.001) for total hip, and -0.015(-0.029, -0.002) for femoral neck. After adjusting for baseline covariates and 2-year weight change, higher baseline plasma concentrations of PFOS, PFNA, and PFDA were associated with greater reduction in BMD in the hip; the ßs (95% CIs) were -0.005(-0.009, -0.001), -0.006(-0.010, -0.001), and -0.005(-0.009, -0.001), respectively. Similar associations were found in hip intertrochanteric area for all PFASs except PFHxS, with ßs ranging from -0.006 for PFOA to -0.008 for PFOS and PFNA. Participants with a higher GRS tended to have less PFAS-related BMD decline in total hip (Pinteraction = 0.005) and the hip intertrochanteric area (Pinteraction = 0.021). There were similar PFAS-related BMD changes by baseline BMI levels, although the interactions did not achieve statistical significance. CONCLUSIONS: This study demonstrated that higher plasma PFAS concentrations were not only associated with a lower BMD at baseline, but also a faster BMD loss in a weight-loss trial setting. Genetic predisposition to larger body size may somewhat attenuate the deleterious effects of PFASs on BMD. Further exploration of the possible impact of PFAS exposures on bone density is warranted.

7.
Plant Physiol Biochem ; 144: 244-253, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593897

RESUMO

The wild Chinese grapevines (Vitis spp.) show varying levels of resistance to powdery mildew caused by Erysiphe necator that is an economically important disease of cultivated grapevines (Vitis vinifera). However, little information is available regarding the cytological mechanisms of powdery mildew resistance in these wild relatives. Here, we studied the cytological responses of three wild Chinese grapevine accessions after they were infected with E. necator (En) NAFU1 in comparison to the susceptible V. vinifera cv. 'Thompson Seedless' grape. The hyphal growth and sporulation of En NAFU1 were significantly restricted in wild species compared to 'Thompson Seedless', which appears to be associated with early cell wall deposition at the attempt sites, encasement of haustoria, and hypersensitive response-like cell death of penetrated epidermal cells. Moreover, endogenous free salicylic acid (SA) was more abundant in wild Chinese Vitis species than in 'Thompson Seedless' under pathogen-free condition. During En NAFU1 colonization, SA conjugates accumulated higher in wild grapevines than in 'Thompson Seedless'. In addition, the species-specific expression patterns of defense-associated genes during En NAFU1 colonization indicated that mechanisms underlying powdery mildew resistance are divergent among different wild Chinese Vitis species. These results contribute to understanding of mechanisms underlying defense responses of wild Chinese Vitis species against powdery mildew.

8.
J Am Chem Soc ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622088

RESUMO

Both arylsulfonyl and alkylsulfonyl azides can be effectively activated by the cobalt(II) complexes of D2-symmetric chiral amidoporphyrins for enantioselective radical 1,5-C-H amination to stereoselectively construct 5-membered cyclic sulfonamides. In addition to C-H bonds with varied electronic properties, the Co(II)-based metalloradical system features chemoselective amination of allylic C-H bonds and is compatible with heteroaryl groups, producing functionalized 5-membered chiral cyclic sulfonamides in high yields with high enantioselectivities. The unique profile of reactivity and selectivity of the Co(II)-catalyzed C-H amination is attributed to its underlying stepwise radical mechanism, which is supported by several lines of experimental evidence.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117651, 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31629980

RESUMO

A novel label-free aptasensor for kanamycin detection was constructed using gold nanoparticles (AuNPs) as absorber to quench the fluorescence of carbon dots (CDs) via the inner filter effect (IFE). The strategy was mainly relied on the fact that the absorption spectra of AuNPs overlapped with the fluorescence excitation spectra of fluorophores as well as the specific binding capacity of Ky2 aptamer to kanamycin. Upon adding kanamycin antibiotic, the free aptamer sequences are firstly exhausted to form some complexes, which leads to AuNPs aggregation in high salt concentration. Consequently, the absorber's absorption spectrum changes and no longer overlaps with the fluorescence emission spectrum of the CDs, which results in obvious fluorescence recovery of the aptasensor. Herein, the effects of some vital parameters like the type and number of nanoparticles on the fluorescent aptasensor have been investigated. Under optimal conditions, the proposed aptasensor can detect kanamycin in a linear range of 0.04-0.24 µM, with a limit of detection (LOD) as low as 18 nM. Moreover, the further studies also validate the applicability of the proposed aptasensor in milk samples, revealing that it may have enormous potential utility for practical kanamycin detection in food products in the future.

