Search Results (764)

Background/Objectives: Patients with chronic kidney disease (CKD) often present with peripheral arterial stiffness (PAS), which is associated with an increased cardiovascular risk. This study assessed the association between circulating osteoprotegerin (OPG), a known mediator of vascular calcification, and PAS, measured as brachial–ankle pulse wave velocity (baPWV), in patients with CKD. Methods: This cross-sectional investigation engaged 200 individuals with non-dialysis CKD. Serum OPG concentrations were measured using a commercial enzyme-linked immunosorbent assay. Participants were classified as having PAS when either left or right baPWV was greater than 18.0 m/s; those with baPWV values of 18.0 m/s or lower were assigned to the control group. Results: Eighty-six patients (43.0%) had PAS. In comparison to controls, PAS patients were older (p < 0.001) and had higher proportions of diabetes mellitus (p = 0.023) and hypertension (p = 0.010); systolic blood pressure was higher (p < 0.001), urine protein-to-creatinine ratio was elevated (p = 0.004), and serum OPG was markedly greater (p < 0.001), whereas estimated glomerular filtration rate was lower (p = 0.003). After full adjustment, OPG levels, in addition to older age and diabetes mellitus, demonstrated an independent association with PAS (odds ratio: 1.008; 95% confidence interval: 1.002–1.015; p = 0.010). The OPG level was positively associated with bilateral baPWV by Spearman’s correlation analysis (p < 0.001). Conclusions: Circulating OPG level showed an independent association with PAS and baPWV in CKD patients not yet on dialysis. Hence, OPG can be a potential marker of vascular risk in this patient population. Full article

Endocrine-disrupting chemicals (EDCs) are important environmental risk factors for urogenital malignancies, but the shared molecular mechanisms underlying their carcinogenic effects remain poorly understood. Here, we systematically investigated the common pro-tumorigenic mechanisms of 12 prevalent EDCs, including anthracene, benzo[a]pyrene (BaP), bisphenol A, clofenotane, di(2-ethylhexyl) phthalate, diazinon, dibutyl phthalate, glyphosate, malathion, perfluorooctanoic acid, polychlorinated biphenyls, and triclosan, across four urogenital cancers, including bladder cancer (BLCA), renal cell carcinoma (RCC), prostate adenocarcinoma (PRAD), and testicular germ cell tumor (TGCT). By integrating network toxicology and protein–protein interaction analysis, we identified shared hub targets linking EDC exposure to tumor progression. EGFR and CASP3 were identified as core targets in BLCA, EGFR and CASP9 in RCC, and CASP3, ESR1, and EGFR in PRAD, whereas KIT emerged as a broadly relevant target in TGCT. Molecular docking and molecular dynamics simulations supported the stable binding of EDCs to these targets. Among the predicted interactions, BaP showed strong binding affinity for CASP9 (ΔG = −9.8 kcal/mol) and was therefore selected for experimental validation. Analysis of TCGA data showed that elevated CASP9 expression was significantly associated with poorer overall survival in patients with RCC. In 786-O and ACHN cells, chronic exposure to an environmentally relevant concentration of BaP significantly increased CASP9 protein stability without altering its mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings identify shared molecular targets of EDCs across urogenital cancers and provide new mechanistic insight into EDC-driven tumor progression, prioritizing potential biomarkers and therapeutic targets for environmentally related malignancies. Full article

Background/Objectives: Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, driven by invasive behavior and frequent resistance to systemic therapies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit patients with EGFR-mutant NSCLC, but their efficacy is often limited by tumor-intrinsic and environmental resistance mechanisms. Benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon from tobacco smoke, combustion, and dietary sources, is a known carcinogen; however, its role in modulating therapeutic responses is poorly understood. Studies, including ours, implicate the platelet-activating factor-receptor (PAFR) pathway in mediating environmental pollutant and therapy-induced effects on tumor growth and microvesicle particle (MVP) release. We hypothesized that PAFR activation mediates BaP-induced NSCLC progression and influences EGFR-TKI responses. Methods: We assessed the effects of BaP, PAFR agonist CPAF, EGFR-TKIs, and their combinations on cell viability, proliferation, migration, anchorage-independent growth, and MVP secretion. Results: BaP did not alter cell survival but significantly increased migration, growth, colony formation, and MVP release, similar to CPAF, and these effects were blocked by a PAFR antagonist or acid sphingomyelinase inhibitor. Notably, BaP did not significantly reduce EGFR-TKI efficacy at tested concentrations. Conclusions: These results show that environmental carcinogens modulate NSCLC behavior through PAFR signaling without compromising EGFR-TKI responsiveness, highlighting PAFR as a potential therapeutic target. Full article

