Anoikis-related gene CDKN2A predicts prognosis and immune response and mediates proliferation and migration in thyroid carcinoma.

Thyroid carcinoma (THCA) is a tumor commonly occurring in the endocrine system, and its incidence rate is increasing yearly. Anoikis is a type of cell death involved in the carcinogenesis process. This study aimed to investigate the prognosis and immune correlations of anoikis in THCA. Our study used several bioinformatics algorithms (co-expression analysis, univariate and multivariate Cox analysis) to screen anoikis-related genes (ARGs) to construct risk models. Through receiver operating characteristic (ROC) curve, nomogram, and independent prognostic analysis found that the constructed model had ideal predictive value for THCA. The consensus clustering method was used to divide ARG patterns into three subgroups, and there were significant differences in survival among the three subgroups. The CIBERSORT algorithm demonstrated strong correlations among immune infiltrating cells, prognostic genes, and risk scores. Univariate and multivariate Cox analysis showed that CDKN2A is an independent prognostic gene. Basic experiments (immunohistochemistry, qRT-PCR, etc.) showed that the expression levels of CDKN2A mRNA and protein were highly expressed in THCA, which was consistent with the results of bioinformatics analysis. In vitro, the knockdown of CDKN2A significantly inhibited the proliferation and migration of THCA cells. In summary, our study utilized eight ARGs to construct an accurate risk model. ARGs, especially CDKN2A, play a crucial role in the occurrence and development of THCA and can become potential targets for treating THCA patients.

Study on the spatial specificity of phenolics in fruit of different jujube varieties.

Phenol, an important bioactive substance in jujube fruit, is one of the most important indexes of fruit quality. In order to clarify the phenolic substance composition, content and distribution characteristics of different varieties of jujube fruits, this study measured and compared the content of total phenols, total flavonoids and phenolic substance composition in different parts of fruits of six jujube varieties, and combined with the principal component analysis, the results showed that: Fourteen phenolic substances were identified in the fruits of different jujube varieties, and proanthocyanidins, epicatechin, catechin and rutin were the main components, accounting for 58.60%, 16.08%, 13.56% and 5.57% of the total phenolic substances, respectively. The total phenolic and total flavonoid contents of jujube fruits of each variety were between 18.11 and 21.45 mg GAE/g DW and 10.56-20.25 mg RE/g DW, respectively, and the differences in the contents between the varieties were significant, and the contents of 'Junzao' and 'Jinlingyuanzao' were higher than those of other varieties.The phenolic content of different parts of jujube fruits showed spatial distribution differences, manifested as the total phenols, total flavonoids and their fractions of the peel were significantly higher than that of the pulp, while the content of the pulp near the kernel was significantly higher than that of other parts of the pulp, This study provides a theoretical basis for analysing the differences in phenolic substances in jujube fruits.

Forecasting the renewable energy consumption of Australia by a novel grey model with conformable fractional opposite-direction accumulation.

The accurate prediction of renewable energy consumption (REC) is of great significance to ensure energy security, reduce dependence on fossil energy, and promote sustainable economic and social development. In this paper, a novel grey model with conformable fractional opposite-direction accumulation (CFOA), abbreviated as the CFOGM (1,1) model, is proposed to forecast REC in Australia. The new model is discussed in detail with a new CFOA operation and the GM (1,1) model and can take full advantage of the information carried by the original data. The CFOGM (1,1) model has lower modeling error and better fitting and forecasting accuracy than other grey, Holt, and ARM models and can better capture the change trend of REC and achieve accurate prediction. The forecasting results present that the REC in Australia is 497-581 petajoules in 2021, 596-728 petajoules in 2022, and 715-912 petajoules in 2023, indicating that the REC in Australia is still accelerating.

Remote SERS detection at a 10-m scale using silica fiber SERS probes coupled with a convolutional neural network.

