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Drospirenone promotes apoptosis in ectopic but inhibits proliferation in eutopic human endometrial stromal cells
Background Endometriosis is a complex gynecological condition characterized by endometrial tissue growing outside the uterus. In many in vitro studies, almost all progestins have indicated the anti-proliferation and apoptosis of endometriotic stromal cells. Drospirenone, a synthetic progestin structurally distinct from traditional progestins, still lacks sufficient data regarding its effects on endometriosis, particularly in terms of antiproliferative and pro-apoptotic activity. This study investigates the antiproliferative effects of drospirenone on eutopic (EU-ESCs) and ectopic human endometrial stromal cells (EC-ESCs), and compare its impact on apoptotic effects in both cell types. Methods and Findings In the study, paired EU-ESCs and EC-ESCs were obtained from patients diagnosed with endometriosis (n = 12). EU-ESCs and EC-ESCs were treated with and without drospirenone. Antiproliferative markers and apoptotic markers were evaluated and compared between the two groups. Interestingly, drospirenone at a concentration of 1 µM significantly affected cell viability in both EU-ESCs and EC-ESCs. In EU-ESCs, Ki-67 expression was significantly reduced compared to controls (0.17 vs. 1; p = 0.003), while in EC-ESCs, the reduction was not statistically significant. Caspase-3 expression was significantly increased in both EU-ESCs (1.13 vs. 1) and EC-ESCs (1.57 vs. 1) (p= 0.02 and p = 0.05, respectively). Additionally, BCL2 expression decreased in both cell types following treatment. BAX expression increased in both EU-ESCs and EC-ESCs. Expression levels of PTEN and P53 also increased in both cell types, with statistical significance observed only in EC-ESCs (p = 0.03 and p = 0.04, respectively). BAK expression decreased in EU-ESCs but increased in EC-ESCs compared to controls. Conclusions Drospirenone exhibits an antiproliferative effect on EU-ESCs and induces a more pronounced apoptotic response in EC-ESCs.
The development and implementation of odd-exponential-ailamujia distribution in python: properties and application in reliability engineering
Genetic insights into number of long-term conditions and their relationship with lifespan
Aims Relationships between the genetic risk for long-term conditions (LTCs) and lifespan have been reported. However, the genetic factors underlying the total number of LTCs an individual has (LTC burden) and their association with lifespan have not been fully investigated. This study aims to investigate the genetics of LTC burden and evaluate its relationship with lifespan. Methods A genome-wide association study (GWAS) and a genetic heritability test were conducted on LTC burden using data from 343,868 UK Biobank individuals. Global and local genetic correlations between the LTC burden and parental lifespan were estimated. A polygenic risk score (PRS LTC ) for LTC burden was derived from a separate set of 34,339 UK Biobank individuals with records of age at death, who were not included in the GWAS analysis. The association between the PRS LTC and lifespan, as well as its ability to predict LTC burden, was assessed. Results Loci in the HLA region were the most significant among the 21 significant independent loci from the GWAS. The estimated SNP heritability of LTC burden was 0.0963 and significantly different from zero (se = 0.0034, p-value = 1.77 x 10 −176 ). The global genetic correlation between LTC burden and parental lifespan exhibited a significant global genetic correlation of −0.7869 (se = 0.0419, p-value 9.57 x 10 −79 ). Additionally, 44 loci showed significant local genetic correlations (p-value < 2.23 x 10 −5 ). Individuals in the highest 10% PRS LTC had, on average, a 0.9-year shorter lifespan and 0.73 more LTCs than those in the lowest 10%. Conclusions This study identifies significant genetic factors associated with LTC burden and their association with lifespan, providing insights into the genetic underpinnings of both multiple LTCs and lifespan.
