In this research, a novel nitinol shape memory alloy particulate (NiTip) reinforced aluminum matrix composites (AMCs) with fine-grained structure was prepared by underwater friction stir processing ...(UFSP). Microstructure observation and NiTip/Al interfacial composition analysis showed that UFSP resulted in an uniform dispersion of NiTip in the simultaneously created fine-grained 5083Al matrix, with no additional intermetallics formed at well-bonded NiTip/Al interfaces. The addition of NiTip could accelerate dynamic recovery (DRV) by increasing matrix deformation and promote dynamic recrystallization (DRX) by particle stimulated nucleation (PSN). Due to lack of serious NiTip/Al interfacial diffusion deteriorating their shape memory effect, the introduced NiTip in the resulting AMCs still exhibited a one-stage reversible phase transformation between martensite and austenite. Also, the shape memory effect of NiTip can be activated through pre-deforming in martensite state and then reheating above austenite transformation temperature, thereby introducing compressive residual stress into the matrix. The fine-grained structure with homogeneous NiTip distribution and well-bonded NiTip/Al interfaces in UFSP AMCs, significantly improved strength without adversely affecting the ductility. A detailed analysis on various strengthening mechanisms contributing to the strength of the UFSP AMCs was carried out. Fine grain strengthening, geometrically necessary dislocation strengthening and load transfer effect were demonstrated to be three main contributors to the improved strength of the UFSP AMCs.
•Fine-grained NiTip/5083Al composites were fabricated by underwater friction stir processing.•NiTip were uniformly dispersed in the matrix, with no intermetallics formed at well-bonded NiTip/Al interfaces.•NiTip retained the initial shape memory effect.•The developed composite exhibited a combination of high strength and good ductility.
Summary
Background
Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB).
Aim
The present study was undertaken to determine whether short‐term use ...of glucocorticoids is associated with the occurrence of peptic ulcer bleeding.
Methods
The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population‐based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28 days using a case‐crossover design.
Results
Of the 8894 enrolled patients, the adjusted self‐matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12–1.68, P = 0.003) for the 7‐day window, 1.66 (95% CI: 1.38–2.00, P < 0.001) for the 14‐day window and 1.84 (95% CI: 1.57–2.16, P < 0.001) for the 28‐day window. Moderate to high, but not low dose glucocorticoids (methylprednisolone <4 mg/day or its equivalence) were associated with an increased risk of peptic ulcer bleeding. Concomitant use of a nonselective nonsteroidal anti‐inflammatory drug (NSAID) or aspirin further elevated the risk. However, it does not eliminate the effect of underlying diseases flare‐up that may have placed the patients at risk for peptic ulcer bleeding in this kind of study design.
Conclusions
Short‐term (7–28 days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose‐dependent and is higher when nonselective NSAIDs or aspirin are used concurrently.
Abstract Background The aim of this study was to evaluate the short-term safety and long-term benefits of radical gastrectomy for gastric cancer in elderly patients. Methods A total of 729 patients ...undergoing gastrectomy for adenocarcinoma between December 2008 and December 2011 were enrolled in this retrospective study. Patients were divided into three groups: young group (<65 years), young–old group (65–79 years) and old–old group (≥80 years). Results Lower albumin levels, higher ASA grades, comorbidities, tumors located in the upper third of the stomach and advanced TNM stages were more common in the young–old and old–old age groups. Overall complications increased significantly with advancing age (15.4%, 24.9%, 48.7%, respectively); respiratory complications largely contributed to the dramatic increase. Severe complications were similar between the young and young–old groups (3.9%, 3.7%), but were significantly increased in the old–old group (12.8%). In multivariate analysis, old–old age, multiple comorbidities and no epidural use were strong predictors for overall complications. Both overall survival and disease-specific survival (DSS) rates declined with advancing age. Multivariate analysis showed that old–old age and TNM stage ≥ II were major independent risk factors for the DSS rate. When adjusted for confounding factors, young–old age was not a risk factor. The median survival time for the old–old patients with stage III tumors was 12.9 months. Conclusions It is relatively safe and beneficial for young–old patients to undergo radical gastrectomy as the young patients. However, the decision to perform radical gastrectomy for old–old patients with TNM stage III tumors should be made carefully.
Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other ...tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying the conversion of normal MSCs into tumour-associated MSCs are unknown. We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma. Ablation of macrophages by clodronate liposome administration reversed the tumour-promoting effect of MSCs educated by tumour cell-derived exosomes (TE-MSCs) on the tumour growth. By comparing the chemokine profile of BM-MSCs with that of TE-MSCs, we found that TE-MSCs produced a large amount of CCR2 ligands, CCL2 and CCL7, which are responsible for macrophage recruitment. CCR2-specific inhibitor was found to block the tumour-promoting effect of TE-MSCs. Thus, our investigations demonstrated that tumour cell-derived exosomes confer BM-MSCs the ability to enhance tumour growth. Therefore, we uncovered a novel mechanism underlying the conversion of normal MSCs to tumour-associated MSCs.