10.
Environ Sci Technol ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31631659

RESUMO

Rice fungal pathogens-responsible severe rice yield loss and biotoxin contamination cause increasing concerns on environmental safety and public health. In paddy environment, we observed that the asymptomatic rice phyllosphere microenvironment was dominated by an indigenous fungus, Aspergillus cvjetkovicii, which positively correlated with alleviated incidence of Magnaporthe oryzae, one of the most aggressive plant pathogens. Through the comparative metabolic profiling for rice phyllosphere microenvironment, two metabolites were assigned as exclusively-enriched metabolic markers in asymptomatic phyllosphere and increased remarkably in a population-dependent manner with A. cvjetkovicii. These two metabolites evidenced to be produced by A. cvjetkovicii in either phyllosphere microenvironment or artificial media, were purified and identified as 2(3H)-benzofuranone and azulene, respectively by GC-QqQ-MS/MS and NMR analyses. Combining with bioassay analysis in vivo and in vitro, we found 2(3H)-benzofuranone and azulene exerted dissimilar actions at the stage of infection-related development of M. oryzae. A. cvjetkovicii produced 2(3H)-benzofuranone at the early stage to suppress MoPer1 gene expression leading to inhibited mycelial growth, while azulene produced lately was involved in block of appressorium formation by down-regulation of MgRac1. More profoundly, the microenvironmental interplay dominated by A. cvjetkovicii significantly blocked M. oryzae epidemics in paddy environment from 54.7% to 68.5% (p < 0.05). Our study first demonstrated implication of the microenvironmental interplay dominated by indigenous and beneficial fungus to ecological balance and safety of paddy environment.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31654831

RESUMO

Using Saccharomyces cerevisiae as an experimental model, the potential toxicological effects of Fe3O4 nanoparticles (Fe3O4-NPs) were investigated following exposure to 0-600 mg/L for 24 h. Results revealed that cell proliferation was significantly inhibited by Fe3O4-NPs with an IC50 value of 326.66 mg/L. Mortality showed a concentration-dependent increase, and the highest concentration in this study (600 mg/L) resulted in 22.30% mortality. In addition, Effects on proliferation and mortality were accounted for Fe3O4-NPs rather than iron ion released from Fe3O4-NPs. Scanning and transmission electron microscope observation showed that Fe3O4-NPs extensively attached on the cell surfaces, causing cells to deform and shrink. Moreover, Fe3O4-NPs could be internalized in S. cerevisiae cells via endocytosis and then be distributed in cytoplasm and vesicles. The data of uptake kinetics demonstrated that the maximal accumulation (4.898 mg/g) was reached at 15 h. Besides, percentage of late apoptosis/necrosis was observably increased (p < 0.01) at 600 mg/L (15.80%), and the expression levels of apoptosis-related genes (SOD, Yca1 and Nuc1) were dramatically increased following exposure to Fe3O4-NPs for 24 h. As expected, mitochondrial transmembrane potential was significantly decreased (p < 0.01) at 50-600 mg/L, and biomarkers of oxidative stress (ROS, CAT and SOD) were also markedly changed following exposure. Altogether, the combined results so far indicated Fe3O4-NPs could induce S. cerevisiae cell apoptosis that mediated by mitochondrial impairment and oxidative stress.

12.
Phys Rev E ; 100(3-1): 033314, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31639949

RESUMO

Based on phase-field theory, we develop a lattice Boltzmann (LB) model for liquid-gas-solid flow from multiphase and particle dynamics algorithms. A modified bounce-back method is developed for the velocity-based LB approach. A curved boundary treatment with second-order accuracy based on velocity interpolation is developed. We propose a predictor-corrector scheme algorithm for specifying the three-phase contact angle on curved boundaries within the framework of structured Cartesian grids. In order to make the algorithm more stable, we combine the implicit particle velocity update scheme and the Galilean invariant momentum exchange method. The proposed method is validated through several single- and multicomponent fluid test cases. It was found the surface tension force associated with the interface acting on the solid structures can be captured. We simulate the sinking of a circular cylinder due to gravity, the numerical results agree well with the experimental data. Finally, we apply the method to the self-assembly process of multiple floating cylinders on water surface.

13.
Brain Struct Funct ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515678

RESUMO

A resting-state network centered at the precuneus has been recently proposed as a precuneus network (PCUN) or "parietal memory network". Due to its spatial adjacency and overlapping with the default mode network (DMN), it is still not consensus to consider PCUN and DMN separately. Whether considering PCUN and DMN as different networks is a critical question that influences our understanding of brain functions and impairments. Previous resting-state studies using multiple methodologies have demonstrated a robust separation of the two networks. However, since there is no gold standard in justifying the functional difference between the networks in resting-state, we still lack of biological evidence to directly support the separation of the two networks. This study compared the responses and functional couplings of PCUN and DMN when participants were watching a movie and examined how the continuity of the movie context modulated the response of the networks. We identified PCUN and DMN in resting-state fMRI of 48 healthy subjects. The networks' response to a context-rich video and its context-shuffled version was characterized using the variance of temporal fluctuations and functional connectivity metrics. The results showed that (1) scrambling the contextual information altered the fluctuation level of DMN and PCUN in reversed ways; (2) compared to DMN, the FC within PCUN showed significantly higher sensitivity to the contextual continuity; (3) PCUN exhibited a significantly stronger functional network connectivity with the primary visual regions than DMN. These findings provide evidence for the distinct functional roles of PCUN and DMN in processing context-rich information and call for separately considering the functions and impairments of these networks in resting-state studies.

