Search Results (4,718)

Background: Local recurrence of rectal cancer is a challenging problem for patients and clinicians. Surgical resection is associated with good outcomes if R0 margins are achieved; however, it is often complex, requires suitable patient fitness, and is associated with long term physical and psychological consequences. Meanwhile, continuing technical advances in radiotherapy have enabled the delivery of highly conformal treatment, thereby enabling dose escalation or pelvic reirradiation to be safely considered—either as definitive management or in the neoadjuvant setting—for patients with locally recurrent rectal cancer. Pelvic reirradiation may refer to patients who have received primary rectal radiotherapy with the aim of neoadjuvant downstaging or reducing the risk of locoregional recurrence, versus radiotherapy for a previous unrelated non-rectal pelvic malignancy. Methods: A literature search of pelvic reirradiation for non-metastatic, locally recurrent rectal cancer was conducted for full text articles published over the last 20 years. Additional papers were identified within the references of these papers. Studies focusing on non-rectal cancers, and patients having primary radiotherapy for locally recurrent rectal cancer were excluded. Due to the heterogenicity of the data, no meta-analysis was performed. Results: A total of 15 papers were included, containing a cohort of 840 patients. Several reirradiation modalities were reported, including external beam radiotherapy, brachytherapy, stereotactic ablative radiotherapy and heavy particle therapy (carbon ion). Carbon ion radiotherapy was the most common reirradiation treatment modality utilised with a median cumulative dose of 70.4 Gray (Gy). Treatment response, defined as either complete or partial improvement in tumour size, was only reported in seven studies, and varied from 14 to 88%. Overall 3-year survival was also variable with rates reported between 18 and 85%. These observations may be due to variation in patient selection, treatment intent, and technique. Pelvic reirradiation was associated with acceptable toxicity, low rates of G3+ toxicity, and improved symptom control. Conclusions: Our review describes the multitude of approaches to pelvic reirradiation for locally recurrent rectal cancer. Reviewing the radiobiological and patient outcomes is challenging in view of the degree of heterogeneity in patient selection, treatment approach, and reported outcomes. However, there is consensus that pelvic reirradiation—either for long term control or to downstage prior to definitive surgery—is feasible with potential utility in this setting. Full article

Butyrophilin-like 2 (BTNL2) is an immunomodulatory molecule critically involved in regulating the host immune response to infection with the avirulent Mycobacterium tuberculosis strain H37Ra. However, its functional role in modulating pyroptosis and associated inflammatory responses remains incompletely characterized. Here, we demonstrate that BTNL2 deficiency exacerbates pyroptosis and the inflammatory response in H37Ra-infected murine peritoneal macrophages via two distinct pathways. First, the loss of BTNL2 induces excessive mitochondrial damage, which leads to aberrant release of mitochondrial DNA (mtDNA) and accumulation of mitochondrial reactive oxygen species (mtROS), thereby triggering NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome activation and gasdermin D (GSDMD)-mediated pyroptosis. Second, cytosolic mtDNA accumulation hyperactivates the cGAS–STING signaling axis, resulting in transcriptional upregulation of NLRP3 and consequent amplification of pro-inflammatory cytokine production. Collectively, these findings demonstrate that BTNL2 acts as a regulator of mitochondrial homeostasis and innate immune balance during H37Ra infection in primary peritoneal macrophages. The results provide mechanistic insights into BTNL2 function in the context of H37Ra-induced pyroptosis. Full article

