Poly(vinylidene fluoride) (PVDF) film shows great potential for applications in the electrostatic energy storage field due to its high dielectric constant and breakdown strength. Polymer film surface ...engineering technology has aroused much concern in plastic film capacitors as an effective strategy for improving dielectric properties and energy storage characteristics. In this paper, biaxially oriented PVDF (BOPVDF) films were prepared by melt extrusion-biaxial stretching and treated with organic impregnation using hydrofluoroether. The insulation properties and energy storage density of the biaxially oriented films were significantly improved by a simple film formation post-treatment. The impregnation treatment effectively suppressed the leakage current of the film at a high electric field. The impregnated BOPVDF exhibited excellent insulation properties with a breakdown strength of 747.84 kV/mm. Meanwhile, the energy storage density of 16.26 J/cm
3
with a charge–discharge efficiency of 78.41% was obtained at 700 kV/mm. This research provided a simple way to improve the energy storage performance of PVDF-based polymers by organic impregnation treatment and has the feasibility of achieving large-scale production.
Purpose
The present study aims to determine whether co-targeting PI3K/Akt and MAPK/ERK pathways in human hypopharyngeal squamous cell carcinoma (HSCC) is a potential anticancer strategy.
Methods
We ...retrospectively analyzed the clinical data of HSCC patients, and the phosphorylation status of Akt and Erk in HSCC and tumor adjacent tissues was evaluated by immunohistochemistry. MTT and colony formation assay were performed to determine the anti-proliferative effect of PI3K/mTOR inhibitor GDC-0980 and MEK inhibitor Refametinib on HSCC cell line Fadu. Wound-healing and Transwell migration assay were used to analyze the anti-migrative capability of the two drugs. The involved anti-tumor mechanism was explored by flow cytometry, qRT-PCR and western blot. The combinational anticancer effect of GDC-0980 and Refametinib was evaluated according to Chou and Talalay’s method.
Results
The levels of p-Akt and p-Erk were increased significantly with the progression of clinical stage of HSCC, suggesting PI3K/Akt and MAPK/ERK pathways might be associated with HSCC occurrence and progression. Furthermore, both GDC-0980 and Refametinib showed obvious antitumor effects on FaDu cells. Treatment by the two drugs arrested FaDu cell cycle progression in G1 phase, with reduction of cyclin D1 and p-Rb, in contrast to enhancement of p27. GDC-0980 inhibited FaDu cell migration and reduced metastasis related proteins including p-PKCζ, p-Integrin β1 and uPA. Combination use of GDC-0980 and Refametinib exhibited strong synergistic anti-tumor effect.
Conclusion
Dual inhibition of PI3K/Akt and MAPK/ERK pathway by GDC-0980 and Refametinib might be a promising treatment strategy for HSCC patients.
Understanding the spatiotemporal characteristics of regional drought is of great significance in decision-making processes such as water resources and agricultural systems management. The North China ...Plain is an important grain production base in China and the most drought-prone region in the country. In this study, the monthly standardized precipitation evapotranspiration index (SPEI) was used to monitor the spatiotemporal variation of agricultural drought in the North China Plain from 1960 to 2017. Seven spatial patterns of drought variability were identified in the North China Plain, such as Huang-Huai Plain, Lower Yangtze River Plain, Haihe Plain, Shandong Hills, Qinling Mountains Margin area, Huangshan Mountain surroundings, and Yanshan Mountain margin area. The spatial models showed different trends in different time stages, indicating that the drought conditions in the North China Plain were complex and changeable in the past 58 years. As an important agricultural area, the North China Plain needs more attention since this region shows a remarkable trend of drought and, as such, will definitely increase the water demand for agricultural irrigation. The strong correlation between these spatial distribution patterns indicates that the climate and weather conditions leading to drought are consistent and that drought conditions are independent for regions that are not correlated. If this trend continues, the characteristics of drought variability in the North China Plain will become more complex, and a more detailed water management strategy will be needed to address the effects of drought on agro-ecosystems. Recognizing the drought variability in the North China Plain can provide a basis for agricultural disaster reduction planning and water resources allocation.
