Search Results (1,501)

The newly identified greisen-hosted Nb-Ta mineralization in the Qidashan iron deposit, Liaoning Province, China, offers a unique opportunity to explore how hydrothermal processes contribute to the enrichment of critical metals. In this study, an integrated analytical approach of petrographic observation and scanning electron microscopy–energy-dispersive spectrometer (SEM-EDS), electron probe microanalyzer (EPMA), and laser ablation inductively coupled plasma mass spectrometer (LA-ICP-MS) U-Pb dating of columbite-group minerals (CGMs) were employed to systematically decipher the paragenetic sequence, micro-structure, elemental composition and mineralization age of CGMs, aiming at the genesis of greisen-hosted Nb-Ta mineralization. The mineralization is characterized by the abundant occurrence of CGMs. Three generations of CGMs and two mineralization stages are distinguished: stage I contains CGM Is and CGM IIs, with Nb₂O₅ ranging from 25.7 to 69.56 wt.% and Ta₂O₅ from 5.8 to 52.5 wt.%; stage II contains CGM IIIs, with Nb₂O₅ between 59.5 and 71.5 wt.% and Ta₂O₅ between 3.5 and 16.2 wt.%. CGM Is consist of euhedral, homogeneous crystals of more than 100 μm, exhibit low Ta/(Nb + Ta) ratios (0.05–0.06) and high Mn/(Fe + Mn) ratios (0.19–0.26), and belong to columbite-Fe. CGM IIs generally overgrow on CGM Is with hydrothermal overprinting textures, and show significant compositional gaps compared to CGM Is, exhibiting higher Ta/(Nb + Ta) ratios (0.13–0.55) and restricted Mn/(Fe + Mn) ratios (0.15–0.18), with some belonging to columbite-Fe and others to tantalite-Fe, which reveals a transition from magma to “hydrosilicate fluid”. CGM IIIs are mainly anhedral and homogeneous, with a grain size of less than 50 μm. However, some CGM IIIs overgrow on CGM IIs and/or CGM Is with patchy textures indicative of subsequent hydrothermal overprinting of hydrosilicate fluid, forming a coarse-grain size over 100 μm. CGM IIIs are characterized by lower Ta/(Nb + Ta) ratios (0.03–0.14) and variable Mn/(Fe + Mn) ratios (0.08–0.26), and they belong to columbite-Fe. LA-ICP-MS U-Pb dating yields weighted mean ²⁰⁶Pb/²³⁸U ages of 2646 ± 15 Ma for stage I and 2500 ± 28 Ma for stage II, indicating two-stage Nb-Ta mineralization. The early mineralization may correlate with the partial melting of volcanic–sedimentary rocks due to the geothermal anomalies associated with ~2.7 Ga submarine volcanism, and the late mineralization formed by the magmatic hydrothermal activities related to emplacement of the Qidashan granite in 2.5 Ga. We therefore propose that the two-stage greisen-hosted Nb-Ta mineralization probably widely occurred in these sedimentary–metamorphic iron deposits in the Anshan–Benxi area and even in the northern edge of the North China Craton, and it may provide new insights for evaluating the Nb-Ta resource potential in similar Algoma-type iron deposits globally. Full article

Combined pulse laser systems combining continuous-wave (CW) lasers and nanosecond pulsed lasers have shown clear advantages in metal ablation and surface modification. However, the plasma shielding effect induced by nanosecond pulses and the associated shock-wave phenomena in hybrid laser systems remain insufficiently investigated, particularly regarding their influence on CW laser energy coupling. In this study, the ablation behavior of metal targets under the combined irradiation of a 500 W CW laser and nanosecond pulsed lasers with pulse energies ranging from 0.4 J to 1.0 J was investigated. High-speed plasma imaging was employed to analyze laser–material interaction characteristics, including absorption behavior and molten material ejection, while high-speed infrared thermography was used to monitor transient temperature evolution during combined pulse laser processing. Macroscopic and microscopic analyses were conducted to characterize damage morphology, and a three-dimensional surface profilometer was used to quantitatively evaluate ablation efficiency. The results show that, under combined pulse laser irradiation, the removed volume increased from 0.05 mm³ to 0.618 mm³ and the ablation depth increased from 0.136 mm to 0.776 mm. Compared with CW laser processing alone, the ablation efficiency was markedly enhanced. This improvement is attributed to the combined effects of optimized energy deposition, thermal distribution, and material response. In addition, the plasma shielding effect was observed to vary with nanosecond pulse energy, indicating that precise energy control is critical for performance enhancement. This study demonstrates the potential of combined pulse laser technology for high-efficiency and high-precision metal surface processing and micro–nano fabrication. Full article

