Genetic alterations of the repressive ETS family transcription factor gene ETV6 are recurrent in several categories of hematopoietic malignancy, including subsets of B-cell and T-cell acute lymphoblastic leukemias (B-ALL and T-ALL), myeloid neoplasms, and mature B-cell lymphomas. ETV6 is essential for adult hematopoietic stem cells (HSCs), contributes to specific functions of some mature immune cells, and plays a key role in thrombopoiesis as demonstrated by familial ETV6 mutations associated with thrombocytopenia and predisposition to hematopoietic cancers, particularly B-ALL. ETV6 appears to have a tumor suppressor role in several hematopoietic lineages, as demonstrated by recurrent somatic loss-of-function (LoF) and putative dominant-negative alterations in leukemias and lymphomas. ETV6 rearrangements contribute to recurrent fusion oncogenes such as the B-ALL-associated transcription factor (TF) fusions ETV6::RUNX1 and PAX5::ETV6, rare drivers such as ETV6::NCOA6, and a spectrum of tyrosine kinase gene fusions encoding hyperactive signaling proteins that self-associate via the ETV6 N-terminal pointed domain. Another subset of recurrent rearrangements involving the ETV6 gene locus appear to function primarily to drive overexpression of the partner gene. This review surveys what is known about the biochemical and genome regulatory properties of ETV6 as well as our current understanding of how alterations in these functions contribute to hematopoietic and nonhematopoietic cancers.

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.

E74-like factor 3 (ELF3) is an important member of the E-twenty-six (ETS) transcription factor family. ELF3 is expressed in various types of cells and regulates a variety of biological behaviors, such as cell proliferation, differentiation, apoptosis, migration, and invasion, by binding to DNA to regulate the expression of other genes. In recent years, studies have shown that ELF3 plays an important role in the occurrence and development of many tumors and inflammation and immune related diseases. ELF3 has different functions and expression patterns in different tumors; it can function as a tumor suppressor gene or an oncogene, highlighting its dual effects of tumor promotion and inhibition. ELF3 also affects the levels of tumor immunity-related cytokines and is involved in the regulation and expression of multiple signaling pathways. In tumor therapy, ELF3 is a complex and multifunctional gene and has become a key focus of targeted treatment research. An in-depth study of the biological function of ELF3 can help to elucidate its role in biological processes and provide ideas and a basis for the development and clinical application of ELF3-related therapeutic methods. This review introduces the structure and physiological and cellular functions of the ELF3 gene, summarizes the mechanisms of action of ELF3 in different types of malignant tumors and its role in immune regulation, inflammation, etc., and discusses treatment methods for ELF3-related diseases, providing significant reference value for scholars studying the ELF3 gene and related diseases.

GGAA motifs in the human TP53 and HELB gene promoters play a part in responding to trans‑resveratrol (Rsv) in HeLa S3 cells. This sequence is also present in the 5\'‑upstream region of the human CDC45 gene, which encodes a component of CMG DNA helicase protein complex. The cells were treated with Rsv (20 µM), then transcripts and the translated protein were analyzed by quantitative RT‑PCR and western blotting, respectively. The results showed that the CDC45 gene and protein expression levels were induced after the treatment. To examine whether they were due to the activation of transcription, a 5\'‑upstream 556‑bp of the CDC45 gene was cloned and inserted into a multi‑cloning site of the Luciferase (Luc) expression vector. In the present study, various deletion/point mutation‑introduced Luc expression plasmids were constructed and they were used for the transient transfection assay. The results showed that the GGAA motif, which is included in a putative RELB protein recognizing sequence, plays a part in the promoter activity with response to Rsv in HeLa S3 cells.

This study examines the effects of China\'s carbon trading policy on firm emissions and explores its impact mechanisms through financial and physical asset investments. The empirical analysis utilizes a fuzzy regression discontinuity design based on a sample of 427 industrial firms in China between 2014 and 2019. The results indicate that China\'s carbon trading policy incentivized firms to increase their financial investments while simultaneously discouraging physical capital investments. These shifts in investment patterns helped firms achieve their emission reduction targets. The study reveals that carbon trading policy in China has contributed to the financialization of firms, resulting in the erosion of firm assets and a decline in their overall competitiveness. Based on these findings, some policy recommendations are put forward.