The critical role of phosphoinositide 3-kinase (PI3K) activation in tumor cell biology has prompted massive efforts to develop PI3K inhibitors (PI3Kis) for cancer therapy. However, recent results ...from clinical trials have shown only a modest therapeutic efficacy of single-agent PI3Kis in solid tumors. Targeting autophagy has controversial context-dependent effects in cancer treatment. As a FDA-approved lysosomotropic agent, hydroxychloroquine (HCQ) has been well tested as an autophagy inhibitor in preclinical models. Here, we elucidated the novel mechanism of HCQ alone or in combination with PI3Ki BKM120 in the treatment of cancer.
The antitumor effects of HCQ and BKM120 on three different types of tumor cells were assessed by in vitro PrestoBlue assay, colony formation assay and in vivo zebrafish and nude mouse xenograft models. The involved molecular mechanisms were investigated by MDC staining, LC3 puncta formation assay, immunofluorescent assay, flow cytometric analysis of apoptosis and ROS, qRT-PCR, Western blot, comet assay, homologous recombination (HR) assay and immunohistochemical staining.
HCQ significantly sensitized cancer cells to BKM120 in vitro and in vivo. Interestingly, the sensitization mediated by HCQ could not be phenocopied by treatment with other autophagy inhibitors (Spautin-1, 3-MA and bafilomycin A1) or knockdown of the essential autophagy genes Atg5/Atg7, suggesting that the sensitizing effect might be mediated independent of autophagy status. Mechanistically, HCQ induced ROS production and activated the transcription factor NRF2. In contrast, BKM120 prevented the elimination of ROS by inactivation of NRF2, leading to accumulation of DNA damage. In addition, HCQ activated ATM to enhance HR repair, a high-fidelity repair for DNA double-strand breaks (DSBs) in cells, while BKM120 inhibited HR repair by blocking the phosphorylation of ATM and the expression of BRCA1/2 and Rad51.
Our study revealed that HCQ and BKM120 synergistically increased DSBs in tumor cells and therefore augmented apoptosis, resulting in enhanced antitumor efficacy. Our findings provide a new insight into how HCQ exhibits antitumor efficacy and synergizes with PI3Ki BKM120, and warn that one should consider the "off target" effects of HCQ when used as autophagy inhibitor in the clinical treatment of cancer.
Regional climate variability assessment is of great significance in decision-making such as agriculture and water resources system management. The identification of sub-regions with similar drought ...variability can provide a basis for agricultural disaster reduction planning and water resource distribution. In this research, a modified daily Standardized Precipitation Evapotranspiration Index (SPEI) was used to monitor the spatial and temporal variation characteristics of agricultural drought in the North China Plain from 1960 to 2017, which was studied by using the rotated empirical orthogonal functions (REOF). Through the seasonal REOF process, 7–9 seasonal drought sub-regions are confirmed by applying time series and the correlation relationship of SPEI original data. The strong correlation of these sub-regions indicates that the climate and weather conditions causing the drought are consistent and the drought conditions are independent for the regions that show no correlation. In general, the results of the seasonal trend analysis show that there has been no significant trend value in most areas since 1960. However, it is worth noting that some regions have the positive and negative temporal trends in different seasons. These results illustrate the importance of seasonal analysis, particularly for agro-ecosystems that depend on timely rainfall during different growing seasons. If this trend continues, seasonal drought will become more complex, then a more elaborate water management strategy will be needed to reduce its impact.
Ovarian cancer is a disease with the highest mortality in gynecologic malignancies. Activation of STAT3 pathway is well known to be associated with tumor progression and metastasis in a number of ...cancers, including ovarian cancer. Therefore, STAT3 may be an ideal target for ovarian cancer treatment.
The present study aims to determine the antitumor activity of STAT3 inhibitor Napabucasin as a single agent or in combination with proteasome inhibitor MG-132 in ovarian cancer cells.
MTT was performed to determine the anti-proliferative effect of Napabucasin on ovarian cancer SKOV-3 cells. The involved anti-tumor mechanism was explored by flow cytometry, qRTPCR and western blot. MDC staining and tandem mRFP-GFP-LC3 fluorescence microscopy were used to analyze the autophagy-inducing capability of Napabucasin with or without MG-132. The combinational anticancer effect of Napabucasin and MG-132 was evaluated according to Chou and Talalay's method (1984).