Phase-inversion in situ implants (PIISIs) represent a versatile polymer platform in which the rational choice of matrix former and solvent system directly governs the macroscopic properties of the resulting depot. This study applied a Quality by Design (QbD) approach to rationalize a bleached shellac–based PIISI, with particular focus on the physicochemical interactions between the polymer and the injection vehicle. Bleached shellac—a natural, low-cost, biodegradable oligomeric resin bearing –COOH, –OH, and ester functional groups—was selected as the matrix former and screened in seven neat solvents and five 1:1 binary combinations at 25% (m/m). Twelve formulations were evaluated against a predefined set of critical quality attributes, including injectability, phase-inversion kinetics, solvent diffusion volume, and implant structure (n = 5 per formulation; mean ± standard deviation (SD); one-way analysis of variance (ANOVA) with Tukey’s post hoc test, p < 0.05). Three lead solvent systems—propylene glycol/N-methylpyrrolidone (PG+NMP), PG/dimethyl sulfoxide (PG+DMSO), and DMSO/benzyl alcohol (DMSO+BA)—were identified as those providing an optimal balance between hydrogen-bond donor/acceptor solvation and controlled solvent extraction. In the second stage, shellac concentration (20–35%) was optimized, with 30% shellac in PG+NMP yielding the fastest phase inversion (~50 s), a structurally uniform matrix, and the lowest swelling (22%). A working mechanistic framework consistent with all observed critical quality attribute (CQA) trends in which solvent hydrogen-bond donor/acceptor balance and water miscibility govern implant architecture is proposed, and it is intended as a hypothesis-generating basis for the rational design of PIISI formulations; direct validation by spectroscopic, thermal-analytical, and biological methods is identified as the next step. The developed formulations are presented as a preliminary physicochemical platform; biological validation (in vitro cytocompatibility and inflammatory response assessment) is required before the system can be considered a validated formulation for dental drug delivery. Full article

Honey is a natural food product which in traditional production represents a clear example of the “farm-to-table” principle, as it excludes any processing of the original product. This study proposes an analytical approach for determining 30 most frequently determined chemical elements (Ag, Al, As, B, Ba, Bi, Ca, Cd, Co, Cr, Cs, Cu, Ga, In, Fe, K, Li, Mg, Mn, Na, Ni, P, Pb, Rb, S, Se, Sr, Te, V, and Zn) in honey, emphasizing the use of a relatively large sample mass to overcome sample heterogeneity and ensure accurate and reliable results. About 31 linden and 16 rapeseed honey samples from different Bulgarian regions were analyzed. Pollen analysis data showed that pollen content ranged from 30 to 78% for linden and 30 to 93% for rapeseed honey. The results identify a group of elements—K, Ca, Mg, Sr, and Rb—whose concentrations show statistically significant dependence on the floral origin and purity of the honey. Based on these findings, these elements are proposed as potential markers for identifying the botanical origin of honey. Furthermore, macronutrients and micronutrients (P, S, B, Cu, Fe, Mn, and Zn), which are generally subject to homeostatic regulation, as well as micro-elements (Al, As, Cd, Co, Cr, and Pb), which are more strongly influenced by environmental factors, showed limited discriminatory potential and no clear correlation with floral purity and botanical origin. Therefore, they should not be used as criteria when assessing the botanical origin of honey, but rather as indicators of environmental pollution and potential quality or safety concerns. Overall, the research contributes to improving the reliability of botanical classification of honey by combining robust analytical methodology with statistically validated elemental markers, while also distinguishing between natural compositional features and contamination-related signals. Full article

