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关键词： apoptosis   deoxynivalenol   human brain endothelial cells   oxidative stress   vitamin E  

摘要： Fusarium mycotoxins are one of the largest families of mycotoxins. Among these mycotoxins, deoxynivalenol is the most widespread pollutant of grains. However, the mechanism underlying the effect of deoxynivalenol on cytotoxicity in human brain endothelial cells was still unclear. This study examined whether deoxynivalenol induced oxidative stress-associated cytotoxicity in primary human brain endothelial cells (HBEC-5i), and explored whether Vitamin E (VE), a selective antioxidant, had protective effects on deoxynivalenol-treated cells. Deoxynivalenol (10-50 mu M) concentration-dependently induced cytotoxicity in HBEC-5i cells. Deoxynivalenol (IC50 = 20 mu M) activated mitochondrial apoptotic pathway by modulating antioxidant protein expressions (Nrf2, HO-1 and NQO1). More significantly, pre-treatment with VE (20 mu M) attenuated the deoxynivalenol-induced cytotoxicity in this cell model. Together, VE significantly alleviated the apoptotic effects of deoxynivalenol in HBEC-5i cells suggesting that it protected the cells against deoxynivalenol-induced oxidative damage. Our findings provided new insight that VE had the potential to ameliorate neurotoxicity of deoxynivalenol.

关键词： Basal insulin   Glargine 300 U   mL   Glycemic control   Type 2 diabetes  

摘要： Introduction Insulin glargine 300 U/mL (Gla-300) is a novel glargine formulation which shows slower and more prolonged absorption following subcutaneous administration in comparison to insulin glargine 100 U/mL. In this prospective, observational, single-arm, multicenter, real-world study conducted in Serbia, we evaluated the effectiveness and safety of Gla-300 in patients with type 2 diabetes mellitus (T2DM) previously inadequately controlled with different basal or premix insulin therapy regimes. Methods A total of 350 patients with T2DM were enrolled by 27 physicians, from date of the first patient in (12 December 2017) to the date of last patient completed/last patient out (30 October 2018), from both medical centers and general hospitals. Patients' observation and data collection were performed at visit 1 (V1), i.e., the inclusion visit (3-6 months after Gla-300 introduction), including collection of retrospective data from the patients' medical charts at the time of Gla-300 introduction, and at visit 2 (V2) (3-6 months after V1). The primary objective was to assess the change in glycated hemoglobin (HbA1c) level from day of the Gla-300 initiation to the end of the observational period, while the secondary objectives included other effectiveness, as well as safety and other clinically relevant data. Results The mean age of the 350 patients was 63.4 +/- 8.4 years and 56.3% were female. The mean duration of diabetes was 13.4 +/- 7.4 years, while the mean duration of insulin therapy prior to Gla-300 initiation was 5.3 +/- 3.9 years. There was a significant reduction in HbA1c level at each visit compared to the previous visit (8.63 +/- 1.52% at baseline prior to Gla-300 initiation, 7.87 +/- 1.13% at V1, 7.45 +/- 1.05% at V2;p < 0.01 vs. previous visit) accompanied by significant reduction of all hypoglycemic events (p < 0.01). Conclusion Initiation of Gla-300 therapy significantly improved glycemic control and reduced the risk of hypoglycemia in patients with T2DM

关键词： carcinoma   fluorodeoxyglucose F18 positron‐   emission tomography   neoplasms   second primary   squamous cell   unknown primary  

摘要： Background To assess the effect of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the pretherapeutic staging of N classification, detection rate of distant metastases, and second primaries. Methods Retrospective study on patients with head and neck carcinoma. We compared pretherapeutic N classification by ultrasound, computed tomography (CT)/magnetic resonance imaging (MRI), and FDG-PET-CT/MRI. Results A change in the N classification due to FDG-PET-CT/MRI was observed in 116 patients (39.5%) compared to N classification by ultrasound and fine-needle aspiration cytology. Patients with advanced nodal classification (>N2a) were more likely to be reclassified. Distant metastases were detected in 19 patients and a total of 36 second primaries were diagnosed by FDG-PET-CT/MRI. Detection of distant metastases was more likely in regional advanced disease (>N2a). Smokers (>10 py) had a significantly higher risk of second primary. Conclusion FDG-PET-CT/MRI leads to a significant change in pretherapeutic N classification. The cumulative incidence of distant metastases and second primaries was 18.7%.

关键词： Insulin therapy withdrawal   Glucotoxicity   Type 2 diabetes  

摘要： Introduction This study aimed to examine retrospectively the clinical backgrounds of Japanese patients with type 2 diabetes (T2D) who successfully withdrew from insulin use after being started on basal insulin in an outpatient setting. Methods The study population comprised 376 insulin-naive patients who were started on basal insulin (glargine U100, glargine U300, or degludec) for the management of T2D and followed the treatment regimen for at least 6 months in 13 institutions in Japan. The clinical courses of the study participants were compared based on outpatient clinic medical records for the three different types of basal insulin prescribed by categorizing the participants into two groups retrospectively: those who successfully withdrew from insulin therapy and those who did not, during a 6-month observation period. The clinical determinants for insulin withdrawal were assessed using a Cox proportional hazard model. Results Glycated hemoglobin was improved in all participants regardless of basal insulin type. Of the 376 study participants, 61 successfully withdrew from basal insulin therapy. After adjustment was made for several confounders, the positive determinant factors for successful withdrawal of insulin were short duration of diabetes and high body mass index at the start of study, and the negative determinant factor was use of insulin secretagogues at the start. The types of basal insulin used by the study participants were not significant determinants of successful insulin withdrawal in this study. Conclusions Use of basal insulin is a powerful option for the treatment of T2D. In patients with high BMI and/or short duration of diabetes, short-term insulin therapy is a promising strategy for the treatment of T2D before the initiation of insulin secretagogues, since such patients have the potential to successfully withdraw from basal insulin use even in an outpatient setting.

