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•A comparative screening strategy was developed to identify all NNIs and r-NNIs;•9 target NNIs and 5 r-NNIs were identified in foodstuffs and indoor dust;•Vegetables, and fruits ...contained the greatest concentrations of NNIs and r-NNIs;•IMI and ACE were two major NNIs detected in indoor environments;•Foodstuffs seem to be more important than dust for NNI and r-NNI intake.
Comparative studies of neonicotinoid insecticides (NNIs) and NNI-related substances (r-NNIs) in foodstuffs and indoor dust are rare. Herein, we investigated the feature fragmentations of nine NNIs in high-energy collision dissociation cells via high-resolution orbitrap mass spectrometry and observed that NNIs can consistently generate several feature fragments (e.g., C6H5NCl+, C4H3NSCl+, and C6H5NF3+). Consequently, NNIs and r-NNIs were comprehensively (targeted, suspect, and feature fragment-dependent) detected in 107 foodstuff and 49 indoor dust samples collected from Nanjing City (eastern China). We fully or tentatively identified 9 target NNIs and 5 r-NNIs in these samples. NNIs and r-NNIs were detected in 93.5% of the analyzed foodstuff samples, and high concentrations were detected in vegetables (mean: 409 ng/g wet weight ww) and fruits (127 ng/g ww). Regarding indoor dust, imidacloprid and acetamiprid exhibited extremely high detection frequencies and contamination levels, and the highest mean concentrations of NNIs and r-NNIs were detected in dormitory samples. Based on the NNI and r-NNI concentrations in the analyzed samples, the mean estimated daily intake values for Chinese adults and children via dietary intake and dust ingestion were 2080–8190 ng/kg bw/day and 378–2680 pg/kg bw/day, respectively.
Type 2 diabetes mellitus (T2DM) is a metabolic disease primarily characterized by insulin resistance (IR) and insufficient insulin secretion. The unfolded protein response (UPR) overactivation ...induced by endoplasmic reticulum stress (ERS) appears to play a key role in this process, although the exact pathogenesis of T2DM is not fully understood. Studies have demonstrated that appropriate exercise can regulate ERS in the heart, liver, pancreas, skeletal muscle, and other body tissues leading to an improvement in diabetes and its complications. However, the exact mechanism remains unclear. By analyzing the relationship between ERS, T2DM pathology, and exercise intervention, this review concludes that exercise can increase insulin sensitivity, inhibit IR, promote insulin secretion and alleviate T2DM by regulating ERS. This paper specifically reviews the signaling pathways by which ERS induces diabetes, the mechanisms of exercise regulation of ERS in diabetes, and the varying effects of different types of exercise on diabetes improvement through ERS mechanisms. Physical exercise is an effective non-pharmacological intervention for T2DM. Thus, further exploration of how exercise regulates ERS in diabetes could refine "precision exercise medicine" for diabetes and identify new drug targets.
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•Endoplasmic reticulum stress is involved in the occurrence and development of type 2 diabetes.•Exercise can improve diabetes by regulating endoplasmic reticulum stress.•Different types of exercise have varying effects on regulating diabetes.
In railway condition monitoring, feature classification is a very critical step, and the extracted features are used to classify the types and levels of the faults. To achieve better accuracy and ...efficiency in the classification, the extracted features must be properly selected. In this paper, maximal information coefficient is employed in two different stages to establish a new feature selection method. By using this proposed two-stage feature selection method, strong features with low redundancy are reserved as the optimal feature subset, which results in the classification process having a more moderate computational cost and good overall performance. To evaluate this proposed two-stage selection method and prove its advantages over others, a case study focusing on the rolling bearing is carried out. The result shows that the proposed selection method can achieve a satisfactory overall classification performance with low-computational cost.
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•We developed a single-phase extraction methodology for lipids in serum samples.•We established a suspect screening database containing 1450 xenobiotics.•Suspect xenobiotic screening ...and lipidomic analysis were conducted for 120 serum samples.•N = 23 active xenobiotics were identified on the basis of high-resolution MS characteristics.•N = 3 active xenobiotics were fully validated by comparison with authentic standards.
