No abstract

Objective. In the development of many tumors, IPO5, as a member of the nuclear transporter family, exerts a significant function. Also, IPO5 is used as a therapeutic target for tumors based on some reports. By studying IPO5 expression in esophageal cancer tissues, the mechanism associated with IPO5 improving esophageal cancer development was explored in this study. Methods. To gain differentially expressed genes, this study utilized mRNA microarray and TCGA database for comprehensive analysis of esophageal cancer tissues and normal esophageal cancer tissues, and then the differentially expressed gene IPO5 was screened by us. To assess esophageal cancer patients’ prognosis, this study also applied the Kaplan-Meier analysis, and we also conducted the GSEA enrichment analysis to investigate IPO5-related signaling pathways. This study performed TISIDB and TIMER online analysis tools to study the correlation between IPO5 and immune regulation and infiltration. We took specimens of esophageal cancer from patients and detected the expression of IPO5 in tumor and normal tissues by immunohistochemistry. The IPO5 gene-silenced esophageal cancer cell model was constructed by lentivirus transfection. Through the Transwell invasion assay, CCK-8 assay, and cell scratch assay, this study investigated the effects of IPO5 on cell propagation, invasion, and transfer. What is more, we identified the influences of IPO5 on the cell cycle through flow cytometry and established a subcutaneous tumor-forming model in nude mice. Immunohistochemistry was used to verify the expression of KI-67, and this study detected the modifications of cell pathway-related proteins using Western blot and applied EMT-related proteins to explain the mechanism of esophageal cancer induced by IPO5. Results. According to database survival analysis, IPO5 high-expression patients had shorter disease-free survival than IPO5 low-expression patients. Compared to normal tissues, the IPO5 expression in cancer tissues was significantly higher in clinical trials ( P < 0.05 ). Through TISIDB and TIMER database studies, we found that IPO5 could affect immune regulation, and the age of IPO5 expression grows with the increase of immune infiltration level. The IPO5 expression in esophageal cancer cells was higher than normal, especially in ECA109 and OE33 cells ( P < 0.01 ). After knocking out IPO5 gene expression, cell proliferation capacity and invasion capacity were reduced ( P < 0.05 ) and decreased ( P < 0.01 ) in the IPO5-interfered group rather than the negative control group. The growth cycle of esophageal carcinoma cells was arrested in the G2/M phase after IPO5 gene silencing ( P < 0.01 ). Tumor-forming experiments in nude mice confirmed that after IPO5 deletion, the tumor shrank, the expression of KI67 decreased, the downstream protein expression level of the RAS pathway decreased after sh-IPO5 interference ( P < 0.01 ), and the level of EMT marker delined ( P < 0.05 ). Conclusion. In esophageal cancer, IPO5 is highly expressed and correlates with survival rate. Esophageal cancer cell growth and migration were significantly affected by the inhibition of IPO5 in vitro and in vivo. IPO5 mediates EMT using the RAS-ERK signaling pathway activation and promotes esophageal cancer cell development in vivo and in vitro.

No abstract

Ticks are notorious ectoparasites and transmit the greatest variety of pathogens than any other arthropods. Cold tolerance is a key determinant of tick abundance and distribution. While studies have shown that DNA methylation is one of the important epigenetic regulations found across many species and plays a significant role in their response to low-temperature stress, its role in the response of ticks to low-temperature stress remains unexplored. Herein, we explored the DNA methylation profile of the tick, Haemaphysalis longicornis, exposed to low-temperature stress (4 °C) using whole-genome bisulfite sequencing (WGBS). We found that approximately 0.95% and 0.94% of the genomic C sites were methylated in the control and low-temperature groups, respectively. Moreover, the methylation level under the CG context was about 3.86% and 3.85% in the control and low-temperature groups, respectively. In addition, a total of 6087 differentially methylated regions (DMRs) were identified between the low-temperature and control groups, including 3288 hypermethylated and 2799 hypomethylated DMRs. Further, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially methylated genes revealed that most of the DMGs were significantly enriched in binding and RNA transport pathways. Taken together, this research confirmed, for the first time, the whole genome DNA methylation profile of H. longicornis and provided new insights into the DNA methylation changes relating to low-temperature stress in H. longicornis, as well as provided a foundation for future studies on the epigenetic mechanism underlying the responses of ticks to abiotic stress.

In recent years, many countries have faced severe economic challenges due to the worldwide outbreak of the covid-19. In July 2022, Sri Lanka officially declared bankruptcy. Now, the declining tourism industry caused by the epidemic, unrealistic agricultural reform bills, severe debt crisis, and the failure of religious politics have directly affected the economic health and sustainability of the country. Every country must think about better solutions to overcome the economic crisis during the worldwide pandemic. This paper will use data analysis and logical reasoning to better explore the complex reasons behind the fact. Through research, this paper draws the following conclusions: Firstly, the bankruptcy of Sri Lanka is mainly related to the debt crisis, among which high inflation and civil war have declined the debt repayment ability. Secondly, the external situation and the wrong decision of the Sri Lankan government are the last straw for oppressing the country.