Accurate electrical load forecasting is of great significance to help power companies in better scheduling and efficient management. Since high levels of uncertainties exist in the load time series, ...it is a challenging task to make accurate short-term load forecast (STLF). In recent years, deep learning approaches provide better performance to predict electrical load in real world cases. The convolutional neural network (CNN) can extract the local trend and capture the same pattern, and the long short-term memory (LSTM) is proposed to learn the relationship in time steps. In this paper, a new deep neural network framework that integrates the hidden feature of the CNN model and the LSTM model is proposed to improve the forecasting accuracy. The proposed model was tested in a real-world case, and detailed experiments were conducted to validate its practicality and stability. The forecasting performance of the proposed model was compared with the LSTM model and the CNN model. The Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE) and Root Mean Square Error (RMSE) were used as the evaluation indexes. The experimental results demonstrate that the proposed model can achieve better and stable performance in STLF.
Tumor recurrence, the chief reason for poor prognosis of glioma, is largely attributed to glioma stem cells (GSCs) and epithelial-mesenchymal transition (EMT). However, the mechanisms among them ...remain unknown. Here, we determined whether leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), known as a stem cell marker for colon cancer and gastric cancer, can serve as a novel GSC marker involved in EMT and a therapeutic target in glioma.
Stemness properties were examined in FACS-isolated LGR5
/LGR5
cells. Reported stem cell markers, EMT and the Wnt/β-catenin pathway were examined in stable LGR5 knockdown or overexpressed GSCs by Western Blot. The treatment experiment was performed in an intracranial orthotopic xenograft model by knockdown of LGR5 or by using the Wnt/β-catenin pathway inhibitor Wnt-C59. LGR5 expression was determined in 268 glioma specimens by immunohistochemistry.
LGR5
cells possessed stronger stemness properties compared to LGR5
cells. The expression of SOX2, Nanog, CD133, CD44, CD24 and EpCAM was modulated by LGR5. Both LGR5 knockdown and Wnt-C59 reduced tumor invasion and migration and blocked EMT by inhibiting the Wnt/β-catenin pathway in vitro and suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Moreover, LGR5 was positively correlated with Ki67, N-cadherin and WHO grade and negatively correlated with IDH1. Glioma patients with high expression of LGR5 showed significantly poorer prognosis.
LGR5 is a new functional GSC marker and prognostic indicator that can promote EMT by activating the Wnt/β-catenin pathway and would thus be a novel therapeutic target for glioma.
The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known ...about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function. In contrast, EBP1 P42 bound to both the F-box domain of FBXW7 as well as FBXW7 substrates. This adapter function of EBP1 P42 stabilized the interaction of FBXW7 with its substrates and promoted FBXW7-mediated degradation of oncogenic targets, enhancing its overall tumor-suppressing function. Overall, our results establish distinct physical and functional interactions between FBXW7 and EBP1 isoforms, which yield their mechanistically unique isoform-specific functions of EBP1 in cancer.
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To investigate the role of miR-221/222 in cell proliferation and apoptosis in human prostate cancer cells, and examine the effects of miR-221/222 on caspase-10 expression.
Prostate cancer cells were ...transfected with miR-221/222 mimics or inhibitors. Cell proliferation was assessed by MTT assay. The expression levels of miR-221/222 were detected with quantitative real-time PCR. Apoptosis was induced with TNF-α/CHX treatment, and evaluated by Hoechst 33342 staining, propidium iodide (PI) flow cytometric analysis, caspase-3 activity measurement, and Western blot analysis. Luciferase activity assay, quantitative real-time PCR, and Western blot were performed to evaluate the effects of miR-221/222 on caspase-10 expression.
