Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that ...some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133
Notch1
, whereas the nerve fibers express the Notch ligand Jagged1. The Notch-induced transcription factor Sox9 promotes the transcription of SOX2 and the methylation level of the NOTCH1 promoter is attenuated by the upregulation of SOX2 to reinforce NOTCH1 expression in GSCs. This positive-feedback loop in a cohort of glioma subjects is correlated with a poor prognosis. Inhibition of Notch signaling attenuates the white-matter-tract tropism of GSCs. These findings provide evidence indicating that the NOTCH1-SOX2 positive-feedback loop controls GSC invasion along white matter tracts.
There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein‐1 (HKDC1) in gastric cancer (GC) ...remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial–mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5‐fluorouracil (5‐Fu) onto GC cells. Furthermore, nuclear factor kappa‐B (NF‐κB) inhibitor PS‐341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF‐κB pathway. In addition, HKDC1‐mediated drug resistance was associated with DNA damage repair, which further activated NF‐κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.
HKDC1 upregulation predicts resistance to cisplatin, oxaliplatin and 5‐FU in patients with GC. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.
High level apoptosis induced by spinal cord injury (SCI) evokes serious damage because of the loss and dysfunction of motor neurons. Our previous studies showed that inhibition of autophagy evokes ...the activation of apoptosis. Interestingly, Baicalein, a medicine with anti-apoptosis activity that is derived from the roots of herb Scutellaria baicalensis, largely induces autophagy by activating phosphatidylinositol 3-kinase (PI3K). In this study, we investigated the effects of intraperitoneal injection of Baicalein on autophagy and apoptosis in SCI mice and evaluated the relationship between autophagy and apoptosis. We demonstrated that Baicalein promoted the functional recovery of motor neurons at 7 d after SCI. In addition, Baicalein enhanced neuronal autophagy and the autophagy-related factor PI3K, while inhibiting the p62 protein. Baicalein treatment decreased neuronal apoptosis at 7 d after SCI. Moreover, when inhibiting autophagy, apoptosis was upgraded by Baicalein treatment after injury. Thus, Baicalein attenuated SCI by inducing autophagy to reduce apoptosis in neurons potentially via activating PI3K.
Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit ...metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation-inducing agent, all-trans retinoic acid, restored the miR20a-MICA/MICB axis and sensitized BCSC to NK cell-mediated killing, thereby reducing immune escape-associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a-MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer.
A piecewise suboptimal threshold (PSOT) is proposed to select the most significant samples (MSSs) of the channel impulse response (CIR) for channel estimation of ultrasonic through-metal (UTM) ...communication. We analyze the correlation of echoes in the UTM channel, i.e., the periodicity and the exponential decay of echoes. The summation of mean-square error (MSE) is partitioned using the periodicity of the echoes so that each partitioned MSE contains only one echo. The PSOT is derived by setting the first derivative of the partitioned MSE to zero. Channel tap energies, namely, the received energies of ultrasonic waves, are required to calculate the PSOT, which can be estimated using the exponential decay of echoes. After selecting MSSs by PSOT, we propose a further selection approach to get rid of possible noise samples in MSS using the correlation of echoes. The simulation results show that the proposed method is robust. Specifically, the performance of the proposed method does not depend on ultrasonic velocity, is unaffected by the estimated number of the echoes at a low signal-to-noise ratio (SNR), and can be applied to UTM channels with different metal thicknesses. The simulation also shows that the proposed method has a lower MSE than other methods, especially at low SNR.
Underwater images often exhibit strong color distortion and hazing due to various degradation factors. A majority of algorithms provide color correction for underwater images, but the color is not as ...vivid as it could be. In order to solve this problem, we propose a method known as adaptive underwater image enhancement guided by generalized imaging components (AUIE-GIC). To the best of our knowledge, this is the first method of utilizing deep learning to develop a generalized imaging model. The proposed method contains two stages: component generation and component guided learning. In the first stage, we obtain the components of a learning-based generalized imaging model. In the second stage, attenuation and transmission features are used to adjust color and semantic information. We propose the attenuation attention module (AAM), and transmission attention module (TAM), which can highlight heavily degraded areas. Finally, the refined network is able to restore underwater images that are rich in semantics and vivid in color. Based on further evaluation and analysis, AUIE-GIC is demonstrated to provide superior performance when compared with state-of-the-art (SOTA) methods.