Tau-associated microRNAs have been implicated in neurodegenerative disorders, yet their behavior during SARS-CoV-2 infection remains insufficiently understood. The aim of this study was to quantify circulating levels of miR-92a-3p, miR-320a, and miR-320b in hospitalized COVID-19 patients and evaluate their relationship with disease severity and established biomarkers of neuroinflammation and neurodegeneration. We conducted a retrospective single-center study including 38 hospitalized COVID-19 patients and 12 healthy controls. MicroRNA plasma levels were quantified by RT-qPCR. Patients were stratified by ARDS severity and ventilation requirements. Correlations between miRNAs and previously published biomarkers were examined. All three miRNAs were elevated in COVID-19 patients compared to healthy controls. miR-92a-3p and miR-320a were increased in both severe and non-severe cases, while miR-320b was significantly elevated only in severe disease. No statistically significant correlations were observed between miRNA levels and NfL, GFAP, MMP-9, or other biomarkers in COVID-19 patients. Tau-associated circulating microRNAs appear dysregulated in acute SARS-CoV-2 infection, but their relationship to neurological injury remains unclear. These findings are preliminary and require validation in larger, longitudinal cohorts with standardized neurological outcomes. Full article

Background/Objectives: Despite recent advances in breast cancer diagnostics, therapies and personalized medicine through genetic profiling, effective treatment of aggressive subtypes, particularly triple-negative breast cancer (TNBC), remains a considerable clinical challenge. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that influence tumor progression and are detectable extracellularly in biofluids, where they are typically protected within extracellular vesicles (e.g., exosomes) or associated with RNA-binding proteins and lipoprotein complexes. This review integrates current evidence on oncogenic and tumor-suppressive extracellular miRNAs in breast cancer, with emphasis on subtype-specific functions and potential clinical relevance as liquid-biopsy biomarkers and therapeutic targets. Methods: A PubMed-based literature review (January 2000–February 2026) was conducted using search terms combining “breast cancer” with “miRNA/microRNA” and “circulating/plasma/serum/exosomal/extracellular vesicle.” Studies were prioritized if they provided validated targets/mechanisms and/or human clinical evidence for diagnostic, prognostic, or predictive utility; discrepant findings were evaluated in a subtype-aware framework. Findings were organized into functional categories (e.g., EMT/metastasis, cell-cycle/DNA damage, immune modulation, and hormone/growth factor signaling). Clinical and translational studies evaluating circulating miRNAs for diagnosis, prognosis, treatment response, and toxicity prediction were synthesized, together with key pre-analytical and analytical variables that affect reproducibility. Results: Across mechanistic and clinical studies, miR-21 and miR-155 recur as prominent oncogenic miRNAs, whereas miR-205 is frequently reported as a tumor-suppressive miRNA that is reduced in breast cancer and in circulation in several cohorts. Panels combining these miRNAs show promise for sensitive and specific breast cancer diagnostics. Additionally, several miRNAs show context- or subtype-dependent effects, with opposing activities reported between TNBC and estrogen receptor (ER)-positive disease (e.g., miR-17-92, miR-425, miR-181 family members, miR-31, and miR-24). Conclusions: Circulating miRNAs represent a promising class of minimally invasive biomarkers and potential therapeutic targets; however, translation is constrained by biological context dependence and by pre-analytical and analytical variability. Standardized protocols and rigorously validated, subtype-aware biomarker panels will be essential for clinical implementation and for enabling miRNA-informed precision oncology in breast cancer. Full article