14.
Curr Gene Ther ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549953

RESUMO

miRNA is not only found in brain tissue, but also ins cerebrospinal fluid as well as in plasma and serum. More and more scholars are trying to use it as a specific biomarker for Alzheimer's Disease (AD). Multiple studies have indicated that miRNAs are associated with poor axonal growth and loss of synaptic structures, both of which are early events in AD. The overall loss of miRNA may be associated with aging, increasing the incidence of AD, and may also be involved in the disease through some specific molecular mechanisms. We used genes as a bridge to connect AD and miRNAs. Firstly, protein-protein interaction network is used to find more AD-related genes by known AD-related genes. Then, each miRNA's correlation with these genes is obtained by miRNA-gene interaction. Finally, each miRNA could get a feature vector representing its correlation with AD. Unlike other studies, we don't generate negative samples randomly with using classification method to identify AD-related miRNAs. Here we use a semi-clustering method 'one-class SVM'. AD-related miRNAs are considered as outliers and our aim is to identify the miRNAs that are similar to known AD-related miRNAs (outliers). We identified 257 novel AD-related miRNAs and compare our method with SVM which is applied by generating negative samples. The AUC of our method is much higher than SVM. At last, we did case studies. 9 miRNAs have been verified to be related to AD by biological experiments.

15.
ACS Appl Mater Interfaces ; 11(40): 36449-36457, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31532178

RESUMO

Multifunctional antibacterial materials have great significance for treating biomedical device-associated infections (BAIs). In the present work, a facile and rational strategy was developed to produce dual-functional implants with antibacterial and osteointegration-promoting properties for the treatment of BAI. A titanium implant, as a representative demo of implants, was first functionalized with ethanediamine-functionalized poly(glycidyl methacrylate) (PGED) brushes. Then, low-molecular-weight quaternized polyethyleneimine (QPEI, a cationic antibacterial agent) and alendronate (ALN, a clinically used drug with high affinity for bone minerals) were covalently conjugated onto PGED brushes to produce dual-functional dental implants (Ti-AQ). The QPEI component imparted Ti-AQ with antibacterial abilities, and the ALN component could balance the cytotoxicity of a cationic antibacterial agent, improving the biocompatibility for osteoblast cells. The effective performances of anti-infection and osteointegration were demonstrated in a BAI animal model. The results indicated that Ti-AQ inhibited bacterial infection at the early stage and enhanced the osteointegration and biomechanical properties between the implants and bone tissues at the late stage. This study will provide one facile and universal strategy for the design and development of novel multifunctional antibacterial implants.

16.
Environ Sci Technol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31525918

RESUMO

Globally, alpine glaciers hold a large quantity of dissolved organic matter (DOM) and are headwaters of numerous rivers supporting downstream heterotrophic metabolism. However, it remains unclear how glacial coverage and distance from the glacial terminus affect the fate of DOM. Here, we elucidate DOM variability in glacial-fed streams on the Tibetan Plateau using field sampling and bioincubation experiments and compare our findings with the existing literature. We found that dissolved organic carbon, DOM absorption a(254), DOM aromaticity, and the relative abundance of lignin compounds in glacial-fed streams and rivers all increased with increasing distance from the glacial terminus and with decreasing glacial coverage. We also found that contribution of protein-like components, the relative abundance of aliphatic compounds, and DOM biolability increased with increasing glacial coverage and with decreasing distance from the glacial terminus. The ratio of glacial coverage to the logarithmic transformed distance from the glacial terminus was better than that of actual glacial coverage and distance from the glacial terminus in tracing the variability of glacial-fed stream DOM. Microbes in surface ice can produce biolabile DOM that is exported downstream with meltwater. This glacial-fed stream and river DOM is an important source of the highly bioavailable material fueling downstream heterotrophic activity.

