Unenhanced magnetic resonance imaging of papillary thyroid carcinoma with emphasis on diffusion kurtosis imaging.

Background: The aim of this study was to investigate the value of unenhanced magnetic resonance imaging (MRI) with diffusion kurtosis imaging (DKI) in diagnosing papillary thyroid carcinoma (PTC). Methods: In all, 77 consecutive patients comprising a total of 77 thyroid nodules were enrolled in this study. Of these nodules, 41 were histopathologically confirmed PTCs and 36 were benign nodules. All patients underwent thyroid MRI including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and DKI. All the images were assessed by 2 radiologists. The signal intensity ratio (SIR) of these nodules on T1WI and T2WI, the apparent diffusion coefficient (ADC) from DWI, and mean diffusivity (MD) and mean kurtosis (MK) from DKI were measured. Morphological features on these images were also evaluated. Univariate and multivariate logistic regression analyses were used to evaluate the value of these parameters as potential predictors of PTC. Results: In the univariate analyses, the features that significantly indicated PTC were decreased ADC value (P<0.001), decreased MD value (P<0.001), increased MK value (P<0.001), younger age (P=0.001), female tendency (P=0.049), smaller tumor diameter (P<0.001), solid component (P<0.001), and irregular margin (P<0.001). In the multivariate analysis, decreased MD value (odds ratio =25.321; P=0.001), smaller diameter (odds ratio =13.751; P=0.006), and irregular margin (odds ratio =16.003; P=0.003) were independent risk factors for PTC. The combined predictor of MD, diameter, and margin showed an area under the receiver operating characteristic (ROC) curve of 0.996 in diagnosing PTC, with an optimal cutoff value of 0.69 (95.1% sensitivity, 100.0% specificity). Conclusions: Lower MD value from DKI, smaller diameter, and irregular margin are useful predictive biomarkers for PTC.

Prognostic significance of CDK6 amplification in esophageal squamous cell carcinoma.

Dysregulation of CDK6 plays crucial roles in the carcinogenesis of many kinds of human malignancies. However, the role of CDK6 in esophageal squamous cell carcinoma (ESCC) is not well known. We investigated the frequency and prognostic value of CDK6 amplification to improve the risk stratification in patients with ESCC. Pan-cancer analysis of CDK6 was conducted on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. CDK6 amplification was detected in 502 ESCC samples by Fluorescence in situ hybridization (FISH) through tissue microarrays (TMA). Pan-cancer analysis revealed that CDK6 mRNA level was much higher in multiple kinds of cancers and higher CDK6 mRNA level indicated a better prognosis in ESCC. In this study, CDK6 amplification was detected in 27.5% (138/502) of patients with ESCC. CDK6 amplification was significantly correlated with tumor size (p = 0.044). Patients with CDK6 amplification tended to have a longer disease-free survival (DFS) (p = 0.228) and overall survival (OS) (p = 0.200) compared with patients without CDK6 amplification but of no significance. When further divided into I-II and III-IV stage, CDK6 amplification was significantly associated with longer DFS and OS in III-IV stage group (DFS, p = 0.036; OS, p = 0.022) rather than in I-II stage group (DFS, p = 0.776; OS, p = 0.611). On univariate and multivariate analysis of Cox hazard model, differentiation, vessel invasion, nerve invasion, invasive depth, lymph node metastasis and clinical stage were significantly associated with DFS and OS. Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis.

TBK1 promotes thyroid cancer progress by activating the PI3K/Akt/mTOR signaling pathway.

INTRODUCTION: Thyroid cancer has received increasing attention; however, its detailed pathogenesis and pathological processes remain unclear. We investigated the role of TANK-binding kinase 1 (TBK1) in the progression of thyroid cancer. METHODS: The expression of TBK1 in thyroid cancer and normal control tissues was analyzed using real-time quantitative polymerase chain reaction. The function of TBK1 on thyroid cancer cells was detected using MTT, colony formation, wound healing, and Transwell assays. The xenograft assay was carried out to check on the role of TBK1 in thyroid cancer. RESULTS: TBK1 was highly expressed in thyroid tumors. High expression of TBK1 raised viability, proliferation, migration, and invasion of thyroid cancer cells. Gene set enrichment analysis revealed that TBK1 activated the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In addition, Myc-associated zinc finger protein (MAZ) was overexpressed in thyroid cancer and transcriptionally activated BK1. MAZ silence reversed the effects of TBK1 overexpression on thyroid cancer progression. Cotransfection with MAZ small-interfering RNA(siRNA) and TBK1 siRNA did not strengthen the inhibitory effect of TBK1 silencing on the thyroid cancer cells. The xenograft tumor assay showed that TBK1 short hairpinRNA inhibited tumor growth. CONCLUSION: MAZ silencing inhibited tumor progress of thyroid cancer cells, whereas this inhibitory effect was reversed by TBK1 overexpression.

