OBJECTIVE Epithelium-specific ETS 3 (Ese-3) is a member of the ETS family that is associated with tumor progression. However, there is little knowledge about Ese-3 in skin cancer. This study was conducted to explore the effects of Ese-3 on clinical prognosis in skin cancer and the functions of HaCaT cells. MATERIALS AND METHODS Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and three GSE datasets (GSE15605, GSE46517, and GSE114445). Comparison of data between groups was performed by Student's t-test and chi square test. Survival analysis was performed using log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models. Enrichment analysis was used to predict Ese-3 related functions. Cell proliferation assays, colony formation assays, and flow cytometry were used to assess cell proliferation, while Transwell assays analyzed cell migration and invasion. RESULTS Compared with normal tissues, the Ese-3 mRNA in cutaneous malignant melanoma (CMM) patients was downregulated (P<0.0001). Ese-3 mRNA was associated with the T stage (χ2=10.015, P=0.018), clinical stage (χ2=4.122, P=0.042), and prognosis in CMM patients (P=0.0219) and was an independent prognostic predictor in CMM (HR=1.878, P=0.048). Enrichment analysis showed that differentially expressed proteins were associated with protein kinase B (AKT) binding. CONCLUSION Ese-3 inhibited the proliferation, migration, and invasion of HaCaT cells by downregulating PSIP1 and NUCKS1 expression levels to inactivate the phosphorylation of AKT.
Relationship between innovation subsidies and corporate strategic choices has been extensively studied. Public innovation subsidies are by no means a certain value, existing in the form of an effective range instead. This means that the public innovation subsidies existing within the reasonable range can achieve the same incentive effect. So, what is the reasonable range or the effective boundaries of public innovation subsidies to promote enterprises that adopt cooperation strategies? There is no definite answer. Based on classical game theory, a stochastic evolutionary game model is proposed in this paper, which takes into account the influence of random disturbance on the strategy evolution process. An effective boundary of public innovation subsidy is provided as the main contribution based on a mature game scenario. A set of experimental data is subsequently selected as the sample for numerical simulation and result verification. The results showed that the probability of noncooperation within the effective value range will successfully converge to zero, which also means that the agents will adopt a collaborative cooperation strategy. The regulation effect of the combination of multiple variables is also discussed.
Real estate gives a huge impetus to the development of the national economy and surging housing prices can easily trigger social problems and financial risks. Considering housing price fluctuations, this study constructs a stochastic evolutionary game model from the perspective of the implicit interest coalitions among local governments, real estate enterprises, and speculators. The stable condition of the model is that local government, local governments decide to regulate, real estate enterprises select not to hype housing prices, and speculators choose not to buy houses. Through numerical simulation, this study finds that the supervision of central government and the regulatory strength of local governments can affect the choices of players differently, which gives a new explanation for the retaliatory rise of housing prices when local governments conduct regulation measures frequently. In addition, gray income, the punishment of hype, and the cost of speculation can make the strategic moves of players different in severity and direction under a stochastic environment. Based on these findings, countermeasures and suggestions are proposed in this study.
PSR B0919+06 generally radiates radio pulses in a normal phase range. It has been known for its occasional perplexing abnormal emission events wherein individual pulses come to an earlier phase range for a few tens of periods and then returns to its usual phase. Heretofore, only a few such events have been available for study. We observed PSR B0919+06 for about 30 hours using the Jiamusi 66-m telescope at Jiamusi Deep Space Station at S-band, and detected 92 abnormal emission events. We identify four types of events based on the abrupted or gradual phase-shifting of individual pulses. The abnormal emission events are seen to occur randomly some every 1000 to 3000 periods, and they affect the leading edge of the mean profile by up to 2\% in amplitude. The abnormal emission events are probably related to gradual changes of emission processing in the pulsar magnetosphere.
Innovation subsidy is of great significance to promoting enterprise innovation development. However, in recent years, the frequent occurrence of R&D subsidy deception in China has greatly reduced effectiveness of innovation. From the perspective of the strategic choice motivation of the innovation subject (including the enterprises, research institutions, and local governments), this paper constructs a multiplayer stochastic evolutionary game model. The influence of each variable on the subject strategy adoption is analyzed by simulation. There are two important findings in this paper. First, the paper confirms that there is an optimal boundary for the high subsidies received by enterprises and academic institutions, and the “subsidy boundary” is solved through the model. Second, this paper analyzes the effectiveness of the regulation of each variable through simulation and provides management and policy implications.