17.
Virus Res ; 273: 197741, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494148

RESUMO

Infectious hematopoietic necrosis virus (IHNV) is a fish viral pathogen that causes severe disease and huge economic losses in the salmonid aquaculture industry. However, anti-IHNV drugs currently are scarce. For the purpose of seeking out anti-IHNV drugs, the anti-IHNV activities of 32 medicinal plants were investigated by using epithelioma papulosum cyprini (EPC) cells. Among these plants, Prunella vulgaris L. (PVL) showed the strongest inhibition on IHNV replication with an inhibitory percentage of 99.3% at the concentration 100 mg/L. Further studies demonstrated that ursolic acid (UA), a major constituent of PVL, also showed a highly effective anti-IHNV activity. The half-maximal inhibitory concentration (IC50) at 72 h of UA on IHNV was 8.0 µM. Besides, UA could significantly decrease cytopathic effect (CPE) and the viral titer induced by IHNV in EPC cells. More importantly, UA also showed a strong anti-IHNV activity in vivo, as indicated by increasing the survival rate of rainbow trout and inhibiting viral gene expression. Intraperitoneal injection of UA increased the relative percentage of survival of rainbow trout by 18.9% and inhibited IHNV glycoprotein mRNA expression by > 90.0% in the spleen at the 1st-day post-infection. Altogether, UA was expected to be a therapeutic agent against IHNV infection in aquaculture.

18.
Phytother Res ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515889

RESUMO

The side effects of docetaxel have limited its antitumor performances in the treatment of nonsmall cell lung cancer (NSCLC). To address the problem, baicalein, a bioactive flavone that exhibits antitumor activity, was combined with docetaxel so as to achieve better efficacy and lower toxicity. The combination treatment enhanced the stabilization of microtubules and halted the cell-cycle progression, thus synergistically inhibiting the proliferation and inducing the apoptosis of A549 cells and Lewis lung carcinoma cells. The decreased expression of Cyclin-dependent kinase 6 and Cyclin B1 confirmed its regulation in cell cycle, with ß-catenin being an important upstream effector, as evidenced by the decreased expression in the cytoplasm and nucleus as well as the attenuated aggregation in the nucleus. Furthermore, baicalein plus docetaxel evinced better antitumor efficacy by the suppressed tumor growth, increased apoptosis, and decreased tumor angiogenesis in vivo, with no increased toxicity discovered in both tumor-bearing and non-tumor-bearing mice, and an improvement in therapeutic index. This study has demonstrated that baicalein plus docetaxel is an appropriate combination simultaneously with augmented antitumor efficacy and acceptable safety, which might be a promising strategy for patients with advanced NSCLC.

19.
Nanoscale ; 11(36): 17031-17040, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31503267

RESUMO

The rational design of nonprecious and high-efficiency bifunctional electrocatalysts with advanced structural and compositional preponderance for water electrolysis is of paramount importance for the generation of sustainable and clean energy. Herein, for the first time, a novel three-dimensional (3D) hollow hybrid electrocatalyst, Co-Fe-P nanoframe immobilized on N,P-doped carbon nanotubes (CoFeP NFs/NPCNT), was synthesized by selectively etching a CNT-composited Co,Fe-based Prussian blue analogue and subsequent phosphorization. Benefiting from its unique 3D hollow nanoarchitecture, which offers rich porosity and abundant catalytically active sites and guarantees excellent conductivity and structural stability, the hollow CoFeP NFs/NPCNT hybrid delivered pronounced catalytic activity for oxygen evolution (or hydrogen evolution) in alkaline electrolyte, with a low overpotential of 278 (or 132) mV at 10 mA cm-2, small Tafel slope of 39.5 (or 62.9) mV dec-1 and prominent long-term stability. Therefore, when CoFeP NFs/NPCNT was employed as the cathode and anode toward overall water-splitting, it required a quite small cell voltage of only 1.56 V to afford a current density of 10 mA cm-2, and displayed outstanding electrocatalytic stability over 60 h, greatly approaching the performance of the commercial Pt/C(-)//RuO2(+) electrolyzer and outperforming most other non-noble-based electrolyzers.

20.
Nat Commun ; 10(1): 4145, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515482

RESUMO

Crystallographic dislocation has been well-known to be one of the major causes responsible for the unfavorable carrier dynamics in conventional semiconductor devices. Halide perovskite has exhibited promising applications in optoelectronic devices. However, how dislocation impacts its carrier dynamics in the 'defects-tolerant' halide perovskite is largely unknown. Here, via a remote epitaxy approach using polar substrates coated with graphene, we synthesize epitaxial halide perovskite with controlled dislocation density. First-principle calculations and molecular-dynamics simulations reveal weak film-substrate interaction and low density dislocation mechanism in remote epitaxy, respectively. High-resolution transmission electron microscopy, high-resolution atomic force microscopy and Cs-corrected scanning transmission electron microscopy unveil the lattice/atomic and dislocation structure of the remote epitaxial film. The controlling of dislocation density enables the unveiling of the dislocation-carrier dynamic relation in halide perovskite. The study provides an avenue to develop free-standing halide perovskite film with low dislocation density and improved carried dynamics.

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