Predicting energy prices and renewable energy adoption through an optimized tree-based learning framework with explainable artificial intelligence
Abstract This research offers a comprehensive analysis of global energy consumption, focusing on predicting two key metrics: the Energy Price Index and the Renewable Energy Share. The study employs advanced Machine Learning (ML) regression techniques, all further optimized using metaheuristic algorithms. In addition, a primary objective of this study is to determine which variables most significantly affect model performance and predictive accuracy. Through SHAP (SHapley Additive exPlanations) and CAM (Cosine Amplitude Method) sensitivity analyses, the study systematically interprets model outputs and quantifies the influence of each input feature. Findings demonstrate that, according to the SHAP-based model interpretation, the prediction of Renewable Energy Share is most strongly influenced by fossil fuel dependency and carbon emissions. These results underscore the pivotal role of consumption intensity and environmental indicators in shaping both global energy price trajectories and renewable energy adoption rates. Integrating optimization algorithms with advanced models improved both predictive accuracy and model robustness. The resulting analytical framework provides a technically rigorous and interpretable approach to global energy forecasting. Such a framework is valuable for informing energy policy, supporting sustainability strategies, and enabling stakeholders to monitor environmental impacts and optimize energy system performance. By leveraging data-driven insights, this study advances practical tools and methodologies for strategic planning in the context of a sustainable global energy future.
Navigating physical activity after a nerve injury in the arm and hand
Peripheral nerve injuries in the arm and hand can lead to significant challenges, impacting every aspect of a person’s life. Still, rehabilitation largely focuses on hand exercises, emphasizing motor function recovery. Targeting sensory relearning poses a significant challenge for the brain, demanding neural adaptation and reorganization. While, physical activity is not a standard component of current rehabilitation, yet it supports recovery and promotes nervous system health across other various conditions. However, it remains unclear whether nerve injuries affecting the arm, hand, or fingers contribute to decreased levels of physical activity. Qualitative methods, specifically semi-structured interviews with content analysis, were used to gain a deeper understanding of participants´ experience of change in physical activity after a nerve injury to the arm and hand. Data from in total 20 participants with different levels of nerve injury in the arm and hand were analysed with content analysis. Two themes emerged ‘barriers’ and ‘facilitators’ for being physically active after the nerve injury. The themes displayed three dimensions: internal factors (e.g., prior experience of physical activity and personality traits), physical factors (e.g., pain and hand function) and external factors (e.g., support from family and health care professionals). Key findings indicate that a nerve injury to the arm and hand leads to decrease in physical activity, regardless of injury severity. Previously inactive individuals faced barriers too significant to overcome independently, highlighting the need for targeted support to facilitate physical activity following nerve injuries. These findings may offer new insights into potential rehabilitation strategies.
A comparative analysis of the performance of large Language models in the dentistry specialty examination
Effective and safe: Long-term aerosol disinfection of slightly acidic electrolyzed water causes no harm in rats
Slightly acidic electrolyzed water (SAEW) has been shown to possess strong bactericidal and virucidal properties, making it a promising candidate for spatial disinfection. In this study, we rigorously evaluated the efficacy and safety of SAEW for aerosol disinfection under controlled conditions. Laser particle size distribution analysis confirmed uniform aerosolization. Additionally, analysis of chlorine concentration ensured stable disinfection conditions. Moreover, SAEW exhibited potent sterilization effects against the model organism Escherichia coli in both direct-contact and aerosol-disinfection experiments. Notably, long-term exposure assessments in rats revealed no adverse effects on body weight, food and water intake, and organ function and histology. Conclusively, these results indicate that SAEW is a highly effective and safe disinfectant for controlling airborne and droplet-mediated infections. In addition to preventing the spread of infectious diseases, including coronaviruses, SAEW is expected to be effectively utilized in the veterinary, agricultural, and food industries.
Optimizing feature selection in cancer microarray data using a heap-driven evolutionary framework for high-dimensional spaces
Energy–structure coupling mechanism and damage evolution model of red sandstone during soaking–softening process
To reveal how different soaking times affect red sandstone’s softening characteristics, this study analyzed red sandstone’s mineral composition, meso-structure, mechanical properties, and energy evolution laws. A damage constitutive model was established based on mechanical property testing and microstructure determination experiments of rock samples. It considers the initial compaction nonlinear section. The prediction bias in the energy dissipation theory damage model during the compaction stage was corrected based on the correction coefficient. The deterioration of mechanical properties of rock samples is positively correlated with immersion time. The results showed that water soaking caused feldspar, calcite, and other minerals to dissolve. It also reduced clay minerals and made pore development more intense. The mechanical properties of rock samples gradually decrease. This happened as soaking duration increased. When the soaking time reached 150 days, the cumulative deterioration degrees reached 44.25% and 30.78% respectively. The turning point of dissipated energy moved forward. The growth inflection point of the damage variable also advanced. The rock sample damage model fitted well with the experimental curve. It could accurately characterize the softening process. The research results explained the “time–structure–energy–damage” coupling mechanism. This mechanism applies to red sandstone softening under water–rock interactions. The explanation covered both macro and meso perspectives. It provided key theoretical support for red sandstone engineering stability assessment and long-term service safety.
