Background The Forkhead box M1 factor (FOXM1) is a crucial activator for cancer cell proliferation. While FOXM1 has been shown to promote hepatocellular carcinoma (HCC) progression, its ...transcriptional mechanisms remain incompletely understood. Methods We performed an in-house tissue microarray on 313 HCC and 37 non-HCC tissue samples, followed by immunohistochemical staining. Gene chips and high throughput sequencing data were used to assess FOXM1 expression and prognosis. To identify candidate targets of FOXM1, we comprehensively reanalyzed 41 chromatin immunoprecipitation followed by sequencing (ChIP-seq) data sets. We predicted FOXM1 transcriptional targets in HCC by intersecting candidate FOXM1 targets with HCC overexpressed genes and FOXM1 correlation genes. Enrichment analysis was employed to address the potential mechanisms of FOXM1 underlying HCC. Finally, single-cell RNA sequencing analysis was performed to confirm the transcriptional activity of FOXM1 on its predicted targets. Results This study, based on 4235 HCC tissue samples and 3461 non-HCC tissue samples, confirmed the upregulation of FOXM1 in HCC at mRNA and protein levels (standardized mean difference = 1.70 1.42, 1.98), making it the largest multi-centered study to do so. Among HCC patients, FOXM1 was increased in Asian and advanced subgroups, and high expression of FOXM1 had a strong ability to differentiate HCC tissue from non-HCC tissue (area under the curve = 0.94, sensitivity = 88.72%, specificity = 87.24%). FOXM1 was also shown to be an independent exposure risk factor for HCC, with a pooled hazard ratio of 2.00 1.77, 2.26. The predicted transcriptional targets of FOXM1 in HCC were predominantly enriched in nuclear division, chromosomal region, and catalytic activity acting on DNA. A gene cluster encoding nine transcriptional factors was predicted to be positively regulated by FOXM1, promoting the cell cycle signaling pathway in HCC. Finally, the transcriptional activity of FOXM1 and its targets was supported by single-cell analysis of HCC cells. Conclusions This study not only confirmed the upregulation of FOXM1 in HCC but also identified it as an independent risk factor. Moreover, our findings enriched our understanding of the complex transcriptional mechanisms underlying HCC pathogenesis, with FOXM1 potentially promoting HCC progression by activating other transcription factors within the cell cycle pathway. Keywords: Forkhead box M1, Hepatocellular carcinoma, Tissue microarray, Immunohistochemistry, High throughput sequencing, Transcriptional regulation
Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on ...triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified
cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study's findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.
Feature selection plays a key role in target recognition especially for multiple combined sensors’ applications. This study presents an improved relief feature selection (Relief‐F) model to rank ...features for multi‐target recognition. Besides, the evaluation of the effectiveness of the method is conducted based on the following three measuring indices: feature redundancy, class separability and overall accuracy. The simulated data acquired by radar infrared combined sensors are used to verify the metrics of the proposed method. The experimental results demonstrate that the Relief‐F method reveals the best results compared to other feature selection methods, including principal component analysis and Fisher linear discriminant analysis. It indicates that Relief‐F can be an effective option for feature selection with high‐class separability and a low feature redundancy rate. Furthermore, high overall accuracy can be obtained using a relatively small amount of features selected by the Relief‐F method.
Radiation therapy toward malignancies is often ineffective owing to radioresistance of cancer cells. On the basis of anti-tumor properties of cordycepin, we examined the effects of cordycepin on ...sensitizing breast cancer cells toward radiotherapy. Cordycepin administration promoted G2/M arrest and apoptosis of MCF-7 and MDA-MB-231 cells resulting in restraining the proliferation of the cells in vitro and in vivo following irradiation. Mechanistic investigations showed that the breast cancer cells cultured with cordycepin harbored higher levels of intracellular reactive oxygen species (ROS) and incremental numbers of γ-H2AX foci after irradiation exposure. Importantly, cordycepin treatment down-regulated the expression levels of Nuclear factor erythroid 2-related factor (Nrf2) and a series of downstream genes, such as heme oxygenase-1 (HO-1), to enhance ROS in breast cancer cells exposed to irradiation. Together, our observations demonstrate that cordycepin treatment sensitizes breast carcinoma cells toward irradiation via Nrf2/HO-1/ROS axis. Thus, our findings provide novel insights into the function and the underlying mechanism of cordycepin in radiotherapy, and suggest that cordycepin might be employed as a radiosensitizer during radiotherapy toward breast cancer in a pre-clinical setting.
•Cordycepin sensitizes breast carcinoma cells toward irradiation covering TNBC.•Cordycepin administration induces DNA damage following irradiation.•Cordycepin hijacks Nrf2/HO-1/ROS axis to sensitize breast cancer cells toward IR.•Clinically, cordycepin might be employed as a radiosensitizer for breast cancer.
We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to ...tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.
FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo.
These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.
The tendency towards an increase in rolling speeds, which is characteristic of the development of modern sheet rolling, causes an increase requirement of accurate prediction on-line control models ...for the thermal crown of work rolls. In this paper, a precision on-line model is proposed for the prediction of thermal crown in hot-strip rolling processes. The heat conduction of the roll temperature can be described by a nonlinear partial differential equation (PDE) in the cylindrical coordinate. After selecting a set of proper basis functions, the spectral methods can be applied to time/space separation and model reduction, and the dynamics of the heat conduction can be described by a model of high-order nonlinear ordinary differential equations (ODE) with a few unknown nonlinearities. Using a technique for further reducing the dimensions of the ODE system, neural networks (NNs) can be trained to identify the unknown nonlinearities. The low-order predicted model of the thermal crown is given in state-space formulation and efficient in computation. The comparisons of prediction values for the thermal crown with the production data in an aluminum alloy hot rolling process show that the proposed method is effective and has high performance.
