Inspection of Liner Wall Thinning and Interface Debonding in Bimetallic Lined Pipes Using Pulsed Eddy Current Testing.

Bimetallic lined pipe (BLP) has been increasingly used in offshore and subsea oil and gas structures, but how to identify the invisible inner defects such as liner wall thinning and interface debonding is a challenge for future development. A nondestructive testing (NDT) method based on pulsed eddy current testing (PECT) has been proposed to face these difficulties. The inspection of the BLP specimen (AISI1020 base tube and SS304 liner) is implemented from outside of the pipe by using a transmitter-receiver-type PECT probe consisting of two induction coils. By simplifying the BLP specimen to stratified conductive plates, the electromagnetic field interaction between the PECT probe and specimen is analytically modeled, and the probe inspection signals due to liner wall thinning and interface debonding are calculated. In order to highlight the weak response (in microvolts) from the liner, the inspection signals are subtracted by the signal, which is calculated in the case of only having a base tube, yielding differential PECT signals. The peak voltage of the differential signal is selected to characterize the liner wall thinning and interface debonding due to its distinguishable and linear variation. Experiment verification is also carried out on a double-walled specimen simulated by a combination of a Q235 casing pipe and SS304 tubes of different sizes. The experimental results basically agree with the analytical predictions. The peak value of the PECT signal has an ascending and descending variation with the increase in the remaining liner wall thickness and debonding gap, respectively, while the negative peak value shows opposite changes. The peak value exhibits a larger sensitivity than the negative peak value. The proposed method shows potential promise in practical applications for the evaluation of the inner defects in BLP lines.

The Fibrosis-5 Index Predicts Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

This study aimed to evaluate the fibrosis-5 (FIB-5) index as a marker of liver fibrosis for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 406 STEMI patients were enrolled in the study. Over an average follow-up of 27 months, 143 of the patients developed MACE. The patients were subgrouped into tertiles based on the FIB-5 index and Kaplan-Meier survival (MACE-free) curves were plotted, showing statistically significant differences (log-rank test, P < .001). In the adjusted Cox regression model, the hazard ratio (HR) of MACE was 1.95 (95% CI 1.21-3.13; P = .006) in tertile 3 and 0.98 (95% CI 0.97-1.00; P = .013) for per unit increase in the FIB-5 index. The area under the curve (AUC) of the FIB-5 index predicting the occurrence of MACE in STEMI patients after PCI was 0.645 (95% CI 0.590-0.701; P < .001). Low FIB-5 may be a useful predictor of MACE in STEMI patients undergoing PCI.

Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma.

In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeutic development and optimization. In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77-6.61, p < 0.001); ( 5-year PFS 45.9% vs. 81.2%, HR: 3.22, 95%CI: 1.71-6.06, p < 0.001); ( 5-year LRRFS 74.6% vs. 87.5%, HR: 3.22, 95%CI: 1.16-8.93, p = 0.027); and ( 5-year DMFS79.2% vs. 93.2%, HR: 2.22, 95%CI: 0.91-5.39, p = 0.086). Upon multivariable analysis, COV+TIL score emerged as an independent prognostic indicator for defining survival in the training cohorts and the validation cohorts. Combining the COV+TIL score and TNM stage improved the prediction ability of the survival. In conclusion, NPC patients with high COV+TIL score showed worse prognosis.

Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development.

Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4+ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72+CD11c+ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4+ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.

High-Efficiency Continuous-Luminescence-Controllable Performance and Antithermal Quenching in Bi3+-Activated Phosphors.

Recently, Bi3+-activated phosphors have been widely researched for phosphor-converted light-emitting diode (pc-LED) applications. Herein, novel full-spectrum A3BO7:Bi3+ (A = Gd, La; B = Sb, Nb) phosphors with a luminescence-tunable performance were achieved by a chemical substitution strategy. In the La3SbO7 host material, a new luminescent center was introduced, with Gd3+ replacing La3+. The photoluminescence (PL) spectra show a large blue shift from 520 to 445 nm, thus achieving regulation from green to blue lights. Moreover, a series of solid solution-phase phosphors La3Sb1-xNbxO7:Bi3+ were prepared by replacing Sb with Nb, and a PL spectral tunability from green (520 nm) to orange-red (592 nm) was realized. Temperature-dependent PL spectra show that La3-xGdxSbO7:Bi3+ phosphors have excellent thermal stability. Upon 350 nm excitation, the PL intensity of La3-xGdxSbO7:Bi3+ phosphors at 150 °C remained at more than 93% at room temperature. With Gd3+ doping, the thermal stability gradually improved, and LaGd2SbO7:0.03Bi3+ represents splendid antithermal quenching (135.2% at 150 °C). Finally, a full-visible spectrum for pc-LED with a high color-rendering index (Ra = 94.4) was obtained. These results indicated that chemical substitution is an effective strategy to adjust the PL of Bi3+, which is of great significance in white-light illumination and accurate plant lighting.

Epidemiology and survival outcomes in adenosquamous carcinoma: a population-based study.

