Summary
This large cross-sectional study examined the associations of dietary intakes of total flavonoids and their subtypes with bone density in women and men. We found that greater flavonoid intake ...was associated with higher bone density in women but not in men.
Introduction
Studies in vitro and in animal models suggest a potential effect of flavonoids on bone health. Few studies have examined the association between the habitual intake of flavonoids and bone mineral density (BMD) in humans.
Methods
The cross-sectional study recruited 2,239 women and 1,078 men. A semiquantitative food frequency questionnaire was administered in face-to-face interviews to assess habitual dietary flavonoid intake using food composition databases. BMD was measured over the whole body (WB) and in the femoral neck (FN) and lumbar spine (LS) by dual-energy X-ray absorptiometry (DXA).
Results
After adjusting for covariates, women who consumed higher total flavonoids, and the subtypes of flavonols, flavan-3-ols, flavones, and proanthocyanidins tended to have greater BMD at the WB, LS, and FN (all P-trend < 0.05). Women in the highest (vs. the lowest) quartile of total flavonoids intake had 0.020 (1.91 %), 0.021 (2.51 %), and 0.013 (1.99 %) g/cm
2
greater BMD at the whole body, LS, and FN, respectively. For the subtypes of flavonoids, the corresponding differences in BMD (in g/cm
2
) were 0.012–0.021 (flavan-3-ols), 0.013–0.020 (flavonols), 0.016–0.019 (flavones), and 0.014–0.016 (proanthocyanidins), respectively. A higher intake of flavonones was associated with a greater BMD at the whole body (P-trend 0.041) and the FN (P-trend 0.022). In men, there were no significant positive associations between the consumption of total flavonoids and the subclasses and BMD at any sites.
Conclusion
Dietary flavonoids intake was positively associated with BMD in women. Further large studies are needed to clarify this issue in men.
The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally ...invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive-predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor-κB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14)-mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers.
Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema pallidum, have been reported to cause treatment failures in patients receiving azithromycin for syphilis. Genotyping of ...T. pallidum strains sequentially isolated from patients with recurrent syphilis is rarely performed. From September 2009 to August 2013, we collected 658 clinical specimens from 375 patients who presented with syphilis for genotyping to examine the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by restriction fragment length polymorphism. Treponemal DNA was identified in 45.2% (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268 (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no A2059G mutation was identified. A total of 14 strains of T. pallidum were identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant strains. Forty patients who presented with recurrent episodes of syphilis had T. pallidum DNA identified from the initial and subsequent episodes, with five cases showing strain discrepancies. One patient had two strains identified from different clinical specimens collected in the same episode. Our findings show that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence of T. pallidum strains that show A2058G or A2059G mutation remains low. Different genotypes of T. pallidum can be identified in patients with recurrent episodes of syphilis.
Quantum Hall ferromagnetic transitions are typically achieved by increasing the Zeeman energy through in-situ sample rotation, while transitions in systems with pseudo-spin indices can be induced by ...gate control. We report here a gate-controlled quantum Hall ferromagnetic transition between two real spin states in a conventional two-dimensional system without any in-plane magnetic field. We show that the ratio of the Zeeman splitting to the cyclotron gap in a Ge two-dimensional hole system increases with decreasing density owing to inter-carrier interactions. Below a critical density of ~2.4 × 10
cm
, this ratio grows greater than 1, resulting in a ferromagnetic ground state at filling factor ν = 2. At the critical density, a resistance peak due to the formation of microscopic domains of opposite spin orientations is observed. Such gate-controlled spin-polarizations in the quantum Hall regime opens the door to realizing Majorana modes using two-dimensional systems in conventional, low-spin-orbit-coupling semiconductors.
Epigenetic modifications are a driving force in carcinogenesis. However, their role in cancer metastasis remains poorly understood. The present study investigated the role of DNA methylation in the ...cervical cancer metastasis. Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference. Using methyl-DNA immunoprecipitation coupled with microarray analysis, we found that the protein tyrosine phosphatase receptor type R (PTPRR) was silenced through DNMT3B-mediated methylation in the cervical cancer. PTPRR inhibited p44/42 MAPK signaling, the expression of the transcription factor AP1, human papillomavirus (HPV) oncogenes E6/E7 and DNMTs. The methylation status of PTPRR increased in cervical scrapings (n=358) in accordance with disease severity, especially in invasive cancer. Methylation of the PTPRR promoter has an important role in the metastasis and may be a biomarker of invasive cervical cancer.
Intra-granular Acicular Ferrite (IAF), as one of the most well-known desirable microstructure of ferrite with a chaotic crystallographic orientation, can not only refine the microstructure and retard ...the propagation of cleavage crack but also provide excellent combination of strength and toughness in steel. The effect of adding cerium on microstructure and controlling proper cerium-based inclusions in order to improve properties in low-carbon commercial steel (SS400) were investigated. The type of inclusions can be controlled by changing S/O ratio and Ce content. Without Ce modification, MnS is a dominate inclusion. After adding Ce, the stable inclusion phases change from AlCeO
to Ce
O
S. The optimum amount of cerium, 0.0235 wt.%, lead in proper grain refinement and formation of cerium oxide, oxy-sulfide and sulfide inclusions. Having a high amount of cerium results in increasing the number of inclusions significantly as a result it cannot be effective enough and the inclusions will act like barriers for others. It is found that the inclusions with a size of about 4∼7 μm can serve as heterogeneous nucleation sites for AF formation. Thermodynamic calculations have been applied to predict the inclusion formation in this molten steel as well, which show a good agreement with experimental one.