Background: Lipid peroxidation is a primary driver of biological membrane damage and mediates the relationship between environmental exposure and adverse health outcomes. Malondialdehyde (MDA) is a widely recognized biomarker for quantifying oxidative stress intensity. Despite numerous studies on oxidative stress and metal exposure, nonlinear relationships between physiological characteristics, serum metal profiles and MDA levels in pubertal children remain insufficiently studied. Methods: The study included 105 conditionally healthy children aged 12–14 years from urban and rural regions of Tatarstan, Russia. Serum MDA concentrations were determined spectrophotometrically using the thiobarbituric acid assay, while Zn, Cu, Fe, Sr and Pb concentrations were measured by atomic absorption spectrometry. A multilayer perceptron neural network was applied to model nonlinear relationships between MDA levels, environmental exposure indicators and morphophysiological characteristics. Because the original relational dataset contained partially replicated participant-derived relational structures, primary validation was performed using independently reconstructed datasets without repeated observations. Additional repeated cross-validation and SHAP-based feature importance analysis were performed. Results: Urban-residing children demonstrated significantly higher serum MDA levels than rural counterparts, independent of sex, with girls consistently showing higher values. Reduction of predictor dimensionality improved model generalization behaviour. Validation using independently reconstructed datasets without repeated observations demonstrated reproducible exploratory predictive behaviour of the reduced neural network model, with independently reconstructed validation datasets yielding mean R² values of 0.901 ± 0.052 and 0.914 ± 0.046, respectively. SHAP analysis demonstrated that zinc, copper and iron consistently represented the dominant contributors to the nonlinear model, although substantial variability in the relative ranking of zinc and copper was observed between validation datasets. Conclusions: The proposed neural network model demonstrated the ability to capture reproducible nonlinear relationships between oxidative stress markers and environmental exposure parameters in a limited biomedical dataset. The model should primarily be interpreted as an exploratory explanatory tool rather than an individual clinical prediction instrument. Because of the limited dataset size, partially reconstructed relational structure and exploratory study design, the findings require cautious interpretation and further external validation. Full article

In this study, we investigated the interaction of a dapagliflozin-containing medicinal product (the commercial drug Forxiga^®) with human serum albumin (HSA) at different temperatures using steady-state fluorescence spectroscopy, competitive displacement assays, UV–Vis absorption spectroscopy, and thermodynamic analysis. Increasing concentrations of Forxiga induced a gradual, concentration-dependent quenching of the intrinsic fluorescence of HSA (${\lambda }_{\mathrm{ex}}=284$ nm; ${\lambda }_{\mathrm{em}\max }\approx 334$–339 nm), indicating perturbation of the microenvironment surrounding Trp-214 located in subdomain IIA. Stern–Volmer analysis showed that the quenching constants were temperature-dependent. Meanwhile, the high apparent bimolecular quenching constants suggested a predominantly static quenching mechanism associated with ground-state complex formation. By performing a modified Scatchard-type double-logarithmic analysis, we identified a primary binding site, particularly at lower temperatures. Van’t Hoff analysis revealed negative enthalpy and entropy changes. This indicates that the interaction was spontaneous and exothermic, mainly driven by hydrogen bonding and van der Waals forces. The competitive displacement assays confirmed preferential binding at Sudlow’s site I, in proximity to Trp-214. Additionally, the UV–Vis spectroscopy, supported by ligand-induced perturbation of aromatic residues, confirmed the absence of significant inner-filter effects. Differential scanning calorimetry suggested partial thermal stabilization of HSA upon ligand binding. This finding is consistent with the formation of a stabilized protein–ligand complex. These results suggest that Forxiga forms a relatively stable ground-state complex with HSA, primarily at Sudlow’s site I, and that the interaction is influenced by temperature-dependent conformational changes in the protein. Full article

Introduction: Vitamin B12 (VB12), particularly its active form methylcobalamin (MeB12), contributes to neuromuscular function and energy metabolism, which may be relevant for sports performance. However, evidence on the acute effects of MeB12 supplementation in athletes remains limited. Objective: To evaluate the effects of short-term (3-day) MeB12 supplementation on anaerobic and cognitive performance in amateur cyclists. Methods: A randomized, triple-blind, placebo-controlled crossover clinical trial was conducted in 18 amateur cyclists. Participants received formulations containing MeB12 (1 mg/day; MecobalActive^®, HTBA, Murcia, Spain) or placebo for three consecutive days. Anaerobic performance was assessed using a repeated Wingate protocol, and cognitive performance was evaluated using a light-based mental agility/reaction test system. Biochemical analyses included serum VB12 concentrations. Primary outcomes included peak power output (absolute and relative), fatigue index across repeated sprints, and cognitive response time. Results: Compared with placebo, MeB12 supplementation was associated with higher peak power output, with increases in absolute maximal power (PMAX: +4.1%, p = 0.016) and relative maximal power (PMAXREL: +4.4%, p = 0.013). MeB12 supplementation was associated with a smaller decline in performance across repeated sprints, with a smaller drop in fatigue index from the first to the fifth sprint (p = 0.012). Pre-exercise cognitive performance improved, with a shorter total reaction test time (−4.9%, p < 0.001) versus placebo. Serum VB12 concentrations increased by 16.8% following MeB12 supplementation. Conclusions: A brief, 3-day intervention with methylcobalamin (1 mg/day) was associated with positive changes, when compared with placebo, in selected markers of anaerobic performance (peak power and fatigue-related decline) and pre-exercise cognitive performance in recreationally trained amateur cyclists, suggesting a possible involvement of peripheral and central mechanisms. Full article

Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin’s lymphoma (NHL), accounting for 30–40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-β, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor–stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL. Full article

The subunit composition and tertiary structure of DNA-dependent RNA polymerases in archaea, bacteria, and eukaryotes are currently well understood. The single RNA polymerase of archaea resembles the nuclear RNA polymerase II of eukaryotes in its composition and consists of 10–12 subunits. Perhaps the only exception that seems to confirm this rule is the Rpo8 subunit (homologue of the eukaryotic Rpb8), which only some classes of archaea have. The development of metagenomic sequencing has led to a significant revision of the classification system of prokaryotes, in particular to the identification of a number of new Archaea evolutionary lineages. This makes it possible to analyze the subunit composition and structure of RNA polymerase of all currently isolated archaeal phyla. Our analysis shows that the Rpo8 subunit is present only in the RNA polymerase of Archaea species from the Thermoproteota of the Thermoproteati superphylum and from the whole superphylum Promethearchaeati, formerly known as the Asgard. After analyzing the changes in the small Rpo6 subunit (homologue of eukaryotic Rpb6), functionally interacting with Rpo8, we noticed that the largest number of changes in the primary and domain structures of this small subunit occurred in archaeal phyla that lack Rpo8. Shortened forms of Rpo6 without N- or C-terminal regions were observed only in representatives of archaea with an RNA polymerase that does not contain the Rpo8 subunit. Our analysis shows that the changes in Rpo6 are an adaptation of a multisubunit transcription complex to the disappearance of Rpo8. Most likely, the Rpo8 subunit was present in the RNA polymerase of the Last Common Ancestor of Archaea (LCAA) and, in the course of evolution, disappeared in the superphyla Euryarchaeota and Nanobdellati and two divisions of the Thermoproteati superphylum: Bathyarchaeota and Thaumarchaeota. Full article

This study aimed to investigate the regulatory effect and cryoprotective mechanism of melatonin (MT) on the physiological functions of Lactobacillus plantarum FQR during freezing and freeze-drying. Results indicated that the addition of 5 mg/mL MT as a cryoprotectant maximized the freeze-drying survival rate to 32.04 ± 2.14%. MT effectively alleviated low-temperature and freeze-drying stress by reducing extracellular alkaline phosphatase activity, enhancing intracellular lactate dehydrogenase activity, and decreasing extracellular β-galactosidase activity without significant differences. Higher survival rates in defining medium further suggested that MT reduced damage to cell wall and membrane structures during lyophilisation, decreased membrane permeability, and preserved cellular physiological functions. In addition, MT supported cellular energy metabolism and protein synthesis, enhanced transmembrane potential to facilitate ATP transport, and helped maintain intracellular and extracellular pH balance. The prepared freeze-drying protectant containing 69.80 mg/mL exopolysaccharides (EPS) and 4.25 mg/mL MT showed better protective effects than the control group. MT also increased bound water content, lowered the freezing point of the solution, and inhibited ice crystal formation. Transcriptomic analysis revealed that amino acid biosynthesis, amino acid metabolism, and ABC transport systems were the primary pathways affected by MT treatment. These findings demonstrate that MT improves freeze-drying tolerance by maintaining membrane integrity, regulating cellular metabolism, and enhancing oxidative stress resistance. Given its natural biosynthetic origin, generally recognized as safe (GRAS) status, and absence of residual solvents or allergenic proteins, MT can be safely considered for incorporation into food and nutraceutical products. This study underscores the practical relevance of MT as a functional component in compound cryoprotectants, providing a feasible strategy to enhance the viability, stability, and industrial applicability of Lactobacillus plantarum during freeze-drying and storage. Full article