A silica fiber surface-enhanced Raman scattering (SERS) probe provides a practical way for remote SERS detection of analytes, but it faces the major bottleneck that the relatively large Raman background of silica fiber itself greatly limits the remote detection sensitivity and distance. In this article, we developed a convolutional neural network (CNN)-based deep learning algorithm to effectively remove the Raman background of silica fiber itself and thus significantly improved the remote detection capability of the silica fiber SERS probes. The CNN model was constructed based on a U-Net architecture and instead of concatenating, the residual connection was adopted to fully leverage the features of both the shallow and deep layers. After training, this CNN model presented an excellent background removal capacity and thus improved the detection sensitivity by an order of magnitude compared with the conventional reference spectrum method (RSM). By combining the CNN algorithm and the highly sensitive fiber SERS probes fabricated by the laser-induced evaporation self-assembly method, a limit of detection (LOD) as low as 10-8 M for Rh6G solution was achieved with a long detection distance of 10 m. To the best of our knowledge, this is the first report of remote SERS detection at a 10-m scale with fiber SERS probes. As the proposed remote detection system with silica fiber SERS probes was very simple and low cost, this work may find important applications in hazardous detection, contaminant monitoring, and other remote spectroscopic detection in biomedicine and environmental sciences.

A novel apparatus for modeling the geological responses of reservoir and fluid-solid production behaviors during hydrate production.

Gas hydrate is a promising alternative energy resource that undergoes complex phase changes and coupled geological responses during hydrate production. Insufficient knowledge of those coupled behaviors still challenge safe and efficient gas production from hydrate. Here, a novel experimental apparatus was developed to simulate the gas-water-sand production and to evaluate the related multifield and multiphase processes. The experimental apparatus is equipped with displacement, ultrasonic, and electrical resistivity sensors and gas/water flowmeters, and this apparatus can work up to a maximum loading stress of 25 MPa and a maximum pore pressure of 20 MPa over a temperature range from -20 to 50 °C. The hydrate production and sand production case were performed on a synthetic specimen with hydrate saturation of 12.8% by using multi-step depressurization. The pressure-temperature conditions, settlement, ultrasonic propagation, electrical resistivity, and permeability of hydrate reservoirs during production were simultaneously monitored to evaluate the geological characteristics and heat and mass transfer characteristics of the hydrate reservoir. The results indicated that the gas/water production mainly occurred during the first third of each depressurization period, and their production rates were low at the beginning. Flowing water mobilized the sand particles, and the addition of gas exacerbated the sand-particle migration. Interpretation of the coupled behaviors supported that the reservoir could maintain a temporary stable structure even when losing a certain amount of sand particles with no sand control methods; however, necessary sand-prevention approaches are wise to support long-term reservoir production operations. These laboratory insights would contribute to optimizing the field strategies for economical gas production from hydrate.

Depression and Insomnia of Front-Line Medical Staff During the COVID-19 Outbreak in China: An On-Line Cross-Sectional Study.

Purpose: During the COVID-19 outbreak, medical staff working in high-risk workplaces had a higher rate of epidemic infection. They also faced heavy workloads and pressure, which means they are more likely to suffer from psychological problems than others. To understand the mental health of medical staff during the epidemic, we explore the characteristics of medical staff susceptible to negative psychological emotions during the outbreak of public safety and health events. At the same time, we provide corresponding prevention and intervention measures to help them relieve negative emotions, this study compared the psychological symptoms of front-line and non-front-line medical staff, then explored its influencing factors. Methods: This research investigated 5,924 medical staff in Guangdong, Beijing, Hubei, Hainan, Jiangxi, and Henan in China. The questionnaires were released online by Questionnaire Star, and levels of depression, anxiety, insomnia, and social support were measured by Patients' Health Questionnaire Depression Scale-9 item (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), Insomnia Severity Index (ISI) and Social Support Rating Scale (SSRS). Results: The depressive, anxious, and insomniac scores of front-line medical staff during the COVID-19 epidemic period were higher than those of non-front-line with significant differences (P < 0.001). In addition, front-line nurses went through the most serious psychological problems. Age, education, and anxiety level were the influencing factors of depression and insomnia in front-line medical staff. Among them, age was a protective factor for depression (OR = 0.71 <1, P = 0.001 <0.05, Beta = -0.34), while educational level was a risk factor for insomnia (OR = 1.27, P = 0.02 <0.05, Beta = 0.24). Conclusions: During the epidemic, front-line medical staff would experience more serious psychological problems, especially those who were younger, less experienced, and insufficiently educated. Attention should be paid to giving them psychological assistance and psychological interventions in the future.

