Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus

Background/Aims: Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase that mediates cell cycle regulation and metabolism. Mounting evidence has indicated that PP2A inhibition exhibits considerable anticancer potency in multiple types of human cancers. However, the efficacy of PP2A inhibition remains unexplored in mucoepidermoid carcinoma (MEC), especially in locally advanced and metastatic cases with limited systemic treatment. In this study, we demonstrated the therapeutic potency of LB100 in mucoepidermoid carcinoma. Methods: In this study, the expression of PP2A was evaluated using immunohistochemical (IHC) staining. The effects associated with LB100 alone and in combination with cisplatin for the treatment of mucoepidermoid carcinoma were investigated both in vitro, regarding metabolism, proliferation, and migration, and in vivo in a mucoepidermoid carcinoma xenograft model. In addition, with LB100 treatment and in response to an insulin stimulus, the expression levels and phosphorylation levels of targets in the PI3K-AKT pathway were determined using western blot analysis and immunoblotting. Results: The expression of protein phosphatase 2A was significantly upregulated in the clinical specimens of high-grade MECs compared with those of low-/medium-grade MECs and normal controls. In this article, we report that a small molecule PP2A inhibitor, LB100, decreased cellular viability and glycolytic activity and induced G2/M cell cycle arrest. Importantly, LB100 enhanced the efficacy of cisplatin in mucoepidermoid carcinoma cells both in vitro and in vivo. PP2A inhibition by LB100 increased the phosphorylation of insulin receptor substrate 1(IRS-1) on serine residues, downregulated the expression of phosphatidylinositol 3-kinase (PI3K) p110 alpha subunit and dephosphorylated AKT at Ser473 and Thr308 in mucoepidermoid carcinoma cells in response to insulin stimulus. Conclusion: These results highlight the translational potential of PP2A inhibition to synergize with cisplatin in mucoepidermoid carcinoma treatment

Tumor-Initiating Cells Are Enriched in CD44hi Population in Murine Salivary Gland Tumor

Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44high (CD44hi) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44hi tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a lower rate than their CD44negative (CD44neg) counterparts, and also retained BrdU for a long period of time. Cell surface maker analysis revealed that 25% of the CD44hi tumor cells co-express other cancer stem cell markers such as CD133 and CD117. As few as 500 CD44hi tumor cells were sufficient to initiate pleomorphic adenomas in one third of the wildtype mice, whereas more than 1×104 CD44neg cells were needed for the same purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81–96 in the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for CD44 upregulation

Peregrine and saker falcon genome sequences provide insights into evolution of a predatory lifestyle

As top predators, falcons possess unique morphological, physiological and behavioral adaptations that allow them to be successful hunters: for example, the peregrine is renowned as the world's fastest animal. To examine the evolutionary basis of predatory adaptations, we sequenced the genomes of both the peregrine (Falco peregrinus) and saker falcon (Falco cherrug), and we present parallel, genome-wide evidence for evolutionary innovation and selection for a predatory lifestyle. The genomes, assembled using Illumina deep sequencing with greater than 100-fold coverage, are both approximately 1.2 Gb in length, with transcriptome-assisted prediction of approximately 16,200 genes for both species. Analysis of 8,424 orthologs in both falcons, chicken, zebra finch and turkey identified consistent evidence for genome-wide rapid evolution in these raptors. SNP-based inference showed contrasting recent demographic trajectories for the two falcons, and gene-based analysis highlighted falcon-specific evolutionary novelties for beak development and olfaction and specifically for homeostasis-related genes in the arid environment–adapted saker

Preparation of Fe-Doped TiO2 Nanotubes and Their Photocatalytic Activities under Visible Light

Fe-doped TiO2 nanotubes (Fe-TNTs) have been prepared by ultrasonic-assisted hydrothermal method. The structure and composition of the as-prepared TiO2 nanotubes were characterized by transmission electron microscopy, X-ray diffraction, and UV-Visible absorption spectroscopy. Their photocatalytic activities were evaluated by the degradation of MO under visible light. The UV-visible absorption spectra of the Fe-TNT showed a red shift and an enhancement of the absorption in the visible region compared to the pure TNT. The Fe-TNTs were provided with good photocatalytic activities and photostability and under visible light irradiation, and the optimum molar ratio of Ti : Fe was found to be 100 : 1 in our experiments