Pancreatic cancer (PAAD) is one of the most malignant cancers and immune microenvironment has been proved to be involved in pathogenesis of PAAD. m6A modification, related to the expression of m6A regulators, participates in the development of multiple cancers. However, the correlation between m6A regulators and immune microenvironment was largely unknown in PAAD. And because of the small sample size of pancreatic cancer in the TCGA database, it is not enough to draw a convincing conclusion. In the present study, we downloaded seven pancreatic cancer datasets with survival data and removed batch effects among these datasets to be used as the PAAD cohort to analyze the immune landscape of PAAD and the expression pattern of m6A regulators and divided the integrated dataset into cluster 1 and cluster 2 by consensus clustering for m6A regulators. Lower m6A regulators were found to be related to higher immune cell infiltration and a better survival. Moreover, we identified six m6A regulators and constructed the prognostic signature of m6A regulators. Patients with low-risk score had a higher response to immune checkpoint inhibitor and a longer overall survival. To figure out the underlying mechanism, we analyzed the cancer immunity cycle, most altered genes, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in risk subtypes. In summary, the present study proved m6A regulators modulated the PAAD immune microenvironment. And risk scores served as predictive indicator for immunotherapy and played a prognostic role for PAAD patients. Our study provided novel therapeutic targets to improve immunotherapy efficacy.
Indoor wireless communication systems have grown rapidly because of their clear advantages such as mobility, flexibility, and inexpensive network reconfiguration. In order to offer higher data rates approaching those provided by wired LANs, a combined OFDM/SDMA-based approach is an effective solution for increasing the system capacity and spectral efficiency. However, in multi-user environments, the system performance is limited by co-channel interference. Multi-input-multi-output (MIMO) smart antennas with prior knowledge of the channel at the transmitter is another promising technique for providing significant increase in system capacity and performance in wireless communication systems. We investigate the use of smart antennas at both the base and mobile stations, operating jointly, to maximize the SINR of each user before multiuser detection. By doing so, the performance of multi-user detection is significantly improved.
Abstract Background: Colorectal cancer (CRC) is one of the most malignant cancers and its pathological mechanism is largely unknown.Unfolded protein response and ferroptosis are both critical factors involved in CRC development. However, their relationship in CRC remains to be explored. Methods: In this study, erastin was used to induce ferroptosis in CRC cells. Cell viability and apoptosis were assessed by CCK-8 and colony formation assayand annexin V/propidium iodide staining, respectively. Ferroptosis was confirmed by the detection of glutathione, malondialdehyde, and lipid reactive oxygen species. Unfolded protein response-related proteins and GPX4 protein were analyzed by western blotting. The CRC datasetswere analyzed using the R software, GEPIA2 and TIMER2.0. Results: The results indicated that GPX4 was decreased when treated with the ferroptosis inducer erastin. As an intrinsic protective pathway, the unfolded protein response was activated and HSPA5 was increasedduring ferroptosis. HSPA5 was found to attenuateerastin-induced GPX4 decrease, repress ferroptosis, and promote CRC cell growth both in vitro and in vivo . Mechanistically, HSPA5 bounddirectly to GPX4 andthe interaction between HSPA5 and GPX4increased when treated with erastinfor a short time period. Although the HSPA5-GPX4 interaction failed to completely reverse erastin-induced GPX4 decrease, HSPA5 slowed down GPX4 degradation process and gave CRC cells more time to adjust to erastin toxicity. Additionally, HSPA5 was demonstrated to play a diagnostic role and correlated to immune microenvironment in CRC patients. Conclusion: Our study demonstrates that increased HSPA5 was an intrinsic protective strategy to resist ferroptosis. Specifically, HSPA5 restrained ferroptosis to promote colorectal cancer development by maintaining GPX4 stability. Our study provides potential diagnostic and therapeutic targets for patients with CRC.
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