Histone deacetylase (HDAC) inhibitors (HDIs) are promising anticancer therapies and have been clinically used for the treatment of hematological malignancy. However, their efficacy in solid tumors is ...marginal and drug resistance hampers their further clinical utility. To develop novel strategies for the HDI-based anticancer therapeutics in non-small cell lung cancer (NSCLC), in the present study, we investigated the mechanisms underlying resistance to HDI treatment in NSCLC cells. We show the STAT3-mediated IGF2/IGF-1R signaling cascade as a key modulator for both acquired and primary HDI resistance. The treatment with HDI upregulated IGF2 transcription in NSCLC cells carrying intrinsic or acquired drug resistance via direct binding of STAT3 in IGF2 P3 and P4 promoters. Acetylated STAT3 emerged upon HDAC inhibition was protected from the proteasome-mediated degradation of STAT3 and functioned as a direct transcription factor for IGF2 expression. Genomic or pharmacological strategies targeting STAT3 diminished the HDI-induced IGF2 mRNA expression and overcame the resistance to HDI treatment in HDI-resistant NSCLC- or patient-derived tumor xenograft models. These findings provide new insights into the role of acetylated STAT3-mediated activation of IGF2 transcription in HDI resistance, suggesting IGF2 or STAT3 as novel targets to overcome HDI resistance in NSCLC.
Abstract
The transient photocurrent is one of the key parameters of the spatial radiation effect of photoelectric devices, and the energy level defect affects the transient photocurrent. In this ...paper, by studying the deep level transient spectrum of a self-designed Schottky diode, the defect properties of the interface region of the anode metal AlCu and Si caused by high-temperature annealing at 150 ℃, 200 ℃ and 300 ℃ for 1200 h have been quantitatively analyzed. The study shows that the defect is located at the position of + 0.41 eV on the valence band, the concentration is 2.8
$$\times$$
×
10
13
/cm
2
, and the capture cross section is
$$\sigma$$
σ
= 8.5
$$\times$$
×
10
17
. The impurity energy level mainly comes from the diffusion of Al atom in anode metal. We found that the defect did not cause the electrical performance degradation and obvious morphology change of the device, but the transient photocurrent increased significantly. The reason is that the high temperature treatment results in a growth in the density of states at the interface between AlCu–Si. The more mismatched dislocations and recombination center increased the reverse current of the heterojunction. The above view is proved by the TCAD simulation test.
Combination PD-1 and CTLA-4 inhibitor therapy has dramatically improved the survival of patients with advanced melanoma but is also associated with significant immune-related toxicities. This study ...sought to identify circulating cytokine biomarkers of treatment response and immune-related toxicity.
The expression of 65 cytokines was profiled longitudinally in 98 patients with melanoma treated with PD-1 inhibitors, alone or in combination with anti-CTLA-4, and in an independent validation cohort of 49 patients treated with combination anti-PD-1 and anti-CTLA-4. Cytokine expression was correlated with RECIST response and immune-related toxicity, defined as toxicity that warranted permanent discontinuation of treatment and administration of high-dose steroids.
Eleven cytokines were significantly upregulated in patients with severe immune-related toxicities at baseline (PRE) and early during treatment (EDT). The expression of these 11 cytokines was integrated into a single toxicity score, the CYTOX (cytokine toxicity) score, and the predictive utility of this score was confirmed in the discovery and validation cohorts. The AUC for the CYTOX score in the validation cohort was 0.68 at PRE 95% confidence interval (CI), 0.51-0.84;
= 0.037 and 0.70 at EDT (95% CI, 0.55-0.85;
= 0.017) using ROC analysis.
The CYTOX score is predictive of severe immune-related toxicity in patients with melanoma treated with combination anti-CTLA-4 and anti-PD-1 immunotherapy. This score, which includes proinflammatory cytokines such as IL1a, IL2, and IFNα2, may help in the early management of severe, potentially life-threatening immune-related toxicity.
.
Summary
Background
Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human ...immunodeficiency virus (HIV) coinfection.
Aim
To evaluate the effectiveness and safety of generic VEL/SOF‐based therapy for HCV infection in patients with or without HIV coinfection in Taiwan.
Methods
Sixty‐nine HIV/HCV‐coinfected and 159 HCV‐monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti‐viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12) were analysed.
Results
The SVR12 was achieved in 67 HIV/HCV‐coinfected patients (97.1%; 95% CI: 90.0%‐99.2%) and in 156 HCV‐monoinfected patients (98.1%; 95% CI: 94.6%‐99.4%) receiving VEL/SOF‐based therapy, respectively. The SVR12 rates were comparable between HIV/HCV‐coinfected and HCV‐monoinfected patients, regardless of pre‐specified baseline characteristics. One hundred twenty‐two (53.5%) and seven (3.1%) patients had baseline resistance‐associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV‐coinfected and HCV‐monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV‐coinfected patients receiving anti‐retroviral therapy containing tenofovir disoproxil fumarate (TDF).
Conclusions
Generic VEL/SOF‐based therapy is well‐tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.
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