Lipidomic analysis has been proven to be a powerful technique to explore the underlying associations between xenobiotics and health status of organisms. Here, we established a strategy that combined the lipidomic analysis with high-throughput suspect contaminant screening technique with an aim to efficiently identify active xenobiotics in humans. Firstly, in the light of single liquid phase equilibrium of chloroform-methanol-water (15:14:2, v/v/v), we developed an efficient method that was able to simultaneously extract both polar and nonpolar lipids in serum samples. By use of this method, targeted and non-targeted lipid analyses were conducted for n = 120 serum samples collected from Wuxi city, China. Secondly, we established a suspect database containing 1450 contaminants that have been previously reported in human samples, and contaminants in this database were screened in the same batch of serum samples by use of high-resolution mass spectrometry (HR-MS). Thirdly, the underlying associations between suspect contaminants and lipids were explored and discussed, and we observed that levels of some lipids were statistically correlated with concentrations of numerous contaminants. Among these active contaminants, 23 ones were identified on the basis of HR MS1 and MS2 characteristics, and these contaminants belonged to the classes of phthalates, phenols, parabens, or perfluorinated compounds (PFCs). Three active xenobiotics were fully validated by comparison with authentic standards, and they were perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and diethyl phthalate (DEP). There were statistically significant changes in levels of triglyceride (TG), lysophosphocholine (LPC), and sphingomyelin (SM) as peak areas of xenobiotics increase. We also observed that, among target lipid molecules, 18:0 lysophosphatidylethanolamine (LPE(18:0)) was very sensitive, and this lipid responded to exposure of various contaminants. Our present study provides novel knowledge on potential alteration of lipid metabolism in humans following exposure to xenobiotics, and provides an efficient strategy for efficiently identifying active xenobiotics in humans.
Induced pluripotent stem cell (iPS cell) holds great potential for applications in regenerative medicine, drug discovery, and disease modeling. We describe here a practical method to generate human ...iPS cells from urine-derived cells (UCs) under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. We showed that this approach could be applied in a large population with different genetic backgrounds. UCs are easily accessible and exhibit high reprogramming efficiency, offering advantages over other cell types used for the purpose of iPS generation. Using the approach described in this study, we have generated 93 iPS cell lines from 20 donors with diverse genetic backgrounds. The non-viral iPS cell bank with these cell lines provides a valuable resource for iPS cells research, facilitating future applications of human iPS cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate ...decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions.Polycomb repressive complex 2 (PRC2) plays an essential role in development by modifying chromatin but what this means at a cellular level is unclear. Here, the authors show that ablation of PRC2 genes in human embryonic stem cells and in mice results in changes in pluripotency and the primed state of cells.
Recent developments in the area of condition monitoring research have been targeted towards predicting machinery health condition for the purpose of preventative maintenance. Typically, published ...research uses data collected from rotating components (bearings, cutting tools, etc.) working in an idealized lab environment as the case study for prognosis algorithm validations. However, the operational implementation in industry is still very sporadic, mainly owing to the lack of proper data allowing sufficiently mature development of comprehensive methodologies. The prognosis methodology presented herein bridges the gap between academic research and industrial implementations by employing a novel time period for prognosis and implementing random coefficients regression models. The definition of the remaining maintenance-free operating period (RMFOP) is proposed first, which helps to transform the usefulness of the degradation data that is readily available from data short of failure. Degradation patterns are subsequently extracted from the original degradation data, before fitting into either of two regression models (linear or exponential). The system residual life distributions are then computed and updated by estimating the parameter statistics within the model. This RMFOP-based methodology is validated using real-world degradation data collected from multiple operational railway switch systems across Great Britain. The results indicate that both the linear model and the exponential model can produce residual life distributions with a sufficient prediction accuracy for this specific application. The exponential model gives better predictions, the accuracy of which also improves as more of system life percentage has elapsed. By using the RMFOP methodology, switch system health condition affected by an incipient overdriving fault is recognized and predicted.
