Abstract
Background
Autophagy is required for oogenesis and plays a critical role in response to aging caused by oxidative stress. However, there have been no reports on regulation of cytoprotective ...autophagy in female germline stem cells (FGSCs) in response to aging caused by oxidative stress.
Results
We found that Spermidine (SPD) significantly increased protein expression of autophagy markers microtubule-associated protein 1 light chain 3 beta-II (MAP1LC3B-II/LC3B-II) and sequestosome-1/p62 (SQSTM1/p62), and evoked autophagic flux in FGSCs. Moreover, SPD increased the number and viability of FGSCs in vitro. Further, we found that SPD significantly reduced basal or hydrogen peroxide (H
2
O
2
)-induced up-regulated protein expression of the aging markers, cyclin dependent kinase inhibitor 2A (p16/CDKN2A) and tumor protein 53 (p53). After knockdown of p62 in FGSCs, p16 protein levels were significant higher compared with controls. However, protein p16 levels were not significantly changed in p62 knockdown FGSCs with SPD treatment compared with without SPD. Moreover, SPD significantly changed the expression of autophagy-related genes and pathways in FGSCs, as shown by bioinformatics analysis of RNA sequencing data. Additionally, SPD significantly inhibited AKT/mTOR phosphorylation.
Conclusions
SPD induces cytoprotective autophagy in FGSCs in vitro and ameliorates cellular senescence of FGSCs induced by H
2
O
2
. Furthermore, SPD can ameliorate cellular senescence of FGSCs through p62. SPD might induce autophagy in FGSCs via the PI3K/Akt pathway. Our findings could be helpful for delaying aging of female germ cells due to oxidative stress and preserving female fertility.
Electromagnetic Acoustic Transducer (EMAT) has become one of the fastest-growing solutions for pipeline weld inspection over the past decade due to its non-contact advantage. One primary problem of ...EMAT is that it has relatively lower energy transition efficiency compared to widely used piezoelectric transducers, coupled with the effect of lift-off and the non-uniformity issue of welding material, the Signal-to-Noise Ratio (SNR) can be significantly restricted. This brings great difficulty in interpreting the EMAT signal measured from pipeline girth welds. To overcome this challenge, this paper presents a deep learning-based ultrasonic pattern recognition method to identify the pipeline girth weld cracking automatically. The proposed method utilizes a deep Convolution Neural Network (CNN) integrated with a pre-trained Support Vector Machine (SVM) classifier to extract the high-level features from the time-frequency representation of A-scan signals measured by bulk-wave EMAT and classify these signals into defective or non-defective groups. To validate the proposed method, a set of experiments is carried out to classify A-scan signals measured from the girth welds of an ex-service type 813-X70 gas pipeline. A comparative investigation is also undertaken to demonstrate the superiority of the proposed method against the conventional ultrasonic pattern recognition methods for evaluation.
Visceral fat is a risk factor for non‐alcoholic fatty liver disease (NAFLD). A reduction in sex hormones is associated with increased abdominal fat. Thus, we investigated whether reduced testosterone ...(T) or oestradiol (E2) levels in men are associated with NAFLD and central obesity. The study involved a survey of 1,882 men between 20 and 60 years of age. We detected hepatic fat infiltration by ultrasound. Early morning serum was analyzed for total testosterone (TT), E2, sex hormone‐binding globulin (SHBG), follicle‐stimulating hormone (FSH) and luteinizing hormone (LH). Free testosterone (FT) was calculated using the Vermeulen method. In the studied population, the prevalence of NAFLD, FSH, LH and SHBG increased with age, TT and FT declined with age, and E2 remained stable. However, in the NAFLD group, TT remained stable, FT and E2 declined, and hepatic fat infiltration increased (P < 0.001 for both). Using multivariate analysis, a correlation was found between E2 and NAFLD, with an odds ratio of 0.954 (95% confidence interval: 0.946–0.967). E2 is one of the protective factors against NAFLD in healthy men. T has no significant correlation with NAFLD. Further investigation would be required to assess the clinical consequences of reduced E2 in men with NAFLD, particularly for men whose TT remained stable.
CFRP (carbon fiber reinforced plastic) has replaced conventional metallic materials in many industrial applications because of its outstanding mechanical performance such as high strength to ratio ...and resistance of fatigue. During the service life of the aerospace composite component, delamination left without detection can cause a sudden breakdown of the structure. Eddy current pulse-compression thermography (ECPuCT) is an emerging technique that combines traditional ECPT and pulse compression techniques. In this work, feature extraction techniques of impulse response have been exploited in terms of principal component analysis (PCA), kernel principal component analysis (K-PCA) and independent component analysis (ICA). Each technique is evaluated using SNR as the index to compare their performance. The results indicate that Kernel-PCA performs better than PCA and ICA based features when dealing with delamination ranged from defect#1(0.46mm) to defect#9 (2.30mm).