Industrial areas, which represent a specific type of urbanised area with an extremely high concentration of material reserves, can be considered key anthropogenic raw material reservoirs in the context of urban mining. Industrial areas, characterised by a high material density and a specific composition of structural systems, show extraordinary potential for providing secondary raw materials with high material and energy value. This increases the need for their systematic evaluation. The aim of the present study was to define the role of the selected industrial area as a strategic node for secondary raw material extraction, to identify the structure and quality of “urban deposits” in the selected location of the Ostrava–Karviná region (CZ), and to provide an analytical framework for its integration into circular planning processes. The methodological approach is based on a combination of pre-demolition audit, material flow mapping, spatial analysis, and structural element characterisation. It is becoming apparent that industrial areas have a high material density and contain significant amounts of recyclable metals, reinforced concrete elements, etc. These stocks are often concentrated in structural systems with predictable geometries, such as serial assembly prefabricated and steel frames, allowing for more accurate estimates of recoverable volumes. The results show that the incorporation of industrial areas into the process of urban mining can significantly reduce the consumption of primary raw materials, mitigate the environmental impacts associated with the extraction of raw materials, and, at the same time, promote the regeneration of industrial areas (or brownfields) through the planned decomposition of structures. The inclusion of urban mining in urban development strategies and the regeneration of industrial sites leads to the prediction that urban mining is one of the key elements for achieving a material-efficient and low-carbon urban environment. Full article

In advanced oxide materials, additive selection is increasingly constrained by the simultaneous requirements of functional response, phase stability, morphology control, processing tolerance, scalability, and critical raw material security. This study develops a ZnO-centered framework to compare boron-based strategies (direct B doping, B₄C/ZnO composite formation, and h-BN/ZnO interface engineering) with rare-earth strategies (Ce/CeO₂, La/La₂O₃, and Y/Y₂O₃). Structural, morphological, chemical-state, and vibrational evidence from XRD, FE-SEM/EDX, XPS, Raman, and FT-IR studies is interpreted through an evidence hierarchy that separates lattice incorporation, surface/grain-boundary segregation, and deliberate secondary-phase or heterointerface formation. The synthesis shows that boron-containing routes usually provide broader phase retention, lower agglomeration tendency, more gradual defect modulation, and greater processing robustness, whereas rare-earth routes offer stronger oxygen-vacancy regulation, redox activity, luminescence tuning, and heterojunction-assisted function but require tighter process control and more rigorous verification of incorporation mode. Reanalysis of seven primary experimental pathways indicates that B₄C/ZnO and h-BN/ZnO are mechanistically non-equivalent: B₄C supports rigid composite-interface growth, while h-BN promotes sheet-mediated interface multiplication and Maxwell–Wagner–Sillars polarization. Türkiye is treated as an illustrative boron-rich producer case within a transferable producer/importer decision model. Dopant selection is therefore framed as a multi-criteria decision involving performance thresholds, reproducibility, technology-readiness potential, and supply-security exposure, not peak output alone. Full article

This study highlights the strong ability of a new bacterial strain, Hafnia paralvei UUNT_MP29, isolated from the gastrointestinal tract (GIT) of common carp (Cyprinus carpio), to break down polystyrene (PS). As an omnivorous bottom feeder, C. carpio is constantly exposed to microplastics, creating a unique environment that favors the evolution of specialized microbiota capable of degrading polymers. Genomic analysis of the isolate identified key homologs involved in xenobiotic breakdown, including alcohol dehydrogenase (Adh), 3-hydroxybutyrate dehydrogenase (HDH), and a small glutamine-rich tetratricopeptide repeat-containing protein (SGTA), showing a strong metabolic system for processing long-chain hydrocarbons. Growth experiments showed the strain quickly adapted, reaching maximum cell density and forming mature biofilms by Day 16. Gravimetric analysis confirmed that H. paralvei UUNT_MP29 uses PS as its primary carbon source, with a significant weight loss of 16.76% over 16 days. Kinetic modeling indicated the degradation follows first-order kinetics (R² = 0.9243) with a high degradation rate constant (k) of 0.2078 day⁻¹. Surface analyses using FTIR and SEM confirmed extensive oxidative changes, as evidenced by the rising Carbonyl Index and surface erosion. TGA also showed reduced thermal stability of the treated polymer, suggesting microbial chain scission. These findings demonstrate the strong degradative ability of H. paralvei UUNT_MP29 and highlight the GIT of plastic-exposed aquatic animals as a promising area for discovering powerful biocatalysts for microplastic cleanup. Full article