Glioblastoma (GBM) is a common and malignant tumor with a poor prognosis. Glioblastoma stem cells (GSCs) have been reported to be involved in tumorigenesis, tumor maintenance and therapeutic ...resistance. Thus, to discover novel candidate therapeutic drugs for anti-GBM and anti-GSCs is an urgent need. We hypothesized that if treatment with a drug could reverse, at least in part, the gene expression signature of GBM and GSCs, this drug may have the potential to inhibit pathways essential in the formation of GBM and thereby treat GBM. Here, we collected 356 GBM gene signatures from public databases and queried the Connectivity Map. We systematically evaluated the in vitro antitumor effects of 79 drugs in GBM cell lines. Of the drugs screened, thioridazine was selected for further characterization because it has potent anti-GBM and anti-GSCs properties. When investigating the mechanisms underlying the cytocidal effects of thioridazine, we found that thioridazine induces autophagy in GBM cell lines, and upregulates AMPK activity. Moreover, LC3-II was upregulated in U87MG sphere cells treated with thioridazine. In addition, thioridazine suppressed GBM tumorigenesis and induced autophagy in vivo. We not only repurposed the antipsychotic drug thioridazine as a potent anti-GBM and anti-GSCs agent, but also provided a new strategy to search for drugs with anticancer and anticancer stem cell properties.
In order to improve the accuracy of emotional recognition by end-to-end automatic learning of emotional features in spatial and temporal dimensions of electroencephalogram (EEG), an EEG emotional ...feature learning and classification method using deep convolution neural network (CNN) was proposed based on temporal features, frequential features, and their combinations of EEG signals in DEAP dataset. The shallow machine learning models including bagging tree (BT), support vector machine (SVM), linear discriminant analysis (LDA), and Bayesian linear discriminant analysis (BLDA) models and deep CNN models were used to make emotional binary classification experiments on DEAP datasets in valence and arousal dimensions. The experimental results showed that the deep CNN models which require no feature engineering achieved the best recognition performance on temporal and frequency combined features in both valence and arousal dimensions, which is 3.58% higher than the performance of the best traditional BT classifier in valence dimension and 3.29% higher than that of BT classifier in arousal dimension.
Hypoxia-inducible factor 1 (HIF-1), a transcription factor that is critical for tumor adaptation to microenvironmental stimuli, represents an attractive chemotherapeutic target. YC-1 is a novel ...antitumor agent that inhibits HIF-1 through previously unexplained mechanisms. In the present study, YC-1 was found to prevent HIF-1α and HIF-1β accumulation in response to hypoxia or mitogen treatment in PC-3 prostate cancer cells. Neither HIF-1α protein half-life nor mRNA level was affected by YC-1. However, YC-1 was found to suppress the PI3K/Akt/mTOR/4E-BP pathway, which serves to regulate HIF-1α expression at the translational step. We demonstrated that YC-1 also inhibited hypoxia-induced activation of nuclear factor (NF)-κB, a downstream target of Akt. Two modulators of the Akt/NF-κB pathway, caffeic acid phenethyl ester and evodiamine, were observed to decrease HIF-1α expression. Additionally, overexpression of NF-κB partly reversed the ability of wortmannin to inhibit HIF-1α-dependent transcriptional activity, suggesting that NF-κB contributes to Akt-mediated HIF-1α accumulation during hypoxia. Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression.
This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at ...Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.
'Obesity paradox' was not consistently observed in Asians with coronary artery disease (CAD).
The study investigated the association between body composition and outcomes in Chinese patients with ...CAD.
Cohort study.
A total of 3280 patients with angiographically validated CAD were consecutively included. Body fat (BF) percentage and lean mass index (LMI) were evaluated using the Clínica Universidad de Navarra-Body Adiposity Estimator. The rate of mortality from any cause was compared across groups classified by the quartiles of LMI.
During a median period of 24 months, 288 (8.8%) participants died. There was a close association between increasing LMI and reducing mortality rate. However, univariate analyses did not find protective effect of BF on survival. After adjusting for age, sex, diabetes, current smoking, systolic blood pressure, creatinine, white blood cell count, haemoglobin and medication, Cox regression analyses showed that the significant relation between higher quartiles (Q) of LMI and survival benefit (Q4, hazard ratio 0.58 (95% confidence interval: 0.36-0.94) vs. Q3, 0.60 (0.39-0.91) vs. Q2, 0.60 (0.41-0.88) vs. Q1, reference) remained.
Low LMI but not BF predicts all-cause mortality in Chinese patients with CAD.
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