Disentangling the relative roles of natural and anthropogenic-induced stressors in shaping benthic ciliate diversity in a heavily disturbed bay

Coastal areas are facing biodiversity loss and degradation of habitats due to intensified human activities. However, our understanding of the relative contribution of natural gradients and human induced disturbance to biodiversity is limited. Here, we investigated the response of three facets of alpha and beta diversity of benthic ciliates to environmental gradients in a highly disturbed estuarine bay in China. We used linear regression and distance-based redundancy analysis to determine the key driving factors for biodiversity. Variation partitioning was further used to examine the relative influence of natural gradients and anthropogenic disturbances on ciliate communities. Our results revealed that ciliate alpha diversity and functional composition remained similar de-spite notable variation in species composition along salinity gradient. Sediment grain size, together with heavy metals were the strongest determinants in shaping both alpha and beta diversity. After controlling for the effect of natural factors, heavy metals still had significant impacts on beta diversity. Human induced nitrogen enrich-ment was positively correlated with algivorous functional group with possible impacts on benthic food webs. These results suggest that beta diversity is overall more sensitive to anthropogenic stressors than alpha diversity and give important insights into the role of anthropogenic disturbance on coastal diversity, being also useful for developing ecosystem protection and conservation strategies. (c) 2021 Elsevier B.V. All rights reserved.Peer reviewe

Analysis of temperature field of grain and drying medium for grain drying integrated mechanical device.

In order to improve the working efficiency of the drying tower and the hot blast stove in the process of grain drying, this paper proposes a method to solve the problems of air pollution and energy waste caused by excessive combustion or insufficient combustion of the hot blast stove. Based on finite element analysis, this paper uses ANSYS software to simulate the drying process of grain. This paper briefly introduces the grain drying device model and working mechanism, analyzes the temperature field of the drying device, and studies the influence on the drying effect of the working parameters (hot water, hot air, hot air hot blast stove combustion temperature) during the grain drying process. The results show that the hot air temperature is 85°C, the hot water temperature is 90°C, the combustion chamber temperature is 480°C, the grain drying effect is good, the combustion efficiency of the combustion furnace is the best, and the energy utilization rate is the highest

Biological Evaluation of Water Quality for Benthos in Typical Rivers of Eastern Jilin Province

Benthos are aquatic organisms living at the bottom of water bodies for all or most of their life history. Apart from the settled and moving living, their forms of habitat are mostly attached to the hard substrate like rocks or soft bases such as mud and sand. In addition, there are benthic species that attach to the plant surfaces or other benthic animals, and inhabit the intertidal zone. In terms of feeding methods, most benthic animals feed on suspended matter and sediment. Most of them are invertebrates and are a complex ecological group. According to the size, they can be divided into macrobenthos and meio-benthos [1]. Benthos are an important part of the water ecosystem. Using a typical river (Gaya River) in eastern Jilin Province, this paper analyzed the water quality, the components of benthic organisms and their biological density through sampling surveys of three typical locations in the upper, middle and lower reaches of the Gaya River. In addition, it made a biological evaluation of the water quality of the Gaya River

Spatial-Temporal Variation Characteristics and Cause Analysis of Water Quality in Yinma River Basin

In order to comprehensively understand the water quality in Yinma River Basin, and to analyze the spatial-temporal variation characteristics of water quality over the years and the causes of water pollution, 15 sections were selected in the Yinma River Basin. Based on the water quality monitoring data in the past decade, 7 evaluation indexes including dissolved oxygen (DO), 5-day biochemical oxygen demand (BOD5), permanganate index (CODMN), chemical oxygen demand (COD), ammonia nitrogen (NH4-N), total phosphorus (TP) and total nitrogen (TN) were determined, according to the Environmental Quality Standard for Surface Water (GB3838-2002) and the historical monitoring data of rivers. The water quality of 15 sections in Yinma River Basin was comprehensively evaluated, and the water quality categories and the evolution of river water quality were analyzed. The pollution sources of Yinma River Basin were analyzed, and the constructive countermeasures were put forward according to the conclusions