Forecasting CO2 Emissions Using A Novel Grey Bernoulli Model: A Case of Shaanxi Province in China.

Accurate predictions of CO2 emissions have important practical significance for determining the best measures for reducing CO2 emissions and accomplishing the target of reaching a carbon peak. Although some existing models have good modeling accuracy, the improvement of model specifications can provide a more accurate grasp of a system's future and thus help relevant departments develop more effective targeting measures. Therefore, considering the shortcomings of the existing grey Bernoulli model, in this paper, the traditional model is optimized from the perspectives of the accumulation mode and background value optimization, and the novel grey Bernoulli model NFOGBM(1,1,α,ß) is constructed. The effectiveness of the model is verified by using CO2 emissions data from seven major industries in Shaanxi Province, China, and future trends are predicted. The conclusions are as follows. First, the new fractional opposite-directional accumulation and optimization methods for background value determination are effective and reasonable, and the prediction performance can be enhanced. Second, the prediction accuracy of the NFOGBM(1,1,α,ß) is higher than that of the NGBM(1,1) and FANGBM(1,1). Third, the forecasting results show that under the current conditions, the CO2 emissions generated by the production and supply of electricity and heat are expected to increase by 23.8% by 2030, and the CO2 emissions of the other six examined industries will decline.

Hardware-Assisted Security Monitoring Unit for Real-Time Ensuring Secure Instruction Execution and Data Processing in Embedded Systems.

The hardware security of embedded systems is raising more and more concerns in numerous safety-critical applications, such as in the automotive, aerospace, avionic, and railway systems. Embedded systems are gaining popularity in these safety-sensitive sectors with high performance, low power, and great reliability, which are ideal control platforms for executing instruction operation and data processing. However, modern embedded systems are still exposing many potential hardware vulnerabilities to malicious attacks, including software-level and hardware-level attacks; these can cause program execution failure and confidential data leakage. For this reason, this paper presents a novel embedded system by integrating a hardware-assisted security monitoring unit (SMU), for achieving a reinforced system-on-chip (SoC) on ensuring program execution and data processing security. This architecture design was implemented and evaluated on a Xilinx Virtex-5 FPGA development board. Based on the evaluation of the SMU hardware implementation in terms of performance overhead, security capability, and resource consumption, the experimental results indicate that the SMU does not lead to a significant speed degradation to processor while executing different benchmarks, and its average performance overhead reduces to 2.18% on typical 8-KB I/D-Caches. Security capability evaluation confirms the monitoring effectiveness of SMU against both instruction and data tampering attacks. Meanwhile, the SoC satisfies a good balance between high-security and resource overhead.

A testing assembly for combination measurements on gas hydrate-bearing sediments using x-ray computed tomography and low-field nuclear magnetic resonance.

Studying the pore-scale characteristics of gas hydrate-bearing sediments (GHBS) is very important for a deep understanding of (i) how fluid flows therein and (ii) the corresponding gas production. Micro X-ray computed tomography (X-CT) and low-field nuclear magnetic resonance (NMR) are often used independently to characterize the pore structure of GHBS. Here, we present a new testing assembly that combines X-CT scans and low-field NMR tests to determine the pore-scale characteristics of GHBS in situ. The main parts of the testing assembly are a removable core holder made of polyether ether ketone, an X-CT system, and a low-field NMR system. The core holder allows for independent pressure control for the formation/dissociation of gas hydrates, which is xenon hydrate here. X-CT scans and low-field NMR tests are conducted successively to obtain not only the hydrate pore-scale behavior but also the transverse relaxation time distributions of GHBS. Correlation analysis between the pore size distributions and the transverse relaxation time curves gives the transverse surface relaxivity of xenon hydrate-bearing sediments during hydrate dissociation. The results show that the hydrate pore occurs as a mixture of grain-coating, cementing, pore-filling, and patchy clusters in a gas-dissolved solution. The peak pore size at the maximum frequency ratio increases with decreasing hydrate saturation. In addition, the transverse surface relaxivity dependence on hydrate pore occurrences is in the range of 67.1-129.3 µm/s when the hydrate saturation is lower than 0.4. The combination measurements for GHBS have a promising potential in understanding the structure evaluation of pore space during gas recovery.

