High-Level Expression of Notch1 Increased the Risk of Metastasis in T1 Stage Clear Cell Renal Cell Carcinoma

Background: Although metastasis of clear cell renal cell carcinoma (ccRCC) is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC. Methodology/Principal Findings: The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1

A Study on Stable Feature Representations for Artificial Olfactory System

University of Technology Sydney. Faculty of Engineering and Information Technology.The electronic nose (e-nose) is an artificial olfactory system, consisting of a gas sensor array, a control system, and algorithms, designed to detect and identify the single or mixtures of odours. Owing to the boom of gas sensor technology and machine learning algorithms, e-noses have found wide applications in many different fields. However, the performance of e-noses in real applications has been challenged due to the 3D issue (i.e., the discreteness issue, the drift issue, and the disturbance issue). This thesis mainly focuses on the discreteness issue, especially the instability in feature representations caused by sensor noises. A kernel regularization modelling-based method is proposed to provide stable representations for target odours. This method regards the e-nose as a whole system. The estimated parameters of the system are applied as features to represent the odour. The use of a smooth and stable kernel in the regularization term helps to overcome the ill-posed problem existing in deconvolution. However, the above-proposed method requires an accurate setting of the initial time (time of gas-on). To avoid a laborious searching of this time point, an improved method based on multiscale wavelet kernel regularization is proposed. The multiscale wavelet kernel inherits the advantage from wavelet function in approximating arbitrary signals and equips the method with the ability in resistance to random noise. Aiming to the drift issue encountered in whisky classification experiment, a framework of "feature extraction -- domain adaptation" is proposed. Aiming at the instability of traditional transient-state features extracted from the noise-contaminated signal, a novel kernel Tikhonov regularization-based numerical differentiation algorithm is proposed. The proposed method can improve such features by directly estimating accurate high-order derivatives from noisy signals. In this experiment, samples of two new whiskies were added to the testing set as disturbances. Accordingly, a framework of "feature extraction -- domain adaptation -- one-class classification" is proposed. In addition, based on stable feature representations, we also proposed two frameworks for food freshness monitoring and evaluation. Monitoring is realized by one-class classification. A single hidden Markov model (HMM) trained only by fresh samples is applied to track the change in freshness. For freshness evaluation, an HMM-based decoding algorithm is proposed to cluster the freshness level when the whole life-span data of meat stored in a specific storage condition is available. Then, HMM for each freshness level is trained and applied in parallel as freshness evaluation models to classify the tested meat samples

Local structural health monitoring system in aircraft based on fiber Bragg grating array

In this study, a structural health monitoring system for aircraft wings based on a fiber-optic grating sensing network was designed, and a three-dimensional position correction algorithm based on fiber Bragg grating (FBG) array test data was developed. Solving the deformation parameters using mathematical models of strain-position offset introduces errors, leading to inaccurate measurements and affecting the preciseness of three-dimensional-reconstructed surfaces. Two fitting algorithms (bitone and spline with linear interpolations) are proposed to improve this method in analyzing errors at the measured points of the wing structure. The relative error of each measurement point of the reconstructed wing structure using the bitone and spline interpolation methods was lower than 4.96%. Furthermore, the absolute error was within 0.014 mm, the average relative error was lower than 3.47%, and the root-mean-square error was lower than 0.01 mm. Compared to linear interpolation, the average relative error decreased by up to 5.84%. The experimental results show that the measurement accuracy of bitone and spline interpolation was significantly higher than that of linear interpolation. FBG array measurements using bitone and spline interpolations for the local structural health monitoring system of aircraft improve the fitting reconstruction effect for the wing structure and stabilize the compensation effect

Design of an efficient electronic nose system for odour analysis and assessment

This paper presents an efficient electronic nose (e-nose) system, named “NOS.E”, for odour analysis and assessment. In addition to the reliable hardware and software designs, an airflow intake system is implemented to ensure the precise odour analysis procedure in the NOS.E system. Additionally, a particular control logic was introduced to improve the test efficiency of the NOS.E by reducing operation time. Furthermore, the fault detection and alarming design can generate a high-reliability performance by constantly monitoring its working status. To evaluate the performance of the NOS.E, three types of alcohols were tested by the NOS.E and compared to data collected by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS). The results indicate that the NOS.E can successfully distinguish three different alcohols with high efficiency and low cost and has the potential to be a universal odour analysis platform implemented in various applications

Association of fat-soluble vitamins (A, D, and E) status with humoral immune response to COVID-19 inactivated vaccination

BackgroundFat-soluble vitamins (A, D, and E) are essential for the proper functioning of the immune system and are of central importance for infection risk in humans. Vitamins A, D, and E have been reported to be associated with the immune response following vaccination; however, their effects on the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination remain unknown.MethodsWe measured the neutralizing antibody titers against wild type and omicron within 98 days after the third homologous boosting shot of inactivated SARS-CoV-2 vaccine (BBIBP-CorV or CoronaVac) in 141 healthy adults in a prospective, open-label study. High-performance liquid chromatography-tandem mass spectroscopy was used to determine the concentrations of plasma vitamins A, D, and E.ResultsWe found that the anti-wide-type virus and anti-omicron variant antibody levels significantly increased compared with baseline antibody levels (P < 0.001) after the third vaccination. 25(OH)D3 was significantly negatively associated with the baseline anti-wide-type virus antibody concentrations [beta (95% CI) = −0.331 (−0.659 ~ −0.003)] after adjusting for covariates. A potentially similar association was also observed on day 98 after the third vaccination [beta (95% CI) = −0.317 (−0.641 ~ 0.007)]. After adjusting for covariates, we also found that 25(OH)D3 was significantly negatively associated with the seropositivity of the anti-omicron variant antibody at day 98 after the third vaccination [OR (95% CI) = 0.940 (0.883 ~ 0.996)]. The association between plasma 25(OH)D3 with anti-wild-type virus antibody levels and seropositivity of anti-omicron variant antibodies were persistent in subgroup analyses. We observed no association between retinol/α-tocopherol and anti-wide-type virus antibody levels or anti-omicron variant antibody seropositive in our study.ConclusionThe third inactivated SARS-CoV-2 vaccination significantly improved the ability of anti-SARS-CoV-2 infection in the human body. Higher vitamin D concentrations could significantly decrease the anti-wide-type virus-neutralizing antibody titers and anti-omicron variant antibody seropositive rate after the inactivated SARS-CoV-2 vaccination in people with adequate levels of vitamin D, better immune status, and stronger immune response; further studies comprising large cohorts of patients with different nutritional status are warranted to verify our results

