Background: Epithelial ovarian cancer (EOC) is the most common gynecological cancer in women. Resistin, an inflammatory adipocytokine, is associated with obesity, insulin resistance, and various ...cancer types. Materials and Methods: We investigated resistin expression in tissues and its association with the clinicopathological characteristics and prognosis of patients with EOC. The SKOV3 and CAOV3 cell lines were treated with exogenous resistin and rapamycin (resistin inhibitor), and the expression of mTOR in SKOV3 and CAOV3 cells was measured. Cell proliferation was measured using the CCK-8 assay. Western blotting analysis was performed to examine the phosphorylation of P70S6K and mTOR. Wound healing and Transwell analyses were conducted to examine the effect of resistin on the migration of SKOV3 and CAOV3 cells. Results: High resistin expression was positively correlated with the pathological grade (P = 0.017) and lymph node metastasis (P = 0.045). However, resistin expression was not correlated with age, FIGO stage, or residual tumor after initial laparotomy (P > 0.05). Cox multivariate analysis showed that resistin expression was an independent factor for determining disease-free survival, whereas lymph node metastasis, resistin expression, and age (≥ 55 years) were independent factors affecting overall survival. Exogenous resistin induced ovarian cancer cell proliferation, whereas rapamycin had the opposite effect. Resistin promoted the proliferation of ovarian cancer cells via the mTOR signaling pathway and was associated with phosphorylating P70S6K. Furthermore, resistin promoted the migration of ovarian cancer cells. Conclusions: Resistin may promote the occurrence of ovarian cancer and is related to the prognosis of patients. This protein may also affect the proliferation of EOC cells through the mTOR signaling pathway. Therefore, resistin shows potential as a molecular therapeutic target in ovarian cancer.
Long non-coding RNA (lncRNA) SOX2 overlapping transcript (SOX2OT) has been shown to play an oncogenic role in diverse cancers, generating eight transcript variants. SOX2 is located in the third ...intron of SOX2OT. However, the biological function of SOX2OT in cervical cancer and implication with SOX2 remain to be further explored. In this study, we screened the expression pattern of different SOX2OT transcript variants in cervical cancer cells. Interestingly, both high-expression levels of SOX2OT transcript 7 (SOX2OT-7) and SOX2 were detected in C-33A (HPV
−
) and SiHa (HPV16
+
) cells. Thus, C-33A and SiHa cells were conducted to investigate the effects of SOX2OT on cell growth, migration and invasion. Finally, rescue experiments were performed to confirm the role of SOX2 in SOX2OT-mediated regulation of cervical cancer progression. The results showed that knockdown of SOX2OT suppressed cell viability, arrested cell cycle and ameliorated migration and invasion ability of C-33A and SiHa cells. Ectopic expression of SOX2OT-7 exacerbated cervical cancer cell proliferation, migration and invasion. In addition, we found that the expression levels and protein stability of SOX2 were positively regulated by SOX2OT. Inhibition of SOX2 could block the malignant phenotypes of C-33A and SiHa cells by SOX2OT-7. In conclusion, these findings indicate that lncRNA SOX2OT contributes to the growth, migration and invasion of cervical cancer cells by modulating SOX2. Importantly, we demonstrate that the transcript SOX2OT-7 may be a novel and promising biomarker for both HPV
−
and HPV16
+
cervical cancer.
Circular RNAs (circRNAs) are a novel class of widespread noncoding RNAs that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open ...reading frames in noncoding RNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, is not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared with matched paracancerous tissue. The hsa-circ-0000437 contains a short open reading frame encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain, and blocking the association between ARNT and TACC3, which led to reduced expression of VEGF, ultimately lead to reduced angiogenesis. The antitumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anticarcinoma therapies and warrants further investigation.