Objectives: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEFV mutations, leading to recurrent fever and inflammation. Dysregulation of innate and adaptive immunity, including altered expression of microRNAs and immune regulatory molecules, may contribute to disease heterogeneity. The role of CTLA-4, DTX1, and selected miRNAs in FMF pathogenesis remains unclear. Methods: We conducted a case–control study including 48 pediatric FMF patients and 36 age- and sex-matched healthy controls. Serum miR-204-3p and miR-223-3p levels were assessed via qRT-PCR. Plasma concentrations of pyrin, CTLA-4, and DTX1 were measured using ELISA. Clinical data and MEFV mutation types were analyzed in relation to biomarker levels. Results: There was no statistical significance between the groups in plasma CTLA-4 levels. Serum miR-204-3p, miR-223-3p, and plasma DTX1 levels were found to be significantly lower in FMF patients, while plasma pyrin levels (p < 0.05, in all) were significantly higher. CTLA-4 levels were positively correlated with pyrin and DTX1 levels (r = 0.602; p < 0.001; r = 0.740; p < 0.001, respectively). Conclusions: miR-204-3p and miR-223-3p may be associated with FMF pathogenesis. Increased levels of the pyrin protein, encoded by the MEFV gene, may have an important role in apoptotic and inflammatory signaling pathways. A decrease in DTX1 levels and a positive correlation between DTX1 and CTLA-4 suggest that subclinical inflammation may continue in attack-free periods in FMF patients. Full article

The elemental composition of the vitreous humor may reflect physiological and pathological processes occurring in the eye. The objective of this study was to provide a complex multielemental analysis of human vitreous humor. Vitreous humor samples (n = 57) were collected post-mortem during autopsies. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to quantify micro-, trace-, ultra-trace, and toxic elements. The study showed the occurrence of elements at the ppm (Na, K, P, Ca, Mg), ppb (Al, Rb, Zn, Fe, Sr, Cu), and ppt (Ce, La, Nd, Tb) levels. Hierarchical clustering using Ward’s method and k-means analysis revealed four distinct clusters, including two major clusters representing the baseline macro- and microelement profile characteristic for the studied population. Correlations between elements revealed statistically significant (p < 0.05) positive and negative correlations between elements with (I) chemical similarity Ce-La, Cs-Rb, Rb-K, Ca-P, Zn-Cu, and Cs-K; (II) a possible common environmental origin, Cd-P, and Rb-P; (III) involvement in similar biological processes as K-P; and (iv) a common geochemical origin and similar biological functions, i.e., Se-Zn. The study identified several quantitative trends in the demographic and medical characteristics of the participants. Alcohol users had significantly higher Zn concentrations than non-alcohol users; women had significantly higher Ca concentrations than men; higher BMI correlated positively with Cs and negatively with Be and Cr levels; and Cu, Sb, Cd, Se, and Ca concentrations increased with age. The presence of several toxic and potentially toxic elements was identified in the vitreous body: Al (>10 ppb); Cd, Cr, Pb, Ni, Mn; and Ba (<10 ppb); As, Hg, Sb, Tl, Bi, Be (<1 ppb). The study showed that, within a given geographic region, the accumulation profiles of toxic metals are quite homogeneous, indicating common sources of exposure. Full article

Background: Noninvasive biomarkers for the detection and monitoring of glioblastoma (GBM) are needed to improve clinical outcomes for patients. The objective of this pilot study was to evaluate the expression of a panel of 48 pre-selected microRNAs (miRNAs) in plasma specimens from GBM patients versus healthy controls to identify candidate miRNA biomarkers for noninvasive diagnosis of GBM. Methods: Selection of candidate miRNA biomarkers was based on a comprehensive literature review and data mining. RNA was extracted from plasma samples obtained prior to resection from patients with GBM (n = 30) and age- and sex-matched healthy controls (n = 30), as well as from matched FFPE GBM tissue samples when available (n = 3). Expression levels of 48 miRNAs were assessed in all samples, and expression data was processed using proprietary software to generate potential biomarkers and train linear classifiers. Results: Overall miRNA expression patterns were similar between matched plasma and FFPE tumor tissues in patients with GBM. miRNA levels were examined in pairs to determine the ratio between two miRNAs, which served to normalize the data. The top five miRNA pairs for distinguishing between GBM and healthy control plasma included miR-17-5p/miR-19b-3p (AUC 0.93, 95% CI = 0.870, 0.970), miR-20a-5p/miR-19b-3p (AUC 0.93, 95% CI = 0.870, 0.970), miR-93-5p/miR-92a-3p (AUC 0.92, 95% CI = 0.875, 0.965), miR-17-5p/miR-92a-3p (AUC 0.91, 95% CI = 0.865, 0.955), and miR-93-5p/miR-19b-3p (AUC 0.90, 95% CI = 0.850, 0.950). For the development of a multi-biomarker combination classifier consisting of up to three miRNA pair biomarkers, miRNA pairs with an AUC ≥ 0.8 were selected to build equal-weight linear classifiers. All possible combinations of three high-performing miRNA pairs were tested across the 60 samples. The top classifier (miR-20a-5p/miR-451a, miR-582-5p/miR-222-3p, and miR-17-5p/miR-222-3p) achieved an AUC value of 0.992, sensitivity of 0.93, specificity of 1, and accuracy of 0.97. Conclusions: These findings support the continued development of a plasma-based miRNA molecular diagnostic approach for the detection of GBM. The strong discriminatory performance observed in this study, including high AUC values, highlights the potential of circulating miRNA signatures as a minimally invasive diagnostic tool. As a pilot analysis, this work establishes a foundation for future prospective studies in larger, independent cohorts—including relevant disease control populations—to further define clinical performance, specificity, and utility in diagnostic and monitoring settings. Collectively, these results represent an important step toward the translation of plasma-based miRNA profiling into clinical application for GBM. Full article

