Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAM) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer invasion and metastasis ...by inducing TAM infiltration remains unclear. In the current study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and colorectal cancer invasion and the underlying mechanism in colorectal cancer cells by overexpressing or silencing PRL-3. We found that PRL-3 upregulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. In addition, IHC analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV colorectal cancer tissues and were associated with a worse prognosis in colorectal cancer patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were cocultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca
of TAMs to increase the expression of IL6 and IL8. In addition, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV colorectal cancer tissues and correlated with CCL26. Moreover, similar results were observed
using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes colorectal cancer invasion and metastasis by upregulating CCL26 to induce TAM infiltration.
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Discovering Out-of-Domain (OOD) intents is essential for developing new skills in a task-oriented dialogue system. Previous methods suffer from poor knowledge transferability from in-domain (IND) ...intents to OOD intents, and inefficient iterative clustering. In this paper, we propose an efficient unified contrastive learning framework to discover OOD intents, bridging the gap between IND pre-training stage and OOD clustering stage. Specifically, we employ a supervised contrastive learning (SCL) objective to learn discriminative pre-trained intent features for clustering. And we introduce an efficient end-to-end contrastive clustering method to jointly learn representations and cluster assignments. Besides, we propose an adaptive contrastive learning (ACL) method to automatically adjust the weights of different negative sample pairs for a given anchor according to their semantic similarities. Extensive experiments on two benchmark datasets show that our method is more robust and achieves substantial improvements over the state-of-the-art methods.
How to improve resource utilization of cloud data centers (CDCs) and ensure users’ quality of service (QoS) through efficient virtual machine (VM) scheduling is an urgent problem. Especially when ...service reliability is taken into consideration, the problem becomes more challenging. However, existing related researches mostly ignore the influence of reliability factors, such as failures and recoveries of computing nodes (CNs), which cannot reflect the realistic situations of real-life CDCs. Therefore, this paper investigates the problem of fault tolerance-aware VM scheduling and formulates it as a multi-objective optimization model with multiple QoS constraints. The proposed model tries to minimize users’ total expenditure and, at the same time, maximize the successful execution rate of their businesses. To solve the proposed optimization model, a greedy-based best fit decreasing (GBFD) algorithm is then developed. The GBFD algorithm adopts a cost efficiency factor whose definition is according to the characteristics of CNs, to select a suitable CN for each VM request. Finally, extensive experiments are conducted to verify the feasibility of the proposed models and algorithm based on both the real-world CDC cluster data sets and the simulation ones. The results show that, first, as expected, fault tolerance significantly influences the performance criteria of VM scheduling and second, in most cases, the developed algorithm can decrease users’ expenditure, increase success rate for executing their business and improve their overall satisfactions. Specifically, under real-world CDC cluster scenario, GBFD algorithm can increase the overall satisfaction of all cloud users by 38.3%, 20.9% and 14.6%, respectively, compared with the other three ones. Thus, the developed algorithm can perform better under fault tolerance-aware cloud environments.
To handle user requests coming from all over the world, online services need to schedule resources to fulfill the corresponding stochastic demands for various resources in geo-distributed data ...centers. In order to make full use of the advantages of cloud resources and tap the potential of private infrastructure, the optimal schedule plan should consider the heterogeneity of different kinds of data centers. It results in a highly complex non-linear programming problem. To find efficient solutions, we introduce a related and simple problem to quickly obtain a feasible solution close to optimal one, and then leverage a differential evolution process with special steps to solve it quickly. By testing the algorithm using simulated and realistic data, we find that our algorithm outperforms the existing algorithms and can increase the revenue by more than 34%.
Introduction Neuroendocrine differentiation (NED) in colorectal cancer (CRC) cells has been known for decades, and our previous meta-analysis indicated that CRC patients with neuroendocrine ...differentiation have a lower 5-year survival rate. In recent years, an increasing number of studies have found that exosome-derived long non-coding RNAs (lncRNAs) play important roles in cancer progression and metastasis. However, the functions and mechanism of exosome-derived lncRNAs in CRC with neuroendocrine differentiation are not yet fully clear. Materials and methods The clinical significance of NED was assessed in a retrospective study of 105 patients. Next-generation sequencing and bioinformatics analysis were conducted to select lnc-HOXB8-1:2 for further study. Using immunohistochemistry, qRT-PCR, western blot, transwell assay, immunofluorescence assay, fluorescence in situ hybridization assay and dual-luciferase reporter assay, the oncogenic role of exosome-derived lnc-HOXB8-1:2 was determined in CRC with NED. The mechanism underlying the lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was also explored. Results NED was a risk factor for the progression and mortality of CRC. lnc-HOXB8-1:2, derived from exosomes secreted by neuroendocrine differentiated colon cancer cells, was identified in our study. The proportion of M2 macrophages and the migration and invasion capacities of tumor-associated macrophages (TAMs) markedly increased after the addition of neuroendocrine differentiated CRC cell-derived exosomes. More excitingly, the expression of lnc-HOXB8-1:2 and the protein level of CXCR3 were also upregulated in TAMs. The lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was predicted via miRanda software and confirmed by the dual-luciferase reporter assay. Furthermore, the increased expression of lnc-HOXB8-1:2 was accompanied by downregulation of hsa-miR-6825-5p expression and upregulation of CXCR3 protein levels. Overexpression of hsa-miR-6825-5p also reduced CXCR3 expression. Conclusion lnc-HOXB8-1:2 in exosomes derived from neuroendocrine differentiated CRC cells acted as a ceRNA competitively binding hsa-miR-6825-5p to upregulate CXCR3 expression and leading to TAM infiltration and M2 polarization, which promotes neuroendocrine differentiated CRC progression. Keywords: Colorectal cancer, Neuroendocrine differentiation, Exosome, lnc-HOXB8-1:2, Tumor-associated macrophage
The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying ...molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification.
Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver.
We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC.
CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC.
Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which ...promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear.
Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET.
In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells.
MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.
Tumor-associated macrophages (TAMs) are known to promote cancer progression and metastasis through the release of a variety of cytokines. Phosphatase of regenerating liver (PRL-3) has been considered ...as a marker of colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL-3 can enhance the metastasis of CRC through the up-regulation of intermediate-conductance Ca2+-activated K+ (KCNN4) channel, which is dependent on the autocrine secretion of tumor necrosis factor-alpha (TNF-α). However, whether TAMs participate in the progression and metastasis of CRC induced by PRL-3 remains unknown.
We used flow cytometry, coculture, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, and immunofluorescence staining to determine the effect of TAMs on the ability of PRL-3 to promote invasiveness of CRC cells.
In this study, we found that TAMs facilitated the metastasis of CRC induced by PRL-3. When TAMs were cocultured with CRC cells, the expression of KCNN4 was increased in TAMs and the invasion of CRC cells was enhanced. Furthermore, cytokines that were secreted by TAMs, such as IL-6 and IL-8, were also significantly increased. This response was attenuated by treating TAMs with the KCNN4 channel-specific inhibitor, 1-(2-chlorophenyl) diphenylmethyl-1H-pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell invasiveness. Moreover, the expression of KCNN4 channels in TAMs was regulated through the NF-κB signal pathway, which is activated by TNF-α from CRC cells. Immunofluorescence analysis of colorectal specimens indicated that IL-6 and IL-8 double positive cells in the stroma showed positive staining for the TAM marker CD68, suggesting that TAMs produce IL-6 and IL-8. Increased numbers of these cells correlated with higher clinical stage.
Our findings suggested that TAMs participate in the metastasis of CRC induced by PRL-3 through the TNF-α mediated secretion of IL-6 and IL-8 in a paracrine manner.
With the rapid development of technology, people’s demand for energy is increasing day by day. Many energy devices electric vehicles and other technological products require high-energy lithium ...secondary batteries to operate. Higher electrochemical energy per unit volume and lower manufacturing cost than lithium batteries are the characteristic advantages of lithium sulfur (LiS) batteries. At the same time, it is environmentally friendly. The global reserves of elemental sulfur are also very abundant, and the cost is low. Therefore, LiS batteries have become one of the most promising secondary batteries in the future. However, LiS batteries also suffer from issues such as poor conductivity of the active substance sulfur, shuttle effect, volume expansion, and lithium dendrites. Research has found that the application of composite materials of metal compounds and sulfur in the cathode of LiS batteries can effectively limit the shuttle effect and poor conductivity of LiS batteries. It can effectively adsorb polysulfides generated in the reaction, optimize the electric performance of cathode sulfur, strengthen the rate performance and cycle stability of lithium ion battery, as well as reduce capacity degradation, significantly improving their electrochemical performance. This article reviews the research progress on the application of metal compounds, mainly metal oxides and metal sulfides, in the cathode of LiS batteries. It explores how this application can suppress shuttle effects and slow down capacity degradation and summarizes and looks forward to its development.
Abstract
In modern society, artificial intelligence (AI) is developing more rapidly. And the Field Programmable Gate Array (FPGA) has always been the focus of research as a driving platform. This ...paper studies in detail the theoretical basis, applications, defects, and future development directions of FPGAs. It is concluded that FPGA has three characteristics: gate array, programmable, and scene, and the detailed positioning of FPGA, the structure, principle, tools, process, and description language of FPGA design. And the unique advantages of FPGA in the field of artificial intelligence: flexible and configurable, special optimizations for convolutional neural networks, and deterministic low latency. Several typical applications of FPGA in the field of artificial intelligence, deficiencies and solutions, and two future development directions. This article will make a great contribution to the development of FPGA in the field of artificial intelligence in the future.
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