Cardiovascular disease (CVD) is a major cause of mortality worldwide. To facilitate early prevention and timely diagnosis of CVD, daily electrocardiogram (ECG) monitoring has become an important ...tool. However, various noises introduced into ECG signals will affect the diagnostic utility of these recordings. In addition, it is hard for non-specialists to interpret the ECG signals. To address this problem, we propose CS-TRANS, a novel deep learning framework for ECG denoising and classification. This framework mainly incorporates: (i) convolutional neural networks (CNN) regulated by stationary wavelet transform (SWT), called CNN-SWT; and (ii) Transformer encoder. The convolution kernel constraints and architecture of SWT are introduced into CNN to learn both the linear and non-linear time-frequency features more efficiently, while the transformer encoder further boosts global feature extraction. We implemented CS-TRANS and compared it with the state of the arts using the MIT-BIH arrhythmia database. The evaluation results show that compared to other algorithms, CS-TRANS improves the output signal-to-noise ratio (SNR) by 10% in denoising, and achieves 0.5% higher accuracy in classification, while saving half to even more than 90% of the parameters of the model.
Abstract Objective To analyze the clinical characteristics and treatment of women with vaginal intraepithelial neoplasia (VAIN), as well as HPV prevalence in this population. Methods A retrospective ...review was undertaken of the medical records of women diagnosed with VAIN at a clinic in Shenyang, China, between January 1, 2009, and December 31, 2012. Results Of the 152 records reviewed, 69 (45.4%) women had low-grade VAIN (VAIN1) and 83 (54.6%) had high-grade VAIN (VAIN2/3). Among 110 patients with an available HPV status, 97 (88.2%) were positive. The predominant HPV types were HPV16, HPV33, HPV81, HPV53, HPV18, HPV58, and HPV66. Previous hysterectomy was documented in 60 (39.5%) patients. Additionally, 80 (52.6%) patients had no history of dysplasia of the lower genital tract. Of patients with VAIN1, 50 (72.5%) were treated by observation only, 31 (62.0%) of whom regressed spontaneously. Of 66 patients with VAIN2, 38 (57.6%) underwent treatment, 14 (36.8%) of whom experienced recurrence or progression. Of 17 patients with VAIN3, 13 (76.5%) underwent treatment, 5 (38.5%) of whom experienced recurrence or progression. Conclusion Evaluation of the entire vagina by colposcopy is warranted in each patient with abnormal cervical screening results. The predominant HPV genotypes among patients with VAIN could be used to establish diagnosis program and develop an HPV vaccine.
Since vehicles from multiple roads frequently merge at intersections, it formulates a typical traffic bottleneck of modern transportation systems. Proper vehicle coordination and motion plan at road ...intersections are of importance to guarantee safety as well as improving the traffic throughput, fuel efficiency and so on. In this paper, we try to present a general dedicated intersection coordination framework for autonomous vehicles, where both high- and low-level planners are appropriately designed and integrated. In the high-level planner, two different strategies are formulated to coordinate the autonomous vehicles to generate reference trajectories and feasible "tunnels ", respectively. Especially, a novel space-time-block based resource allocation scheme is presented to describe the feasible tunnels. Furthermore, to avoid collisions with unexpected obstacles such as pedestrians, bicycles or other vehicles with human drivers, a low-level planner is designed to generate practical trajectories based on the solutions from the high-level planner, according to their local on-board observations. Simulations and practical experiments are carried out, to show that our proposed coordination framework can achieve obvious performance advantages in various traffic metrics, including the throughput, fairness in driving maneuvers and driving comfort, etc. We also find that the high-level planner is effective in eliminating possible deadlocks among autonomous vehicles, which is rarely discussed in existing investigations.
The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, ...Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P<0.001). In contrast, the expression of B7-H3 and B7-H4 was negatively correlated with IL-2 (P<0.05). B7-H3, B7-H4 and Foxp3 may be useful biomarkers in patients with cervical cancer for predicting treatment.
Epidemiological studies have shown that ambient fine particulate matter (PM) can cause various neurodegenerative diseases, including Alzheimer's disease. Reactive astrocytes are strongly induced by ...ambient fine PM, although their role is poorly understood. Herein, we show that A1 reactive astrocytes (A1s) were induced by neuroinflammatory microglia activated by PM with an aerodynamic diameter ≤ 0.2 μm (PM0.2). The activated-microglia induced A1s by secreting interleukin-1α, tumor necrosis factor-α, and complement 1q, and these cytokines acting together were necessary and sufficient to induce A1s. PM0.2-induced A1s could promote synaptic damage in neurons by secreting complement 3 (C3). SB 290157, a highly selective C3aR nonpeptide antagonist, partially ameliorated glial conditioned medium-induced synaptic injury. In vitro synaptic damage was partially prevented when A1 formation was blocked by minocycline. Finally, this study showed that N-acetyl-L-cysteine ameliorated PM0.2-induced neural damage independent of A1 differentiation. Collectively, these findings explain why central nervous system neurons suffer synaptic damage and neuroinflammation after PM0.2 exposure and suggest that this exposure induces A1s to contribute to synaptic damage of neurons. This study indicates a potential approach for developing improved treatment of these diseases induced by particulate exposure.