Additive effects of high intensity interval training and therapeutic adenosine on gene and protein expression in lipid metabolism and weight loss in high fat diet-induced obese rats
Maternal slow-release nitrogen diets during late gestation optimize the energy metabolism in calves’ skeletal muscle
The current study aimed to determine the enriched biological process, through proteomic and transcriptome data, associated with maternal slow-release nitrogen diets received during late gestation on the skeletal muscle of the offspring. At day 180 to day 268 of gestation a total of 16 pregnant Brahman cows, were assigned into Control treatment (CON; n = 7), where cows were fed ad libitum a low crude protein basal diet plus mineral mixture; or Slow-released nitrogen (SRN, n = 9) based diet, where cows were fed a basal diet plus a slow-release nitrogen supplement. Muscle biopsy was performed at day 45 of age in calves and used to perform RNA sequencing (RNA-seq) and proteomic (HPLC-MS/MS) analyses. Although the experimental treatment did not show effects on transcript abundance, proteomic analysis revealed significant differences in protein expression. Enriched (adjusted p -value ≤ 0.05) biological processes from the exclusive proteins identified in calves’ skeletal muscle from SRN group are related to central energy metabolism (synthesis of Acetyl-CoA, tricarboxylic acid cycle, isocitrate metabolic process), regulation of calcium and nitrogen transport, and protein folding. Protein-protein interaction network assessed in the differentially abundant proteins (DAPs) revealed 4 main enriched biological processes, including ATP metabolic process, glucose metabolism, tricarboxylic acid cycle, and sarcomere organization. These findings suggest that maternal supplementation whit slow-release nitrogen during late gestation can positively influence postnatal energy metabolism in calf skeletal muscle.
IL2Pepscan: A machine learning framework for predicting IL-2 inducing peptides and their identification across global viral proteomes
Study on the influence of anti stripping agent on the rheological properties of asphalt at high and low temperatures
In order to compare the effects of different anti stripping agents on the rheological properties of asphalt at high and low temperatures, four typical anti stripping agents, amine PA-1, non amine XT-2, hydrated lime, and cement, were selected. The complex modulus (G*), phase angle (δ), rutting factor (G*/sinδ), creep stiffness (S), and creep rate (m) were measured using the dynamic shear rheometer (DSR) and the bending beam rheometer (BBR). The microscopic mechanism was analyzed using fourier transform infrared spectroscopy (FTIR) and fluorescence microscopy (FM). The results showed that lime and cement significantly improved the high temperature performance of asphalt, with an average increase of 1.4 and 0.8 times in G */sinδ. However, PA and XT reduced the high temperature performance, with an average decrease of 19% and 11% in G */sinδ. PA and XT have little effect on the low temperature performance of asphalt, but lime and cement will reduce the low temperature performance, with an average increase of 64% and 49% in S. The results of FTIR and FM indicate that lime and cement undergo chemical reactions with asphalt, while PA and XT do not, but PA and XT can promote the swelling of modifiers in asphalt.
Secure IoMT smartwatch-based blood glucose monitoring using multimodal activity and nutrition data with transfer learning
Phytophthora capsici carries and differentially expresses genes for the RNA interference pathway
The RNA interference (RNAi) pathway is an epigenetic mechanism that has recently gained attention for its role in regulating the virulence of plant pathogens. However, little is known about this gene silencing pathway in Phytophthora capsici , a broad-host-range pathogen that affects many important food crops. In the present study, we identified key genes and proteins involved in the synthesis, transport, and processing of sRNAs using in silico approaches based on the reference genome and proteome, and through transcriptional analysis of P. capsici . Our results showed that the P. capsici genome encodes Dcl1, Dcl2, Exportin-5, Rdr, and six Ago proteins, suggesting the presence of a complete RNAi pathway in this pathogen. These genes were syntenic and phylogenetically related to those of other oomycetes in the genus Phytophthora . We also analyzed their expression levels after infecting chili pepper and broccoli across two generations, revealing different expression patterns depending on the infection history of the pathogen. To our knowledge, this is the first report on the EXPORTIN-5 gene in P. capsici and other oomycetes. Additionally, the expression of all these RNAi-related genes in the pathogen after isolation from different hosts suggests that the host may influence the RNAi pathway of P. capsici . This study paves the way for functional studies to confirm the role of RNAi in regulating virulence in P. capsici .