Instant diagnosis of gastroscopic biopsy via deep-learned single-shot femtosecond stimulated Raman histology.

Gastroscopic biopsy provides the only effective method for gastric cancer diagnosis, but the gold standard histopathology is time-consuming and incompatible with gastroscopy. Conventional stimulated Raman scattering (SRS) microscopy has shown promise in label-free diagnosis on human tissues, yet it requires the tuning of picosecond lasers to achieve chemical specificity at the cost of time and complexity. Here, we demonstrate that single-shot femtosecond SRS (femto-SRS) reaches the maximum speed and sensitivity with preserved chemical resolution by integrating with U-Net. Fresh gastroscopic biopsy is imaged in <60 s, revealing essential histoarchitectural hallmarks perfectly agreed with standard histopathology. Moreover, a diagnostic neural network (CNN) is constructed based on images from 279 patients that predicts gastric cancer with accuracy >96%. We further demonstrate semantic segmentation of intratumor heterogeneity and evaluation of resection margins of endoscopic submucosal dissection (ESD) tissues to simulate rapid and automated intraoperative diagnosis. Our method holds potential for synchronizing gastroscopy and histopathological diagnosis.

Molecular Dynamics Simulations of the Thermal Decomposition of 3,4-Bis(3-nitrofurazan-4-yl)furoxan.

When stimulated, for example, by a high temperature, the physical and chemical properties of energetic materials (EMs) may change, and, in turn, their overall performance is affected. Therefore, thermal stability is crucial for EMs, especially the thermal dynamic behavior. In the past decade, significant efforts have been made to study the thermal dynamic behavior of 3,4-bis(3-nitrofurazan-4-yl)furoxan (DNTF), one of the new high-energy-density materials (HEDMs). However, the thermal decomposition mechanism of DNTF is still not specific or comprehensive. In this study, the self-consistent-charge density-functional tight-binding method was combined with molecular dynamics (MD) simulations to reveal the differences in the thermal decomposition of DNTF under four heating conditions. The O-N (O) bond would fracture first during DNTF initial thermal decomposition at medium and low temperatures, thus triggering the cracking of the whole structure. At 2000 and 2500 K, NO2 loss on outer ring I is the fastest initial thermal decomposition pathway, and it determines that the decomposition mechanism is different from that of a medium-low temperature. NO2 is found to be the most active intermediate product; large molecular fragments, such as C2N2O, are found for the first time. Hopefully, these results could provide some insights into the decomposition mechanism of new HEDMs.

Authentication of emission monitoring data and optimization of desulfurization in the molybdenum roasting process based on BAT-OOPN and the response surface method.

This paper presents a quantitative pollutant discharge model for a typical molybdenum roasting plant, which combines the best available technology and object-oriented Petri net concepts. The proposed model was used to verify whether the best available technology in a molybdenum roasting process meeting the current pollutant emission limits by comparing the results of multiple simulations with online monitoring data records. Theoretical SO2 emission values were obtained via multiple simulations and compared with the online monitoring data of a typical molybdenum roasting plant to verify the authenticity of the online monitoring data. The relationship between the different operating parameters and desulfurization efficiency is established through analyzing the historical operation parameters of the enterprise and response surface method. It was found that the optimal operating parameters for the flue gas desulfurization system of this plant could be characterized by a flue gas temperature of 90-93 °C, a pH range of 6.20-6.30, and a liquid-gas ratio of 23-25 L/m3.

Tunable optical delay with low intensity loss in a cascade structure Er3+-doped optical fiber amplifier.