Abstract With the acceleration of global industrialisation, the scarcity and depletion of the world’s energy resources has become a problem that no country can ignore. It is a serious obstacle to the ...long-term stable development of society. Exploring and developing new energy sources has become the trend of global energy development. In this paper, hydrogen peroxide is used to treat carbon fibre materials. In addition, the thermoelectric reinforcing agent Bi2Te3 is doped into carbon fibre film materials by electrochemical deposition for the purpose of measuring the Seebeck coefficient and electrical conductivity. Technical abbreviations will be explained at the first use. By investigating how changes in the surface structure of carbon fibre fabrics and the addition of bismuth telluride affect their thermoelectric properties, this study establishes a framework for improving the thermoelectric capabilities of carbon fibre fabrics. Experimental results show that carbon fiber fabric treated with H 2 O 2 have excellent thermoelectric and mechanical properties.
Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience ...partial improvement.
This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response.
A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively.
The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications.
This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .
Background Accumulating evidence implicates that gut fungi are associated with the pathogenesis of colorectal cancer (CRC). Our previous study has revealed that Candida tropicalis (C. tropicalis) ...promotes colorectal tumorigenesis by enhancing immunosuppressive function of myeloid-derived suppressor cells (MDSCs) and increasing accumulation of MDSCs, but the underlying mechanisms remain unestablished. Methods Bone marrow-derived MDSCs were stimulated with C. tropicalis. RNA-sequencing analysis was performed to screen the differentially expressed genes. Quantitative real-time PCR and western blot were used to measure the expression of related proteins. Co-culture assay of MDSCs and CD8.sup.+ T cells was used to determine the immunosuppressive ability of MDSCs. Metabolomic analysis was conducted to detect metabolic reprogramming of MDSCs. Aerobic glycolysis of MDSCs was assessed by extracellular acidification rate (ECAR), glucose consumption and lactate production. A CAC mouse model was induced by AOM and DSS to determine the therapeutic action of TEPP-46. IHC and immunofluorescence were performed to examine the expression of PKM2, PKM2 (p-Y105) and iNOS in human CRC-infiltrated MDSCs. Results C. tropicalis facilitates immunosuppressive function of MDSCs by increasing the expression of iNOS, COX2 and NOX2, production of nitric oxide (NO) and reactive oxygen species (ROS). Mechanistically, C. tropicalis facilitates the immunosuppressive function of MDSCs through the C-type lectin receptors Dectin-3 and Syk. C. tropicalis-enhanced immunosuppressive function of MDSCs is further dependent on aerobic glycolysis. On the one hand, NO produced by MDSCs enhanced aerobic glycolysis in a positive feedback manner. On the other hand, C. tropicalis promotes p-Syk binding to PKM2, which results in PKM2 Tyr105 phosphorylation and PKM2 nuclear translocation in MDSCs. Nuclear PKM2 interacts with HIF-1alpha and subsequently upregulates the expression of HIF-1alpha target genes encoding glycolytic enzymes, GLUT1, HK2, PKM2, LDHA and PDK1, which are required for the C. tropicalis-induced aerobic glycolysis of MDSCs. Blockade of PKM2 nuclear translocation attenuates C. tropicalis-mediated colorectal tumorigenesis. The high expression of PKM2, PKM2 (p-Y105) and iNOS in CRC-infiltrated MDSCs correlates with the development of human CRC. Conclusion C. tropicalis enhances immunosuppressive function of MDSCs via Syk-PKM2-HIF-1alpha-glycolysis signaling axis, which drives CRC. Therefore, we identify the Syk-PKM2-HIF-1alpha-glycolysis signaling axis as a potential therapeutic target for CRC. Keywords: Candida tropicalis, Colorectal cancer, Myeloid-derived suppressor cells, Syk, PKM2, Aerobic glycolysis
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