The peri-implantation window is a tightly regulated temporal phase during which the human endometrium undergoes coordinated molecular remodeling to establish receptivity. MicroRNAs (miRNAs) contribute to implantation-related processes; however, whether dynamic endometrial regulatory signals are functionally reflected in circulation within a defined temporal framework remains unclear. We hypothesized that although individual miRNA identities differ between endometrial tissue and plasma, temporally regulated miRNAs in both compartments may exhibit overlap at the level of enriched biological pathways during the peri-implantation window. To test this hypothesis, we performed time-resolved small RNA sequencing on paired endometrial and plasma samples collected from 62 participants across progesterone exposure days P+3 to P+7 in hormonally controlled cycles. Temporal modeling identified 27 dynamic miRNAs in endometrial tissue and 17 in plasma (FDR < 0.05). Despite limited overlap at the individual miRNA level, functional enrichment analysis revealed recurrent overlap in apoptosis-, cell cycle-, aging-, inflammatory-, and metabolic-related pathways across compartments. Four miRNAs exhibited concordant directional temporal trends between tissue and plasma with moderate correlation coefficients. These findings suggest that dynamic miRNA-associated enrichment patterns during the peri-implantation window may exhibit pathway-level overlap despite divergence in specific molecular identities. This temporally aligned integrative framework provides a pathway-centric perspective for interpreting cross-compartment miRNA-associated temporal patterns and supports a hypothesis-generating systems-level view of human implantation biology. Full article

Mycelium-based composites (MBCs) have emerged as promising biofabricated materials that align with circular economy and clean technology goals by utilizing fungal networks to transform lignocellulosic residues into functional, biodegradable composites. Despite the MBC’s potentials, the intrinsic nature of the fungal strain, substrate physico-chemical composition and engineering property variability remain significant hurdles that should be critically surmounted. Substrate treatment is central to determining growth kinetics, microstructural uniformity, and mechanical performance in MBC production. This review highlights recent advancements in physical, chemical, biological, and hybrid pretreatment methods, including comminution, pasteurization, alkali hydrolysis, enzymatic conditioning, microwave-assisted hydrolysis, ultrasound pretreatment, steam explosion, plasma activation, and irradiation. These technologies collectively enhance substrate digestibility, aeration, and permeability while reducing contamination. Optimization parameters—temperature, pH, C:N ratio, moisture content, particle size, porosity, and aeration—are examined as critical process levers influencing hyphal density, bonding efficiency, and composite uniformity. Evidence suggests that properly engineered substrate treatments accelerate colonization, strengthen hyphal networks, and significantly improve compressive, tensile, and flexural material properties. The review discusses emerging process control tools such as AI-assisted modeling, micro-CT porosity analysis, and sensor-integrated bioreactors that enable reproducible and energy-efficient fabrication. Collectively, the findings position substrate engineering as a foundational technology for scaling high-performance mycelium composites and advancing sustainable material innovation. Full article

