Vav1-dependent Rac1 activation mediates hypoxia-induced gemcitabine resistance in pancreatic ductal adenocarcinoma cells through upregulation of HIF-1α expression.

Hypoxia has been shown to induce gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC) cells, however, the underlying mechanisms remain to be clarified. In the present study, we investigated whether activation of Vav1/Rac1/HIF-1α axis is responsible for hypoxia-induced GEM resistance in PDAC cells. Our results showed that Rac1 activation contributed to hypoxia-induced GEM resistance in PANC-1 cells. Hypoxia treatment led to an increased expression level of Vav1, which was responsible for Rac1 activation and GEM resistance in PDAC cells. Furthermore, Rac1 mediated hypoxia-induced GEM resistance by upregulating HIF-1α in PDAC cells. Taken together, these findings suggest that hypoxia induces GEM resistance in PDAC cells by activating the Vav1/Rac1/HIF-1α signaling pathway.

A Consortium Blockchain-Based Agricultural Machinery Scheduling System.

The introduction of a consortium blockchain-based agricultural machinery scheduling system will help improve the transparency and efficiency of the data flow within the sector. Currently, the traditional agricultural machinery centralized scheduling systems suffer when there is a failure of the single point control system, and it also comes with high cost managing with little transparency, not leaving out the wastage of resources. This paper proposes a consortium blockchain-based agricultural machinery scheduling system for solving the problems of single point of failure, high-cost, low transparency, and waste of resources. The consortium blockchain-based system eliminates the central server in the traditional way, optimizes the matching function and scheduling algorithm in the smart contract, and improves the scheduling efficiency. The data in the system can be traced, which increases transparency and improves the efficiency of decision-making in the process of scheduling. In addition, this system adopts a crowdsourcing scheduling mode, making full use of idle agricultural machinery in the society, which can effectively solve the problem of resource waste. Then, the proposed system implements authentication access mechanisms, and allows only authorized users into the system. It includes transactions based on digital currency and eliminates third-party platform to charge service fees. Moreover, participating organizations have the opportunity to obtain benefits and reduce transaction costs. Finally, the upper layers supervision improves the efficiency and security of consensus algorithm, allows supervisors to block users with malicious motives, and always ensures system security.

Using Machine Learning Methods to Provision Virtual Sensors in Sensor-Cloud.

The advent of sensor-cloud technology alleviates the limitations of traditional wireless sensor networks (WSNs) in terms of energy, storage, and computing, which has tremendous potential in various agricultural internet of things (IoT) applications. In the sensor-cloud environment, virtual sensor provisioning is an essential task. It chooses physical sensors to create virtual sensors in response to the users' requests. Considering the capricious meteorological environment of the outdoors, this paper presents an measurements similarity-based virtual-sensor provisioning scheme by taking advantage of machine learning in data analysis. First, to distinguish the changing trends, we classified all the physical sensors into several categories using historical data. Then, the k-means clustering algorithm was exploited for each class to cluster the physical sensors with high similarity. Finally, one representative physical sensor from each cluster was selected to create the corresponding virtual sensors. The experimental results show the reformation of our scheme with respect to energy efficiency, network lifetime, and data accuracy compared with the benchmark schemes.

Downregulation of SLC5A8 inhibits hepatocellular carcinoma progression through regulation of Wnt/ß-catenin signaling.

SLC5A8 has been shown to be associated with a large number of cancer progressions. However, the biological functions of SLC5A8 in hepatocellular carcinoma (HCC) remain largely unclear. Therefore, we performed this research to explore the functions of SLC5A8 in HCC progression. In this study, SLC5A8 protein and mRNA expression were examined by immunohistochemistry and quantitative real-time PCR, respectively, and we found significantly lower expression levels in HCCs than in the corresponding normal liver tissues. Low SLC5A8 expression was significantly correlated with the clinicopathological features of HCC patients. Patients with low SLC5A8 expression have a shorter overall survival time. This interpretation is confirmed by the results obtained from our in vitro experiments; functional assays indicated that overexpression of SLC5A8, by infection with a recombinant plasmid containing SLC5A8, significantly suppressed HCC cell growth, invasion, and migration and induced HCC cell apoptosis. Moreover, the expression levels of beta-catenin, cyclin D1, c-Myc, MMP-2, and FAK detected by western blotting were downregulated in SLC5A8-transfected HCC cells compared with control-transfected cells, indicating that SLC5A8 has a tumor-suppressive function that acts by interfering with Wnt/ß-catenin signaling in HCC.