U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes

Background: Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare. Objective: We investigated the association between plasma manganese and newly diagnosed T2D as well as whether the association could be modified by manganese superoxide dismutase (MnSOD) polymorphisms. Methods: We conducted a case–control study of 3,228 participants in China: 1,614 T2D patients and 1,614 controls. Concentrations of plasma magnesium were measured, and all participants were genotyped for the MnSOD Val16Ala polymorphism (rs4880). Results: A U-shaped association was observed between plasma manganese and T2D, with increased odds ratios (ORs) in relation to either low or high plasma manganese levels. Compared with the middle tertile, the multivariate-adjusted ORs [95% confidence intervals (CIs)] of T2D associated with the lowest tertile and the highest tertile of plasma manganese were 1.89 (1.53, 2.33) and 1.56 (1.23, 1.97), respectively. In spline analysis, the U-shaped association was consistently indicated, with the lowest odds of T2D at the plasma manganese concentration of 4.95 μg/L. Minor allele frequencies (C allele) of the MnSOD Val16Ala polymorphism (rs4880) in the normal glucose tolerance (NGT) and the T2D groups were 13.57% and 14.50%, respectively. The MnSOD rs4880 polymorphism was not associated with T2D, and no interaction was found between plasma manganese and the MnSOD rs4880 polymorphism in relation to T2D. Conclusions: Our results suggested a U-shaped association between plasma manganese and T2D; both low and high levels of plasma manganese were associated with higher odds of newly diagnosed T2D. The U-shaped association was not modified by the MnSOD rs4880 polymorphism. Citation: Shan Z, Chen S, Sun T, Luo C, Guo Y, Yu X, Yang W, Hu FB, Liu L. 2016. U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124:1876–1881; http://dx.doi.org/10.1289/EHP17

Procyanidins Extracted from Lotus Seedpod Ameliorate Amyloid-β-Induced Toxicity in Rat Pheochromocytoma Cells

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, which is characterized by extracellular senile plaque deposits, intracellular neurofibrillary tangles, and neuronal apoptosis. Amyloid-β (Aβ) plays a critical role in AD that may cause oxidative stress and downregulation of CREB/BDNF signaling. Anti-Aβ effect has been discussed as a potential therapeutic strategy for AD. This study aimed to identify the amelioration of procyanidins extracted from lotus seedpod (LSPC) on Aβ-induced damage with associated pathways for AD treatment. Rat pheochromocytoma (PC12) cells incubated with Aβ25–35 serve as an Aβ damage model to evaluate the effect of LSPC in vitro. Our findings illustrated that LSPC maintained the cellular morphology from deformation and reduced apoptosis rates of cells induced by Aβ25–35. The mechanisms of LSPC to protect cells from Aβ-induced damage were based on its regulation of oxidation index and activation of CREB/BDNF signaling, including brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP-responsive element-binding (CREB), protein kinase B (also known as AKT), and the extracellular signal-regulated kinase (ERK). Of note, by high-performance liquid chromatography-tandem mass spectroscopy (LC-MS/MS), several metabolites were detected to accumulate in vivo, part of which could take primary responsibility for the amelioration of Aβ-induced damage on PC12 cells. Taken together, our research elucidated the effect of LSPC on neuroprotection through anti-Aβ, indicating it as a potential pretreatment for Alzheimer’s disease

Plasma Transthyretin Levels and Risk of Type 2 Diabetes Mellitus and Impaired Glucose Regulation in a Chinese Population

Plasma transthyretin may be engaged in glucose regulation. We aimed to investigate the association between plasma transthyretin levels and the risk of newly diagnosed T2DM and impaired glucose regulation (IGR) in a Chinese population. We conducted a case-control study including 1244 newly diagnosed T2DM patients, 837 newly diagnosed IGR patients, and 1244 individuals with normal glucose tolerance (NGT) matched by sex and age. Multivariate logistic regression analysis was utilized to estimate the independent association of plasma transthyretin concentrations with the risk of T2DM and IGR. Plasma transthyretin concentrations were significantly higher in T2DM and IGR patients compared with control subjects (p < 0.005). After multiple adjustment and comparison with the lowest quartile of plasma transthyretin concentrations, the odds ratios (95% confidence intervals) of T2DM and IGR in the highest quartile were 2.22 (1.66, 2.98) and 2.29 (1.72, 3.05), respectively. Plasma transthyretin concentrations also showed a great performance in predicting the risk of T2DM (AUC: 0.76). Moreover, a potential nonlinear trend was observed. Our results demonstrated that higher plasma transthyretin concentrations, especially more than 290 mg/L, were associated with an increased risk of T2DM and IGR. Further studies are warranted to confirm our findings and elucidate the potential mechanisms