High-Efficiency Parallel Cryptographic Accelerator for Real-Time Guaranteeing Dynamic Data Security in Embedded Systems.

Dynamic data security in embedded systems is raising more and more concerns in numerous safety-critical applications. In particular, the data exchanges in embedded Systems-on-Chip (SoCs) using main memory are exposing many security vulnerabilities to external attacks, which will cause confidential information leakages and program execution failures for SoCs at key points. Therefore, this paper presents a security SoC architecture with integrating a four-parallel Advanced Encryption Standard-Galois/Counter Mode (AES-GCM) cryptographic accelerator for achieving high-efficiency data processing to guarantee data exchange security between the SoC and main memory against bus monitoring, off-line analysis, and data tampering attacks. The architecture design has been implemented and verified on a Xilinx Virtex-5 Field Programmable Gate Array (FPGA) platform. Based on evaluation of the cryptographic accelerator in terms of performance overhead, security capability, processing efficiency, and resource consumption, experimental results show that the parallel cryptographic accelerator does not incur significant performance overhead on providing confidentiality and integrity protections for exchanged data; its average performance overhead reduces to as low as 2.65% on typical 8-KB I/D-Caches, and its data processing efficiency is around 3 times that of the pipelined AES-GCM construction. The reinforced SoC under the data tampering attacks and benchmark tests confirms the effectiveness against external physical attacks and satisfies a good trade-off between high-efficiency and hardware overhead.

Protective and Risk Factors for Medical and Nursing Staff Suffering From Psychological Symptoms During COVID-19.

Background: With the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in China, the general public but also medical staff were confronted with psychological challenges, suffering from the highly infectious and unknown characteristics of COVID-19. In this study, we surveyed psychological symptoms including anxiety, depression, and sleep disorders in medical staff. Method: A questionnaire star/WeChat link-based survey assessing the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9 depression, the Insomnia Severity Index, Social Support scales in addition to lifestyle, and income level was conducted and included 8,288 medical staff from 24 provinces in China. Pearson Chi-square and Mann-Whitney U-tests were used to evaluate single risk factors and significant differences in psychological symptoms before and during the outbreak of COVID-19. Binary logistic regression analyses were conducted for the risk factors of anxiety, depression, and sleep disorder symptoms. Results: Medical staff had a high incidence of psychological symptoms, which was more prominent during the COVID-19 epidemic. Comparatively, females, nurses, first-line department, never exercised, and low income were risk factors for psychological symptoms. Social support including objective support, subjective support, support utility, and regular sports over 3 times per week were protective and manageable elements that could protect from and manage the psychological symptoms of medical staff. Conclusion: The susceptibility of psychological symptoms among medical staff should be of concern to policymakers and the public in the long-term, and the aggravation of mental health problems of medical staff could be eased by providing adequate social support during and after the COVID-19 outbreak.

HOX transcript antisense RNA is elevated in gastric carcinogenesis and regulated by the NF-κB pathway.

The expression pattern of HOX transcript antisense RNA (HOTAIR) in the progression of gastric cancer and the regulation of its expression are still unclear. In the current study, HOTAIR expressions in gastric tissues collected from patients with superficial gastritis, atrophic gastritis, atypical hyperplasia, and gastric cancer as well as normal controls was quantitatively examined. The results showed that the expression of HOTAIR was higher in gastric cancer than in normal tissues, but reached the highest level in atrophic gastritis, suggesting that HOTAIR may be involved in the molecular process of nonresolving inflammation. Then tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a known gene associated with nonresolving inflammation, was overexpressed and the results showed that the promotion in TIPE2 expression triggered HOTAIR reduction, this result was further verified by microarray analysis and TIPE2 knockout mice. Subsequently, the data obtained from HOTAIR knockdown experiment showed that it significantly enhanced colony forming capability and inhibited p27 expression in AGS cells. Furthermore, deletion constructs and luciferase-based activity assays indicated that the -475 to -443bp region of HOTAIR promoter contained a crucial regulatory element. Transcription factor prediction with software TRANSFAC revealed that nuclear factor-κB signaling protein p65 had a binding site in this region and might have roles in HOTAIR expression. The binding of phosphor-p65 to HOTAIR promoter was verified by chromatin immunoprecipitation, and succeeding experiment results demonstrated that p65 reduction by p65 small interfering RNA and TIPE2 overexpression also decreased HOTAIR expression. Conclusively, our results suggest that HOTAIR was associated with nonresolving inflammation, and its expression is regulated by p65.