Genetic diversity analysis can contribute to comparing the relationships between different germplasm resources. Self-recombination is one of the main strategies for the innovation of germplasm resources. In this study, a total of 588 accessions, including two parents and their 586 F_2:4 recombinant individuals originated via the single seed descent (SSD) method, were used to explore the genetic diversity of 17 phenotypic traits. The results indicated that most traits of the recombinants represented continuous distribution and transgressive segregation, with their minimum and maximum values exceeding the parental ranges. Correlation analysis shows that 17 phenotypic traits could be roughly divided into three clusters. There was a significant correlation between traits in the same cluster, such as primary stem height, plant height, and plant canopy diameter in Cluster I; transverse diameter of fruit, fruit shape of apex, node pubescence density, and lamina transverse section morphology in Cluster II; and internode anthocyanin pigmentation, immature fruit color, and leaf color in Cluster III, respectively. The 586 recombinant individuals and two parents were generally clustered into three groups, Group I, Group II, and Group III, which contained 320, 226, and 42 recombinants, respectively. In addition, six principal components were extracted from the 17 phenotypic traits, which could explain 62.97% of the cumulative variance contribution. Importantly, ten recombinants with both purple and long fruit were screened as breeding materials. Overall, this study provides useful information and breeding materials for the utilization and innovation of pepper germplasm resources as well as genetic improvement of pepper. Full article

Background: Trigeminal neuralgia (TN) is clinically defined, but patients presenting to tertiary practice with trigeminal-region pain are often diagnostically heterogeneous and may follow prolonged medication, dental, imaging, and procedural pathways before a stable phenotype is established. We aimed to characterize diagnostic phenotypes, secondary causes, and treatment-escalation patterns in a large retrospective tertiary-center trigeminal pain cohort derived from routine free-text clinical documentation. Methods: We conducted a retrospective single-center cohort study based on a clinical dataset containing 18,007 note fragments linked to 672 unique patient records between 12 October 2010 and 21 April 2026. A rule-based natural-language-processing-assisted chart review framework was used to identify patients with trigeminal pain and to extract documentation-derived demographic features, pain distribution, secondary causes, dental pathway variables, imaging signals, medication exposure, procedures, and outcome language. Patients were grouped into primary/classical TN, secondary TN/trigeminal pain, and dental-first or mimic pathways using predefined operational criteria. Results: A total of 455 patients met criteria for the analytic trigeminal pain cohort; 311 (68.4%) carried explicit TN terminology. Mean age was 58.7 years, median age 60 years, and 267 of 428 patients with recoverable sex data (62.4%) were women. Trigeminal branch involvement could be extracted in 351 patients (77.1%), with V2 involvement documented in 256 (56.3%), V3 involvement in 218 (47.9%), and V1 involvement in 138 (30.3%). The final NLP-derived phenotypic distribution comprised 201 primary/classical TN cases (44.2%), 146 secondary TN/trigeminal pain cases (32.1%), and 108 dental-first or mimic presentations (23.7%). MRI was documented in 384 patients (84.4%), neurovascular conflict or vascular loop in 253 (55.6%), multiple-sclerosis-related disease in 69 (15.2%), and tumor-related trigeminal involvement in 84 (18.5%). Prior dental evaluation was identified in 169 patients (37.1%), and prior dental procedures in 114 (25.1%). Carbamazepine exposure was documented in 367 patients (80.7%), pregabalin in 221 (48.6%), gabapentin in 150 (33.0%), oxcarbazepine in 116 (25.5%), and phenytoin in 73 (16.0%). At least one invasive or image-guided procedure was documented in 390 patients (85.7%), including nerve blocks/injections in 355 (78.0%), radiofrequency procedures in 126 (27.7%), balloon compression in 90 (19.8%), microvascular decompression in 113 (24.8%), and stereotactic radiosurgery in 55 (12.1%). Dental-first patients were significantly more likely to have undergone prior dental procedures (65.7% vs. 3.5% in primary/classical TN and 24.7% in secondary TN; p < 0.001), whereas secondary TN/trigeminal pain was associated with higher use of radiofrequency procedures (36.3%; p = 0.017), higher use of stereotactic radiosurgery (19.9%; p = 0.002), higher recurrence documentation (70.5%; p = 0.001), and a higher rate of complete pain relief documented at last follow-up (46.6%; p = 0.004). Conclusions: In tertiary practice, trigeminal pain is substantially broader than a formal TN label. Secondary disease and dental-first pathways account for a large fraction of referrals, and management is characterized by heavy medication burden, frequent escalation, and recurrent retreatment. A structured phenotyping approach may help convert routine clinical documentation into a clinically meaningful framework for diagnostic triage and treatment selection, although imaging and outcome variables require cautious interpretation when derived from retrospective free text. Full article