关键词： Porous media   VARANS equations   Perforated caisson   Rubble-mound foundation  

摘要： Rubble-mound foundation can be regarded as a form of porous structure that is widely used in engineering practice. Porous medium flow must be considered when simulating wave interactions with perforated caisson sitting on a rubble-mound foundation. In this paper, volume-averaged/Reynolds averaged Navier-Stokes (VARANS) equations are adopted to describe the flow inside and outside the porous structure. Moreover, they are combined with the volume averaged k - epsilon model to simulate the turbulence effect. In addition, the three-step finite element method is applied to solve VARANS equations numerically, and the CLEAR-VOF method is applied to capture the free fluid surface. The resistance-type porosity numerical model is proposed and verified by several test cases and then used to simulate wave interactions with perforated caisson sitting on a rubble-mound foundation. The porosity model gives reliable results compared to the experiments with respect to the wave height, the pressure distribution, and the total vertical wave force. The model can be adopted to study the wave interaction with perforated caisson sitting on a rubble-mound foundation and used for the design of such caisson in engineering practice.

关键词： angiotensins   ATP   cell physiology   intracellular calcium   meninges   potassium channels  

摘要： The meninges shield the nervous system from diverse, rather harmful stimuli and pathogens from the periphery. This tissue is composed of brain endothelial cells (BECs) that express diverse ion channels and chemical-transmitter receptors also expressed by neurons and glial cells to communicate with each other. However, information about the effects of ATP and angiotensin II on BECs is scarce, despite their essential roles in blood physiology. This work investigated in vitro if BECs from the meninges from rat forebrain respond to ATP, angiotensin II and high extracellular potassium, with intracellular calcium mobilizations and its second messenger-associated pathways. We found that in primary BEC cultures, both ATP and angiotensin II produced intracellular calcium responses linked to the activation of inositol trisphosphate receptors and ryanodine receptors, which led to calcium release from intracellular stores. We also used RT-PCR to explore what potassium channel subunits are expressed by primary BEC cultures and freshly isolated meningeal tissue, and which might be linked to the observed effects. We found that BECs mainly expressed the inward rectifier potassium channel subunits Kir1.1, Kir3.3, Kir 4.1 and Kir6.2. This study contributes to the understanding of the functions elicited by ATP and angiotensin II in BECs from rat meninges.

ISBN: (纸本)9787030692443

关键词： ancient architectures   deep learning   GAN   image inpainting   routine inspection   segmentation  

摘要： Ancient architectures have a lot of distinctive patterns on their component surfaces. But due to the wind and the Sun, the patterns will present extensive deficiencies, which are not conducive to the routine inspections and the subsequent repair work. To overcome these limits, an automatic deep learning-based method of segmentation, inpainting, and classification for defective patterns on ancient architecture is proposed. First, You Only Look At CoefficienTs, which is a real-time instance segmentation network, is applied to obtain the mask of the defective parts. Then Generative Image Inpainting with Contextual Attention, which is an image inpainting algorithm, is used to reconstruct the defective parts. Finally, Residual Neural Network-50 is used to classify the reconstructed images. In this paper, three types of dragon motifs in the Forbidden City were studied. The results show that the classification accuracy of the reconstructed images is increased by an average of 13.1%, with the maximum increasing by 23.5%. The proposed methods can prepare for future routine inspections in advance.

关键词： Cellular senescence   Ovarian cancer   Transcriptome  

摘要： Various types of human endothelial cells, including human umbilical vein endothelial cells (HUVECs) and the established hybrid EAhy926 cells, are used in experimental research. Here, we compared the biological properties of HUVECs and EAhy926 cells under normal (5 mM) and high glucose (30 mM;HG) conditions. The results showed that HG induced cellular senescence and a stronger DNA damage response in HUVECs than in EAhy926 cells. The magnitude of oxidative stress elicited in HUVECs by HG was also greater than that elicited in their established counterparts. Both endothelial cell types promoted the progression of breast (MCF7), ovarian (OVCAR-3), and lung (A549) cancer cells;however, the effects elicited by HG-treated HUVECs on adhesion (MCF7, OVCAR-3), proliferation (OVCAR-3), and migration (OVCAR-3) were more pronounced. Finally, HG stimulated the production of a higher number of proangiogenic agents in HUVECs than in EAhy926 cells. Collectively, our study shows that the functional properties of primary and established endothelial cells exposed to HG differ substantially, which seems to result from the higher sensitivity of the former to this stressor. The interchangeability of both types of endothelial cells in biomedical research should be considered with great care to avoid losing some biological effects due to the choice of cells with higher stress tolerance.