Linc00662 m6A promotes the progression and metastasis of pancreatic cancer by activating focal adhesion through the GTF2B-ITGA1-FAK pathway.

Recurrence and metastasis are major factors associated with the poor prognosis of pancreatic cancer (PC). Previous studies have indicated that METTL3-mediated N6-methyladenosine (m6A) modification is closely associated with PC progression and prognosis. However, its underlying regulatory mechanisms remain unclear. In this study, we found that METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC. Linc00662 was screened as a m6A-enriched RNA that promoted tumor growth and metastasis in PC cells and mouse models and was associated with poor clinical prognosis. Four m6A motifs were identified in Linc00662, which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo. ITGA1 was identified as a downstream gene regulated by Linc00662. Linc00662 recruites GTF2B to activate the transcription of ITGA1 in a m6A-dependent manner and initiates the formation of focal adhesions through the ITGA1-FAK-Erk pathway, thereby promoting malignant behavior in PC cells. The FAK inhibitor-Y15 obviously repressed tumor progression in Linc00662-overexpressing PC cells in vitro and in vivo. This study proposes a novel regulatory mechanism of Linc00662 in oncogene activation in PC and indicates that Linc00662 and its downstream genes are potential targets for PC therapy.

ACTR3 promotes cell migration and invasion by inducing epithelial mesenchymal transition in pancreatic ductal adenocarcinoma.

BACKGROUND: Recurrence and metastasis are the major causes of pancreatic ductal adenocarcinoma (PDAC) mortality after treatment. The underlying molecular mechanism is poorly understood. Actin-related protein 3 (ACTR3) is an important component of the actin-related protein 2/3 complex, which is involved in the regulation of cell motility and epithelial mesenchymal transition (EMT) process. Previously published studies have indicated that ACTR3 expression is upregulated in several types of cancers, and promotes tumor development, including gastric cancer and hepatocellular carcinoma. However, to date, the expression levels and the role of ACTR3 in PDAC are not well understood. METHODS: In the present study, the expression levels of ACTR3 in PDAC tissue and the relationship of ACTR3 expression with clinical prognosis were analyzed by mRNA microarray and bioinformatics. The biological functions and underlying mechanism of ACTR3 in PDAC were examined by a series of assays, including Cell Counting Kit-8 (CCK-8), transwell assay, and Western blotting. RESULTS: We found that the expression of ACTR3 was significantly increased in PDAC tissues and cell lines. A higher expression of ACTR3 was predictive of poor outcome for patients with PDAC. In vitro, the knockdown of ACTR3 expression significantly inhibited the invasive and migratory capacity of PDAC cells, and altered the distribution of F-actin and the expression of EMT markers. CONCLUSIONS: The findings of our study indicated that ACTR3 promotes cell migration and invasion by inducing EMT in PDAC, which may be a potential therapeutic target and prognostic indicator for PDAC patients.

Dendritic cell vaccine for the effective immunotherapy of breast cancer.

Cancer vaccine is widely considered as a powerful tool in immunotherapy. In particular, the effective antigen processing and presentation natures of dendritic cell (DC) have made it a promising target for the development of therapeutic vaccine for cancer treatment. Here in our study, a versatile cancer cell membrane (CCM) coated calcium carbonate (CC) nanoparticles (MC) that capable of generating in situ tumor-associated antigens (TAAs) for DC vaccination is developed. Low-dose doxorubicin hydrochloride (Dox) could be encapsulated in the CC core of MC to trigger immunogenic cell death (ICD) while chlorins e6 (Ce6), a commonly adopted photosensitizer, was loaded in the CCM of MC for effective photodynamic therapy (PDT) through the generation of reactive oxygen species (ROS) to finally construct the vaccine (MC/Dox/Ce6). Most importantly, our in-depth study revealed the treatment of MC/Dox/Ce6 was able to elicit TAAs population and DC recruitment, triggering the following immune response cascade. In particular, the recruited DC cells could be stimulated in situ for effective vaccinations. Both in vitro and in vivo experiments suggested the capability of this all-in-one DDS to enhance DCs maturation to finally result in effective inhibition of both primary and distant growth of breast cancer upon single administration of low dose Dox and Ce6.