Our results showed that miR-221/222 could promote the proliferation of prostate cancer cells, including LNCaP and PC3 cells. After transfection and apoptosis induction, Hoechst 33342 staining and PI flow cytometric assay showed that apoptosis was dramatically decreased in prostate cancer cells treated with miR-221/222 mimics. Moreover, caspase-3 activity was dramatically decreased, and the cleaved forms of caspase-3 were reduced, in the miR-221/222 mimic-treated group. On the contrary, miR-221/222 knockdown sensitized the prostate cancer cells to TNF-α/CHX-induced apoptosis. In addition, a negative correlation was observed between the expressions of miR-221/222 and caspase-10 in prostate cancer cells. miR-221/222 could repress the expression of caspase-10, which was confirmed by the luciferase reporter assay.
miR-221/222 promote cell proliferation and repress apoptosis, through suppressing caspase-10, in prostate cancer cells. Our results provide promising evidence for the miRNA-based therapeutic strategy of prostate cancers.
•miR-221/222 promote proliferation and suppress apoptosis in prostate cancer cells.•Caspase-10 is recognized as a novel target of miR-221/222 in prostate cancer cells.•miR-221/222 repress caspase-10 expression in prostate cancer cells via mRNA decay.
Donor-specific antibodies (DSAs) play a key role in chronic kidney allograft injury. Follicular T helper (Tfh) cells trigger the humoral alloimmune response and promote DSA generation, while ...T-follicular regulatory (Tfr) cells inhibit antibody production by suppressing Tfh and B cells. Interleukin (IL)-21 exerts a distinct effect on Tfh and Tfr. Here, we studied whether blocking IL-21R with anti-IL-21R monoclonal antibody (αIL-21R) changes the Tfh/Tfr balance and inhibits DSA generation. First, we investigated the impact of αIL-21R on CD4
T cell proliferation and apoptosis. The results showed that αIL-21R did not have cytotoxic effects on CD4
T cells. Next, we examined Tfh and regulatory T cells (Tregs) in an
conditioned culture model. Naïve CD4
T cells were isolated from 3-month-old C57BL/6 mice and cultured in Tfh differentiation inducing conditions in presence of αIL-21R or isotype IgG and differentiation was evaluated by CXCR5 expression, a key Tfh marker. αIL-21R significantly inhibited Tfh differentiation. In contrast, under Treg differentiation conditions, FOXP3 expression was inhibited by IL-21. Notably, αIL-21R rescued IL-21-inhibited Treg differentiation. For
investigation, a fully mismatched skin transplantation model was utilized to trigger the humoral alloimmune response. Consistently, flow cytometry revealed a reduced Tfh/Tfr ratio in recipients treated with αIL-21R. Germinal center response was evaluated by flow cytometry and lectin histochemistry. We observed that αIL-21R significantly inhibited germinal center reaction. Most importantly, DSA levels after transplantation were significantly inhibited by αIL-21R at different time points. In summary, our results demonstrate that αIL-21R shifts the Tfh/Tfr balance toward DSA inhibition. Therefore, αIL-21R may be a useful therapeutic agent to prevent chronic antibody mediated rejection after organ transplantation.
Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which is a key problem associated with ...the long-term kidney grafts survival. This study investigated the role played by PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR. We showed that CAAMR and CAMR patients' allografts dysfunction with declined survival rate, which suggested that earlier diagnosis and treatment of CAAMR might be important to prevent irreversible chronic injury of CAMR progression. We found PSMP was an important factor in the development of chronic antibody-mediated rejection. The PSMP expression increased significantly in CAAMR biopsy samples but not in CAMR and control patients, which distinguished CAAMR patients from CAMR and non-rejection patients. Moreover, our results showed that infiltration of CD68
macrophages in CAAMR increased, and the correlation between CD68
macrophages and PSMP expression in CAAMR patients was significant. Additionally, our data also revealed that intimal arteritis (v-lesion) accompanied by increased macrophage infiltration might have contributed to more graft loss in CAAMR, and PSMP expression was significantly associated with the v-lesion score. These results indicated that PSMP played an important role in the recruitment of macrophages and promote intimal arteritis inducing allograft lost in CAAMR progression. In future study PSMP could be a potential histopathological diagnostic biomarker and treatment target for CAAMR in kidney transplantation.
CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin ...remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR) in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression.
The viable application of soft electronics/robotics relies on the development of power devices which are desired to be flexible, deformable, or even self-healable. We report here a shape-adaptive, ...self-healable triboelectric nanogenerator (SS-TENG) for harvesting biomechanical energies. The use of a viscoelastic polymer, normally known as Silly Putty, as the electrification material and as the matrix of a carbon-nanotube-filled composite (CNT-putty) electrode endows the SS-TENG the capability of adapting to arbitrary irregular surfaces and instantaneous healing from mechanical damage (almost completely recovered in 3 min without extra stimuli). Furthermore, the output performances of the SS-TENG have also been significantly improved because (i) the ideal soft contact is achieved at the solid–solid interfaces for more effective contact electrification and (ii) the introduced cation dopants make the putty even more tribo-negative than polytetrafluoroethylene. The SS-TENG can be adhered to any curvy surface, tailored, and reshaped into arbitrary configurations and utilized as a power supply for small electronics, suggesting promising applications in soft electronics/robotics in the future.
Gastric cancer stem cells (GCSCs) have been used as a therapeutic target. This study aims to estimate the role of miR-98-5p (termed miR-98) in the development of GCSCs.
The expression of miR-98 in ...CD44
GCSCs was verified by RT-PCR. The miR-98 was overexpressed in CD44
GCSCs by Lentivirus. The ability of self-renewal, invasion, chemoresistance and tumorigenicity was detected in vitro or in vivo after overexpression of miR-98. The target genes of miR-98 were predicted and verified by luciferase reporter assays. The effects miR-98/BCAT1 signaling on the chemoresistance and tumorigenicity of CD44
GCSCs were investigated in a xenograft model by rescue experiments.
We have shown that miR-98 was decreased in CD44
GCSCs. The overexpression of miR-98 could inhibit the expression of stem-related genes and the ability of self-renewal, invasion, and tumorigenicity of GCSCs. Also, we found that miR-98 overexpression enhances the sensitivity to cisplatin treatment in vitro. Using a xenograft model, we showed that miR-98 overexpression reversed paclitaxel resistance to CD44
GCSCs. Finally, we found that branched-chain aminotransferases 1 (BCAT1) is a target gene of miR-98. Overexpressed BCAT1 reversed xenograft tumor formation ability and attenuated the paclitaxel chemosensitivity induced by miR-98 downregulation. Furthermore, BCAT1 restoration affected the expression of invasion and drug resistance-related genes.
This study revealed miR-98 inhibits gastric cancer cell stemness and chemoresistance by targeting BCAT1, suggesting that this miR-98/BCAT1 axis represents a potential therapeutic target in gastric cancer.
We report the chemical vapor deposition (CVD) growth, characterization, and low-temperature magnetotransport of 1T phase multilayer single-crystalline VTe2 nanoplates. The transport studies reveal ...that no sign of intrinsic long-range ferromagnetism but localized magnetic moments exist in the individual multilayer metallic VTe2 nanoplates. The localized moments give rise to the Kondo effect, evidenced by logarithmical increment of resistivity with decreasing temperature and negative magnetoresistance (NMR) regardless of the direction of magnetic field at temperatures below the resistivity minimum. The low-temperature resistivity upturn is well described by the Hamann equation, and the NMR at different temperatures, a manifestation of the magnetization of the localized spins, is well fitted to a Brillouin function for S = 1/2. Density functional theory calculations reveal that the localized magnetic moments mainly come from the interstitial vanadium ions in the VTe2 nanoplates. Our results will shed light on the study of magnetic properties, strong correlation, and many-body physics in two-dimensional metallic transition metal dichalcogenides.
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