Hard-to-heal wounds pose a significant challenge in clinical practice due to the fact that the conventional treatments used are not always effective. For this reason, it is necessary to design alternatives to achieve an adequate resolution. In this context, a new Advanced Therapy product was produced in a Good Manufactured Practices Facility in the setting of a clinical trial authorised for the European Medicines Agency (EUCT 2023-505017-25-02). Briefly, an autologous plasma scaffold containing bone marrow mononuclear cells was applied to a 63-year-old male patient who presented a non-healing wound despite two months of self-care and three months of primary care treatment. After cleaning the affected area, a single-dose plasma scaffold with embedded bone marrow mononuclear cells was applied over the wound. Six weeks after treatment, the wound exhibited remarkable healing with complete closure as evidenced by follow-up assessments at different time points. Quality of life measures significantly improved, aligning with clinical findings, and no adverse effects were observed. While further studies are needed, the issues presented in this case report show the promising results obtained forthe first patient included in the trial and treated with this innovative alternative, which supports the potential of mononuclear cells combined with plasma as a therapeutic option for chronic wounds. Full article

This study investigated the application of six machine learning regression algorithms such as Random Forest, CatBoost, K-Nearest Neighbours, XGBoost, LightGBM, and Gradient Boosting, paired with Molecular ACCess System (MACCS) key fingerprints for the quantitative prediction of aromatase (CYP19A1) inhibitory potency, expressed as pIC₅₀. A dataset of 187 compounds was assembled from the ChEMBL database (version 33, Target ID: CHEMBL1978) following by systematic data curation workflow encompassing duplicate removal, pIC₅₀ transformation, and activity-based filtering. Model performance was rigorously evaluated using an 80/20 stratified train/test split, 5-fold cross-validation, and Y-randomisation testing to ensure unbiased assessment of predictive generalisation. Feature selection via CatBoost permutation importance on the held-out test set identified the top 20 predictive MACCS keys from an initial 166-bit space, substantially reducing dimensionality and improving generalisation across all models. Among the algorithms evaluated, CatBoost trained on the top 20 features achieved the strongest test-set performance (R² = 0.693, RMSE = 0.794, MAE = 0.659) with the most stable cross-validation R² (0.062 ± 0.304), outperforming all other algorithms. Y-randomisation testing returned an empirical p-value of <0.01, confirming that model performance reflects genuine structure–activity relationships rather than statistical chance. Permutation importance and SHAP analysis identified nitrogen-containing heterocyclic fragments (MACCS_41, MACCS_145) and halide-bearing substructures (MACCS_109) as the primary structural determinants of aromatase inhibitory potency, consistent with established CYP19A1 pharmacophoric requirements. Application of the model to ten representative plasticizers demonstrated that the refined applicability domain (h* = 0.423) accommodated eight of the ten compounds, enabling reliable potency predictions across phthalate esters and bisphenol analogues. These findings establish a transparent and reproducible QSAR framework for first-tier endocrine disruption risk screening of plasticizers and highlight the importance of permutation-based feature selection and applicability domain assessment in QSAR model development. Full article