Bisphenol A (BPA), one of the most frequently detected emerging pollutants in the environment, has been implicated in adverse effects in male and female reproduction at extremely low concentrations. ...This study aimed to investigate the effects and potential mechanism of BPA on mouse ovarian follicular development and female germline stem cells (FGSCs). Female CD-1 adult mice were administered gradient concentrations of BPA (12.5, 25, and 50 mg/kg/day) by intraperitoneal injection. We found that the number of atretic ovarian follicles was significantly increased at high BPA concentrations. Additionally, the numbers of primordial follicles, primary follicles, and corpus luteum (CL) were significantly reduced at high BPA concentrations. Interestingly, the number of FGSCs was remarkably reduced in BPA-treated ovaries. Furthermore, the increased apoptotic rate of FGSCs
in vitro
was triggered by BPA accompanied by increased BPA concentrations. To investigate the mechanism of BPA in ovarian follicular development, 193 differentially expressed proteins were identified in BPA-treated ovaries by the isobaric tags for relative and absolute quantification-coupled 2D liquid chromatography-mass spectrometry technique. A total of 106 proteins were downregulated and 85 proteins were upregulated. Among these proteins, the apoptosis-related protein SAFB-like transcriptional modulator (SLTM) was remarkably upregulated, and this result was consistent with western blotting. Taken together, our results suggest that an ovarian follicular development, especially, the development of primordial follicles, primary follicles, and the CL, is inhibited by high BPA concentrations, and the ovarian follicle atresia is initiated by BPA through upregulated expression of SLTM. Furthermore, BPA induces apoptosis of cultured FGSCs. The effect of BPA on ovarian follicular development and FGSCs, especially the effect on FGSCs, suggests a novel mechanism of how BPA causes female infertility.
This study was conducted to evaluate the effect of supplementing hydroxy selenomethionine (OH-SeMet) on performance, selenium (Se) deposition in the breast muscle, quality and oxidative stability, ...and expression of selenoprotein encoding genes of breast meat of the native slow-growing yellow-feathered broiler birds. A total of 375 one-day-old local yellow male birds were randomly assigned into 5 dietary treatments, supplemented with Se 0.0, 0.2, 0.4, 0.6, and 0.8 mg/kg in the form of OH-SeMet. Each treatment consisted of 5 replicates and each replicate had 15 birds, the birds were fed on basal diet containing corn and soybean meal, and the experiment lasted for 63 d. The results showed that dietary Se supplementation linearly increased (P < 0.001) Se contents in both serum and muscle, no significant changes (P > 0.05) were observed on growth performance, yield of breast, meat color, and intramuscular fat deposition of the breast muscle. Dietary Se addition improved water-holding capacity, the pH24h value, and tenderness of breast muscle, evidenced by a linear decreases of shear force (P < 0.05), accompanied by lower thiobarbituric acid reactive substances and higher glutathione reductase activity. The mRNA abundance of selenoprotein encoding genes also responded to dietary Se levels. It is concluded that, dietary supplementation with OH-SeMet improved muscular Se deposition and meat quality of the native yellow birds, with enhanced antioxidant capability and regulation in selenogenome.
Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum ...tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations n = 1; 125 mg, hyperphosphatemia n = 1; 150 mg, grade 1 corneal toxicity n = 1 and grade 3 aminotransferase elevations n = 1). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses six confirmed) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers.
Female germline stem cells (FGSCs) are adult stem cells that can both self-renew and differentiate into mature oocytes. Although small-molecule compounds are capable of regulating the development of ...FGSCs, the effects and mechanisms of action of metformin, a commonly used drug for diabetes, on FGSCs are largely unknown. Here, we found that metformin promoted the viability and proliferation of FGSCs through H3K27ac modification. To elucidate the mechanism by which metformin promoted FGSCs proliferation, Chromatin Immunoprecipitation Sequencing of histone 3 lysine 27 acetylation (H3K27ac) in FGSCs was performed with or without metformin-treatment. The results indicate that metformin modulates FGSCs via the mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor receptor associated factor 2 (Traf2) was identified as an important target gene for H3K27ac modification during FGSCs proliferation. Subsequent experiments showed metformin promoted FGSCs proliferation by H3K27ac modification of Traf2 to regulate MAPK signaling. Our findings deepen understanding of how H3K27ac modifications regulate FGSCs development and provide a theoretical basis for the prevention and treatment of premature ovarian failure, polycystic ovary syndrome, infertility, and related diseases.
•Couplingpulse eddy current sensing architecturefordeeperdefects detection.•Increase the ratio of indirect coupling energy to direct coupling energy.•Detection sensitivity of different duty cycles ...and peak difference are discussedforanalyzingthe defect depth.
Deep defect detection for ferromagnetic materials is a challenging task for Eddy Current testing (ECT) due to the skin effect of the low penetration depth. Pulsed Eddy Current testing (PECT) is a potential and effective method for detecting deep subsurface defects as it can obtain multiple depth information owing to its wide spectrum range. A novel weak coupling sensing structure of pulsed eddy current is proposed. In particular, the structure improves the ratio of the indirect coupling energy by reducing the direct coupling energy between the excitation and the detection coils. It obviously improves the ability to detect deep subsurface defects of ferromagnetic materials. The principle of penetration and the analysis of its equivalent circuit are presented. In addition, both experiments and simulations on different defects detection have been studied. The results have confirmed that all types of defects can be detected and it has shown the relatively monotonic linear relationships and reliability.
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