PM0.2-activated neuroinflammatory microglia induced A1 reactive astrocytes (A1s) by secreting IL-1α, TNF-α, and C1q. PM0.2-induced A1s could promote synaptic damage of neuron by secreting complement 3.
This study found that microglia were activated by PM0.2 and secreted interleukin (IL)-1α, tumor necrosis factor (TNF)-α, and complement 1q (C1q). These cytokines induced astrocytes to differentiate into A1 type (A1s). A1s lost the ability to promote neuronal synaptogenesis and induced synaptic damage of neurons by secreting C3. Moreover, the activated microglia produced many ROS, directly leading to neuronal damage. Display omitted
•PM0.2-activated neuroinflammatory microglia secreted IL-1α, TNF-α, and C1q to induce A1s.•PM0.2-induced A1s could promote synaptic damage of neuron by secreting C3.•Minocycline ameliorated PM0.2-induced synaptic damage by blocking A1 differentiation.•NAC ameliorated PM0.2-induced synaptic damage independent of A1 differentiation.
The Raman spectroscopy analysis has been applied to the detection and research of oral cancer. One of the essential works in this technique is the Raman spectral data analysis method, which is mainly ...divided into two categories: traditional machine learning and deep learning. Especially, the deep learning method is proved that it could obtain higher accuracy in oral cancer identification than the traditional machine learning method. The purpose of this study is to test, compare, and analyze the performance of existing classical deep neural network models (AlexNet, VGGNet, ResNet50, MobileNetV2, Transformer) that recognize multiple types of oral cancer tissues. To achieve this goal, 16,200 Raman spectra are first collected from 180 tissue samples of 90 patients who have undergone a surgical resection due to tongue squamous cell carcinoma, gingival squamous cell carcinoma, and buccal squamous cell carcinoma. Then, the models are trained and predicted at the patient level. The experimental results demonstrate that the ResNet50 has the best performance in the identification of oral cancer tissue and normal tissue with an overall accuracy rate of 92.81%, an overall precision rate of 92.93%, and an overall recall rate of 92.86%. With this foundation, we further develop a prototype intelligent detection system with above five classical deep neural network models to realize multi-types of oral cancer tissue detection. Hopefully, our work can provide a guide for oral cancer detection using the deep learning method with Raman spectroscopy analysis and promote the development of clinical diagnosis system for oral cancer. The code is available at https://github.com/ISCLab-Bistu/deep-learning-for-OSCC.
Studies have indicated that metal exposure is associated with an increased risk of metabolic syndrome (MetS). However, it is unclear whether overexposure to heavy metals occurs in miners and is ...associated with MetS risk remains unclear. In a cross-sectional study, analysis for metal exposure levels of 3428 participants from three types of workplaces was conducted. Relationships between metals in urine and MetS were characterized using a multivariate binary logistic regression model and restricted cubic spline analysis. The association between urinary metals and workplaces with respect to MetS was studied via mediation analysis and multiplicative interaction analysis. And a sensitivity analysis was performed to assess the robustness of the association between MetS and urinary metals in participants without obesity (
n
= 2811). Zn, Cu, Fe, Co, and Ni were found to be associated with MetS in the single-metal models, whereas only Zn and Cu showed considerable associations in the multimetal model. The odds ratios (95% CI) for MetS in the highest quartiles were 2.089 (1.611, 2.707) for urinary Zn and 1.394 (1.084, 1.794) for urinary Cu (both false discovery rate for both was < 0.05). Urinary Zn and Cu were positively associated with hypertriglyceridemia. In addition, higher Zn exposure was confirmed in underground workers than ground workers and office workers, and there was a significant association between urinary metal exposure and workplace, which together influenced the occurrence of MetS. These results provided scientific evidence for the relationship between Zn, Cu, workplaces, and MetS in coal workers and indicated that it is critical to reduce occupational metal exposure, especially in underground workers.