This study presents an integrated process for the recovery and purification of lithium hydroxide (LiOH) from lithium sulfate (Li₂SO₄) solution obtained by sulfuric acid leaching of spent crucibles used for producing the cathodes of LIBs. The recovered leachate contains considerable concentrations of metallic impurities, including Na, K, Mg, Ca, Al, and Ni, which hinder the direct production of high-purity LiOH. To overcome this limitation, a pretreatment step combining cation- and anion-exchange resins was introduced to control impurity levels and condition the solution prior to conversion. Under the optimized ion-exchange condition of 10 g cation-exchange resin and 50 g anion-exchange resin, the solution pH was adjusted to 6–7, resulting in effective impurity removal through combined ion-exchange and solution-conditioning effects. More than 90% of Al was removed, while Mg, Ca, Na, K, and Ni were removed by approximately 70–75%. After purification, LiOH was produced through a double-displacement conversion reaction using Ba(OH)₂. The results showed that the reaction temperature and the [OH]:[Li] molar ratio were the key parameters governing the sulfate-removal-based apparent conversion efficiency and filtrate-based LiOH purity. Excess OH⁻ promoted the formation of dissolved and complexed species, thereby lowering the purity of the LiOH-containing filtrate. In contrast, the optimum condition was identified at 70 °C and an [OH]:[Li] molar ratio of 1:1, under which SO₄²⁻ was effectively removed as solid BaSO₄. Under these conditions, the sulfate-removal-based apparent conversion efficiency reached 91.91%, and the filtrate-based LiOH purity was 98.84%. X-ray diffraction analysis confirmed the coexistence of LiOH·H₂O and LiOH phases in the final recovered product, whereas the precipitate was identified as single-phase BaSO₄, indicating effective sulfate removal. Overall, this study demonstrates the feasibility of producing high-purity LiOH from sulfation-derived Li₂SO₄ leachate through a sequential process consisting of impurity removal, conversion, and drying. The findings provide fundamental process data for the design of lithium recovery and purification routes using spent cathode crucibles as secondary lithium resources. Full article

A three-year (January 2020–December 2022) daily dataset of 16 polycyclic aromatic hydrocarbons (PAHs) collected in parallel with PM_2.5 and a suite of meteorological variables at a coastal Mediterranean urban site in southern Italy (Pomigliano d’Arco, Campania) is presented and analysed. Raw PAH time series were decomposed into a long-term trend component (LT), a seasonal component (ST), and a residual component (RT) using an iterative missing-value-robust Kolmogorov–Zurbenko (KZ) moving-average filter. Spearman rank correlations between PAH concentrations and four meteorological predictors (mean temperature, relative humidity, mean wind speed, and maximum wind speed) were computed for each congener. Diagnostic molecular ratios—Fla/(Fla + Pyr), BaP/BghiP, Indeno[1,2,3-cd]pyrene/(IcdP + BghiP), and BaA/(BaA + Chr)—were evaluated seasonally and interpreted jointly with an information-theoretic Bayesian mixture modelling procedure (SNOB/MML) and with the documented susceptibility of some PAH ratios, especially BaP-containing ratios, to atmospheric ageing, phase repartitioning and summer photodegradation. Total PAH concentrations (sum of 16 congeners) ranged from <1 ng m⁻³ in summer to 46 ng m⁻³ during winter high-pollution episodes, with BaP peaking at ≈6.7 ng m⁻³. Because BaP was measured in the PM_2.5 fraction, comparisons with the EU annual target value of 1 ng m⁻³ established for PM₁₀-bound BaP are treated as indicative context only, not as formal compliance statements. Pronounced seasonal variability was driven primarily by residential heating emissions, and the incremental lifetime cancer risk (ILCR) for inhalation exposure reached $1.03\times {10}^{-4}$ (95% CI: $0.88$–$1.20\times {10}^{-4}$) during the heating season under a continuous outdoor-exposure worst-case scenario. The absolute ILCR magnitude is conditional on the selected TEF scheme and on the adopted BaP unit-risk coefficient; under an additional indoor-dominated scenario (16 h day⁻¹, infiltration factor 0.6), the corresponding risk remained above the conventional ${10}^{-6}$ benchmark. An anomalous near-background PAH signal during spring 2020 is attributed to the COVID-19 national lockdown, which reduced total PAH concentrations by approximately 85% relative to the seasonal component predicted by the iterative moving-average filter for the same calendar window. Source apportionment via diagnostic ratios identifies residential/biomass combustion as the dominant cold-season source and vehicular emissions as the prevailing warm-season source. These results provide a novel characterisation of PAH pollution dynamics in the undersampled southern Mediterranean and provide evidence to support targeted abatement policies. Full article