MMP-11 promotes papillary thyroid cell proliferation and invasion via the NF-κB pathway.

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, and its incidence is on the rise. It has been reported that some matrix metalloproteinases (MMPs) are abnormally expressed in PTC and can be used as diagnostic markers. However, few studies have explored the underlying mechanisms by which MMPs promote tumor progression. In this study, we used microarray analysis to compare the variations of gene expression within the PTC cell populations and their adjacent normal tissues and found that MMP-11 was the most differentially expressed MMP. To investigate the role of MMP-11 in the mediation of thyroid cancer cell development, pEnter-MMP-11 plasmid, and MMP-11 small interfering RNA were applied to up- and downregulate MMP-11 expression of in cultured PTC cell lines K1 and BCPAP. The results suggested that the levels of proliferation and migration of cells transfected with MMP-11 siRNA were significantly reduced, while the levels in MMP-11-plasmid-transfected cells were increased. In terms of the mechanism, experimental data showed that the change in cyclin D1 is consistent with MMP-11 expression, which may explain the changes in proliferation. In addition, Western blot assay was conducted to analyze the p65 and activated (phospho-) p65 protein levels concomitant with MMP-11 adjustments. Variations in intracellular MMP-11 significantly altered the amount of phospho-p65 in thyroid cells, while p65 knockdown did not affect MMP-11 expression. These results suggest that MMP-11 is located upstream of p65 and regulates its activity. Interestingly, the data for the Transwell assay suggested that MMP-11 regulatory migration is also associated with the NF-κB p65 signaling pathway. In conclusion, this report describes the important role of MMP-11 in the regulation of thyroid cell proliferation and migration. Mechanistic studies have shown that cyclin D1 and p65 are important mediators in the processes, which provides a new way to study the mechanism of MMPs promoting the progression of thyroid cancer.

Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence.

The role of perfluorodecanoic acid (PFDA) in gastric carcinogenesis and its mechanism remains unknown. Our previous research revealed that PFDA regulated the growth of human gastric cells. However, its core molecules and basic mechanisms are still not clear. In the present study, cDNA microarrays were used to determine mRNA changes in AGS cells after treatment with PFDA. DAVID analysis of the genes with >2­fold increased expression in microarray data revealed five genes which were involved in cancer pathways. The most upregulated gene was cIAP2, whose upregulation in AGS was confirmed by western blot analysis and quantitative PCR (qPCR) analyses. In order to investigate the role of cIAP2 in cell proliferation, cIAP2 siRNA was employed to regulate cIAP2 expression following PFDA treatment. The results revealed that the growth rate of cIAP2­knockdown cells was reduced by about 50% compared to the control. Given that our previous flow cytometric assays revealed no significant change (3.7 vs. 6.4%) in the percentage of apoptotic cells when PFDA was added to the medium and cIAP2 expression was upregulated, we next applied flow cytometry to assess whether cIAP2 would lead to cell cycle variations. The research data revealed that the proportion of cells in the G1, S and G2 phases was not significantly altered with the decrease of cIAP2 expression. Finally, the role of cIAP2 in AGS cell senescence was investigated, and the results indicated that cell senescence was significantly increased in the cIAP2 siRNA group in comparison to the control siRNA group. Since p53 has been identified as a tumor suppressor and its molecular alterations are common in different human tumors, we investigated the relationship of p53 with cIAP2. The experimental results demonstrated that cIAP2 regulated the expression of p53 and thus was likely to be a potential mechanism for PFDA­induced growth promotion. Overall, the results revealed that PFDA may suppress cellular senescence induced by p53 through the regulation of cIAP2 protein expression.