Background. Blood cannot be artificially manufactured, and there is currently no substitute for human blood. The supply of blood in transfusion facilities requires constant and timely collection of blood from donors. Modeling and forecasting trends in blood collections are critical for determining both the current and future capacity requirements and appropriate models of adequate blood provision. Objectives. The objective of this study is to determine blood collection or donation patterns and develop time-series models that can be updated and refined in predicting future blood donations in Zimbabwe when given the historical data. Materials and Methods. Monthly blood donation data for the period 2009 to 2019 were collected retrospectively from the National Blood Service Zimbabwe database. Time-series models (i.e., the Seasonal Autoregressive Integrated Moving Average [SARIMA] and Error, Trend and Seasonal [ETS]) models were applied and compared. The models were chosen because of their ability to handle the seasonality and other time-series components evident in the blood donation data. Expert opinions and experience were used in selecting the models and in making inferences in the analysis. Results. Time-series plots of blood donations showed seasonal patterns, with significant drops in blood donations in months associated with Zimbabwe\'s school holidays (April, August, and December) and public holidays. During these holidays, there is a reduced number of school donors, while at about the same time, there is increasing blood demand as a result of road accidents. Model identification procedures established the SARIMA(1,1,2)(0,1,1)12 model as the appropriate model for forecasting total blood donation in Zimbabwe. The results and forecasts show an upward trend in blood donations. According to the accuracy measures used, the SARIMA model outperforms the ETS model. Conclusions. Expert knowledge in the blood donation process, coupled with statistical models, can help explain trends exhibited in blood donation data in Zimbabwe. These findings help the blood authorities plan for blood donor campaign drives. The findings are key indicators of where to allocate more resources toward blood donation and when to collect more blood units. The increasing blood donation projections ensure a stable blood bank inventory in the near future.
UNASSIGNED: A SARIMA model can be used to predict the flow of blood donations in Zimbabwe.The seasonal blood donation pattern peaks in the months of March, June/July, and September.The donations troughs are in the months of April, August, December, and January. These are the months coinciding with school holidays in Zimbabwe.Both the SARIMA and ETS models provided similar forecasts, but measures of fit and expert knowledge gave a slight preference to the SARIMA(1,1,2)(0,1,1)12 model in predicting the flow of blood donations in Zimbabwe.These model results are useful for guiding allocation of blood donation resources and blood donation drive timing.

Certain nations have opted for stimulus-based regulations to curtail emissions, build a liveable, environmentally friendly setting, and work towards aspirational mitigation targets. New Zealand (NZ) prefers an Emission Trading Scheme (ETS) to taxation, mitigating emissions on one hand while retaining incentives for economic growth on the other. As a result, NZ has initiated a legal framework since 2008 to allow its economic sectors to engage in ETS and minimize emissions. Yet, selecting the appropriate sectors and effectively adjusting sector-specific regulations remain critical and complex challenges in the global design of ETS since both excessive and insufficient intervention can lead to inefficiencies in the system\'s functioning. Therefore, this study begins validating the NZ ETS\'s abatement potential regarding sectoral carbon intensity by executing the double machine learning techniques, consolidating the ETS efficacy that has robustly mitigated sectoral carbon intensity in NZ during 2006-2020. However, this conclusion seems invalid at the disaggregated level when focusing on forward-backward linkages, where NZ\'s input-output tables furnish a compelling scenario of sectoral dependencies and the products (residuals) they provide. Altogether, the regulatory requirements are either too strict or too lax, leaving out five of the 24 (as a whole) key sectors. Rather, the ETS could be powerful, providing these five key sectors are well tackled, necessitating a reformulation of the ongoing ETS regulatory regime.

Noncoding mutation hotspots have been identified in melanoma and many of them occur at the binding sites of E26 transformation-specific (ETS) proteins; however, their formation mechanism and functional impacts are not fully understood. Here, we used UV (Ultraviolet) damage sequencing data and analyzed cyclobutane pyrimidine dimer (CPD) formation, DNA repair, and CPD deamination in human cells at single-nucleotide resolution. Our data show prominent CPD hotspots immediately after UV irradiation at ETS binding sites, particularly at sites with a conserved TTCCGG motif, which correlate with mutation hotspots identified in cutaneous melanoma. Additionally, CPDs are repaired slower at ETS binding sites than in flanking DNA. Cytosine deamination in CPDs to uracil is suggested as an important step for UV mutagenesis. However, we found that CPD deamination is significantly suppressed at ETS binding sites, particularly for the CPD hotspot on the 5\' side of the ETS motif, arguing against a role for CPD deamination in promoting ETS-associated UV mutations. Finally, we analyzed a subset of frequently mutated promoters, including the ribosomal protein genes RPL13A and RPS20, and found that mutations in the ETS motif can significantly reduce the promoter activity. Thus, our data identify high UV damage and low repair, but not CPD deamination, as the main mechanism for ETS-associated mutations in melanoma and uncover important roles of often-overlooked mutation hotspots in perturbing gene transcription.

Seasonal influenza is a serious public health issue in China. This study aimed to develop a new hybrid model for seasonal influenza incidence prediction and provide reference information for early warning management before outbreaks.
Data on the monthly incidence of seasonal influenza between 2004 and 2018 were obtained from the China Public Health Science Data Center website. A single seasonal autoregressive integrated moving average (SARIMA) model and a single error trend and seasonality (ETS) model were built. On this basis, we constructed SARIMA, ETS, and support vector regression (SARIMA-ETS-SVR) hybrid model. The prediction performance was determined by comparing mean absolute error (MAE), mean square error (MSE), mean absolute percentage error (MAPE), and root mean square error (RMSE) indices.
The optimum SARIMA model was SARIMA (0,1,0) (0,0,1)12. Error trend and seasonality (ETS) (M,A,M) was the SARIMA optimal model. For the fitting performance, the SARIMA-ETS-SVR hybrid model achieved the lowest values of MAE, MSE, and RMSE, in addition to the MAPE. In terms of predictive performance, the SARIMA-ETS-SVR hybrid model had the lowest MAE, MSE, MAPE, and RMSE values among the three models.
The study demonstrated that the SARIMA-ETS-SVR hybrid model provides better generalization ability than a single SARIMA model and a single ETS model, and the predictions will provide a useful tool for preventing this infectious disease.

BACKGROUND: ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking.
RESULTS: The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation.
CONCLUSIONS: Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.