Napabucasin showed obvious tumor-inhibitory effects against SKOV-3 cells. Treatment by Napabucasin arrested cell cycle progression in G2/M phase. Mechanistically, elevated expression of p21 may contribute to the blockade of the cell cycle. Moreover, we demonstrated that Napabucasin induced autophagy in SKOV-3 cells by using various assays, including MDC staining, autophagic flux examination, and detection of the autophagy markers. In addition, a combination of Napabucaisin with MG-132 exhibited a significant synergistic anti-proliferative effect, probably by inducing apoptosis through a mitochondria-dependent pathway. The two compounds induced pro-survival autophagies, and co-treatment with autophagy inhibiter might further enhance their antitumor effects.
Napabucasin alone or in combination with MG-132 might be promising treatment strategy for ovarian cancer patients.
•Recent advances in triboelectric nanogenerators, biofuel cells, and hydrovoltaic generators for human motion energy harvesting.•Integration strategies for wearable applications in textiles, ...clothing, accessories, and implantable biomedical devices.•Prospects of hybrid energy harvesting, self-powered sensing, closed-loop bioelectronic systems, and eco-friendly materials.
Recent advancements in wearable electronics and implantable devices have driven the demand for sustainable and autonomous energy sources, with human motion energy emerging as a promising candidate. This review provides a comprehensive overview of the latest developments in electrochemical human motion energy harvesting technologies, focusing on the sources and characteristics of human body energy, key electrochemical transduction mechanisms, and integration strategies for practical applications. The review delves into the working principles, material and structural designs, and performance enhancements of triboelectric nanogenerators (TENGs), biofuel cells (BFCs), and hydrovoltaic effect generators (HEGs), highlighting their potential for converting mechanical, chemical, and thermal energy from human motion into electrical energy. Furthermore, the challenges and future prospects of these technologies are discussed, emphasizing the importance of hybridization, self-powered sensing, closed-loop bioelectronic systems, and eco-friendly materials. This review aims to provide valuable insights and inspiration for researchers and engineers working towards the development of efficient, sustainable, and autonomous energy solutions for wearable and implantable devices.
Prostate cancer is one of the most frequent causes of cancer death in men worldwide, and novel drugs for prostate cancer therapies are still being developed. Palmitic acid is a common saturated ...long-chain fatty acid that is known to exhibit anti-inflammatory and metabolic regulatory effects and antitumor activities in several types of tumors. The present study aims to explore the antiproliferative and antimetastatic activities of palmitic acid on human prostate cancer cells and the underlying mechanism.
MTT and colony formation assays were utilized to determine the antiproliferative effect of palmitic acid. Cell metastasis was evaluated by wound healing, Transwell migration and invasion assay. The in vivo anticancer effect was assessed by a nude mouse xenograft model of prostate cancer. The involved molecular mechanisms were investigated by flow cytometry and Western blot analysis.
Palmitic acid significantly suppressed prostate cancer cell growth in vitro and in vivo. Treatment with palmitic acid induced G1 phase arrest, which was associated with downregulation of cyclin D1 and p-Rb and upregulation of p27. In addition, palmitic acid could inhibit prostate cancer cell metastasis, in which suppression of PKCζ and p-Integrinβ1 and an increase in E-cadherin expression might be involved. Furthermore, a mechanistic study indicated that palmitic acid inhibited the key molecules of the PI3K/Akt pathway to block prostate cancer proliferation and metastasis.
Our findings suggested the antitumor potential of palmitic acid for prostate cancer by targeting the PI3K/Akt pathway.
In this paper, a novel continual learning classification method (SCLM) in small sample cases is proposed, which inspired by the immune system's continuous improvement of immunity through injecting ...vaccines. Data-driven classification method requires a large number of historical data to establish a pattern recognition model with good generalization performance. However, in practice, the data that can be used for training is usually small and unbalanced, which lead to poor classification accuracy. In addition, batch learning method cannot improve continually classification performance by learning test phase data. In view of the above problems, SCLM generates sample as vaccine by finding the group center of training samples, so that B cells mature and activate memory cells in the train phase. In the test phase, the recognition ability of SCLM is further improved by learning new samples and updating memory cells. In order to evaluate its performance under the condition of less training samples and its possible advantages, the experiments on well-known datasets in UCI repository and reciprocating compressor faults diagnose were performed. The results show that SCLM has better classification performance than other methods when the number of training samples is insufficient. At the same time, the method of generating data has significantly improved the classification performance of other methods.
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