High on-clopidogrel platelet reactivity among diabetic female patients with acute ischaemic stroke
Application of the Er:YAG laser in pulpotomy for mature permanent teeth with pulpitis: An animal study
Objective To apply Erbium-doped Yttrium Aluminum Garnet (Er:YAG) laser in pulpotomy for experimentally induced pulpitis in mature permanent teeth of rats, and investigate whether Er:YAG laser can improve the effect of pulpotomy in mature permanent teeth with pulpitis. Methods Thirty-six 3-month-old male Sprague-Dawley (SD) rats were selected, with bilateral maxillary first molars as experimental teeth. 4 rats (8 experimental teeth) were selected to construct the pulpitis model. After confirming the successful establishment of the model by this method, 32 rats were randomly divided into the control group and the experimental group, and the pulpitis models were constructed in the same way. The control group(mechanical group, 16 rats, 32 experimental teeth) received pulpotomy with conventional sterile excavators. The experimental group (laser group, 16 rats, 32 experimental teeth) received pulpotomy using Er:YAG laser. At 3, 7, 14, and 28 days post-operation, four rats from each group were randomly euthanized. Pathological changes in the dental pulp were observed using hematoxylin - eosin (HE) staining. Immunohistochemical (IHC) assessment and mean optical density (MOD) measurement were performed to evaluate the expression of interleukin-1β (IL-1β) and partitioning defective protein 3 (Par3). Inter-group differences were analyzed using the Mann-Whitney U test or the independent samples t-test. Results Histological examination by HE staining demonstrated favorable pulpal repair in the laser-treated group. The total histopathological scores were significantly lower in the laser group compared to the mechanical group at days 3 and 7 post-operation ( p < 0.05). However, no statistically significant difference was observed between the two groups at days 14 and 28. IHC analysis revealed that the mean optical density (MOD) values for IL-1β were consistently lower in the laser group at all four time points ( p < 0.05), while the MOD values for Par3 were consistently higher in the laser group ( p < 0.05). Conclusion The Er:YAG laser used during pulpotomy in mature permanent rat teeth with pulpitis preserves the remaining healthy pulp tissue, reduces IL-1β expression, and enhances Par3 expression, thereby alleviating inflammation and promoting tissue repair.
Modeling of conductivity for carbon black nanocomposites incorporating network concentration, interphase conductivity and tunneling dimensions
Physiological responses of Cucurbita pepo seeds to cadmium and copper stress: Differential impacts on reserve mobilization, metabolic efficiency, and growth
Heavy metal contamination poses a significant threat to agricultural productivity. This study investigated the physiological and biochemical responses of Cucurbita pepo seeds to cadmium (Cd) and copper (Cu) stress (100–200 µM) during germination. Although germination rates remained high (86.67–93.33%), seed vigor indices declined significantly under metal stress. Cadmium exhibited stronger growth inhibition, reducing total seedling length by 63.02% at 200 µM, whereas copper primarily affected biomass accumulation, reducing the seedling weight-based vigor index (SVI W ) by 40.4%. Biochemical analyses revealed metal-specific impacts on reserve mobilization. Cadmium exposure (200 µM) decreased soluble sugars in cotyledons by 16%, while maintaining protein content at 106% of control levels, indicating inhibition of protein degradation and impaired reserve utilization. In contrast, copper at 100 µM increased cotyledonary sugars by 63%, reflecting its dual role as both a micronutrient and stressor. Principal component analysis confirmed the greater toxicity of Cd, which explained 79.7% of the variance in metabolic disruption. These findings demonstrate that cadmium consistently impairs seedling establishment by disrupting nutrient mobilization pathways, while copper exhibits concentration-dependent effects, being stimulatory at low concentrations but inhibitory at higher levels. This study provides crucial insights into heavy metal phytotoxicity mechanisms and underscores the importance of monitoring metal pollution in agricultural systems to enhance crop resilience.