A LS-SVM based Measurement Points Classification Algorithm for Adjacent Targets in WSNs.

In wireless sensor networks (WSNs), the problem of measurement origin uncertainty for observed data has a significant impact on the precision of multi-target tracking. In this paper, a novel algorithm based on least squares support vector machine (LS-SVM) is proposed to classify measurement points for adjacent targets. Extended Kalman filter (EKF) algorithm is firstly adopted to compute the predicted classification line for each sampling period, which will be used to classify sampling points and calculate observed centers of closely moving targets. Then LS-SVM algorithm is utilized to train the classified points and get the best classification line, which will then be the reference classification line for the next sampling period. Finally, the locations of the targets will be precisely estimated by using observed centers based on EKF. A series of simulations validate the feasibility and accuracy of the new algorithm, while the experimental results verify the efficiency and effectiveness of the proposal.

Novel Mutations in PRPF31 Causing Retinitis Pigmentosa Identified Using Whole-Exome Sequencing.

Purpose: The purpose of this study was to investigate the disease-causing mutations for retinitis pigmentosa (RP) patients and function of mutations. Methods: We recruited RP families and sporadic RP patients, and performed whole-exome sequencing (WES) to screen for sequence variations. Subsequently, we investigated the expression of green fluorescent protein (GFP) merged expression vectors containing PRPF31 wild type (WT) and its variants. We determined protein stability by cycloheximide (CHX) treatment. Results: Two frameshift variants, c.547delG (p.E183fs) and c.804delG (p.L268fs), and one stopgain variant, c.1060C>T (p.R354X), in the pre-mRNA processing factor 31 gene (PRPF31) were identified in three RP families. In comparison with WT, the expressions of GFP-fused PRPF31 (GFP-PRPF31) protein with the mutation c.547delG or c.804delG in HEK293 cells were significantly reduced. However, the expression of GFP-PRPF31 containing the stopgain mutation (GFP-PRPF31sg) was increased. CHX treatment of HEK293 showed the GFP-PRPF31sg protein was more stable than GFP-PRPF31 WT. The WT protein expression was localized in the nuclei, and the mutants in both nuclei and cytoplasm. We screened for PRPF31 mutations in 131 sporadic RP patients by WES and successfully identified three novel mutations: c.G781C (p.G261R), c.A1373T (p.Q458L), and c.C1222T (p.R408W). Conclusions: Our study revealed novel mutations of PRPF31 in RP. Our results also showed that the two mutations (c.547delG or c.804delG) affect gene expression and GFP-PRPF31sg has increased protein stability.

Elevated plasma levels of Mac-2 binding protein predict poor cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND: Mac-2 binding protein (M2BP) is an inflammatory glycoprotein associated with carotid atherosclerosis and all-cause mortality in patients with suspected coronary artery diseases. We aimed to explore the potential association of plasma M2BP levels with unstable plaque morphology and cardiovascular outcomes in patients with acute coronary syndrome (ACS). PATIENTS AND METHODS: We compared plasma M2BP levels among three groups: 216 patients with ACS, 82 patients with stable angina pectoris, and 50 controls. Angiographic analyses of complex lesions were carried out in patients with ACS and they were followed up prospectively for 12 months for the occurrence of major adverse cardiovascular outcomes (MACEs). RESULTS: Patients with ACS showed significantly higher plasma levels of M2BP than patients with stable angina pectoris (P<0.001) and controls (P<0.001). M2BP levels correlated positively with the presence (P<0.001) and extent (P=0.005) of complex lesions. During follow-up, 45 (20.8%) cases of MACEs occurred. Survival analysis indicated that high M2BP levels were associated with a poor prognosis (log-rank P=0.008). After Cox multivariate adjustment, plasma M2BP levels remained an independent predictor of MACEs either as a continuous variable (hazard ratio: 1.178, 95% confidence interval: 1.093-1.270, P<0.001) or as a categorical variable (hazard ratio: 2.783, 95% confidence interval: 1.433-5.404, P=0.002). CONCLUSION: Plasma M2BP levels might be predictive of unstable plaque and were associated independently with poor cardiovascular outcomes in patients with ACS.