Methods based on vibration analysis are currently regarded as the most conclusive means for fault diagnosis and health prognostics in rotary machinery. However, changing working conditions mean that ...the vibration signals originating from rotary machinery exhibit different levels of complexity. This complexity leads to increased difficulty in constructing health indicators (HIs). In this paper, we propose a multiscale Tsallis permutation entropy (MTPE) to construct the HIs of rotary machinery under different working conditions. MTPE values are a function of an entropy index and scale, which have the universality for handling the complexity of a permutated time series. The health condition of the rotary machinery was effectively represented by the MTPEs in conditional monitoring; the initial point of the unhealthy stage was found using the 3σ interval. This was set as the alarm threshold according to the varying HI trend. Once this was established, dividing the stages into two-stage health stages (HS) was straightforward. Using a rolling bearing, a run-to-failure experiment was conducted and results suggested that the proposed method effectively assessed the status of the rotary machinery. Taken together, this study provided a novel complexity measure based on a methodology for constructing the HIs of rotary machinery and enriches conditional monitoring theory.
Real‐time monitoring and accurate prediction of photovoltaic (PV) power generation operation parameters are essential to ensure stable operation. In this paper, a set of online PV power generation ...parameter measurement and monitoring devices characterized by simple structure, high sampling accuracy, small data fluctuations, and ease of measurement, are designed. Sensors based on the zero‐flux principle are employed in the real‐time collection of the output electrical signals in the process of PV power generation, realizing the accurate collection of electric parameter signals. Next, the basic structure and working principle of PV cells are analyzed, a mathematical model of PV cells for engineering purposes is established, a wavelet neural network is selected to predict the short‐term PV power generation, and particle swarm optimization and adding momentum are used to optimize the weight of wavelet neural network (WNN) as well as the parameters of the wavelet basis function. Finally, the historical power generation data and meteorological data of the power station are taken as the training samples to train and simulate the prediction sub‐models of different weather types to verify the effectiveness and accuracy of the PV power generation short‐term prediction model for optimizing the WNN based on the particle swarm optimization algorithm. The research results of this paper can realize real‐time monitoring of the output parameters and accurate prediction and evaluation of power generation during the operation of the PV‐power‐generation system.
This paper concentrates on the short term prediction of photovoltaic (PV) power generation, the wavelet neural network (WNN) prediction algorithm was used to conduct short‐term prediction of PV‐power generation, and the particle swarm optimization (PSO) was used to optimize the learning rate and weight of WNN. The results showed that the PSO‐WNN‐based prediction model was found to be more effective for the short‐term prediction of PV power generation, and the predicted values were closer to the actual power generation data.
To investigate the influence of thermal effects on the hydrogen desorption performance of the metal hydride hydrogen storage system, a two-dimensional numerical model was established based on a small ...metal hydride hydrogen storage tank, and its accuracy was verified by the temperature variations in the reaction zone of the hydrogen storage tank during hydrogen desorption. In addition, the influence of the heat transfer medium on the heat and mass transfer performance of the hydrogen desorption reaction was analyzed. An external heat transfer bath was added to simulate the thermal effect of the model during the hydrogen desorption reaction. The temperature and type of heat transfer medium in the heat transfer bath were modified, and the temperature and reaction fraction variations in each zone of the hydrogen storage model were analyzed. The results showed that under heat transfer water flow, the reaction rate in the center region of the hydrogen storage tank was gradually lower than that in the wall region. The higher the temperature of water flow, the shorter the total time required for the hydrogen desorption reaction and the shortening amplitude is reduced. The variations in the temperature and hydrogen storage capacity during hydrogen desorption were similar, with water and oil as the heat transfer medium, under the same flow rate and heat transfer temperature, however, the heat transfer time and hydrogen desorption time of water were about 10% and 5% shorter than that of oil, respectively. When the air was used as the heat transfer medium, the heat transfer rate of the air convection in the channel was lower than the heat transfer rate of the tank wall, reducing the temperature difference between the air and alloy on both sides of the wall, decreasing heat transfer efficiency, and significantly prolonging the time required for hydrogen desorption.
Compared with current low-Earth-orbit synthetic aperture radar (SAR), geosynchronous SAR (GEO SAR) is featured with its ultrahigh orbit and ultralong integration time. In this letter, we answer the ...question whether the orbital perturbation items have effects on GEO SAR imaging during the long integration time and, if so, how they produce errors. To achieve these goals, we first develop a perturbing orbital elements errors model based on perturbation analysis. Then, we propose an accurate analytical expression of first to fourth Doppler parameters for GEO SAR and analyze the effects of perturbing orbital elements errors on the Doppler parameters. Furthermore, the relationship between the perturbing Doppler errors and the phase coherence of GEO SAR signal is deduced. Experiment and simulation results demonstrate the image defocusing caused by orbital perturbation. The conclusions are that the orbital perturbation does affect GEO SAR imaging by producing nonnegligible phase errors and that the required accuracy of the orbit determination should be at centimeter level in the radial direction.
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