Uncontrolled scrap tire fires represent high-intensity episodic emission events that pose severe toxicological threats to urban environments. This study employs atmospheric dispersion modelling to quantify the impact of a tire stockpile fire on a distal educational receptor, evaluating two distinct dynamic stages of the event: an initial high-intensity open flame scenario (E1, 4 h) and a prolonged smouldering/suppression scenario (E2, 6 h), induced by firefighting interventions. Results reveal extreme pollutant loading at the receptor site during E1, with PM₁₀ and SO₂ concentrations peaking at 23,766 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$ and 7821 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$ respectively, indicating an immediate risk of acute respiratory distress. The organic fraction was dominated by volatile organic compounds (VOCs) (8691 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$) and a ∑16 PAHs flux of 313.9 ${\displaystyle \frac{\mathsf{\mu }\mathrm{g}}{{\mathrm{m}}^3}}$. Toxicological assessment identified Benzo[a]pyrene (BaP) as the primary driver of health hazards, contributing approximately 70% to the carcinogenic risk profile. A critical disparity was observed between Mutagenic Equivalency (MEQ) of 18.32 and Toxic Equivalency (TEQ) of 15.37, suggesting that standard monitoring significantly underestimates the biological threat to sensitive paediatric populations. These findings demonstrate that acute, oxygen-limited tire combustion creates a concentrated toxic slug of high-molecular-weight PAHs. The study underscores the necessity of integrating mutagenicity-based models into emergency response protocols to accurately safeguard vulnerable communities against the long-term toxicological legacy of elastomer thermolysis. Full article

Although species identification is crucial for land-snail eggs, limited effort has been made to identify the species responsible for producing the eggs. In this study, we used laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) to measure 54 elements in both the eggshells and adult shells of Bradybaena ravida and Cathaica fasciola and we used scanning electron microscope (SEM) to analyze the microstructure of the eggshells of the two species. Our results reveal that while the concentrations of Sr, Na, Mg, P, and Ba in the adult shells of the two species are not distinct, they are distinct or partially distinct between their eggshells, indicating that these elements have the potential to differentiate the eggs of the two species. Moreover, the eggshells of C. fasciola exhibit a blocky morphology without cavities, whereas those of B. ravida, while also blocky, contain irregular cavities. These distinct elemental and microstructural characteristics enable the effective differentiation of the eggs of B. ravida and C. fasciola. Our study demonstrates the feasibility of a critical microscopic methodology for identifying land-snail eggs at the genus/species level, thereby facilitating deeper exploration of their value in understanding biological, climatic, and ecological changes. Full article

Background: Acquired resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib, often mediated by EGFR triple mutations, poses a major clinical challenge in non-small cell lung cancer (NSCLC) treatment. Among these, some rare mutations, such as L858R/T790M/L792H and L858R/T790M/G796R, create steric hindrance that directly interferes with osimertinib binding, yet effective targeted therapeutic strategies for these specific mutations remain lacking. Cudratricusxanthone A (CTXA), a natural xanthone derivative isolated from Cudrania tricuspidata Bur., has demonstrated various pharmacological activities, but its effects against EGFR triple-mutant NSCLC have not been systematically investigated. Methods: Stable Ba/F3 and NIH/3T3 cell lines expressing EGFR L858R/T790M/L792H or L858R/T790M/G796R triple mutations were generated via electroporation. The antiproliferative effects of CTXA were evaluated by MTT/MTS assays, colony formation, and wound healing assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression of EGFR signaling pathway components (p-EGFR, p-ERK, p-AKT, p-STAT3) and cell cycle regulators (Cyclin D1, CDK4) were examined by Western blotting. Molecular docking and 200 ns molecular dynamics simulations were performed to investigate the stability and binding modes of CTXA to the mutant EGFR kinase domains. Results: The successfully established triple-mutant cell lines exhibited high EGFR expression, IL-3-independent growth, and significant resistance to osimertinib. CTXA inhibited the proliferation of all triple-mutant cell lines in a time- and concentration-dependent manner, with 48 h IC₅₀ values ranging from 0.362 to 2.488 μM. Mechanistically, CTXA suppressed EGFR autophosphorylation and downregulated downstream p-ERK, p-AKT, and p-STAT3. CTXA induced G1 phase cell cycle arrest by downregulating Cyclin D1 and CDK4, significantly promoted apoptosis, and inhibited cell migration. Molecular docking revealed that while osimertinib binding was blocked by steric hindrance from His-792 or Arg-796, CTXA adapted to the mutated ATP-binding pockets through multiple hydrogen bonds and extensive hydrophobic interactions. Molecular dynamics simulations confirmed the stable binding of CTXA to both mutant EGFR proteins over the 200 ns simulations. Conclusions: This study demonstrates for the first time that the natural compound CTXA possesses antitumor efficacy against EGFR L858R/T790M/L792H and L858R/T790M/G796R mutants by regulating EGFR-ERK/AKT/STAT3 signaling. Our findings position CTXA as a promising lead compound for tackling this challenging form of acquired resistance and highlight the value of natural products in multi-target antitumor drug discovery. Full article