Memory technologies and applications implemented fully or partially using emerging 2D materials have attracted increasing interest in the research community in recent years. Their unique ...characteristics provide new possibilities for highly integrated circuits with superior performances and low power consumption, as well as special functionalities. Here, an overview of progress in 2D‐material‐based memory technologies and applications on the circuit level is presented. In the material growth and fabrication aspects, the advantages and disadvantages of various methods for producing large‐scale 2D memory devices are discussed. Reports on 2D‐material‐based integrated memory circuits, from conventional dynamic random‐access memory, static random‐access memory, and flash memory arrays, to emerging memristive crossbar structures, all the way to 3D monolithic stacking architecture, are systematically reviewed. Comparisons between experimental implementations and theoretical estimations for different integration architectures are given in terms of the critical parameters in 2D memory devices. Attempts to use 2D memory arrays for in‐memory computing applications, mostly on logic‐in‐memory and neuromorphic computing, are summarized here. Finally, challenges that impede the large‐scale applications of 2D‐material‐based memory are reviewed, and perspectives on possible approaches toward a more reliable system‐level fabrication are also given, hopefully shedding some light on future research.
The developments of circuit‐level memory technologies and in‐memory computing applications realized experimentally using 2D materials are reviewed. Reports on large‐scale material synthesis methods, circuits with different levels of integration, logic‐in‐memory, and neuromorphic computing applications are systematically summarized. Major challenges and perspectives of large‐scale 2D‐material‐based integrated memory are provided.
Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of ...labor as a result of increased expression of inducible cyclooxygenase 2 (COX‐2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography‐mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase‐ and lipoxygenasepathway‐derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti‐inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.—Maddipati, K. R., Romero, R., Chaiworapongsa, T., Zhou, S.‐L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Munoz, H., Honn, K. V., Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. FASEB J. 28, 4835–4846 (2014). www.fasebj.org
The invasion of malignant glioma cells into the surrounding normal brain tissues is crucial for causing the poor outcome of this tumor type. Recent studies suggest that glioma stem-like cells (GSLCs) ...mediate tumor invasion. However, it is not clear whether microenvironment factors, such as tumor-associated microglia/macrophages (TAM/Ms), also play important roles in promoting GSLC invasion. In this study, we found that in primary human gliomas and orthotopical transplanted syngeneic glioma, the number of TAM/Ms at the invasive front was correlated with the presence of CD133(+) GSLCs, and these TAM/Ms produced high levels of TGF-β1. CD133(+) GSLCs isolated from murine transplanted gliomas exhibited higher invasive potential after being cocultured with TAM/Ms, and the invasiveness was inhibited by neutralization of TGF-β1. We also found that human glioma-derived CD133(+) GSLCs became more invasive upon treatment with TGF-β1. In addition, compared with CD133(-) committed tumor cells, CD133(+) GSLCs expressed higher levels of type II TGF-β receptor (TGFBR2) mRNA and protein, and downregulation of TGFBR2 with short hairpin RNA inhibited the invasiveness of GSLCs. Mechanism studies revealed that TGF-β1 released by TAM/Ms promoted the expression of MMP-9 by GSLCs, and TGFBR2 knockdown reduced the invasiveness of these cells in vivo. These results demonstrate that TAM/Ms enhance the invasiveness of CD133(+) GSLCs via the release of TGF-β1, which increases the production of MMP-9 by GSLCs. Therefore, the TGF-β1 signaling pathway is a potential therapeutic target for limiting the invasiveness of GSLCs.
Objectives
Circular RNAs (circRNAs) exist extensively in the eukaryotic genome. The study aimed to identify the role of hsa_circ_0008365 (Circ‐SERPINE2) in gastric carcinoma (GC) cells and its ...downstream mechanisms.
Materials and methods
Gene Expression Omnibus (GEO) database was applied to screen differentially expressed circRNAs. CircInteractome, TargetScan and miRecords websites were used to predict target relationships. qRT‐PCR and RNase R treatment were utilised to detect molecule expression and confirm the existence of circ‐SERPINE2. RNA pull‐down assay and dual‐luciferase reporter assay were performed for interaction between circRNA and miRNA or mRNA. EdU assay, colony formation assay, and flow cytometry for apoptosis and cell cycle detections were utilised to assess cell function. Western blot and immunohistochemistry (IHC) assays were applied for detection of proteins in tissues or cells.
Results
Circ‐SERPINE2 and YWHAZ were upregulated, and miR‐375 was downregulated in GC tissues and cells. Circ‐SERPINE2 and YWHAZ targetedly bound to miR‐375. Circ‐SERPINE2 promoted cell proliferation and cell cycle progress and inhibited cell apoptosis by sponging miR‐375 and regulating YWHAZ expression in vitro. Circ‐SERPINE2 repressed solid tumour growth through enhancing miR‐375 expression and reducing YWHAZ expression in vivo.
Conclusions
Circ‐SERPINE2 is a novel proliferative promoter through the regulation of miR‐375/YWHAZ. Circ‐SERPINE2/miR‐375/YWHAZ axis might provide a novel therapeutic target of GC.
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