WNT10A/ß­catenin pathway in tumorigenesis of papillary thyroid carcinoma.

Papillary thyroid carcinoma is the most common thyroid cancer and the incidence is increasing. Aberrant activation of the WNT/ß­catenin pathway plays an important role in carcinogenesis. In the present study, microarray analysis was employed to compare tissues from papillary thyroid cancer and adjacent normal tissues to determine candidate genes facilitating tumor invasion. The result demonstrated that genes involved in WNT/ß­catenin signaling pathway were activated in papillary thyroid cancer, WNT10A expression was found to be upregulated >4-fold. The variations in gene expression were verified in tissues obtained from other papillary thyroid cancer patients. Molecular mechanism exploration in thyroid cells showed that enhanced WNT10A/ß­catenin signaling pathway activation promoted cell proliferation and migration. The promotion was validated by RNA interference of WNT10A and LEF1 expression. Moreover, results from flow cytometry demonstrated that WNT/ß­catenin signaling pathway activation reduced the percentage of late apoptotic thyroid cells. Conclusively, the results suggest for the first time that WNT10A/ß­catenin signaling pathway plays a crucial role in human papillary thyroid cancer.

Long-Term Prognostic Value of Lipoprotein(a) in Symptomatic Patients With Nonobstructive Coronary Artery Disease.

Our study aimed to evaluate the association of lipoprotein(a) [Lp(a)] and prognosis in patients with nonobstructive coronary artery disease (CAD). A total of 4,254 symptomatic patients with suspected CAD referred for coronary angiography were analyzed and 451 patients (250 women, average age 58 ± 9 years) with nonobstructive CAD (defined as no angiographic stenosis ≥50% in any major epicardial artery) were finally included in our cohort. Subjects were categorized into tertile groups according to Lp(a) levels on admission. The primary end point was major adverse cardiovascular events (MACEs), defined as cardiac death and incident acute coronary syndrome. Over a mean follow-up of 32 ± 22 months, 37 (8%) MACE (15 cases of cardiac death and 22 cases of acute coronary syndrome) occurred. Kaplan-Meier analysis revealed that elevated Lp(a) level was associated with worse prognosis (p = 0.001). After Cox multivariate adjustment for other clinical confounders, an elevated Lp(a) level remained an independent predictor of MACE either as a continuous variable (hazard ratio 1.031, 95% confidence interval 1.019 to 1.043, p <0.001) or as a categorical variable (hazard ratio 3.155, 95% confidence interval 1.599 to 6.229, p = 0.001). Furthermore, addition of Lp(a) to established coronary risk factors significantly improved the predictive value of reference models for MACE. In conclusion, an elevated Lp(a) level is independently associated with worse prognosis and may provide useful risk stratification in symptomatic patients with nonobstructive CAD.

Curcumin suppresses 4-hydroxytamoxifen resistance in breast cancer cells by targeting SLUG/Hexokinase 2 pathway.

Triple negative breast cancer (TNBC) is the hardest breast cancer subtype to treat due to lacking therapeutic target and treatment options. In this study, we found that SLUG expression was much higher in TNBC MDA-MB-231 cells than estrogen receptor alpha (ERα) positive breast cancer MCF7 cells. 4-hydroxytamoxifen (4-OHT) promoted SLUG expression, which was blocked by curcumin. Further investigation showed that SLUG activated the transcription of hexokinase-2 (HK2) by binding to HK2 promoter. SLUG knockdown inhibited HK2 expression and weakened 4-OHT resistance of MDA-MB-231 cells. Conversely, SLUG overexpression elevated HK2 level and increased 4-OHT resistance of MCF7 cells. Combination of curcumin and 4-OHT suppressed SLUG and HK2 expression, leading to mitochondrion-mediated apoptosis. These results suggested SLUG as a potential target and curcumin as a promising natural agent for overcoming 4-OHT resistance of TNBC.