This study aimed to investigate the effects of dietary bile acids (BA) supplementation on serum antioxidant capacity, fecal fermentation characteristics, microbial diversity, and community composition in culled ewes. Twenty 5-year-old culled Hu ewes with similar body weights (42.95 ± 1.07 kg) were randomly allocated to two groups (n = 10 per group). The control group (CON) received a basal diet, while the treatment group (BA400) was fed the same basal diet supplemented with 400 mg/kg BA. Compared with the CON group, the BA400 group showed enhanced serum activities of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase, while also showing reduced concentrations of cortisol, malondialdehyde, and reactive oxygen species (p < 0.05). Fecal pH, ammonia nitrogen, total volatile fatty acids, and the concentrations and proportions of individual volatile fatty acids remained unaffected by BA supplementation (p > 0.05). Microbial analysis revealed that the BA400 group exhibited higher fecal bacterial richness and diversity than the CON group (p < 0.05). Analysis of similarities revealed significant differences between the CON and BA400 groups (R = 1.000, p = 0.007). Specifically, BA supplementation increased the relative abundances of beneficial taxa, including Verrucomicrobiota and Akkermansia, while decreasing potentially pathogenic bacteria such as Campylobacterota and Proteobacteria. These findings indicate that dietary BA supplementation improves serum antioxidant capacity and modulates fecal microbial diversity and community structure in culled ewes, suggesting that hindgut microbiota may contribute to the health benefits of BA supplementation in ruminant production. Full article

Background/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case–control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 µg/L; additionally, a lower cut-off of 7.0 µg/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 µg/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p < 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS > 0.91. A Naïve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients. Conclusions: Interpretation of GHST should include the patient’s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children. Full article

This study investigated sub-basin variability in dissolved (dBa)–excess particulate (Ba_xs) barium relationships and Ba flux patterns across the western and central Mediterranean Sea during late spring 2017 (PEACETIME cruise). The dBa concentrations increased from ~35 nmol L⁻¹ near the surface to ~70 nmol L⁻¹ at 2500 m, consistent with the relatively weak vertical dBa gradient typical of the Mediterranean. Depth profiles of dBa showed distributions consistent with Ba_xs dynamics associated with organic matter remineralization at mesopelagic depths (100–1000 m). Ba_xs exhibited basin-dependent maxima, with lower (<300 pM) depth-weighted average concentrations confined to the upper mesopelagic in the Tyrrhenian and Ionian basins and higher (up to 650 pM) and deeper concentrations (to ~1000 m) in the Algero–Provençal basin, suggesting contrasted remineralization horizon structures. A simplified steady-state 1-D approach yielded first-order mesopelagic dBa removal fluxes of ~0.3 ± 0.1 µmol m⁻² d⁻¹ in the Algero–Provençal basin to 1.7 ± 1.0 µmol m⁻² d⁻¹ in the Ionian basin, consistent with previous estimates obtained from a coupled dBa and parametric optimum multiparameter approach. Together, these paired dissolved and particulate Ba observations refined the Mediterranean Ba cycle framework and provided additional geochemical constraints for interpreting mesopelagic carbon remineralization processes. Full article

