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.

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.

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.

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.

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.

Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.

BACKGROUND: Ajania Poljakov, an Asteraceae family member, grows mostly in Asia\'s arid and semi-desert areas and is a significant commercial and decorative plant. Nevertheless, the genus\' classification has been disputed, and the evolutionary connections within the genus have not been thoroughly defined. Hence, we sequenced and analyzed Ajania\'s plastid genomes and combined them with ETS data to assess their phylogenetic relationships.
RESULTS: We obtained a total of six new Ajania plastid genomes and nine ETS sequences. The whole plastome lengths of the six species sampled ranged from 151,002 bp to 151,115 bp, showing conserved structures. Combined with publicly available data from GenBank, we constructed six datasets to reconstruct the phylogenetic relationships, detecting nucleoplasmic clashes. Our results reveal the affinities of Artemisia, Chrysanthemum and Stilpnolepis to Ajania and validate the early taxonomy reclassification. Some of the plastid genes with low phylogenetic information and gene trees with topological differences may have contributed to the ambiguous phylogenetic results of Ajania. There is extensive evolutionary rate heterogeneity in plastid genes. The psbH and ycf2 genes, which are involved in photosynthesis and ATP transport, are under selective pressure. Plastomes from Ajania species diverged, and structural aspects of plastomes may indicate some of the real evolutionary connections. We suggest the ycf1 gene as a viable plastid DNA barcode because it has significant nucleotide diversity and better reflects evolutionary connections.
CONCLUSIONS: Our findings validate the early Ajania taxonomy reclassification and show evolutionary rate heterogeneity, genetic variety, and phylogenetic heterogeneity of plastid genes. This research might provide new insights into the taxonomy and evolution of Ajania, as well as provide useful information for germplasm innovation and genetic enhancement in horticultural species.

Glia play multifaceted roles in nervous systems in response to injury. Depending on the species, extent of injury and glial cell type in question, glia can help or hinder the regeneration of neurons. Studying glia in the context of successful regeneration could reveal features of pro-regenerative glia that could be exploited for new human therapies. Planarian flatworms completely regenerate their nervous systems after injury - including glia - and thus provide a strong model system for exploring glia in the context of regeneration. Here, we report that planarian glia regenerate after neurons, and that neurons are required for correct glial numbers and localization during regeneration. We also identify the planarian transcription factor-encoding gene ets-1 as a key regulator of glial cell maintenance and regeneration. Using ets-1 (RNAi) to perturb glia, we show that glial loss is associated with altered neuronal gene expression, impeded animal movement and impaired nervous system architecture - particularly within the neuropil. Importantly, our work reveals the inter-relationships of glia and neurons in the context of robust neural regeneration.

The experience of the COVID-19 pandemic showed the importance of timely monitoring of admissions to the ICU admissions. The ability to promptly forecast the epidemic impact on the occupancy of beds in the ICU is a key issue for adequate management of the health care system.Despite this, most of the literature on predictive COVID-19 models in Italy has focused on predicting the number of infections, leaving trends in ordinary hospitalizations and ICU occupancies in the background.This work aims to present an ETS approach (Exponential Smoothing Time Series) time series forecasting tool for admissions to the ICU admissions based on ETS models. The results of the forecasting model are presented for the regions most affected by the epidemic, such as Veneto, Lombardy, Emilia-Romagna, and Piedmont.The mean absolute percentage errors (MAPE) between observed and predicted admissions to the ICU admissions remain lower than 11% for all considered geographical areas.In this epidemiological context, the proposed ETS forecasting model could be suitable to monitor, in a timely manner, the impact of COVID-19 disease on the health care system, not only during the early stages of the pandemic but also during the vaccination campaign, to quickly adapt possible preventive interventions.

Accelerated globalization especially in the late 1980s has provided opportunities for economic progress in the world of emerging economies. The BRICS nations\' economies are distinguishable from other emerging economies due to their rate of expansion and sheer size. As a result of their economic prosperity, health spending in the BRICS countries has been increasing. However, health security is still a distant dream in these countries due to low public health spending, lack of pre-paid health coverage, and heavy out-of-pocket spending. There is a need for changing the health expenditure composition to address the challenge of regressive health spending and ensure equitable access to comprehensive healthcare services.
Present study examined the health expenditure trend among the BRICS from 2000 to 2019 and made predictions with an emphasis on public, pre-paid, and out-of-pocket expenditures for 2035.
Health expenditure data for 2000-2019 were taken from the OECD iLibrary database. The exponential smoothing model in R software (ets ()) was used for forecasting.
Except for India and Brazil, all of the BRICS countries show a long-term increase in per capita PPP health expenditure. Only India\'s health expenditure is expected to decrease as a share of GDP after the completion of the SDG years. China accounts for the steepest rise in per capita expenditure until 2035, while Russia is expected to achieve the highest absolute values.
The BRICS countries have the potential to be important leaders in a variety of social policies such as health. Each BRICS country has set a national pledge to the right to health and is working on health system reforms to achieve universal health coverage (UHC). The estimations of future health expenditures by these emerging market powers should help policymakers decide how to allocate resources to achieve this goal.