Myelodysplastic syndromes (MDSs) are clonal hematopoietic disorders characterized by ineffective hematopoiesis and their diagnosis remains challenging, requiring integration of clinical, morphological, and genetic data. MicroRNAs (miRNAs) have emerged as potential biomarkers in MDS, offering insights into disease mechanisms and patient stratification. This study aimed to evaluate the diagnostic and prognostic significance of five plasma microRNAs (miR-22-3p, miR-144-3p, miR-16-5p, let-7a-5p, and miR-451a) in 40 patients with MDS, diagnosed according to WHO 2016 criteria and stratified by R-IPSS, and ten healthy controls. Plasma miRNA levels were measured by RT-qPCR. Expression profiles were compared between patients and controls, and further assessed in relation to disease subtypes, risk categories, and clinicopathological features. Expression analysis showed that miR-144-3p, miR-16-5p, let-7a-5p, and miR-451a were significantly lower in MDS patients compared to controls. MiR-451a demonstrated the highest diagnostic predictive value (p = 0.0022), followed by miR-16-5p (p = 0.0055), miR-144-3p (p = 0.0074), and let-7a-5p (p = 0.0092). Let-7a-5p was higher in MDS with excess blasts and both let-7a-5p and miR-451a were lower in the low-risk R-IPSS group. Strong correlations between miR-16-5p, miR-144-3p, and miR-451a were observed, probably reflecting their function in erythropoiesis. None of the investigated microRNAs showed independent prognostic significance for overall survival. In conclusion, circulating microRNAs, particularly miR-451a and let-7a-5p, show promise as supportive biomarkers that may complement existing diagnostic and risk assessment tools in MDS. Further studies are needed to validate their clinical applicability. Full article

This study investigates the tribological properties of 17-4PH martensitic stainless steel modified by plasma-based low-energy nitrogen ion implantation to enhance its surface hardness and wear resistance. The steel was nitrided at temperatures of 350 °C, 450 °C, and 550 °C for 4 h, and the resultant layers were characterized with respect to microstructure, hardness, and composition. Tribological tests were performed using a ball-on-disk tribometer under dry sliding conditions against an Si₃N₄ ceramic ball, with normal loads of 2–8 N and sliding speeds of 0.15–0.60 m/s. The results demonstrate that the nitrided layer thickness increased from 11 μm to 27 μm and the surface nitrogen concentration rose from 29.7 at.% to 33.1 at.% with increasing temperature, accompanied by an increase in nanocrystallite size from 2 nm to 15 nm and enhanced hardness from 13.51 GPa to 15.66 GPa. All nitrided layers exhibited significantly improved wear resistance relative to the unmodified steel. The layer nitrided at 450 °C demonstrated optimal performance due to a refined nanostructure and minor CrN that enhance plastic deformation resistance and facilitate oxide film formation. While, the 350 °C treated layer exhibits diminished thickness and reduced hardness, and the 550 °C treatment induces excessive CrN precipitation and micro-cracking, consequently compromising both toughness and wear resistance. Full article

Objective: Abdominal aortic aneurysm (AAA) epidemiology differs significantly between the sexes; the biological factors behind this are mostly unknown. MicroRNAs (miRNAs) are short RNA molecules providing post-transcriptional regulation of protein synthesis. Several miRNAs have been associated with the development and growth of AAA, but only in men. We investigated whether the associations between some selected miRNAs and aortic size differ by sex and the possible target pathways for such differences. Methods: A cross-sectional study included subjects with AAA (30–58 mm) and normal aortas. Clinical data were collected through questionnaires. Abdominal aortic diameters were measured using ultrasound. The levels of 17 miRNAs were measured in plasma. The association between miRNA levels, aortic diameter, and sex were analysed using multivariable linear regression. Results: A total of 242 subjects were included, with 85 women and 157 men. In the group with aortic diameters below 30 mm were 122 men (15–29 mm) and 50 women (13–29 mm). There were 35 men (30–54 mm) and 35 women (30–58 mm) with AAA. The associations between six miRNAs and aortic diameter were influenced by sex: miR-125 (p = 0.013), miR-128–1 (p = 0.017), miR-24 (p = 0.013), miR-26a (p = 0.022), miR-93 (p = 0.0015), and miR-194 (p = 0.013). Bioinformatic analysis indicated Hippo and TGF-beta as the two signalling pathways most likely affected by these differences. Conclusions: This exploratory study found sex differences in the associations between miRNA levels and aortic diameter, involving signalling pathways that control organ size and maintain tissue homeostasis by regulating cell proliferation, survival, and differentiation. Full article