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are major risk factors for lung cancer and other diseases, acting through the aryl hydrocarbon receptor (AHR). Alveolar macrophages (AMs) help regulate the lung microenvironment by responding to inhaled toxicants and resident microbiota. Although small extracellular vesicles (sEVs, aka exosomes) released by AMs mediate intercellular communication and immune responses, the influence of lung microbiota on sEV biogenesis and the mechanisms underlying sEV dysregulation during PAH exposure remain unknown. Here, we investigated the interplay between AMs, B[a]P, and lung microbiota, focusing on sEV-associated miRNAs (exo-miRNAs). Murine AMs (MH-S) were exposed to varying B[a]P concentrations in the presence or absence of murine lung microbiota with or without an AHR antagonist. sEVs from each condition were characterized and profiled for miRNA. Distinct miRNA signatures emerged: high-dose B[a]P enriched miRNAs linked to cancer progression, whereas lung microbiota alone or with low-dose B[a]P induced tumor-suppressor miRNAs that limit proliferation and metastasis and promote apoptosis, an effect enhanced by AHR antagonism. Lung microbiota appeared to counteract high-dose B[a]P by modulating tumor-suppressive exo-miRNAs. This study demonstrates that lung microbiota-induced exo-miRNAs critically shape AM-derived sEV-miRNA signaling during PAH exposure. The identified exosomal miRNAs could serve as important exposure biomarkers and therapeutic targets for mitigating B[a]P-induced toxicity and cancer development. Full article

Background: Pediatric surgical care in Germany is delivered within a highly decentralized system, and training structures vary considerably between institutions. Adequate operative exposure is essential for competency-based training. The specialty requires a high number of operative procedures during training, yet concerns have been raised that residents may not achieve the required case numbers within the standard training period. The German Model Training Regulations (Musterweiterbildungsordnung, MWBO) define 22 procedural categories with specific case number targets for pediatric surgery. However, the extent to which current training structures allow for the fulfillment of these requirements remains unclear. This study examines the distribution of procedures and residents across different hospital types and estimates whether the available procedural volume may be sufficient under simplified allocation assumptions. Methods: We conducted a nationwide analysis of pediatric surgical training capacity in Germany using procedural data from hospital quality reports published by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) between 2012 and 2023. A total of 3440 OPS codes were assigned to 22 training categories, and case volumes were analyzed across different hospital types. The estimated training capacity was calculated assuming even distribution of cases among residents, and that all eligible procedures are performed with full resident access. Results: Data from an average of 82.3 pediatric surgical departments per year were analyzed, including 29.7% university hospitals, 58.7% non-university departments, and 11.7% other institutions. Most departments reported fewer than five residents. Between 2012 and 2023, the mean number of residents increased slightly across all hospital types, while inpatient numbers declined. Consequently, inpatient exposure decreased from 469.8 to 354.0 cases per resident per year. Patient exposure differed significantly by institutional category (p < 0.001), with higher exposure in non-university departments compared with university hospitals. Across all hospital types, the mean number of fulfilled procedural training categories declined over time. No institution met the target numbers for all categories without cooperation with other units. Thoracic surgery procedures were least frequently covered, whereas appendectomies and inguinal hernia repairs were most consistently fulfilled. Distinct patterns of subspecialization emerged, with trauma procedures less frequently reported at university hospitals and thoracic procedures less frequently reported at non-university departments. Although the overall national procedural volume appears sufficient for most training requirements, low-volume and highly specialized procedures were concentrated at selected centers, limiting their accessibility for trainees. Conclusions: Even though there are sufficient pediatric surgical procedures in Germany, they are unevenly distributed between hospitals. Under a simplified allocation model, many pediatric surgical departments in Germany currently lack sufficient procedural volume to meet training requirements in the defined training timeframe for all trainees. Structural reforms—including mandatory national documentation, minor MWBO adjustments and the creation of training networks—are necessary to ensure comprehensive and equitable pediatric surgical education. Without these changes, extended training durations and reduced trainee satisfaction may contribute to workforce shortages and limit the future quality of pediatric surgical care in Germany. Full article