BACKGROUND: The relationship between the location of the primary tumor and survival of adenosquamous carcinoma (ASC) remains poorly understood. This study aimed to evaluate the impact of primary tumor location on the survival outcome of patients with ASC. METHODS: Patients with ASC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with ≥ 150 cases per tumor location. The Kaplan-Meier method was used to generate survival curves and differences among them were compared using the log-rank test. On the other hand, Cox proportional hazards models were used to evaluate factors that had independent predictive effects on cancer-specific survival (CSS). RESULTS: A total of 14,829 eligible patients with ASC were included in this study. Lung and bronchus ASC accounted for 51.1%, followed by the cervix uteri (17.0%), corpus uteri (13.9%), pancreas (4.9%), esophagus (3.1%), gallbladder (2.5%), stomach (2.2%), colon and rectum (2.0%), head and neck (1.8%), and breast ASC (1.3%). The 5-year CSS of breast, cervix uteri, colon and rectum, corpus uteri, esophagus, gallbladder, head and neck, lung and bronchus, pancreas, and stomach ASC was 76.9%, 66.0%, 34.8%, 72.9%, 12.0%, 10.8%, 45.0%, 24.7%, 4.3%, and 17.3%, respectively. COX analysis demonstrated that the primary tumor location was an independent prognostic factor for CSS. Besides, the breast, uterine corpus, and cervix as well as head and neck ASC were significantly associated with better prognosis, while pancreas and gallbladder ASC were significantly associated with poor CSS; stomach and colorectal were roughly the same as ASC prognosis. CONCLUSION: Our study showed that the CSS of patients with ASC depends on the location of the primary tumor. Besides, tumor location is an important factor that should guide the use of chemotherapy and radiation.

MFSD4A inhibits the malignant progression of nasopharyngeal carcinoma by targeting EPHA2.

DNA Methylation can lead to abnormal gene expression. In the present study, we investigated whether the expression of methylated MFSD4A (major facilitator superfamily domain containing 4 A) was downregulated in nasopharyngeal carcinoma (NPC) and whether it is associated with malignant progression and poor prognosis of NPC. Bioinformatic analysis, bisulfite pyrosequencing, quantitative real-time reverse transcription PCR, and western blotting assays were performed to explore the relationship between hypermethylation of MFSD4A and its expression in NPC. The role of MFSD4A in NPC was verified by Cell Cycle Kit 8, transwell assays and flow cytometry in vitro and by animal experiments in vivo. Mass spectrometry, co-immunoprecipitation, and immunofluorescence assays were applied to explore the mechanism by which MFSD4A inhibits NPC. The prognostic significance of MFSD4A or EPHA2 was investigated by immunohistochemical analysis of clinical specimens. Hypermethylation of the promoter region of MFSD4A led to decreased expression of MFSD4A. When MFSD4A expression was upregulated or downregulated, the proliferation, apoptosis, migration, and invasion abilities of NPC cells were altered accordingly. Mechanistically, MFSD4A could specifically bind to and degrade EPH receptor A2 (EPHA2) by recruiting ring finger protein 149 (RNF149), which led to alterations in the EPHA2-mediated PI3K-AKT-ERK1/2 pathway and epithelial-mesenchymal transition (EMT), thereby affecting NPC progression. Clinically, high MFSD4A expression or low-EPHA2 expression was associated with better prognosis for patients with NPC. In all, reduced MFSD4A expression in NPC is caused by promoter hypermethylation. MFSD4A or EPHA2 expression is associated with the malignant biological behavior and prognosis of NPC. MFSD4A is a promising potential therapeutic target for NPC.

Methylation-associated silencing of miR-9-1 promotes nasopharyngeal carcinoma progression and glycolysis via HK2.

Characteristically, cancer cells metabolize glucose through aerobic glycolysis, known as the Warburg effect. Accumulating evidence suggest that during cancer formation, microRNAs (miRNAs) could regulate such metabolic reprogramming. In the present study, miR-9-1 was identified as significantly hypermethylated in nasopharyngeal carcinoma (NPC) cell lines and clinical tissues. Ectopic expression of miR-9-1 inhibited NPC cell growth and glycolytic metabolism, including reduced glycolysis, by reducing lactate production, glucose uptake, cellular glucose-6-phosphate levels, and ATP generation in vitro and tumor proliferation in vivo. HK2 (encoding hexokinase 2) was identified as a direct target of miR-9-1 using luciferase reporter assays and Western blotting. In NPC cells, hypermethylation regulates miR-9-1 expression and inhibits HK2 translation by directly targeting its 3' untranslated region. MiR-9-1 overexpression markedly reduced HK2 protein levels. Restoration of HK2 expression attenuated the inhibitory effect of miR-9-1 on NPC cell proliferation and glycolysis. Fluorescence in situ hybridization results indicated that miR-9-1 expression was an independent prognostic factor in NPC. Our findings revealed the role of the miR-9-1/HK2 axis in the metabolic reprogramming of NPC, providing a potential therapeutic strategy for NPC.