Objectives: The peritoneal cavity is a cavity outside the bloodstream, with a specific hormonal, immunological and microbiological micro-environment distinct from plasma. The mesothelial cells lining the peritoneal cavity react within seconds to minor trauma, such as blood, with retraction, acute inflammation and later inflammation. This mesothelial cell retraction exposes the basal membrane, facilitating the implantation of tumour cells. Acute inflammation enhances adhesion formation after surgery and causes pain. The aim of the review was to check the hypothesis that retrograde menstruation, occurring in most women, is sufficient to cause some peritoneal irritation. Design: A systematic review of menstrual C-reactive protein (CRP) concentrations, a non-specific marker of peritoneal inflammation (PROSPERO ID 536306). Results: All articles (n = 8) showed a variable increase in CRP concentrations during the menstrual and early follicular phase of 80 ± 36%. Conclusions: CRP concentrations are slightly increased during menstruation and the early follicular phase. This increase is likely due to retrograde menstruation, causing mesothelial cell retraction and acute pelvic inflammation. It seems logical that mesothelial cell retraction facilitates endometrial cell implantation and accounts for the anatomical distribution of endometriosis lesions. Acute pelvic inflammation may enhance postoperative adhesion formation. Full article

Background/Objectives: Cryptorchidism is a common cause of male infertility and often results in azoospermia. However, the metabolic perturbations underlying cryptorchidism complicated with azoospermia and their association with surgical sperm retrieval outcomes remain poorly defined. Methods: A total of 35 patients with cryptorchidism and azoospermia, as well as 40 controls with normal semen parameters, were enrolled in the study. Seminal plasma samples from all participants were subjected to metabolomic analysis. Additionally, some patients underwent micro-TESE; the association between metabolomic features and the success or failure of surgical sperm retrieval was further analyzed. Results: A total of 931 differential metabolites were identified between patients and controls, primarily enriched in lipid metabolism and amino acid metabolism pathways. Lipid metabolites were broadly downregulated in patients, while several inflammation-related metabolites, including Prostaglandin E2, were upregulated. Routine clinical parameters showed no significant differences between patients with successful and failed micro-TESE. However, metabolomic profiles effectively distinguished these two subgroups. These differential metabolites between the two subgroups were mainly involved in three key pathways: phenylalanine–tyrosine–tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, and folate biosynthesis. Most metabolites in the first two pathways were downregulated in the successful retrieval group, while those in the folate biosynthesis pathway showed the opposite regulatory trend. Four metabolites, including Leucine, 7,8-Dihydroneopterin, L-Tyrosine and Pterin, exhibited robust predictive value for micro-TESE outcomes. Conclusions: This study reveals distinct metabolic signatures in patients of cryptorchidism with azoospermia. The identified metabolic biomarkers provide valuable references for clinical decision-making regarding micro-TESE, facilitating a personalized assessment of sperm retrieval feasibility. Full article

Electrical Discharge Machining (EDM) enables precision post-weld finishing of AISI 304 stainless steel, but stochastic spark overlaps make the fatigue-critical maximum peak-to-valley height (R_max) difficult to predict. This study develops a validated physics-based framework quantifying how crater overlap governs R_max evolution. Experiments on unwelded AISI 304 cylinders—proxying weld metal while excluding heat-affected zone (HAZ) effects—used Central Composite Design (20 trials, 900–9380 μJ discharge energies). Profilometry and scanning electron microscopy (SEM) correlated the crater size, overlap intensity, micro-cracking, and R_max escalation from 18 to 85 μm. Primary and secondary crater formation under minimum and maximum overlap configurations were simulated using a 2D axisymmetric finite element model with Gaussian heat flux and temperature-dependent thermophysical properties. The predictive metric R_max,num = (d_initial + d_secondary)/2 achieved 11–19% average error against the experimental R_max,exp, with complementary valley depth (R_v) validation at 13% error. The Specimen 7 outlier (~50% error) reveals the limitations of deterministic modelling under stochastic debris accumulation and plasma instability at intermediate energies. Crater overlap generates secondary dimples, sharp inter-crater peaks, and rim micro-crack networks, driving the 4.7-fold R_max increase—approaching International Institute of Welding (IIW) fatigue thresholds (<25 μm for high-cycle categories). The framework explicitly links the discharge energy, plasma channel radius (R_pc), and overlap geometry to surface topography, enabling process optimization (I·t_on < 60 A·s maintains R_max < 25 μm). Mesh independence (<2.5% convergence) and six centre-point replicates (CV = 4.2%) confirm robustness. This validated upper-bound R_max predictor supports the digital co-optimization of welding and EDM parameters for aerospace/energy applications, with planned extensions to stochastic 3D models incorporating adaptive remeshing and real weld topographies. Full article