In this paper, we propose a new pumping scheme-a dual-frequency laser-pumped cascade structure of Er3+-doped optical fiber based on the theory of coherent population oscillation. While realizing slow light transmission, the loss of output signal light power is reduced. Using numerical simulation, we compare the effects of a single fiber without pumping, a 980 nm single pumping single fiber, and a dual-frequency laser-pumped cascade structure of Er3+-doped optical fiber on signal light intensity loss coefficient τ and maximum time delay with the increase of input signal light power. The results show that the signal light intensity loss coefficient τ of the three structures decreases gradually with the increase of input signal light power. However, the transmission of lower signal light intensity loss coefficient τ=0.0823 and a larger time delay of 0.15 ms can be obtained under the dual-frequency laser-pumped cascade structure of Er3+-doped optical fiber. On the basis of the dual-frequency laser-pumped cascade structure of Er3+-doped optical fiber, the signal light intensity loss coefficient τ decreases gradually with the increase of pump ratio M (M=P1480∶P980) and the decrease of length ratio N (N=L2∶L1; L1 and L2 represent the length of the first and second cascaded optical fibers, respectively). Moreover, we compare the effects of ion density of the Er3+-doped optical fiber on the time delay of three structures. The dual-frequency laser-pumped cascade structure of Er3+-doped optical fiber can provide a larger time delay and smaller signal light intensity loss coefficient τ at low ion density of the Er3+-doped optical fiber.

SETD3 reduces KLC4 expression to improve the sensitization of cervical cancer cell to radiotherapy.

Resistance to radiotherapy accounts for most therapeutic failures in cervical cancer patients who undergo radical radiation therapy. To indicate the possible molecular mechanism of radioresistance and improve the 5-year survival rate, we focused on how SET domain protein 3 (SETD3) regulated radioresistance in human cervical cancer cells in this study. Our results indicated that SETD3 over-expression markedly increased the radiosensitivity of cervical cancer cells with radioresistance, as evidenced by the further reduced cell viability, proliferation, DNA damage and cell death. In addition, we found that SETD3 down-regulated the expression of kinesin light chain 4 (KLC4), contributing to the radiosensitivity of cervical cancer cells, and the regulatory role of SETD3 could be abolished by KLC4 over-expression. Moreover, nitric oxide (NO) production was significantly reduced by SETD3 over-expression through repressing the expression of inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) in cervical cancer cells. In vivo studies using xenograft animal models also demonstrated that SETD3 over-expression combined with irradiation treatment markedly inhibited tumor growth and induced apoptosis. In summary, our data demonstrated that down-regulated SETD3 expression markedly led to the progression of radioresistance and that promoting SETD3 expression could sensitized cervical cancer cells to radiotherapy, thereby targeting SETD3 might be a potential strategy for the clinical management of cervical cancer to improve the curative effect of radiation in cervical cancer.

MFAP5 suppression inhibits migration/invasion, regulates cell cycle and induces apoptosis via promoting ROS production in cervical cancer.

Cervical cancer is one of the most lethal types of cancer among female. Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix (ECM) glycoprotein, and is confirmed to be involved in cell signaling during microfibril assembly, elastinogenesis and cell survival. However, the role of MFAP5 in cervical cancer development and progression remains poorly understood. In the study, MFAP5 was over-expressed in human cervical cancers, and in different cervical cancer cell lines. Patients suffering from cervical cancer with low MFAP5 expression exhibited better survival rate. Suppressing MFAP5 in cervical cancer cells markedly reduced the cell proliferation, migration and invasion by modulating epithelial-mesenchymal transition (EMT)-related signaling pathway. In addition, MFAP5 knockdown induced large number of cells distributed in G2/M phase, along with reduced Cyclin B1, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) expressions, and enhanced p21 and p53 levels. Moreover, apoptosis was highly induced by MFAP5 silence through reducing Bcl-xl and Bcl-2 expressions, and promoting Bax, cleaved Caspase-3 and poly (ADP-Ribose) polymerase (PARP) expressions in cervical cancer cells. Reactive oxygen species (ROS) production levels were also higher in MFAP5-knockdown cells, along with Jun-N-terminal kinase (JNK) activation. Importantly, we found that MFAP5 knockdown-inhibited cervical cancer cell growth was dependent on ROS production. Finally, the depletion of MFAP5 prevented cervical cancer progression in vivo. In summary, our study identified a critical role played by MFAP5 in the progression of cervical cancer and the potential mechanisms by which exerted its effects, indicating that targeting MFAP5-related pathways could be conducive to the therapies for cervical cancer.