Feasibility and efficiency of double-agent versus single-agent concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the mainstay of treatment for nasopharyngeal carcinoma (NPC) patients. It remains unclear whether double-agent CCRT (d-CCRT) is more effective than single-agent CCRT (s-CCRT). In this study, we compared the treatment efficiency and toxicity of d-CCRT with s-CCRT in NPC patients. METHODS AND MATERIALS: Patients with stage II-IV NPC treated with d-CCRT or s-CCRT were retrospectively reviewed. The d-CCRT group patients were compared with s-CCRT group patients for overall survival (OS), locoregional relapse-free survival (LRRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and toxicity. Differences in baseline characteristics were adjusted using the pair-matching method. RESULTS: In this study, 933 patients who received CCRT for NPC between 2011 and 2014 were pair-matched at a 1:2 ratio (n = 311 for d-CCRT; n = 622 for s-CCRT). The d-CCRT treated patients showed no significant advantages in terms of 4-year OS (87.2% vs. 85.5%), DFS (84.1% vs. 79.5%), LRRFS (94.6% vs. 91.8%), DMFS (87.5% vs. 85.5%) compared with s-CCRT treated patients (P = 0.450, 0.106, 0.203, 0.366, respectively). Multivariate analysis showed that CCRT regimen had no significant effects on survival. In the d-CCRT group, the incidence of grade 3-4 hematological toxicities was significantly higher. CONCLUSIONS: The d-CCRT regimen did not confer significant survival benefits compared with the s-CCRT regimen in the treatment of stage II-IV NPC patients. Furthermore, patients treated with the d-CCRT regimen experienced greater hematological toxicity.

Hyperthermia exposure induces apoptosis and inhibits proliferation in HCT116 cells by upregulating miR-34a and causing transcriptional activation of p53.

Hyperthermia, as an anticancer therapeutic strategy, presents notable advantages in conjunction with irradiation and/or chemotherapy in the treatment of cancer by promoting apoptosis and inhibiting proliferation. A number of studies have documented that hyperthermia inhibits cancer progression through transcriptional activation of p53, which promotes cell cycle arrest and apoptosis. However, the underlying molecular mechanisms of hyperthermia-regulated apoptosis and proliferation dependent on p53 remain largely unknown. To investigate the effects and molecular mechanism of hyperthermia on the apoptosis and proliferation of colorectal carcinoma (CRC) HCT116 cells, the present study assessed cell apoptosis and proliferation following exposure to hyperthermia (42°C for 2-4 h). The results indicated that, compared with the control group at 0 h, hyperthermia exposure for 2 and 4 h induced the apoptosis of HCT116 cells (P<0.05), inhibited cell proliferation by causing cell cycle arrest at G1/G0 phase (P<0.05), and significantly increased microRNA (miR)-34a expression (P<0.05), but not miR-34b, miR-34c, miR-215 and miR-504 expression. The transcriptional activity of p53 on its consensus sequence and downstream target genes, namely p21, B cell lymphoma 2-associated X protein, mouse double minute 2 homolog, p53 upregulated modulator of apoptosis and growth arrest and DNA-damage-inducible 45α, was subsequently detected. The data indicated significantly higher transcriptional activity of p53 following hyperthermia exposure for 2 and 4 h (P<0.05), and these observations were similar to the effects of transfection with miR-34a mimics in HCT116 cells. Furthermore, transfection with miR-34a antagomiR supressed hyperthermia-induced apoptosis and promoted cell cycle progression following hyperthermia exposure when compared with transfection controls (P<0.05). Collectively, these findings indicate that miR-34a may serve an important role in hyperthermia-regulated apoptosis and proliferation in HCT116 cells by influencing the transcriptional activity of p53.

FOXQ1 mediates the crosstalk between TGF-ß and Wnt signaling pathways in the progression of colorectal cancer.

A wide variety of signaling transduction pathways contribute to tumorigenesis. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including colorectal cancer. However, the molecular mechanisms by which FOXQ1 promotes tumorigenesis, especially cancer cell invasion and metastasis in colorectal cancer, have not been fully elucidated. In the present study, we demonstrate that FOXQ1 is overexpressed in colorectal tumor tissues and its expression level is closely correlated with the stage and lymph node metastasis of colorectal cancer. In in vitro cultured SW480 colorectal cancer cells, knockdown of FOXQ1 expression by small interfering RNA greatly diminished the aggressive tumor behaviors of SW480 cells, including angiogenesis, invasion, epithelial-mesenchymal transition, and resistance to chemotherapy drug-induced apoptosis. Further mechanistic investigation showed that FOXQ1 silencing prevents the nuclear translocation of ß-catenin, thus reducing the activity of Wnt signaling. Moreover, TGF-ß1 induced the expression of FOXQ1 as well as the migration and invasion of SW480 cells, which was partially prevented following knockdown of FOXQ1. Our results demonstrate that FOXQ1 plays a critical role during the tumorigenesis of colorectal cancer and is a mediator of the crosstalk between Wnt and TGF-ß signaling pathways. Our findings provide further insight into the cancer biology of colorectal cancer and suggest that FOXQ1 is a potential therapeutic target for the development of therapies for colorectal cancer.